Longitudinal Study of Different Progression Patterns in High-Risk Cutaneous Squamous Cell Carcinoma. / Estudio longitudinal de los diferentes patrones de progresión en el carcinoma cutáneo de células escamosas de alto riesgo.

BACKGROUND AND OBJECTIVE: Cutaneous squamous cell carcinoma (cSCC) is the second leading cause of skin cancer mortality in Europe. Few studies have analyzed the different pathways of this tumor progression in its natural history. The main objective of this study was to analyze the different metastatic and progression pathways and their temporal occurrence in the evolution of cSCC. MATERIAL AND METHOD: We conducted a multicenter, retrospective, and observational study of consecutive high-risk sSCCs included in the SQUAMATA project. RESULTS: A total of 222 out of the 1346 patients included relapsed. The most frequent route of progression was the lymphatic one (62.6%). A total of 20.2% of the cases with lymphatic progression developed distant metastases. Only 1 case (3.1%) of distant metastasis followed local recurrence without previous lymphatic metastasis. The median time to disease-related mortality was longer in patients who developed systemic metastases than in those who died of locoregional progression. CONCLUSIONS: The mortality of patients with cSCC is mostly due to the regional progression of their lymphatic metastases. The appearance of distant metastases is practically always (96.9%) associated with previous lymphatic metastatic progression. Therefore, in the future, new studies will be needed to assess the regional management of cSCC in both surgical and adjuvant therapies.

Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors / Impacto de la pandemia de COVID-19 en el carcinoma de células escamosas cutáneo: un estudio unicéntrico de los factores epidemiológicos, clínicos e histopatológicos

Background: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. Objective To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. Material & methods: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. Results: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. Conclusions: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future. (AU)

Antecedentes: La pandemia de COVID-19 ha podido afectar negativamente el diagnóstico precoz del cáncer de piel. Objetivo Comparar las características epidemiológicas, clínicas e histopatológicas en los pacientes intervenidos de carcinoma de células escamosas (CCE) cutáneo antes de la pandemia y después del inicio de la pandemia. Material y métodos: Se diseñó un estudio transversal que incluía 2 series de pacientes: 1) pacientes intervenidos de CCE el año posterior a la declaración del confinamiento general en España (15 de marzo de 2020), y 2) pacientes intervenidos de CCE el año previo. Se recogieron variables epidemiológicas, clínicas e histopatológicas, así como el estadio tumoral y el grado de riesgo. Resultados: Se incluyeron 248 pacientes (127 intervenidos antes de la pandemia y 121 intervenidos después de la pandemia). Tras el inicio de la pandemia, el porcentaje de CCE de alto riesgo aumentó significativamente de 32,3 a 45,5% (p=0,011). No obstante, no se encontraron diferencias significativas en el grosor tumoral, la invasión perineural o la presencia de metástasis. Conclusiones: Aunque no se produjo una reducción significativa en el número de CCE intervenidos después de la pandemia, ha habido un incremento significativo en los CCE de alto riesgo. Todo ello puede conllevar un incremento en la mortalidad por cáncer de piel en el futuro. (AU)

[Artículo traducido] Impacto de la pandemia COVID-19 en el carcinoma de células escamosas cutáneo: un estudio unicéntrico de los factores epidemiológicos, clínicos e histopatológicos / Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors

Antecedentes: La pandemia de COVID-19ha podido afectar negativamente el diagnóstico precoz del cáncer de piel. Objetivo Comparar las características epidemiológicas, clínicas e histopatológicas en los pacientes intervenidos de carcinoma de células escamosas (CCE) cutáneo antes de la pandemia y después del inicio de la pandemia. Material y métodos: Se diseñó un estudio transversal que incluía 2 series de pacientes: 1) pacientes intervenidos de CCE el año posterior a la declaración del confinamiento general en España (15 de marzo de 2020), y 2) pacientes intervenidos de CCE el año previo. Se recogieron variables epidemiológicas, clínicas e histopatológicas, así como el estadio tumoral y el grado de riesgo. Resultados: Se incluyeron 248 pacientes (127 intervenidos antes de la pandemia y 121 intervenidos después de la pandemia). Tras el inicio de la pandemia, el porcentaje de CCE de alto riesgo aumentó significativamente de 32,3 a 45,5% (p=0,011). No obstante, no se encontraron diferencias significativas en el grosor tumoral, la invasión perineural o la presencia de metástasis. Conclusiones: Aunque no se produjo una reducción significativa en el número de CCE intervenidos después de la pandemia, ha habido un incremento significativo en los CCE de alto riesgo. Todo ello puede conllevar un incremento en la mortalidad por cáncer de piel en el futuro. (AU)

Background: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. Objective To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. Material & methods: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. Results: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. Conclusions: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future. (AU)

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.

Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors. / [Artículo traducido] Impacto de la pandemia COVID-19 en el carcinoma de células escamosas cutáneo: un estudio unicéntrico de los factores epidemiológicos, clínicos e histopatológicos.

BACKGROUND: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. OBJECTIVE: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. MATERIAL & METHODS: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. RESULTS: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. CONCLUSIONS: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.

