Stool Glycoproteomics Signatures of Pre-Cancerous Lesions and Colorectal Cancer.

Colorectal cancer (CRC) screening relies primarily on stool analysis to identify occult blood. However, its sensitivity for detecting precancerous lesions is limited, requiring the development of new tools to improve CRC screening. Carcinogenesis involves significant alterations in mucosal epithelium glycocalyx that decisively contribute to disease progression. Building on this knowledge, we examined patient series comprehending premalignant lesions, colorectal tumors, and healthy controls for the T-antigen-a short-chain O-glycosylation of proteins considered a surrogate marker of malignancy in multiple solid cancers. We found the T-antigen in the secretions of dysplastic lesions as well as in cancer. In CRC, T-antigen expression was associated with the presence of distant metastases. In parallel, we analyzed a broad number of stools from individuals who underwent colonoscopy, which showed high T expressions in high-grade dysplasia and carcinomas. Employing mass spectrometry-based lectin-affinity enrichment, we identified a total of 262 proteins, 67% of which potentially exhibited altered glycosylation patterns associated with cancer and advanced pre-cancerous lesions. Also, we found that the stool (glyco)proteome of pre-cancerous lesions is enriched for protein species involved in key biological processes linked to humoral and innate immune responses. This study offers a thorough analysis of the stool glycoproteome, laying the groundwork for harnessing glycosylation alterations to improve non-invasive cancer detection.

Differential Retrospective Analysis in Oral Cancerous, Pre-cancerous, and Benign Tissue Biopsies.

Background/Aim Oral epithelia demonstrate a broad spectrum of pre-cancerous, cancerous, and benign lesions. The aim of this study was to record and analyze the prevalence of various oral and intraosseous lesions, highlighting malignancies that are hard to clinically identify as such too. Materials and methods A series of 536 oral lesions were collected covering a period of 8.5 years. Epidemiological and clinico-histopathological data were stratified and analyzed retrospectively. Results According to extensive differential analysis, the male to female ratio for oral squamous cell carcinoma was estimated at 1:1, for pre-cancerous lesions at 1:2, and for lichen planus at 1:5. The prevalent diagnostic category were cysts (n = 223, 41.6%). The biological behavior of lesions differed among anatomic sites (P<0.001). Concordance between clinical suspicion of pre-cancerous or malignant lesions and histological verification was 96.4% (P<0.001). Conclusions Primary intraosseous squamous cell carcinoma, acinic cell carcinoma, clear cell myoepithelial carcinoma, aggressive osteoblastoma/parosteal osteosarcoma, and undifferentiated carcinoma raised no clinical suspicion of malignancy reflecting the importance of training in oral biopsy taking.

Targeting IL-17alpha to promote anti-PD-1 therapy effect by screening the tumor immune microenvironment in a mouse oral carcinogenesis model.

BACKGROUND: Resistance to PD-1 blocking agents is not uncommon, limiting their wide clinical success. Certain tumor-infiltrating immune cells (e.g., TILs/CTLs) have emerged as biomarkers of response, and absence of such immune cells contributes to resistance. OBJECTIVE: We deconvoluted the dynamic immune microenvironment in a mouse model of oral carcinogenesis for augmenting the resistance to PD-1 blocking agents by combination. METHODS: Bioinformatics methods and routine biological experiments were adopted such as morphological analysis and ELISA in the 4NQO-treated mice model. RESULTS: Our findings revealed that dysplastic tongue tissues from 4NQO-treated mice were characterized by an immunosuppressive tumor microenvironment. Tongue tissues from mice treated with 4NQO for 12 weeks had higher levels of Th2 cells and Tregs compared to tissues taken from control mice or mice treated with 4NQO for 28 weeks; these results suggested a potential therapeutic benefit of anti-PD-1 in the oral cancer. The IL-17 pathway was significantly upregulated during progression from normal mucosa to hyperplasia and tumor formation in mice. Inhibition of IL-17α combined with PD-1 blockade delayed the development of 4NQO-induced precancerous and cancerous lesions and prolonged the survival of 4NQO-treated mice. CONCLUSIONS: Our data suggested a strong rationale of IL-17α blockade as a potential approach to augment the tumor-eliminating effects of anti-PD-1 therapy.

