Anterior lamellar corneoscleral keratoplasty for the management of corneal thinning following treatment with mitomycin-C and interferon to treat highly suspected ocular surface squamous neoplasia: a case report

ABSTRACT A patient presented with corneoscleral thinning five months after the treatment of suspected ocular squamous surface neoplasia with mitomycin-C and interferon. For tectonic and aesthetic purposes, we decided to perform lamellar corneoscleral transplantation. The approach used established new tectonic support and corneal homeostasis. This technique might be an option in similar cases.

Carcinoma escamoso variedad sarcomatoide de lengua. Reporte de caso / Sarcomatoid variant squamous cell carcinoma of the tongue. Case report

Introducción. El carcinoma de células escamosas es una patología relativamente frecuente en Paraguay, que debe ser diagnosticada y tratada a tiempo. La variedad sarcomatoide es un subtipo poco frecuente, pero mucho más agresivo que la presentación convencional, con altas tasas de recurrencia y metástasis linfática. La exposición previa a radiación es uno de los principales factores desencadenantes. Caso clínico. Paciente de 83 años con antecedente de radioterapia por carcinoma escamocelular del paladar blando, quien consultó por una masa en el borde lateral de la lengua que correspondió a un carcinoma escamocelular del subtipo sarcomatoide. Resultados. El paciente fue sometido a cirugía y quimioterapia, pero presentó recaída tumoral a los cuatro meses, sin aceptar una cirugía de rescate, optando por el tratamiento paliativo y falleciendo a los pocos meses. Conclusión. El examen exhaustivo de la cavidad oral en una primera consulta permite identificar lesiones en estadios tempranos y el tratamiento multidisciplinario temprano puede mejorar la supervivencia global. El pronóstico de estos pacientes en estadios avanzados es desalentador. Actualmente la cirugía microvascular es la mejor opción terapéutica, pero la hemiglosectomía sin reconstrucción sigue siendo una opción aceptable en nuestro medio, conociendo los altos costos de la primera y el requerimiento de un grupo mayor de especialistas, largos tiempos quirúrgicos y estancias hospitalarias.

Introduction. Squamous cell carcinoma is a relatively common pathology in Paraguay, which must be diagnosed and treated on time. The sarcomatoid variety is a rare subtype, but much more aggressive than the conventional presentation, with high rates of recurrence and lymphatic metastasis. Previous exposure to radiation is one of the main triggering factors. Clinical case. An 83-year-old patient with a history of radiotherapy for squamous cell carcinoma of the soft palate, who consulted for a mass on the lateral edge of the tongue that corresponded to a squamous cell carcinoma of the sarcomatoid subtype. Results. The patient underwent surgery and chemotherapy, but had tumor relapse after four months, without accepting salvage surgery, opting for palliative treatment and dying a few months later. Conclusion. Exhaustive examination of the oral cavity in a first consultation allows lesions to be identified in early stages and early multidisciplinary treatment can improve overall survival. The prognosis of these patients in advanced stages is discouraging. Currently, microvascular surgery is the best therapeutic option, but hemiglossectomy without reconstruction continues to be an acceptable option in our environment, knowing the high costs of the former and the requirement for a larger group of specialists, long surgical times and hospital stays.

Expression analysis and biological regulation of silencing regulatory protein 6 (SIRT6) in cutaneous squamous cell carcinoma

Abstract Background Cutaneous squamous cell carcinoma (CSCC) is one of the most common types of skin cancer worldwide. Therefore, the identification of biomarkers associated with CSCC progression could aid in the early detection of high-risk squamous cell carcinoma and the development of novel therapeutic strategies. Objective This study aimed to investigate the expression patterns of silent mating type Information Regulation 2 homolog 6 (SIRT6) in CSCC and its clinical significance. Methods The protein expression level of SIRT6 in tissues was detected by immunohistochemistry, and the correlation between SIRT6 expression and clinicopathological parameters in CSCC patients was analyzed. The relative expression of SIRT6 in CSCC cell lineage and tissue specimens was determined by western blotting and PCR. The effect of SIRT6 silencing on cell proliferation was evaluated using cell counting kit 8. Wound healing, transwell method, and flow cytometry were used to investigate the migration, invasion, and cell cycle distribution/apoptosis of CSCC cells after SIRT6 silencing, respectively. Western blot was used to detect the expression of EMT (Epithelial-Mesenchymal Transition), cycle, apoptosis, and other related proteins. Results The high expression of SIRT6 was correlated with the location of cancer tissue and Broder staging in CSCC patients. Knockdown of SIRT6 inhibited the proliferation, migration, invasion and EMT of CSCC cells, and promoted their apoptosis, with cells blocked in G1 phase. Study limitations No animal experiments were conducted to further verify the results. Conclusion Decreased expression of SIRT6 can inhibit the occurrence and development of CSCC.