EVALUATION OF THE IMMUNOLOCALIZATION OF THE PHOSPHATIDYL INOSITOL-3 RECEPTOR (IP3R) IN BASAL CELL AND SQUAMOUS CELL SKIN CARCINOMAS / AVALIAÇÃO DA IMUNOLOCALIZAÇÃO DO RECEPTOR DO FOSFATIDIL INOSITOL-3 (IP3R) EM CARCINOMAS BASOCELULAR E DE CÉLULAS ESCAMOSAS DE PELE

Introduction: Non-melanoma skin neoplasms (basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) form the most common group of all types of neoplasms. Although cancer is not yet being classified as a channelopathy, it has been suggested that pumps and ionic channels contribute to its progression by affecting autophagy, which could become an important therapeutic target in this context. Objective: To evaluate the immunohistochemical expression of IP3R in both skin tumors. Method: Immunohistochemistry was performed on 60 slides of non-melanoma cancer using primary anti-IP3R antibodies, verifying their presence and quantifying Results: For the first time, IP3R immunolocalization was identified in non-melanoma skin neoplasms, being evident above 90% of neoplastic cells was observed in all slides studied, regardless of the histological pattern, invasion and other tumor characteristics. Unlike what was seen in the internal control of normal skin, in which there was immunolocalization of IP3R in basal cell, in tumors, immunohistochemical expression occurred throughout the entire body of the neoplasm. Conclusion: There was immunolocalization of IP3R in tumor cells in both BCC and SCC. It was not possible to establish a correlation between tumor characteristics and IP3R expression, as immunostaining was similar in all analyzed samples. Despite this, IP3R to be associated with the pathophysiology of non-melanoma skin cancer, but its expression does not seem to be associated with tumor aggressiveness.

Introdução: As neoplasias de pele não melanoma (carcinoma basocelular (CBC) e carcinoma espinocelular (CEC) formam o grupo mais comum de todos os tipos de neoplasias. Embora o câncer ainda não esteja sendo pautado como canalopatia, tem sido sugerido que bombas e canais iônicos contribuem para a sua progressão por afetar a autofagia. Proteínas iônicas, em especial as de canais de cálcio, como o receptor da fosfatidil inositol 3 (IP3R) participam de maneira ativa na autofagia por estarem envolvidas na etapa inicial de formação do autofagossomo, podendo se tornar em alvo terapêutico importante neste contexto. Objetivo: Avaliar a expressão imuno histoquímica do IP3R em ambos os tumores de pele. Método: Foi realizada imuno histoquímica em 60 lâminas de câncer não melanoma utilizando anticorpos primários anti-IP3R verificando a sua expressão. Resultados: Pela primeira vez foi identificada a imunolocalização do IP3R em câncer de pele não melanoma, sendo evidente em mais de 90% das células neoplásicas em todas as lâminas estudadas, independentemente do padrão histológico, invasão e demais características tumorais. Diferentemente do visualizado no controle interno de pele normal, no qual houve imunolocalização de IP3R em células basais, nos tumores, a expressão imuno histoquímica ocorreu em todo o corpo da neoplasia. Conclusão: Houve imunolocalização de IP3R em células tumorais tanto em CBC quanto em CEC. Não foi possível estabelecer correlação entre as características tumorais e a expressão de IP3R, pois a imunomarcação apresentou-se de forma similar em todas as amostras analisadas. Apesar disso, IP3R está associado à fisiopatologia do câncer de pele não melanoma, mas a sua expressão não parece estar associada à agressividade tumoral.

Indução da morte celular imunogênica em linhagens celulares de leucoplasia e carcinoma de células escamosas oral sob tratamento de artemisinina e cisplatina / Induction of immunogenic cell death in leukoplakia and oral squamous cell carcinoma cell lines under artemisinin and cisplatin treatment

Novos fármacos, como a artemisinina (ART), podem ser promissores no tratamento de lesões potencialmente malignas (LPM) e podem ser úteis quando usados em associação com outros quimioterápicos, especialmente na redução dos seus efeitos colaterais. A leucoplasia oral (LO) é a LPM mais comum da cavidade bucal e, pode evoluir para um carcinoma de células escamosas oral (CCEO). Não há terapia para evitar a sua transformação maligna, a quimioprevenção pode iniciar a morte celular imunogênica (MCI) que ativa o sistema imunológico para que reconheça e elimine as células malignas ou pré-malignas, sendo um potencial tratamento para as LPM. O presente estudo objetivou avaliar se a ART e a cisplatina (CSP) associadas ou não seriam capazes de induzir a MCI em linhagens celulares de LO (DOK) e CCEO SCC180). Material e métodos: As linhagens celulares HaCat (controle), DOK e SCC-180 foram tratadas por ART e CSP de forma combinada ou isolada, a fim de analisar a citotoxicidade e a genotoxicidade destes fármacos, além da capacidade destes em reduzir a migração celular e, se os compostos seriam capazes de induzir a expressão da proteína box de alta mobilidade (HGMB-1), caspase 3, 8, 9, e Calreticulina (CALR). Resultados: Em todas as linhagens celulares a CSP e CSP+ART causaram uma resposta dose dependente, apresentando maior citotoxicidade com doses mais altas, o que não foi observado com a ART. A formação de micronúcleos não foi observada no teste de genotoxicidade. A taxa de migração foi reduzida com as concentrações de IC50 de CSP e ART+CSP para as células de CCEO. Não foram encontradas expressões significativas de proteínas relacionadas à MCI ou apoptose nas linhagens de LO e CCEO, tratadas com ART, CSP ou ART+CSP, indicando que outro tipo de morte celular possa ter ocorrido. Conclusão: A MCI e a apoptose não foram evidenciadas como forma de morte celular após as linhagens de LO e CCEO receberem tratamentos com ART, CSP e a associação de ambas. Efeitos genotóxicos não foram observados nas doses testadas. O tratamento de CSP e ART+CSP foi capaz de reduzir a migração de células de CCEO. Também concluímos que novos estudos são necessários para elucidar se a ART e CSP podem ocasionar a MCI ou apoptose em linhagens celulares de LO e CCEO (AU)