Effect of successive endoscopic procedures in polyp and adenoma detection rates: Too early is not always too good.

BACKGROUND AND AIMS: There is conflicting evidence regarding the impact of hypothetical cumulative fatigue after performing too many endoscopic procedures on both polyp and adenoma detection rates (PDR, and ADR, respectively). The aim of this study is to evaluate the effect of successive endoscopic procedures on PDR and ADR. METHODS: A retrospective cross-sectional study was undertaken among consecutive patients on whom colonoscopy and/or esophagogastroduodenoscopy were performed between January 2012 and August 2014. Data regarding polyp and adenoma detection, cecal intubation, and bowel cleansing quality as well as demographical data of subjects were extracted. Endoscopic procedures were classified according to the time slots of the procedures throughout the endoscopy session in three groups: from the 1st to 4th endoscopy study (round 1), from the 5th to the 8th study (round 2), above the 9th study (round 3). We compared PDR and ADR among rounds. RESULTS: Overall, 3388 patients were enrolled. Median age was 50 years (range 18-95) and 52.39% were female. There was a significant difference in terms of PDR among rounds (36.83%, 41.24%, and 43.38%, respectively, p = 0.007) and a non-significant numerical difference when ADR was compared (23.2%, 25.71%, and 26.78%, p = 0.07). On multivariate analysis, ADR was significantly associated with age (odds ratio [OR] 1.02 [1.01-1.03]), and male sex (OR 1.64 [1.38-1.94]). CONCLUSION: Theoretical endoscopist's fatigue due to cumulative performance of endoscopies does not diminish colonoscopy quality. Both PDR and ADR seem to improve after endoscopist's cumulative rounds of performed endoscopies. This could be due to a "warm-up" effect.

Liquid based-cytology Pap smear dataset for automated multi-class diagnosis of pre-cancerous and cervical cancer lesions.

While a publicly available benchmark dataset provides a base for the development of new algorithms and comparison of results, hospital-based data collected from the real-world clinical setup is also very important in AI-based medical research for automated disease diagnosis, prediction or classifications as per standard protocol. Primary data must be constantly updated so that the developed algorithms achieve as much accuracy as possible in the regional context. This dataset would support research work related to image segmentation and final classification for a complete decision support system (https://doi.org/10.1016/j.tice.2020.101347) [1]. Liquid-based cytology (LBC) is one of the cervical screening tests. The repository consists of a total of 963 LBC images sub-divided into four sets representing the four classes: NILM, LSIL, HSIL, and SCC. It comprises pre-cancerous and cancerous lesions related to cervical cancer as per standards under The Bethesda System (TBS). The images were captured in 40x magnification using Leica ICC50 HD microscope collected with due consent from 460 patients visiting the O&G department of the public hospital with various gynaecological problems. The images were then viewed and categorized by experts of the pathology department.

Lesiones cancerígenas y precancerosas bucales. Factores de riesgos asociados. Policlínico Bernardo Posse. Año 2017 / Cancerous and pre-cancerous buccal lesions. Associated risk factors. Policlínico Bernardo Posse Years 2017