Histoplasmosis oral como diagnóstico diferencial de cáncer oral. Serie de casos y revisión de la literatura / Oral histoplasmosis as a differential diagnosis of oral cancer. Case series and literature review

Objetivo: La histoplasmosis es una infección fúngica sistémica prevalente en la región del Río de la Plata. Puede exhibir manifestaciones orales, cutáneas y/o sistémicas. Las lesiones bucales significan un desafío diagnóstico debido a su semejanza clínica con el carcinoma oral de células escamosas (COCE). El objetivo de este trabajo fue presentar una serie de casos de histoplasmosis oral enfatizando la importancia del diagnóstico diferencial clínico con el COCE. Casos clínicos: Se describen casos de histoplasmosis oral diagnosticados en los últimos 5 años en la Cátedra de Estomatología "A" de la Facultad de Odontología de la Universidad Nacional de Córdoba, Córdoba, Argentina. En forma paralela, se realizó una revisión de la literatura de los últimos 10 años. Los casos corresponden a 9 pacientes, 6 varones y 3 mujeres, cuya edad promedio fue de 58,6 años. 4 pacientes eran VIH positivos. Se planteó la sospecha de COCE en 5 pacientes, cuya presentación clínica intraoral consistía en úlceras o lesiones ulcerovegetantes, mayormente únicas, ubicadas en la encía. La revisión bibliográfica arrojó un resultado de 48 artículos que incluyeron 60 casos de histoplasmosis oral, con una prevalencia mayor en hombres y similitudes clínicas con COCE en el 80% de los casos. La lesión más predominante fue la úlcera en el 85% de los casos, ubicada en lengua, seguido por el paladar. El diagnóstico de histoplasmosis oral es desafiante y requiere un amplio diferencial, ya que se asemeja a múltiples patologías, debiendo ser considerada ante lesiones ulcerativas orales. Un diagnóstico preciso, de manera interdisciplinaria, es esencial para un tratamiento efectivo.(AU)

Aim: Histoplasmosis is a systemic fungal infection prevalent in the Río de la Plata region. It could present oral, cutaneous and/or systemic manifestations. Oral lesions represent a diagnostic challenge due to their clinical similarity to oral squamous cell carcinoma (OSCC). The objective of this work is to present a case series of oral histoplasmosis emphasizing the importance of clinical differential diagnosis with OSCC. Clinical cases: Cases of oral histoplasmosis diagnosed in the last 5 years in the Oral Medicine Department "A" of the Facultad de Odontología of the Universidad Nacional de Córdoba, Córdoba, Argentina are discribed. Alongside, a literature review of the last 10 years was carried out. 9 patients are described, 6 men and 3 women, whose average age was 58.6 years. 4 patients were HIV positive. The suspicion of OSCC was raised in 5 patients, whose intraoral clinical presentation consisted of single ulcers or vegetating ulcers, mostly single, located in the gingiva. The literature review included a total of 48 articles with 60 cases of oral histoplasmosis, with a higher prevalence in men and clinical similarities with OSCC in 80% of cases. The most predominant lesion was the ulcer in 85% of the cases, mostly located on the tongue, followed by the palate. The diagnosis of oral histoplasmosis is challenging and requires a wide differential, since it can mimic multiple pathologies, and should be considered in oral ulcerative lesions. An accurate diagnosis, in an interdisciplinary framework, is essential for effective treatment.(AU)

Colgajos libres para reconstrucción de cabeza y cuello: experiencia de un centro oncológico chileno

Objetivo: eportar nuestra experiencia en la reconstrucción de pacientes con tumores de cabeza y cuello. Materiales y Métodos: Revisión retrospectiva de fichas clínicas de los pacientes sometidos a reconstrucciones con colgajos microquirúrgicos entre los años 2007 y 2020 en la Fundación Arturo López Pérez. Resultados: En este período 186 cirugías fueron realizadas, lo que correspondió a 173 pacientes, la mediana de edad fue de 59 años, 55% eran hombres. 29% correspondieron a rescates quirúrgicos. Al diagnóstico 110 (54%) tenían una enfermedad localmente avanzada (T3-T4). El sitio anatómico más frecuentemente reconstruido fue la cavidad oral, 83(45%). La histología más frecuente fue el carcinoma escamoso. Los colgajos más utilizados fueron el osteocutáneo de peroné, anterolateral de muslo (ALT) y antebraquial. La sobrevida global a 5 años fue 44,3%, con amplia variabilidad entre las distintas histologías. Discusión: En el análisis de nuestros resultados en dos períodos de siete años (2007-2013 y 2014-2020), el porcentaje de falla de colgajo disminuyó (10% versus 2,6%; p = 0,012); al igual que la estadía hospitalaria que disminuyó (de una mediana de 23 días a 18 días; p = 0,041). El uso del colgajo ALT aumentó de 14% a 29%, esto último aprovechando la versatilidad del colgajo de ALT para la fabricación de múltiples paletas cutáneas, que permiten reconstrucciones más complejas. Conclusión: Las reconstrucciones microquirúrgicas en nuestra institución son una opción estandarizada, confiable y comparable con centros internacionales.

Objective: To report our experience, and success rate for head and neck reconstruction in a Chilean oncologic center. Methods: Charts were reviewed retrospectively for all patients treated surgically for head and neck tumors that needed a free flap reconstruction from 2007 to 2020. The demographics and epidemiologic variables were described. Overall survival was calculated with the Kaplan-Meier method. Results: One hundred and eighty-six operations were performed on 173 patients; the median age was 59 years, and 55% were male. Twenty-nine percent of patients required a surgical rescue. The most frequently used free flaps were the anterolateral thigh, fibula osteocutaneous, and radial forearm. A second free flap was needed in 13 patients. Five-year overall survival for the whole cohort was 44.3% and varied according to histology: 28.2% for squamous cell carcinoma and 68.9% for salivary gland histology. Discussion: In analysis of our results in two seven-year periods (2007-2013 and 2014-2020), the percentage of flaps that failed decreased (10% earlier versus 2.6% later; p =.012); the length of hospital stay declined (median 23 days earlier vs 18 days later; p =.041), and the use of anterolateral thigh flaps increased 14% vs 29%, taking advantage of the versatility of the anterolateral thigh flap for the fabrication of multiple skin palettes, allowing for more complex reconstructions. Conclusion: In our institution, outcomes with free flap reconstruction for head and neck were satisfactory and improved with operator experience.