New drugs, such as artemisinin (ART), may be promising in the treatment of potentially malignant lesions (PML) and may be useful when used in combination with other chemotherapy drugs, especially in reducing their side effects. Oral leukoplakia (OL) is the most common LPM of the oral cavity and can progress to oral squamous cell carcinoma (OSCC). There is no therapy to prevent its malignant transformation, chemoprevention can initiate immunogenic cell death (ICM) that activates the immune system to recognize and eliminate malignant or pre-malignant cells, being a potential treatment for LPM. The present study aimed to evaluate whether or not ART and cisplatin (CSP) combined would be capable of inducing MCI in LO (DOK) and CCEO SCC-180) cell lines. Material and methods: HaCat (control), DOK and SCC-180 cell lines were treated by ART and CSP in combination or alone, in order to analyze the cytotoxicity and genotoxicity of these drugs, in addition to their ability to reduce cell and, whether the compounds would be able to induce the expression of high mobility box protein (HGMB-1), caspase 3, 8, 9, and Calreticulin (CALR). Results: In cytotoxicity at higher doses, which was not observed with ART. The formation of micronuclei was not observed in the genotoxicity test. The migration rate was reduced with the IC50 concentrations of CSP and ART+CSP for OSCC cells. No significant expressions of proteins related to MCI or apoptosis were found in the LO and CCEO lines, treated with ART, CSP or ART+CSP, indicating that another type of cell death may have occurred. Conclusion: MCI and apoptosis were not evidenced as a form of cell death after the LO and CCEO lines received treatments with ART, CSP and the combination of both. Genotoxic effects were not observed at the doses tested. CSP and ART+CSP treatment was able to reduce OSCC cell migration. We also conclude that new studies are necessary to elucidate whether ART and CSP can cause MCI or apoptosis in LO and CCEO cell lines.(AU)

Carcinoma de células escamosas de lábio inferior: Excisão e reconstrução com retalho nasolabial / Squamous cell carcinoma of the lower lip: Excision and reconstruction with nasolabial flap

Introdução: O carcinoma de células escamosas é o tumor maligno mais frequente dos lábios e acomete principalmente o lábio inferior. O tratamento adequado desta neoplasia deve ser precoce e radical, pois metástases podem ocorrer. Considerando que os lábios têm extrema relevância na dinâmica e motricidade da face, a reconstrução labial após grandes ressecções nesta região é um desafio para o cirurgião na busca de bons resultados estéticos e funcionais. Este estudo busca apresentar uma técnica já consagrada e confiável para a reconstrução do lábio inferior após ressecções tumorais, o retalho de Karapandizic. Método: Nesta revisão de casos são avaliados, retrospectivamente, 4 pacientes que tiveram o lábio inferior reconstruído por meio da técnica de Karapandzic no período de 2013-2022. Resultados: As complicações mais frequentemente observadas foram cicatriz hipertrófica, deiscência de sutura em vermelhão de lábio e microstomia (redução da abertura oral). A redução da fenda labial (microstomia) foi corrigida parcialmente através do uso de órteses odontológicas, não havendo necessidade de indicação de comissuroplastia em nenhum dos casos. Outra colaboração deste trabalho refere-se à utilização do ecoDoppler colorido pré-operatório, que permite o planejamento do retalho verificando a viabilidade do pedículo vascular e o real posicionamento deste pedículo, reduzindo as chances de lesão inadvertida dos vasos durante a cirurgia. Conclusão: Mesmo sendo a microstomia uma limitação deste retalho, concluímos que esta técnica atende à necessidade de reconstrução de lábio inferior em grandes ressecções, uma vez que é capaz de proporcionar resultados satisfatórios em termos oncológicos, funcionais e estéticos.

Introduction: Squamous cell carcinoma is the most common malignant tumor of the lips and mainly affects the lower lip. Adequate treatment of this neoplasm must be early and radical, as metastases can occur. Considering that the lips are extremely important in the dynamics and motricity of the face, lip reconstruction after major resections in this region is a challenge for the surgeon in the search for good aesthetic and functional results. This study seeks to present an already established and reliable technique for reconstructing the lower lip after tumor resection, the Karapandizic flap. Method: In this case review, 4 patients with lower lips reconstructed using the Karapandzic technique in 2013-2022 are retrospectively evaluated. Results: The most frequently observed complications were hypertrophic scar, lip vermilion suture dehiscence, and microstomia (reduction of oral opening). The cleft lip (microstomia) reduction was partially corrected through dental orthoses, with no need for commissuroplasty in any of the cases. Another contribution of this work is the use of preoperative color echoDoppler, which allows flap planning by checking the viability of the vascular pedicle and the actual positioning of this pedicle, reducing the chances of inadvertent injury to the vessels during surgery. Conclusion: Even though microstomy is a limitation of this flap, we conclude that this technique meets the need for lower lip reconstruction in large resections, as it can provide satisfactory results in oncological, functional, and aesthetic terms.