RESUMEN Introducción: el cáncer bucal constituye uno de los mayores problemas de salud al cual se enfrenta la humanidad, no solo en el ámbito de salud pública sino también en la ciencia en general, que afecta un grupo significativo de personas en todo el mundo. Objetivo: describir el comportamiento de las lesiones precancerígenas y cancerígenas de la cavidad bucal y los factores de riesgos asociados en individuos pertenecientes al Policlínico Bernardo Posse, municipio San Miguel del Padrón, La Habana, 2017. Materiales y métodos: se realizó un estudio analítico retrospectivo en pacientes de más de 15 años de edad entre enero y noviembre del 2017 sobre los factores de riesgo asociados con la aparición de lesiones premalignas y malignas del complejo bucal con un universo de 631 pacientes. Se operacionalizaron las variables en estudio. Resultados: se mostró un predominio del sexo masculino en un 52,9 %, siendo el grupo de edad más frecuente el comprendido entre 35 a 59 años para un 53.2%. Las lesiones precancerígenas de la cavidad bucal fueron más frecuentes en los grupos etáreos mayor de 60 años para un 1,42 %. De los pacientes examinados, el 53.2% consumen bebidas alcohólicas de forma habitual. Conclusiones: en el estudio predominaron las personas del sexo masculino y los mayores de 35 años de edad. Las lesiones precancerígenas de la cavidad bucal fueron más frecuentes en los grupos etáreos de mayor de 60 años. Se constató relación entre los factores de riesgo estudiados y la presencia de lesiones malignas y premalignas (AU).

ABSTRACT Introduction: cancer is one the major health problems in humanity, not only in the field of public health, but also in science in general.It affects a significant group of persons in the world. Objetive: to describe the behavior of the cancerous and pre-cancerous lesions in the buccal cavity and risk factors associated with patients assisted in Bernardo Posse Clinic, located in San Miguel del Padrón municipality, Havana, 2017. Materials and methods: an analytic and retrospective study about risk factors associated with cancerous and pre-cancerous lesions in the buccal cavity in patients aged 15 and over, between January and November, 2017. There is a universe of 631 patients. Some variable were analyzed in the study. Results: the male sex predominated prove a predominance of sex masculine with a 52, 9 %. The 35 and 59 age group was the most affected, with a 53,2%. The age group older than 60 was the most affected with pre-cancerous lesions in the buccal cavity, with a 1, 42 %. From the patients examined throughout the research, the 53, 2% consumed alcohol in a regular way. Conclusions: in the study predominated the persons of male sex and the older than 35 years. The pre-cancerous lesions were more frequent in the age group older than 60 years .If was proved the relation between the risk factors and the cancerous and pre-cancerous lesions (AU).

Lesiones cancerígenas y precancerosas bucales. Factores de riesgos asociados. Policlínico Bernardo Posse. Año 2017 / Cancerous and pre-cancerous buccal lesions. Associated risk factors. Policlínico Bernardo Posse Years 2017

RESUMEN Introducción: el cáncer bucal constituye uno de los mayores problemas de salud al cual se enfrenta la humanidad, no solo en el ámbito de salud pública sino también en la ciencia en general, que afecta un grupo significativo de personas en todo el mundo. Objetivo: describir el comportamiento de las lesiones precancerígenas y cancerígenas de la cavidad bucal y los factores de riesgos asociados en individuos pertenecientes al Policlínico Bernardo Posse, municipio San Miguel del Padrón, La Habana, 2017. Materiales y métodos: se realizó un estudio analítico retrospectivo en pacientes de más de 15 años de edad entre enero y noviembre del 2017 sobre los factores de riesgo asociados con la aparición de lesiones premalignas y malignas del complejo bucal con un universo de 631 pacientes. Se operacionalizaron las variables en estudio. Resultados: se mostró un predominio del sexo masculino en un 52,9 %, siendo el grupo de edad más frecuente el comprendido entre 35 a 59 años para un 53.2%. Las lesiones precancerígenas de la cavidad bucal fueron más frecuentes en los grupos etáreos mayor de 60 años para un 1,42 %. De los pacientes examinados, el 53.2% consumen bebidas alcohólicas de forma habitual. Conclusiones: en el estudio predominaron las personas del sexo masculino y los mayores de 35 años de edad. Las lesiones precancerígenas de la cavidad bucal fueron más frecuentes en los grupos etáreos de mayor de 60 años. Se constató relación entre los factores de riesgo estudiados y la presencia de lesiones malignas y premalignas.