Comparison of Anatomically of Medial Plantar Flap versus Reverse Sural Fasciocutaneous Flap in the Treatment of Skin Defects After Cutaneous Squamous Cell Carcinoma Excision

SUMMARY: To compare the advantages and disadvantages of reverse sural fasciocutaneous flap (RSFF) versus medial plantar flap (MPF) in the treatment of skin defects after excision of squamous cell carcinoma (SCC) of the heel. The research participants were 80 SCC patients admitted to Lishui People's Hospital between January 2019 and April 2022, who were assigned to RSFF group (n=37) and MPF group (n=43) according to the flap type. After a one-year follow-up, the survival, flap necrosis and ulceration, as well as pain and tactile sensation recovery of both groups were counted. At the last follow-up, the clinical response was evaluated, and Short-Form 36 Item Health Survey (SF-36) and appearance satisfaction surveys were conducted. No patients died in either group, and one patient in each group developed flap necrosis. The MPF group had better sensory recovery and a lower incidence of flap ulceration (P0.05). The cosmetic satisfaction was higher in MPF group than in RSFF group (P<0.05). MPF contributes to beautiful appearance, better sensory recovery, and low risk of long-term ulceration, while RSFF is suitable for lesions with large defects or those located at the lateral heel.

El objetivo del estudio fue comparar las ventajas y desventajas del colgajo fasciocutáneo sural inverso (RSFF) versus el colgajo plantar medial (MPF) en el tratamiento de defectos de la piel después de la escisión de un carcinoma de células escamosas (CCE) del talón. Los participantes de la investigación fueron 80 pacientes con CCE ingresados en el Hospital Popular de Lishui entre enero de 2019 y abril de 2022, que fueron asignados al grupo RSFF (n=37) y al grupo MPF (n=43) según el tipo de colgajo. Después de un año de seguimiento, se observó la supervivencia, la necrosis y ulceración del colgajo, así como la recuperación del dolor y la sensación táctil de ambos grupos. En el último seguimiento, se evaluó la respuesta clínica y se realizaron encuestas de salud de formato corto de 36 ítems (SF-36) y encuestas de satisfacción. Ningún paciente falleció en ninguno de los grupos y un paciente de cada grupo desarrolló necrosis del colgajo. El grupo MPF tuvo una mejor recuperación sensorial y una menor incidencia de ulceración del colgajo (P 0,05). La satisfacción cosmética fue mayor en el grupo MPF que en el grupo RSFF (P<0,05). MPF contribuye a una mejor apariencia, mejor recuperación sensorial y un bajo riesgo de ulceración a largo plazo, mientras que RSFF es adecuado para lesiones con defectos grandes o localizados en la parte lateral del talón.

Tumoración en dorso de mano: a propósito de un caso / Tumor on the back of the hand: about a case

Spinocellular carcinoma is a tumor lesion that frequently occurs in photo-exposed areas, presenting characteristics such as keratinization, scaly areas and even ulcerations. Its potential for metastasis makes early identification and diagnosis essential in order to carry out correct treatment of said lesion. In the spectrum of spinocelullar carcinomas is Keratoacanthoma, which has been in debate about its origin and its benignity. We present the clinical evolution, treatment, results, and bibliographic review of a keratoacanthoma.

El carcinoma espinocelular es una lesión tumoral que se da frecuentemente en zonas foto-expuestas, presentando características tales como queratinización, zonas descamativas e incluso ulceraciones. Su potencial de metástasis hace imprescindible la identificación y diagnóstico precoz para poder realizar un correcto tratamiento de dicha lesión. Dentro de su espectro se encuentra el Queratoacantoma, el cual ha estado en debate sobre su origen y su benignidad. Nosotros presentamos la evolución clínica, tratamiento, resultados y revisión bibliográfica de un queratoacantoma.

Avaliação dos principais fatores de risco associados ao desenvolvimento do carcinoma espinocelular: revisão narrativa de literatura / Evaluation of the main risk factors associated with the development of spinocellular carcinoma: narrative literature review

Introdução: A detecção precoce de lesões malignas na cavidade oral é crucial para a prevenção do câncer oral. Cirurgiões-dentistas desempenham um papel vital ao compreender os fatores de risco do carcinoma espinocelular (CEC) a fim de facilitar essa prevenção. No entanto, a identificação do câncer bucal é complexa, sendo a falta de capacitação um obstáculo para diagnósticos oportunos. Objetivo: Este estudo visa apresentar, por meio de uma revisão de literatura, os fatores de risco associados ao desenvolvimento do CEC a estudantes e profissionais da área. Materiais e métodos: Foi realizada uma busca de artigos científicos publicados entre 2015 e 2023 nas bases de dados SciELO, Pubmed e ScienceDirect. As palavras-chave foram escolhidas com base nos Descritores em Ciências da Saúde (DeCS), abrangendo "Neoplasias Bucais" e "Carcinoma Oral de Células Escamosas". Resultados: Foram identificados 502 documentos. Após critérios de exclusão, 26 artigos científicos originais relacionados ao tema foram considerados elegíveis. Conclusão: O papel do cirurgião-dentista é essencial na prevenção e detecção precoce do câncer oral, exigindo total atualização sobre os fatores de risco para um desempenho eficaz.