Carcinoma de células escamosas y el rol discutido de la irritación mecánica crónica. Informe de un caso / Squamous oral cell carcinoma and the discussed role of chronic mechanical irritation. Report of a case

Resumen Objetivo Describir el desarrollo de un carcinoma oral de células escamosas, en el que la irritación mecánica crónica aparenta tomar un rol protagonista en la carcinogénesis. Caso clínico Un paciente de 41 años de edad, argentino, con antecedentes de fisura labio alvéolo palatina, diabetes mellitus, convulsiones, consumo de cocaína y marihuana, enolismo crónico y tabaquismo, acude al Servicio de Odontología del Hospital Central de Mendoza para la evaluación de una úlcera dolorosa en el dorso de su lengua, de varias semanas de evolución, en íntima relación con un primer premolar superior derecho y una pieza supernumeraria. Se realizó una biopsia y de la anatomía patológica resultó el diagnóstico de carcinoma oral de células escamosas. Se ofreció al paciente posibles tratamientos que rechazó, por lo que se inició terapia paliativa y sintomática. Al avanzar su mal estado general, falleció por complicaciones relacionadas a la deglución. Si bien no está definido el rol de la irritación mecánica crónica en la etiología de la carcinogénesis, ejerce un efecto promotor del daño causado por el tabaco y el alcohol. Si bien el paciente era fumador y bebía alcohol, se puede observar que desarrolló un carcinoma de células escamosas en evidente relación a un trauma crónico, ya que la lesión en la cara dorsal de lengua está en íntimo contacto con el factor irritante. Aun así, la evidencia actual disponible es limitada y discute el protagonismo del trauma crónico por lo que se necesitan más estudios para evaluar y definir la posible relación causal de la irritación mecánica crónica en la carcinogénesis.

Abstract Aim To describe the development of an oral squamous cell carcinoma, in which chronic mechanical irritation appears to play a significant role in carcinogenesis. Clinical case A 41-year-old patient, from Argentina, with a history of cleft lip and palate, diabetes mellitus, seizures, cocaine and cannabis use, chronic alcoholism and smoking, comes to the Dentistry Service of the Central Hospital for the evaluation of a painful ulcer on the dorsum of the tongue, which had been developing for several weeks, in close relation to an upper right first premolar and a supernumerary tooth. A biopsy was performed, and the pathological anatomy resulted in the diagnosis of oral squamous cell carcinoma. Possible treatments were offered to the patient, which he rejected, so palliative and symptomatic therapy was initiated instead. As his poor general condition progressed, he died due to complications related to swallowing. Although the role of chronic mechanical irritation in the development of carcinogenesis is not yet fully defined, it has been shown to have a promoting effect on the damage caused by tobacco and alcohol. Although the patient was a smoker and drank alcohol, it can be observed that he developed a squamous cell carcinoma in obvious relation to a chronic trauma, since the lesion develops on the dorsal face of the tongue in close contact with the irritant factor. Still, the current evidence available is limited and discusses the role of chronic trauma, so more studies are needed to evaluate and define the possible causal relationship of chronic mechanical irritation in the development of carcinogenesis.

Effect of Survivin Down-Regulation by Egr1-Survivin shRNA Combined with Radiotherapy on Radiosensitivity of Esophageal Squamous Carcinoma / Efecto de la Regulación Negativa de Survivina por shRNA de Egr1-Survivina Combinado con Radioterapia sobre la Radiosensibilidad del Carcinoma Escamoso de Esófago

SUMMARY: This study is to investigate the effect of survivin down-regulation by Egr1-survivin shRNA combined with radiotherapy on the apoptosis and radiosensitivity of esophageal squamous cell carcinoma ECA109 and KYSE150 cells. ECA109 and KYSE150 cells were transfected with Egr1-survivin shRNA, and then treated with radiotherapy. After 24 h, the mRNA and protein levels of Egr1-survivin were detected by qPCR and Western-Blot. Cell cycle and apoptosis were detected by flow cytometry. Western blot also detected levels of cleavaged Caspase 3 and Caspase 9. YM155 was used as a positive control to inhibit survivin expression. The levels of survivin mRNA and protein in ECA109 and KYSE150 cells treated with Egr1-survivin shRNA combined with radiotherapy were significantly lower than those of the blank control group, the empty vector control group, and, the YM155 + radiotherapy group (P<0.05). Meanwhile, after survivin down-regulation, the ratio of G2 to S phase of ECA109 and KYSE150 cells increased significantly, leading to significant G2 and S phase arrest. Additionally, apoptosis of ECA109 and KYSE150 cells increased significantly (P <0.01). Further, protein levels of cleavaged Caspase 3 and Caspase 9 significantly increased in Egr1-survivin shRNA combined with radiotherapy group. Egr1-survivin shRNA combined with radiotherapy can down-regulate survivin expression, which further increases the apoptosis, and enhances the radiosensitivity of ECA109 and KYSE150 cells.

Este estudio tuvo como objetivo investigar el efecto de la regulación negativa de survivina por el shRNA de Egr1-survivina combinado con radioterapia sobre la apoptosis y la radiosensibilidad del carcinoma de células escamosas de esófago Células ECA109 y KYSE150. Las células ECA109 y KYSE150 se transfectaron con shRNA de survivina Egr1 y luego se trataron con radioterapia. Después de 24 h, los niveles de ARNm y proteína de Egr1-survivina se detectaron mediante qPCR y Western-Blot. El ciclo celular y la apoptosis se detectaron mediante citometría de flujo. La transferencia Western también detectó niveles de Caspasa 3 y Caspasa 9 escindidas. Se usó YM155 como control positivo para inhibir la expresión de survivina. Los niveles de ARNm y proteína de survivina en células ECA109 y KYSE150 tratadas con shRNA de survivina Egr1 combinado con radioterapia fueron significativamente más bajos que los del grupo control en blanco, el grupo control de vector vacío y el grupo de radioterapia YM155 + (P <0,05). Mientras tanto, después de la regulación negativa de survivina, la proporción entre las fases G2 y S de las células ECA109 y KYSE150 aumentó significativamente, lo que llevó a una detención significativa de las fases G2 y S. Además, la apoptosis de las células ECA109 y KYSE150 aumentó significativamente (P <0,01). Además, los niveles de proteína de Caspasa 3 y Caspasa 9 escindidas aumentaron significativamente en el shRNA de Egr1- survivina combinado con el grupo de radioterapia. El shRNA de survivina de Egr1 combinado con radioterapia puede regular negativamente la expresión de survivina, lo que aumenta aún más la apoptosis y mejora la radiosensibilidad de las células ECA109 y KYSE150.