ABSTRACT Introduction: cancer is one the major health problems in humanity, not only in the field of public health, but also in science in general.It affects a significant group of persons in the world. Objetive: to describe the behavior of the cancerous and pre-cancerous lesions in the buccal cavity and risk factors associated with patients assisted in Bernardo Posse Clinic, located in San Miguel del Padrón municipality, Havana, 2017. Materials and methods: an analytic and retrospective study about risk factors associated with cancerous and pre-cancerous lesions in the buccal cavity in patients aged 15 and over, between January and November, 2017. There is a universe of 631 patients. Some variable were analyzed in the study. Results: the male sex predominated prove a predominance of sex masculine with a 52, 9 %. The 35 and 59 age group was the most affected, with a 53,2%. The age group older than 60 was the most affected with pre-cancerous lesions in the buccal cavity, with a 1, 42 %. From the patients examined throughout the research, the 53, 2% consumed alcohol in a regular way. Conclusions: in the study predominated the persons of male sex and the older than 35 years. The pre-cancerous lesions were more frequent in the age group older than 60 years .If was proved the relation between the risk factors and the cancerous and pre-cancerous lesions.

Blockade of PD-1 effectively inhibits in vivo malignant transformation of oral mucosa.

Curbing PD-1 immunosuppressive signaling represents an effective immune awakening or immune-reactivation approach for tumor eradication for many cancers. Yet, the potential involvement of this critical PD-1 immunosuppressive signaling in de novo malignant transformation of epithelial cells to pre-cancerous or cancerous lesions is largely unknown. In this study, we demonstrate that PD-1 signaling is critically involved in de novo malignant transformation of oral mucosa upon carcinogen exposure in vivo. Our findings revealed that 4NQO-treated mice had almost double the numbers of PD-1-positive CD4+ cells and PD-1-positive CD8+ cells in peripheral blood lymphocytes as well as elevated PD-1 expression in tumor infiltrating lymphocytes (when compared to that of control-treated mice), strongly supportive of a general immune-suppression induced by carcinogen challenges in vivo. Importantly, inhibition of PD-1 signaling during the carcinogenesis process (immediately after 4NQO challenge) significantly reduced and delayed de novo formation of both pre-cancerous and cancerous lesions in vivo, in conjunction with effective PD-1 down-modulation in the tumor infiltrating leukocyte and peripheral lymph organs. Lastly, reduction of carcinogen-induced lesions upon PD-1 mAb treatment in vivo was accompanied by reduction of potent immunosuppressive myeloid-derived suppressor cells (MDSCs), and increase in "activated" T cell accumulations in the lesion-microenvironment (127% increase) and peripheral lymph nodes (25% increase). These data support PD-1 blockade as a new approach to enhance the efficacy of T-cell immunotherapy and reduce canceration rate in premalignant lesions.

[Human papillomavirus nonavalent vaccine. Update 2017]. / Vacuna nonavalente frente al virus del papiloma humano. Actualización 2017.

Human papillomavirus (HPV) is the causative agent of 5% of human cancers. HPV infection is necessary for the development of cervical cancer and is responsible of a variable percentage of cancers of anus, vulva, vagina, penis, and oropharynx. Since 2007, 2 vaccines against HPV have been commercially available in Spain: bivalent (HPV types 16/18), and tetravalent (HPV types 6/11/16/18). In order to extend the protection afforded by HPV vaccines, a clinical program was launched in 2006 for the new nonavalent vaccine, including 9 HPV types (6/11/16/18/31/33/45/52/58). These types are responsible for 90% of cervical cancers, 82% of high-grade ano-genital pre-cancerous lesions, and 90% of genital warts. The purpose of this publication is to provide healthcare professionals with the scientific evidence that supports the new vaccine, as well as the clinical value that it offers in our environment.

Potentially malignant disorders of the oral cavity: a clinical study.