Introduction: Early detection of malignant lesions in the oral cavity is crucial for the prevention of oral cancer. Surgeons-dentists play a vital role in understanding the risk factors of squamous cell carcinoma (SCC) in order to facilitate this prevention. However, the identification of oral cancer is complex, being the lack of training an obstacle for timely diagnoses. Objective: This study aims to present, through a literature review, the risk factors associated with the development of CEC to students and professionals of the area. Materials and methods: A search was carried out for scientific articles published between 2015 and 2023 in the SciELO, Pubmed and ScienceDirect databases. The keywords were chosen based on the Describers in Health Sciences (DeCS), encompassing "Buccal Neoplasms" and "Oral Squamous Cell Carcinoma". Results: Foram identified 502 documents. After exclusion criteria, 26 original scientific articles related to the topic were considered eligible. Conclusion: The role of dental surgery is essential in the prevention and early detection of oral cancer, requiring full updating on risk factors for effective performance.

Study of p40 is superior to p63 for the diagnosis of pulmonary squamous cell carcinoma on cytological smears

Background: Histology and genetically driven management are the current standard in carcinoma lung. Adequate tissue is a challenge in a few cases. While liquid biopsy is an, it’s an always preferred to get an initial cyto/histo morphological confirmation. While the immune-histo chemistry (IHC) is a proven method to differentiate the squamous vs adeno carcinoma, the role of various “immuno-cyto-chemical” makers were not studied widely. Methods: This is a retrospective (July 2018 to December 2018) for random sample collection and prospective (Jan 2019-August 2019) study conducted from in the Department of pathology, govt. chest hospital Osmania medical college, Hyderabad as a part of PG dissertation, 120 subjects with cytological diagnosis of non-small cell lung carcinoma were analyzed during this period and others were excluded. Results: Out of 120 cases 80-adenocarcinoma (ADC) and 40-squamous cell carcinoma (SCC). Most of the patients are in 61-70 years, 20 are 71-80 years, 20 between 51-60 and 10 are between 40-50 years. In this study sensitivity of p63 and p40 is equal, but specificity and positive predictive value are higher for p40 for diagnosis of SCC. Conclusions: Immuno-cyto-chemistry is still a valid option in selected cases where getting a biopsy is difficult. Our findings recommend the use of p40 immuno staining rather than p63 as a squamous cell marker.

Prediction of Prognostic Features Based on Neutrophil-Related Genes for Lung Squamous Cell Carcinoma Reveals Immune Landscape and Drug Candidates

ABSTRACT Background: Since to the prognosis of lung squamous cell carcinoma is generally poor, there is an urgent need to innovate new prognostic biomarkers and therapeutic targets to improve patient outcomes. Objectives: Our goal was to develop a novel multi-gene prognostic model linked to neutrophils for predicting lung squamous cell carcinoma prognosis. Methods: We utilized messenger RNA expression profiles and relevant clinical data of lung squamous cell carcinoma patients from the Cancer Genome Atlas database. Through K-means clustering, least absolute shrinkage and selection operator regression, and univariate/multivariate Cox regression analyses, we identified 12 neutrophil-related genes strongly related to patient survival and constructed a prognostic model. We verified the stability of the model in the Cancer Genome Atlas database and gene expression omnibus validation set, demonstrating the robust predictive performance of the model. Results: Immunoinfiltration analysis revealed remarkably elevated levels of infiltration for natural killer cells resting and monocytes in the high-risk group compared to the low-risk group, while macrophages had considerably lower infiltration in the high risk group. Most immune checkpoint genes, including programmed cell death protein 1 and cytotoxic T-lymphocyte-associated antigen 4, exhibited high expression levels in the high risk group. Tumor immune dysfunction and exclusion scores and immunophenoscore results suggested a potential inclination toward immunotherapy in the "RIC" version V2 revised high risk group. Moreover, prediction results from the CellMiner database revealed great correlations between drug sensitivity (e.g., Vinorelbine and PKI-587) and prognostic genes. Conclusion: Overall, our study established a reliable prognostic risk model that possessed significant value in predicting the overall survival of lung squamous cell carcinoma patients and may guide personalized treatment strategies. (Rev Invest Clin. 2024;76(2):116-31)

Network meta-analysis of pembrolizumab as monotherapy and in combination with chemotherapy for first-line treatment of recurrent or metastatic head and neck squamous cell carcinoma / Metanálise em rede comparativa de pembrolizumabe como monoterapia e em combinação com quimioterapia para tratamento de primeira linha de carcinoma de células escamosas da cabeça e pescoço recorrente ou metastático

Pembrolizumab monotherapy or in combination with chemotherapy is approved as first-line treatment in recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC) based on improved overall survival (OS) versus EXTREME regimen in the KEYNOTE-048 trial. The clinical outcomes of pembrolizumab were compared with other recommended first-line treatments in R/M HNSCC in this study through a Bayesian network meta-analysis. A systematic literature review was conducted in July 2022, from which six trials that matched the KEYNOTE-048 patient eligibility criteria were included in the network. The OS and progression-free survival (PFS) outcomes were compared in the approved pembrolizumab indication (i.e., total population for pembrolizumab in combination with chemotherapy and combined positive score [CPS] ≥ 1 population for pembrolizumab monotherapy). A significant OS improvement was observed for pembrolizumab in combination with chemotherapy and pembrolizumab monotherapy versus EXTREME regimen (hazard ratio, 95% credible interval: 0.72, 0.60-0.86; 0.73, 0.60-0.88), platinum+5- FU (0.58, 0.43-0.76; 0.58, 0.44-0.78), and platinum+paclitaxel (0.53, 0.35-0.79; 0.53, 0.35-0.81), respectively. A non-significant numeric trend in OS improvement was observed versus the TPEx regimen. PFS was comparable with most first-line treatments and was improved versus platinum+5-FU (0.48, 0.36-0.64; 0.59, 0.45-0.79). Additional analyses in higher CPS subgroups also showed consistent results. Overall, our study results showed an improvement in OS outcomes versus alternative first-line treatments, consistent with the findings of the KEYNOTE-048 trial. These data support using pembrolizumab as a suitable firstline treatment option in R/M HNSCC.