Impact of COVID-19 Pandemic on Cutaneous Squamous Cell Carcinoma: A Single-Centre Study of Epidemiologic, Clinic and Histopathological Factors.

BACKGROUND: The COVID-19 pandemic may have adversely affected the early diagnosis of skin cancer. OBJECTIVE: To compare epidemiological, clinical and histopathological characteristics in patients undergoing cutaneous squamous cell carcinoma (SCC) surgery before and after the beginning of the pandemic. MATERIAL & METHODS: We conducted a cross-sectional study including two case series: (1) patients operated on for SCC in the year after the first state of alarm in Spain (15 March 2020), and (2) patients with SCC operated on in the previous year. Epidemiological, clinical and histopathological variables, tumour stage and risk grade were collected. RESULTS: 248 patients were included (127 undergoing surgery before the pandemic and 121 after the pandemic). After the beginning of the pandemic, the percentage of high-risk SCC significantly increased from 35.3% to 46.2% (p=0.011). However, no significant differences were found in thickness, perineural invasion or metastases. CONCLUSIONS: Although there has not been a significant reduction in the number of SCC operated on after the pandemic, there has been a significant increase in high-risk SCC. All this could lead to an increase in skin cancer mortality in the future.

Queilite actínica ("Lábios de Marinheiro"): uma Revisão para o Clínico / Actinic cheilitis ("sailor's lips"): A review for the clinician

A Queilite Actínica (QA), também conhecida como "lábios de marinheiro", é uma patologia com potencial de malignização e, ainda que seja de fácil diagnóstico e prevenção, casos diagnosticados tardiamente podem evoluir para carcinoma de lábios. Seu principal fator etiológico é a exposição aos raios ultravioletas, e por este motivo, indivíduos que se expõem muito ao sol, incluindo militares, podem ser considerados grupo de risco para a doença. O objetivo principal deste trabalho foi descrever os principais fatores de risco e prognósticos da QA e apresentar uma revisão para o cirurgião-dentista, facilitando a identificação e conduta. Para tal, foi realizada busca de artigos pertinentes ao tema nas bases de dados Medline, Lilacs, SciELO e PubMed, de 1987 a 2022. O seguinte perfil do paciente com QA foi identificado: homem, na quinta década de vida, pele clara, com lesões no lábio inferior e com histórico de longo tempo de atividades ocupacionais ao ar livre/intensa exposição solar. O cirurgião-dentista possui papel fundamental na identificação dos grupos de risco, no reconhecimento precoce da doença e, em casos mais avançados, realizar o diagnóstico e o correto encaminhamento para atendimento especializado.

Actinic Cheilitis (AC), also known as "sailor's lips", is a premalignant pathology, and although it is easy to diagnose and prevent, late diagnosed cases may progress to lip carcinoma. Since its main etiological factor is exposure to ultraviolet rays, individuals often exposed to the sun, including military personnel, can be considered a risk group for the disease. The aim of this study was to describe the main risk and prognostic factors of AC and to create a clinical protocol for dental surgeons, making easier to identify and conduct each case. For this purpose, a search for articles relevant to the topic was carried out in Medline, Lilacs, SciELO and PubMed databases, from 1987 to 2022. The following AC patient profile was identified: male, in the fifth decade of life, fair skinned, with lesions on the lower lip and with a long history of outdoor occupational activities/intense sun exposure. The dentist has a fundamental role in identifying risk groups, early recognition of the disease and in more advanced cases, making the correct diagnosis and recommendation to specialized care.

Survival of patients living with HIV and cancer in Cali, Colombia

Background: People living with HIV have an increased risk of cancer compared to the general population. However, with the increase in life expectancy and advances in antiretroviral therapy, the survival of patients with cancer and HIV has changed. Objective: To determine the survival of patients living with HIV and cancer in Cali, Colombia Methods: A retrospective cohort study was conducted at the Fundación Valle del Lili, Cali, Colombia. Data from the HIV database was crossed with data from the hospital and population-based cancer registries between 2011-2019. Patients <18 years, limited available clinical information on the diagnosis and treatment of HIV and cancer, and non-oncological tumor diagnosis were excluded. Results: A total of 173 patients were included. The frequencies of AIDS-defining neoplasms were: Non-Hodgkin lymphoma (42.8%), Kaposi sarcoma (27.8%), and cervical cancer (4.6%). Overall survival was 76.4% (95% CI 68.9-82.3) at five years. Poorer survival was found in patients with AIDS-defining infections (56.9% vs. 77.8%, p=0.027) and non-AIDS-defining infections (57.8% vs. 84.2%, p=0.013), while there was better survival in patients who received antiretroviral therapy (65.9% vs. 17.9%, p=0.021) and oncological treatment (66.7% vs. 35.4%, p<0.001). The presence of non-AIDS-defining infections increases the risk of dying (HR = 2.39, 95% CI 1.05-5.46, p=0.038), while oncological treatment decreases it (HR = 0.33, 95% CI 0.14-0.80, p=0.014). Conclusions: In people living with HIV, Non-Hodgkin lymphoma and Kaposi sarcoma are the most common neoplasms. Factors such as AIDS-associated and non-AIDS-associated infections have been identified as determinants of survival. Cancer treatment seems to improve survival.