Oral cancers in India, unlike in the West are the most common cancers encountered, be it a primary or a tertiary referral practice. This makes the study and management of these cancers an important issue especially for the otolaryngologist. It is well known that the most common variant of oral cancers is the squamous cell carcinoma. Also the etiology is well established; with tobacco use in both smoking and smokeless forms, alcohol, betel nut and recently the Human Papilloma virus infection being implicated. Certain conditions which definitely increase the probability of getting oral cancers are known and this study aims in revisiting these aspects of pre-malignancy. The progression from a pre-cancerous lesion/condition to frank cancer is well established across many studies and many specialties. Also timely recognizing these pre-cancerous conditions and administration of proper treatment will greatly help in reducing the morbidity and mortality from subsequent much advanced and dangerous oral cancer. Keeping these facts in mind this study was planned to study the established pre-cancerous lesions which are known to progress to oral cancers.

Low resource screening method of pre-cancerous lesions and its reversal by Triphala in teen-age Indian population.

BACKGROUND: Cancer screening is the main weapon for early detection at a pre-invasive or premalignant stage. It has been reported that over 12 million people use some form of tobacco, which is one of the high risk factors and has hence become an alarming world-wide problem. AIM: To evaluate the effective diagnostic screening of disease in its early stage by inexpensive method and also to evaluate the effect of indigenous mouthrinse on reversal of pre-cancerous lesions. MATERIALS AND METHODS: The screening for teenagers belonging to low socio-economic status was carried out. Suspected subjects were evaluated for the reversal of the lesions by use of Ayurvedic preparation as a mouthwash. From 13 to19 years working-child population of North India was selected for the study. Screening was performed by new method-visual inspection with acetic acid. The positive subjects were further investigated by pap smear and biopsy was done as a confirmatory histopathological report. In second phase, the subjects showing positive lesions were advised indigenous anti-cancer mouth rinse and its effect was evaluated after 6 month and 9 month of prescribing the rinse. RESULTS: The total 1095 children were screened (831 boys and 264 girls). Out of total 34 teenager boys were diagnosed, as acetowhite positive lesion. All the acetowhite positive lesions were found exclusively in males. Histological findings after 9 month use of Triphala mouth rinse revealed no changes in cells in 23 (85.2%), hyperkeratinization in 2 (7.4%), hyperkeratinization and spongiosis was evident in 1 (3.7%), mild pleomorphism in 1 (3.7%) patient. Comparative evaluation from 0-9 month showed statistically highly significant test (P < 0.01). CONCLUSION: Use of different forms of tobacco and betel nut showed convincing relationship between developments of oral pre-cancerous lesions. Triphala was found to have great potential for reversal of these lesions.

Diversity of HPV types in cancerous and pre-cancerous penile lesions of South African men: implications for future HPV vaccination strategies.

This study reports the detection of HPV types from cancerous and pre-cancerous penile lesions that were diagnosed histologically. Sixty-six (22 pre-cancerous and 44 cancerous lesions) tissue biopsies, received between 2004 and 2011 by the Anatomical Pathology Department at Dr. George Mukhari Hospital were selected for this study. Total DNA was extracted and genotyped using type specific real-time quantitative polymerase chain reaction (qPCR) for 18 HPV types. Of 66 samples, only 51 were included in the analysis. Overall, HPV 11 (50.9%) and HPV 16 (49.1%) showed almost similar incidence in the study patients. In pre-cancerous lesions, HPV 11 was more frequent (80.0%), followed by HPV 31 and HPV 16 at 25.0% each and other HPV types included 35 (15.0%), 59 (15.0%), 53 (10.0%), 33 (10.0%), 18 (5.0%), 51 (5.0%), 52 (5.0%), 56 (5.0%), and 67 (5.0%). For cancerous lesions, HPV 16 was the most detected (62.9%), followed by HPV 11 (34.3%), and other HPV types included 18 (11.4%), 33 (5.7%), 39 (5.7%), 45 (5.7%), 66 (5.7%), 52 (2.9%), 58 (2.9%), 6 (2.9%), and 67 (2.9%). Several lesions demonstrated multiple HPV infections, ranging from two to six different types in one lesion. The study showed high diversity of HPV types in cancerous and pre-cancerous lesions of South African males with the most frequent being HPV types 11 and 16. The data suggest that boys could directly benefit from vaccination as they are exposed to variety of HPV types as early as 10 years of age in Africa.