Pembrolizumabe em monoterapia ou em combinação com quimioterapia é aprovado como tratamento de primeira linha em carcinoma de células escamosas recorrente/metastático de cabeça e pescoço (CECCP R/M) com base na melhora da sobrevida global (OS), em comparação com o esquema EXTREME no estudo KEYNOTE-048. Esse estudo comparou os resultados clínicos de pembrolizumabe com outros tratamentos recomendados de primeira linha em CECCP R/M por meio de uma metanálise de rede bayesiana. Uma revisão sistemática da literatura foi conduzida em julho de 2022, a partir da qual seis ensaios clínicos que atendiam aos critérios de elegibilidade de pacientes do KEYNOTE-048 foram incluídos na rede. Os desfechos de OS e sobrevida livre de progressão (PFS) foram comparados na indicação de pembrolizumabe (população total para pembrolizumabe em combinação com quimioterapia e população com escore positivo combinado [CPS] ≥ 1 em monoterapia com pembrolizumabe). Foi observada melhora significativa na OS para pembrolizumabe em combinação com quimioterapia e monoterapia com pembrolizumabe versus o esquema EXTREME (razão de risco, intervalo de confiança de 95%: 0,72, 0,60-0,86; 0,73, 0,60-0,88), platina+5-FU (0,58, 0,43-0,76; 0,58, 0,44-0,78) e platina+paclitaxel (0,53, 0,35-0,79; 0,53, 0,35-0,81), respectivamente. Uma tendência numérica não significativa de melhoria na OS foi observada em relação ao esquema TPEx. A PFS foi comparável com a maioria dos tratamentos de primeira linha e melhor em relação à platina+5-FU (0,48, 0,36-0,64; 0,59, 0,45-0,79). Análises adicionais em subgrupos com CPS mais elevado também mostraram resultados consistentes. No geral, os resultados de nosso estudo mostraram melhora nos desfechos de OS em comparação aos tratamentos de primeira linha alternativos, consistentes com os achados do estudo KEYNOTE-048. Esses dados apoiam o uso de pembrolizumabe como opção de tratamento em primeira linha em pacientes com CECCP R/M.

Biopsia en carcinoma escamoso de orofaringe

La biopsia en carcinoma escamoso de orofaringe es un paso fundamental para su diagnóstico, por lo que es relevante conocer los diferentes tipos de ésta. Actualmente, se reconocen 4 tipos de biopsia en este tipo de carcinoma, cada uno de las cuales presentan indicaciones específicas: Biopsia incisional, excisional, punción con aguja fina (PAF) y biopsia liquida. La más frecuente y recomendada es la biopsia incisional por su rapidez y poca morbilidad asociada. Tanto la biopsia excisional como la PAF se reservan para casos de metástasis cervical de primario desconocido dependiendo de la etapa del análisis del paciente en particular. Finalmente, existe un fuerte desarrollo de la biopsia liquida, especialmente mediante el estudio del biomarcador ctHPV-DNA, el cual al ser un marcador sensible y específico para este tipo de carcinoma puede cambiar el paradigma del diagnóstico en un futuro cercano.

Oropharyngeal squamous cell carcinoma biopsy is a fundamental step in the diagnosis; therefore, it is relevant to know its different types. Currently, four types of biopsy are recognized for this type of carcinoma, each of which has specific indications: incisional biopsy, excisional biopsy, fine needle aspiration (FNA), and liquid biopsy. The most frequent and recommended procedure is incisional biopsy, because of its speed and low associated morbidity. Both excisional biopsy and FNA are reserved for cases of cervical metastasis of unknown primary depending on the stage of analysis of the particular patient. Finally, there is a strong development in liquid biopsy, especially through the study of the ctHPV-DNA biomarker, which is a sensitive and specific marker for this type of carcinoma, and may change the diagnostic paradigm in the near future.

Overexpression SPRY2 Suppresses Esophageal Squamous Cell Carcinoma Progression Via Inactivation of ERK/AKT Signaling / La Sobreexpresión SPRY2 Suprime la Evolución del Carcinoma de Células Escamosas de Esófago Mediante la Inactivación de la Señalización ERK/AKT

SUMMARY: Esophageal cancer is one of the most aggressive gastrointestinal cancers. Invasion and metastasis are the main causes of poor prognosis of esophageal cancer. SPRY2 has been reported to exert promoting effects in human cancers, which controls signal pathways including PI3K/AKT and MAPKs. However, the expression of SPRY2 in esophageal squamous cell carcinoma (ESCC) and its underlying mechanism remain unclear. In the present study, we aimed to investigate the detailed role of SPRY2 in the regulation of cell proliferation, invasion and ERK/AKT signaling pathway in ESCC. It was identified that the expression level of SPRY2 in ESCC was remarkably decreased compared with normal tissues, and it was related to clinicopathologic features and prognosis ESCC patients. The upregulation of SPRY2 expression notably inhibited the proliferation, migration and invasion of Eca-109 cells. In addition, the activity of ERK /AKT signaling was also suppressed by the SPRY2 upregulation in Eca-109 cells. Our study suggests that overexpression of SPRY2 suppress cancer cell proliferation and invasion of by through suppression of the ERK/AKT signaling pathways in ESCC. Therefore, SPRY2 may be a promising prognostic marker and therapeutic target for ESCC.