Antecedentes: Las personas que viven con VIH tienen un riesgo mayor de cáncer en comparación con la población general. Sin embargo, con el aumento de la esperanza de vida y los avances en la terapia antirretroviral, la supervivencia de los pacientes con cáncer y VIH ha cambiado. Objetivo: Determinar la supervivencia de los pacientes que viven con VIH y cáncer en Cali, Colombia. Métodos: Se realizó un estudio de cohorte retrospectivo en la Fundación Valle del Lili, Cali, Colombia. Los datos de la base de datos de VIH se cruzaron con los datos de los registros de cáncer de base hospitalaria y poblacional entre 2011-2019. Se excluyeron los pacientes <18 años, con información clínica limitada disponible sobre el diagnóstico y tratamiento del VIH y el cáncer y los casos con diagnóstico de tumor no oncológico. Resultados: Se incluyeron un total de 173 pacientes. Las frecuencias de neoplasias definitorias de SIDA fueron: linfoma no Hodgkin (42.8%), sarcoma de Kaposi (27.8%) y cáncer cervical (4.6%). La supervivencia global fue del 76.4% (IC 95% 68.9-82.3) a los cinco años. Se encontró una peor supervivencia en pacientes con infecciones definitorias de SIDA (56.9% vs. 77.8%, p=0.027) e infecciones no definitorias de SIDA (57.8% vs. 84.2%, p=0.013), mientras que hubo una mejor supervivencia en pacientes que recibieron terapia antirretroviral (65.9% vs. 17.9%, p=0.021) y tratamiento oncológico (66.7% vs. 35.4%, p<0.001). La presencia de infecciones no definitorias de SIDA aumentó el riesgo de morir (HR = 2.39, IC 95% 1.05-5.46, p=0.038), mientras que el tratamiento oncológico lo disminuyó (HR = 0.33, IC 95% 0.14-0.80, p=0.014). Conclusiones: En las personas que viven con VIH, el linfoma no Hodgkin y el sarcoma de Kaposi son las neoplasias más comunes. Se han identificado factores como las infecciones asociadas al SIDA y las infecciones no asociadas al SIDA como determinantes de la supervivencia. El tratamiento del cáncer parece mejorar la supervivencia.

Immunohistochemical expression of COX-2, Ki-67, Bcl-2, Bax, VEGF and CD105 according to histological grading in oral squamous cell carcinoma / Expresión inmunohistoquímica de COX-2, Ki-67, Bcl-2, Bax, VEGF y CD105 según el grado histológico en el carcinoma oral de células escamosas

Introduction: Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck cancer. Few studies have analyzed the expression of proteins related to inflammation (COX-2) and tumor progression according to the histological grade of OSCC. Objective: Analyze the immunohistochemical expression of COX-2, Ki-67 (cell proliferation), Bcl-2/Bax (apoptosis), VEGF, and CD105 (angiogenesis) according to histological grades of OSCC.Material and methodsThe immunohistochemical expression of COX-2, Ki-67, Bcl-2, Bax, VEGF, and CD105 of 58 cases of OSCC was analyzed. 13 cases of oral mucosa (OM) were analyzed as controls. Results: COX-2, VEGF, CD105, and Ki-67 were higher in OSCC than in OM, particularly in poorly differentiated OSCC (p<0.05). Bax expression was lower in poorly differentiated OSCC (p<0.001). The Bcl-2/Bax ratio was higher in OSCC compared to MO (p<0.05). Conclusion: There are immunohistochemical differences according to histological grades of OSCC, which could influence clinical behavior.(AU)

Introducción: El carcinoma oral de células escamosas (COCE) es el cáncer de cabeza y cuello más prevalente. Escasos estudios analizan la expresión de proteínas relacionadas a inflamación (COX-2) y progresión tumoral según el grado histológico de COCE. Objetivo: Analizar la expresión inmunohistoquímica de COX-2, Ki-67 (proliferación celular), Bcl-2/Bax (apoptosis), VEGF y CD105 (angiogénesis) según grados histológicos de COCE.Material y métodos. Se analizó la expresión inmunohistoquímica de COX-2, Ki-67, Bcl-2, Bax, VEGF y CD105 de 58 casos de COCE. Trece casos de mucosa oral (MO) fueron analizados como control. Resultados: Las expresiones de COX-2, VEGF, CD105 y Ki-67 fueron mayores en el COCE comparadas con la MO, particularmente en el COCE pobremente diferenciado (p < 0,05). La expresión de Bax fue menor en el COCE pobremente diferenciado (p < 0,001). La razón Bcl-2/Bax fue mayor en COCE comparado con MO (p < 0,05). Conclusión: Existen diferencias inmunohistoquímicas según grados histológicos de COCE, lo que podría determinar una evolución clínica diferenciada.(AU)

Hiperplasia pseudoepiteliomatosa: carcinoma escamocelular versus paracoccidioidomicosis oral, un caso con mirada dermatológica / Pseudoepitheliomatous hyperplasia: Squamous cell carcinoma versus oral paracoccidioidomycosis, a case from a dermatological perspective

La paracoccidioidomicosis es una micosis sistémica endémica en Latinoamérica. La presentación más frecuente compromete crónicamente los pulmones, la piel y las mucosas. Al inicio, este paciente presentó, por varios años, una lesión única en la mucosa oral que, en ausencia de otros síntomas, se relacionó con una neoplasia maligna, específicamente con un carcinoma escamocelular. La diferenciación entre los dos diagnósticos se hace mediante un examen directo, un estudio histopatológico y cultivos iniciales y subsecuentes. Sin embargo, tales estudios no fueron concluyentes. Después de varias consultas y pruebas, con los resultados del examen directo, la inmunodifusión y la PCR en tiempo real se confirmó el diagnóstico de paracoccidioidomicosis crónica multifocal. Este caso alerta sobre la ausencia de sospecha clínica de micosis endémicas, dada la presencia de lesiones mucocutaneas que pueden ser producidas por hongos como Paracoccidioides spp, y la importancia de considerarlas entre los diagnósticos diferenciales.