[Twelve months of colposcopy use at the Brazzaville University Hospital Gynecology Clinic]. / Bilan d'un an de colposcopie à la maternité du CHU de Brazzaville

OBJECTIVE: To assess the utility of a colposcope after 12 months of use at the Brazzaville University Hospital. PATIENTS AND METHODS: This retrospective study took place in the gynecology unit of the Brazzaville University Hospital and reviewed records dating from January 11, 2010, through January 10, 2011. In all, 150 women (13.5% of all gynecology consultations) underwent colposcopies in the department, for one of two indications: diagnostic colposcopy after an abnormal cervical smear, 91 cases (60.7%), and primary colposcopy in women admitted without a cervical smear, 59 cases (39.3%). High-grade squamous intraepithelial lesions (HGILs) were noted in 36.7% of the cases; the colposcopy was normal in 17.3% of the cases, and squamous cell carcinoma was found in 8.6% of the cases. Colposcopy found HGILs on 14 smears of 24 cervical smears reporting low-grade squamous intraepithelial lesions (LGIL), six of seven initially reported as HGIL, and 10 of 20 initially reported as atypical squamous cells of undetermined significance (ASCUS) on 20. In all, 93 women (62%) had biopsies. Cervical intraepithelial neoplasia 2 (CIN2) lesions were noted on 19 of the 55 biopsies of HGIL colposcopies and CIN3 on four of the 55. DISCUSSION: Colposcopy remains unavailable to too many women, largely because of the difficulty in obtaining a primary cervical smear tests. This also explains the overuse of primary colposcopy or, at least, the uncertainty about its role.

Uso do colposcópio (estomatoscópio) para exame de lesões da cavidade oral / The use of colposcope (stomatoscope) for the examination of the oral cavity lesions

Introdução: o câncer da cavidade oral está dentre os dez mais comuns cânceres no mundo. Apesar da facilidade para o acesso e o exame da cavidade oral, cerca de 50% desses tumores são diagnosticados tardiamente. Existe a necessidade de encontrar-se um método não invasivo para o diagnóstico precoce das lesões malignas. Objetivo: avaliar a colposcopia (estomatoscopia) no exame de lesões da cavidade oral, após a oroscopia. Método: Observou-se a mucosa orcal em geral, as bordas e a periferia das lesões, interessando as alterações da cor, as ulcerações superficiais e as alterações vasculares. Aplicou-se o teste do azul de toluidina. Foram incluídos 100 pacientes, com 130 lesões. Resultados: Foi diagnosticado carcinoma espinocelular em 57,4 % das eritroplasias, 66% das leuco-eritroplasias, 20% das leucoplasias, 65% das atipias vasculares e em 60 % das ulcerações superficiais. Das nove eritroplasias em salpicado, 55,5% eramcarcinomas. Conclusão: a estomatoscopia permite a identificação de lesões iniciais.

Introduction: The oral cavity cancer is one of the commonest cancers all over the world. In spite of the easy approach and examination of the oral cavity, some 50% out of those tumors are diagnosed in advanced stages. It is necessary to find a non invasive method for the early diagnosis of those malignant lesions. Objective: to evaluate the colposcopy (stomatoscopy) applied to the oral cavity lesions diagnosis. Methods: The oral mucosa in general, the edges and the lesions neighboring were examined, paying attention to colors changes, superficial ulcerations and vascular alterations. The toluidine blue test was performed. The casuistics included 100 patients with 130 lesions. Results: The carcinoma was diagnosed in 57.4% of the erytroplakias (55% when it was em salpicado), 66% of the leuco-erytroplasias, 20% of the leucoplasias, 65% of the vascular atypias and 60% of the superficial ulcerations. Conclusion: The stomatoscopy allows the identification of early lesions.