El cáncer de esófago es uno de los cánceres gastrointestinales más agresivos. La invasión y la metástasis son las principales causas de mal pronóstico del cáncer de esófago. Se ha informado que SPRY2 ejerce efectos promotores en los cánceres humanos, que controla las vías de señales, incluidas PI3K/AKT y MAPK. Sin embargo, la expresión de SPRY2 en el carcinoma de células escamosas de esófago (ESCC) y su mecanismo subyacente aún no están claros. En el presente estudio, nuestro objetivo fue investigar el papel detallado de SPRY2 en la regulación de la proliferación celular, la invasión y la vía de señalización ERK/AKT en ESCC. Se identificó que el nivel de expresión de SPRY2 en ESCC estaba notablemente disminuido en comparación con los tejidos normales, y estaba relacionado con las características clínico-patológicas y el pronóstico de los pacientes con ESCC. La regulación positiva de la expresión de SPRY2 inhibió notablemente la proliferación, migración e invasión de células Eca-109. Además, la actividad de la señalización de ERK/AKT también fue suprimida por la regulación positiva de SPRY2 en las células Eca-109. Nuestro estudio sugiere que la sobreexpresión de SPRY2 suprime la proliferación y la invasión de células cancerosas mediante la supresión de las vías de señalización ERK/AKT en ESCC. Por lo tanto, SPRY2 puede ser un marcador de pronóstico prometedor y un objetivo terapéutico para la ESCC.

Effect of targeted CXCL5 silencing on biological function of laryngeal squamous cell carcinoma cell line AMC-HN-8 and its regulation analysis / 中国生物制品学杂志

@#Objective To investigate the effects of targeted silencing of CXCL5 on the related biological functions of laryngeal squamous cell carcinoma(LSCC)cell line AMC-HN-8,and analyze the regulation through TCGA database.Methods RNA-seq data related to LSCC were obtained from TCGA database,and the expression differences of CXCL5 gene in LSCC and the adjacent tissues were analyzed. Total 60 samples of LSCC and the adjacent tissues from January 2019 to December 2020 were selected from the First Hospital of Shanxi Medical University,and the expression of CXCL5 protein in LSCC tissues was detected by immunohistochemical staining. Human LSCC cell line AMC-HN-8 was cultured and the mRNA transcription level of CXCL5 in AMC-HN-8 cells was detected by qPCR. Two groups of SiRNA with high knock-down efficiency were screened,CCK8 assay was used to detect the cell proliferation,Transwell test was used to measure the cell invasion and migration,and flow cytometry was used to detect the cell cycle and apoptosis. The correlation between CXCL5and tumor immune invasion level of LSCC was analyzed by ssGSEA,and CXCL5 co-expression gene network was constructed and analyzed for GO and KEGG enrichment.Results Compared with the adjacent tissues and the cells in control group,the expression of CXCL5 in LSCC tissues and cells increased,which was consistent with the analysis of TCGA database;Inhibition of CXCL5 expression in AMC-HN-8 cells inhibited the proliferation,invasion and migration of tumor cells,and promoted the apoptosis through inhibiting the cell cycle in G1 phase;The immune cell scores in DC,neutrophils,NK and TH17 cells were different.Conclusion CXCL5gene is highly expressed in LSCC tissues,which might be one of the targets of LSCC targeted therapy.

Photodynamic therapy in the treatment of the right buccal mucosa verrucous carcinoma: a case report and literature review / 口腔疾病防治

Objective@#To explore the photodynamic treatment method and therapeutic effect of oral verrucous carcinoma and to provide a reference for the clinic.@*Methods@#This study follows the requirements of medical ethics. This paper summarized the photodynamic treatment of an oral verrucous carcinoma with a diameter of approximately 2.5 cm in the right buccal mucosa and retrospectively analyzed the characteristics and treatment of oral verrucous carcinoma and the photodynamic treatment of potential malignant lesions of the oral mucosa through a review of the literature.@*Results@#After four rounds of photodynamic therapy, the size of the right buccal lesion was significantly reduced. After 6 months of follow-up, the white verrucous hyperplasia of the right buccal mucosa had completely subsided, and there was no obvious scar formation. Three years after treatment, there was no recurrence of the lesion in the right buccal mucosa and no obvious scar formation in the treated area. The degree of mouth opening was 3 fingers, and there was no lymph node enlargement in the bilateral submandibular, submental or neck. The literature review shows that oral verrucous carcinoma is a rare subtype of squamous cell carcinoma with the characteristics and biological behaviors of slow growth, low malignancy, and rare metastasis. Surgery is the preferred treatment, but there are some limitations. Photodynamic therapy is a minimally invasive, repeatable treatment with mild adverse reactions. In recent years, photodynamic therapy has been gradually applied for the treatment of potential malignant disorders of the oral mucosa and early oral squamous cell carcinoma and has achieved positive results, but it has not been reported for the treatment of oral verrucous cancer@*Conclusion@#Photodynamic therapy is a new option for nonsurgical resection of oral verrucous carcinoma.