Paracoccidioidomycosis is a systemic mycosis endemic in Latin America. The most frequent form involves a chronic compromise of the lungs, skin, and mucosa. The patient started with a single oral lesion that lasted for several years. The absence of other symptoms pointed out a possible malignant neoplasm, specifically a squamous cell carcinoma. Differentiation between both diagnoses-fungal infection and carcinoma-depends on the results of the direct examination, the histopathological study, and the initial and subsequent cultures. However, in this case, those findings were not conclusive. The coexistence of both diagnoses is frequent and increases the diagnostic challenge. After several consultations and tests, direct examination, immunodiffusion and real-time PCR findings the multifocal chronic paracoccidioidomycosis diagnosis was confirmed. This case warns about a systematical absence of clinical suspicion of endemic mycoses before the appereance of mucocutaneous lesions, which can be produced by fungi like Paracoccidioides spp, and the importance of considering those mycoses among the differential diagnoses.

Immunoexpression of ALDH1A1, FGFR2, CD44 and Caspase-3 in Oral Squamous Cell Carcinoma and Leukoplakia: A pilot study

Current research highlighted the importance to recognize feasible biomarkers for early diagnoses and treatment in oral cancer. Our study analyzed the expression and spatial distribution of ALDH1A1, FGFR2, caspase-3, and CD44 in Oral Squamous Cell Carcinoma (OSCC) and leukoplakia with and without oral mucosal dysplasia. Paraffin-embedded samples of OSCC (n=5), leukoplakia with (n=5) and without (n=5) dysplasia obtained by incisional biopsies were processed using conventional histochemical techniques. Immunohistochemistry was performed using antibodies against ALDH1A1, FGFR2, caspase-3, and CD44. Images of the immunohistochemically stained tissue sections were analyzed according to the intensity of the immunostaining of each marker and classified in Scores. The Kruskal- Wallis test was performed (p≤0.05). Our results demonstrated a statically difference in the expression of all immunomarkers between OSCC and leukoplakia without dysplasia, being more significant in FGFR2 and ALDH1A1. Within the limitations of this study, our data showed that all biomarkers were overexpressed in OSCC and leukoplakia with oral mucosa dysplasia, suggesting that the presence of dysplasia is a significant clinic-pathologic predictor for malignant transformation.

La actual evidencia científica enfatiza la importancia de reconocer biomarcadores viables para el diagnóstico y tratamiento temprano del cáncer oral. Nuestro estudio piloto analizó la expresión y distribución espacial de ALDH1A1, FGFR2, caspasa-3 y CD44 en carcinoma oral de células escamosas (COCE) y en leucoplasia con o sin displasia de la mucosa oral. Las muestras incluidas en parafina de COCE (n=5), con (n=5) y sin (n=5) displasia fueron obtenidas mediante biopsias incisionales, las cuales se procesaron utilizando técnicas histoquímicas convencionales. El análisis inmunohistoquímico se realizó utilizando anticuerpos contra ALDH1A1, FGFR2, caspasa-3 y CD44. Las imágenes de las secciones de cada muestra fueron analizadas según la intensidad de inmunoexpresión de cada marcador y se clasificaron en diferentes escalas (scores). Se realizó la prueba de Kruskal-Wallis (valores de p<0,05). Nuestros resultados demostraron una diferencia estadística en la expresión de todos los inmunomarcadores entre COCE y las muestras con leucoplasia sin displasia, siendo más significativa en FGFR2 y ALDH1A1. Considerando las limitaciones de este estudio, los datos sugieren que la presencia de displasia en la mucosa oral es un importante predictor clínico-patológico de transformación maligna.

In-vivo lymphoscintigraphy of sinonasal tumors identifies retropharyngeal node and level I as predominant sentinel nodes.

OBJECTIVE: To evaluate by in- vivo lymphoscintigraphy and SPECT-CT imaging, the lymphatic drainage patterns of para-nasal sinus(PNS) tumors. To confirm or refute the belief of the retropharyngeal lymph node (RPLN) being the significant draining lymph node for such tumors. METHODS: Prospective cohort study conducted on previously untreated PNS tumors with no clinico-radiological evidence of lymph node metastasis. Lymphoscintigraphy undertaken by nasal endoscopic assisted peritumoral injection of 99mTc Sulfur colloid. Injections were classified as anterior or posterior as per a vertical line along the maxillary sinus ostium. RESULTS: 17 patients were included. Lymphoscintigraphy successfully identified 17 sentinel nodes in 15 patients and was unsuccessful (lymphoscintigraphy failure) in 2 patients. Predominant sites of sentinel lymphatic drainage were noted to be the RPLN (n = 8; 47%), and Level I (n = 7; 42%). Occasional drainage was identified at the peri-parotid node(n = 1) and at Level II (n = 1). Contralateral drainage was noted in 2 patients (level I-1 and RPLN-1). Anterior injections drained predominantly to Level I (6/8) and RPLN (2/8), while posterior injections drained predominantly to the RPLN ( 6/7). The relative risk of RPLN being identified as the sentinel node was significantly higher for posteriorly placed injections than for anteriorly placed injections (RR- 3.43; 95% CI-1.0-11.8, p = 0.05). CONCLUSION: The RPLN is noted as a frequent draining node for sino-nasal tumours and merits routine attention in all sino-nasal tumors. The radio-colloid SPECT-CT technique described here offers an excellent in-vivo technique to further explore and validate the lymphatic drainage pathways of these tumours.