Network pharmacology and molecular docking reveal the mechanism of resveratrol in oral squamous cell carcinoma treatment / 口腔疾病防治

Objective@#To explore the molecular mechanism of resveratrol (RES) in the treatment of oral squamous cell carcinoma (OSCC) through the use of biological information methods such as network pharmacology and molecular docking and to provide a theoretical reference for the clinical application of RES in the treatment of OSCC.@*Methods@#The Swiss Target Prediction(http://www.swisstargetprediction.ch), SEA (http://sea.bkslab.org)database, and Pharm mapper database(http://lilab-ecust.cn) were used to retrieve RES-related targets, and the DISGENET (www.disgenet.org), OMIM (https://omim.org) and GeneCards (https://www.genecards.org) databases were used to screen OSCC disease targets. The intersection of drugs and disease targets was determined, and Cytoscape 3.7.2 software was used to construct a "drug-diseasetarget pathway" network. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) database was used to construct a target protein interaction network, and the DAVID database was used for enrichment analysis of key proteins. Finally, molecular docking validation of key proteins was performed using AutoDock and PyMOL. The enrichment analysis and molecular docking results were integrated to predict the possible molecular mechanisms of RES treatment in OSCC; western blot was used to determine the effect of resveratrol at different concentrations (50, 100) μmol/L on the expression of Src tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), estrogen receptor gene 1 (ESR1), and phosphatidylinositol 3 kinase/protein kinase B (PI3K/AKT) signaling pathway proteins in OSCC HSC-3 cells.@*Results@#A total of 243 targets of RES drugs and 6 094 targets of OSCC were identified. A total of 116 potential common targets were obtained by intersecting drugs with disease targets. These potential targets mainly participate in biological processes such as in vivo protein self-phosphorylation, peptide tyrosine phosphorylation, transmembrane receptor protein tyrosine kinase signaling pathway, and positive regulation of RNA polymerase Ⅱ promoter transcription, and they interfere with the PI3K/AKT signaling pathway to exert anti-OSCC effects. The docking results of resveratrol with OSCC molecules indicated that key targets, such as EGFR, ESR1, and SRC, have good binding activity. The results of cell-based experiments showed that resveratrol inhibited the protein expression of SRC, EGFR, ESR1, p-PI3K, and p-AKT in HSC-3 cells in a dose-dependent manner.@*Conclusion@#RES can inhibit the expression of its targets EGFR, ESR1, SRC, p-PI3K, and p-AKT in OSCC cells.

Establishment and verification of a prognostic nomogram for survival of tongue squa-mous cell carcinoma patients who underwent cervical dissection / 北京大学学报(医学版)

Objective:To evaluate the prognostic significance of inflammatory biomarkers,prognostic nutritional index and clinicopathological characteristics in tongue squamous cell carcinoma(TSCC)patients who underwent cervical dissection.Methods:The retrospective cohort study consisted of 297 patients undergoing tumor resection for TSCC between January 2017 and July 2018.The study population was divided into the training set and validation set by 7:3 randomly.The peripheral blood indices of interest were preoperative neutrophil-to-lymphocyte ratio(NLR),lymphocyte-to-monocyte ratio(LMR),platelet-to-lymphocyte ratio(PLR),systemic immune-inflammation index(SII),systemic inflammation score(SIS)and prognostic nutritional index(PNI).Kaplan-Meier survival analysis and multivariable Cox regression analysis were used to evaluate independent prognostic factors for overall survival(OS)and disease-specific survival(DSS).The nomogram's accuracy was internally validated using concordance index,receiver operating characteristic(ROC)curve,area under the curve(AUC),calibration plot and decision curve analysis.Results:According to the univariate Cox regression analysis,clinical TNM stage,clinical T category,clinical N category,differentiation grade,depth of invasion(DOI),tumor size and pre-treatment PNI were the prognostic factors of TSCC.Multivariate Cox regression analysis revealed that pre-treatment PNI,clinical N category,DOI and tumor size were independent prognostic factors for OS or DSS(P＜0.05).Positive neck nodal status(N≥1),PNI≤50.65 and DOI＞2.4 cm were associated with the poorer 5-year OS,while a positive neck nodal status(N≥1),PNI≤50.65 and tumor size＞3.4 cm were associated with poorer 5-year DSS.The concordance index of the nomograms based on independent prognostic factors was 0.708(95％CI,0.625-0.791)for OS and 0.717(95％CI,0.600-0.834)for DSS.The C-indexes for external validation of OS and DSS were 0.659(95％CI,0.550-0.767)and 0.780(95％CI,0.669-0.890),respectively.The 1-,3-and 5-year time-dependent ROC analyses(AUC=0.66,0.71 and 0.72,and AUC=0.68,0.77 and 0.79,respec-tively)of the nomogram for the OS and DSS pronounced robust discriminative ability of the model.The calibration curves showed good agreement between the predicted and actual observations of OS and DSS,while the decision curve confirmed its pronounced application value.Conclusion:Pre-treatment PNI,clinical N category,DOI and tumor size can potentially be used to predict OS and DSS of patients with TSCC.The prognostic nomogram based on these variables exhibited good accurary in predicting OS and DSS in patients with TSCC who underwent cervical dissection.They are effective tools for predicting sur-vival and helps to choose appropriate treatment strategies to improve the prognosis.

Effect of PD-L1 on proliferation,migration,and invasion of human oral squamous carcinoma cells / 吉林大学学报(医学版)

Objective:To discuss the expression of programmed cell death-ligand 1(PD-L1)in the oral squamous cell carcinoma(OSCC)cells and its effect on biological behavior of the OSCC CAL27 cells,and to clarify the possible mechanism.Methods:Western blotting method was used to detect the expression levels of PD-L1 protein in the oral epithelial HOK cells and OSCC CAL27,TCA8113,and SCC15 cells;immunofluorescence staining method was used to detect the expression and localization of PD-L1 protein in the CAL27 cells.The CAL27 cells were divided into control group(transfected with si-NC)and si-PD-L1 group(transfected with si-PD-L1).Western blotting method was used to detect the interference efficiency of the cells in two groups;CCK-8 assay was used to detect the proliferative activities of the cells in two groups at different time points;plate clone formation assay was used to detect the numbers of clone formation of the cells in two groups;cell scratch healing assay was used to detect the scratch healing rates of the cells in two groups;Transwell chamber assay was used to detect the numbers of migration and invasion cells in two groups.Results:The expression level of PD-L1 protein in the OSCC cells was higher than that in the HOK cells(P<0.05 or P<0.01);PD-L1 expressed in the cytoplasm and nucleus of the CAL27 cells.The CCK-8 assay and plate clone formation assay results showed that compared with control group,the proliferative activities of the CAL27 cells in si-PD-L1 group at different time points were significantly decreased(P<0.05 or P<0.01),and the numbers of clone formation were significantly decreased(P<0.01).The cell scratch healing assay results showed that compared with control group,the scratch healing rates of the cells in si-PD-L1 group were significantly decreased(P<0.05 or P<0.01).The Transwell chamber assay results showed that compared with control group,the numbers of migration and invasion cells in si-PD-L1 group were significantly decreased(P<0.01).Conclusion:The expression of PD-L1 in the OSCC cells is higher than that in normal oral epithelial cells,and knocking down PD-L1 expression can inhibit the proliferation,clone formation,migration and invasion capabilities of the OSCC cells.

Expression and significance of PIK3CA,p-AKT and PTEN in sinonasal squamous cell carcinoma / 重庆医学

Objective To investigate the expression of PIK3CA,phosphorylated protein kinase B(p-AKT)and phosphatase and tensin homologue deleted on chromosome 10(PTEN)in sinonasal squamous cell carcinoma(SNSCC).Methods The expressions of PIK3CA and PTEN in head and neck squamous cell carci-noma(HNSCC)were analyzed through the data set of HNSCC in the cancer genome map of UCSC Xena data-base.The immunohistochemical SP method was used to measure the expression of PIK3CA,p-AKT and PTEN in 43 cases of SNSCC tissues,20 cases of normal inferior concha tissues.The relationship between the expressions of PIK3CA,p-AKT and PTEN protein with the clinicopathological features and prognosis of the patients with SNSCC was analyzed.Results The results of bioinformatic analysis showed that PIK3CA mR-NA expression in HNSCC tissues was higher than that in paracancerous tissues(P＜0.01),while the PTEN mRNA expression was lower than that in paracancerous tissues(P＜0.05).The immunohistochemical detec-tion results showed that the positive expressions rates of PIK3CA and p-AKT proteins in normal nasal mucosa tissues were significantly lower than those in SNSCC tissues,while the positive expression rate of PTEN pro-tein in SNSCC tissues was significantly higher than that in normal inferior nasal concha mucosa tissues,and the differences were statistically significant(P＜0.01).The expressions of PIK3CA and p-AKT protein were related to the clinical stage,differentiation degree and primary site(P＜0.05),but were not related to age,gender,smoking and drinking(P＞0.05);the PTEN protein expression was not related with the clinical stage,differentiation degree,primary site,age,smoking and drinking(P＞0.05).The Spearman analysis showed that the expression of PIK3CA in SNSCC tissues was positively correlated with p-AKT protein ex-pression(r=0.664,P＜0.01),and PIK3CA was negatively correlated with PTEN protein(r=-0.414,P＜0.01).The expression of p-AKT was negatively correlated with PTEN protein(r=-0.453,P＜0.01).The Kaplan-Meier analysis showed that the median survival time of the patients with PIK3CA and p-AKT protein positive expression was shorter than that of the patients with negative expression(P＜0.01).There was no statistically significant difference in median survival between the patients with PTEN protein positive expres-sion and those with negative expression.Conclusion The overexpressions of PIK3CA and p-AKT accompa-nied by the loss of PTEN expression participate in the development and progression of SNSCC,moreover the PIK3CA and p-AKT expressions are related to the poor prognosis of the patients.

Expression and clinical significance of phosphorylated FGFR1Y654 in esophageal squamous cell carcinoma / 陆军军医大学学报

Objective To explore the relationship between p-FGFR1Y654 expression and clinical pathological characteristics of esophageal squamous cell carcinoma patients and its prognostic value.Methods Tumor tissue samples from 103 cases of esophageal squamous cell carcinoma and 58 normal esophageal tissues were surgically collected in the General Hospital of Western Theater between January 2017 and July 2020.The expression of p-FGFR1Y654 in the tissues was detected using immunohistochemical assay,and its correlation with relevant clinicopathological parameters and prognosis was analyzed.Results The expression of p-FGFR1Y654 in esophageal squamous cell carcinoma tissues was significantly higher than that in normal tissue(P＜0.01).Its expression level was closely related to overall survival(OS,P＜0.05),but not related to age,gender,tumor stage or tumor size.Multivariate COX regression analysis showed that N-stage was identified as an independent prognostic factor for recurrence free survival(RFS)in esophageal squamous cell carcinoma patients.Survival analysis indicated that patients with low expression of p-FGFR1Y654 had significantly higher RFS and OS than those with high expression(P=0.032,95％CI:1.08～4.65;P=0.004,95％CI:2.14-11.51).Conclusion p-FGFR1Y654 is highly expressed in esophageal squamous cell carcinoma tissue,and is associated with poor prognosis in these patients.p-FGFR1Y654 may be a potential therapeutic target for esophageal squamous cell carcinoma.