Immunohistochemical expression of COX-2, Ki-67, Bcl-2, Bax, VEGF and CD105 according to histological grading in oral squamous cell carcinoma.

INTRODUCTION: Oral squamous cell carcinoma (OSCC) is the most prevalent head and neck cancer. Few studies have analyzed the expression of proteins related to inflammation (COX-2) and tumor progression according to the histological grade of OSCC. OBJECTIVE: Analyze the immunohistochemical expression of COX-2, Ki-67 (cell proliferation), Bcl-2/Bax (apoptosis), VEGF, and CD105 (angiogenesis) according to histological grades of OSCC. MATERIAL AND METHODS: The immunohistochemical expression of COX-2, Ki-67, Bcl-2, Bax, VEGF, and CD105 of 58 cases of OSCC was analyzed. 13 cases of oral mucosa (OM) were analyzed as controls. RESULTS: COX-2, VEGF, CD105, and Ki-67 were higher in OSCC than in OM, particularly in poorly differentiated OSCC (p<0.05). Bax expression was lower in poorly differentiated OSCC (p<0.001). The Bcl-2/Bax ratio was higher in OSCC compared to MO (p<0.05). CONCLUSION: There are immunohistochemical differences according to histological grades of OSCC, which could influence clinical behavior.

Marjolin ulcer: the importance of early diagnosis and excision / Úlcera de Marjolin: a importância do diagnóstico e excisão precoces

Introduction: Marjolin's ulcer is a rare disease characterized by the malignancy of chronic wounds that present healing disorders, often due to chronic irritation and repetitive trauma in this area. The diagnosis is made mainly through clinical history and histopathological examination. The differential diagnoses of other diseases that course with ulcers must always be researched and ruled out. Method: The present work presents a bibliographic review to elucidate the subject's relevance for medical students, physicians and nurses, to assist in early diagnosis. Results: Nine observational studies were selected to compose the discussion. Conclusion: The most effective treatment for this condition is surgery, and lymph node dissection is suggested in some cases. Chemotherapy has not shown satisfactory results, while radiotherapy is used in selected cases. Given the rapid evolution, tissue damage, and worse prognosis, diagnosis, and excision should be performed early for a better clinical outcome.

Introdução: A úlcera de Marjolin é uma doença rara, caracterizada pela malignização de feridas crônicas que apresentaram distúrbios cicatriciais, muitas vezes devido à irritação crônica e a traumas repetitivos nesta área. O diagnóstico é realizado sobretudo através da história clínica e de exame histopatológico. Os diagnósticos diferenciais de outras doenças que cursam com úlceras devem sempre ser pesquisados e afastados. Método: O presente trabalho apresenta uma revisão bibliográfica, a fim de elucidar a relevância do tema para acadêmicos de medicina, médicos e enfermeiros, com o propósito de auxiliar no diagnóstico precoce. Resultados: Foram selecionados 9 estudos observacionais para compor a discussão. Conclusão: O tratamento mais eficaz desta condição é o cirúrgico, e o esvaziamento linfonodal é sugerido em alguns casos. A quimioterapia não demonstrou resultados satisfatórios, enquanto a radioterapia é utilizada em casos selecionados. O diagnóstico e a excisão devem ser feitos precocemente para melhor desfecho clínico, visto a rapidez da evolução, o prejuízo tecidual e pior prognóstico.

Masquerade syndrome in ocular surface squamous neoplasia / Síndrome mascarada em neoplasia escamosa da superfície ocular

ABSTRACT The aim of this study was to alert the ophthalmic community to an atypical manifestation of ocular surface squamous neoplasia, which may delay diagnosis and treatment and result in a guarded visual prognosis and significant sequelae. A 61-year-old immunocompetent man presented with an initial diagnosis of necrotizing scleritis in the right eye for 3 months. He was treated with systemic prednisone but experienced persistent pain and low visual acuity. Conjunctival biopsy of the affected region confirmed the diagnosis of invasive ocular surface squamous neoplasia, which progressed with intraocular and orbital invasion; thus, exenteration was performed. Masquerade syndrome should be suspected in patients with nodulo-ulcerative lesions of the conjunctiva and sclera. This clinical can be more aggressive, with a greater likelihood of intraocular and orbital involvement. The earlier the diagnosis and treatment, the better the patient prognosis.

RESUMO O objetivo é alertar a comunidade oftalmológica sobre uma manifestação atípica de neoplasia escamosa da superfície ocular (OSSN) que pode levar a um atraso no diagnóstico e tratamento, evoluindo com prognóstico reservado e significativas sequelas. Homem, imunocompetente, 61 anos com diagnóstico inicial de esclerite necrosante em olho direito há 3 meses, em tratamento com prednisona sistêmica porém com persistência da dor e baixa acuidade visual. Realizado biópsia conjuntival em região acometida e diagnosticado como neoplasia escamosa da superfície ocular invasiva. Evolui com invasão intraocular e orbital sendo submetido a exenteração. Assim sendo, deve-se suspeitar de síndrome mascarada frente a um paciente com lesões nódulo-ulcerativas da conjuntiva e esclera. Essa forma clínica pode ser mais agressiva, com maior chance de comprometimento intraocular e orbital. Quanto mais precoces o diagnóstico e o tratamento, melhor o prognóstico para o paciente.