Carcinoma neuroendocrino de la piel: Carcinoma de células de Merkel. Revisión de la Literatura, a propósito de un caso / Neuroendocrine skin carcinoma: Merkel cell carcinoma. Review of literature, about a case

El carcinoma de células de Merkel, también llamado carcinoma neuroendocrino de la piel, es un tipo de cáncer de piel muy poco frecuente que generalmente aparece como un nódulo de color carne o rojo azulado, más frecuentemente en región facial, cabeza y cuello. El carcinoma de células de Merkel se desarrolla principalmente en personas mayores ya que la exposición al sol a largo plazo o un sistema inmunitario débil pueden aumentar el riesgo de desarrollarlo. Las células de Merkel se encuentran en la base de la capa más externa de la piel (epidermis) y están conectadas a las terminaciones nerviosas que son responsables del sentido del tacto. Tiende a crecer rápido y diseminarse a otras partes del cuerpo. Por tanto, las opciones de tratamiento para el carcinoma de células de Merkel dependen de si el cáncer se ha diseminado más allá de la piel

Merkel cell carcinoma, also called neuroendocrine skin of the skin, is a very rare type of skin cancer that generally appears as a bluish meat or red color nodule, more frequently in the facial, head and neck region. Merkel cell carcinoma develops mainly in older people since long -term exposure or a weak immune system can increase the risk of developing it. Merkel cells are at the base of the outermost layer of the skin (epidermis) and are connected to nerve endings that are responsible for the sense of touch. It tends to grow quickly and spread to other parts of the body. Therefore, the treatment options for Merkel cell carcinoma depend on whether cancer has spread beyond the skin

Arsenic Trioxide: Pharmacological Applications / Trióxido de Arsénico: Aplicaciones farmacológicas

Background: Arsenic trioxide is a chemical compound that has been used as a treatment for various diseases. Despite being potentially toxic, this compound has been used as a therapy to treat Acute Myeloid Leukemia and is being investigated as a possible treatment for different types of cancer. Objectives: The present review aims to describe the use and studies reported in the literature of Arsenic Trioxide as a possible therapeutic agent for Acute Myeloid Leukemia, Acute Promyelocytic Leukemia, Chronic Myeloid Leukemia, Multiple Myeloma, Myelodysplastic Syndrome, Hepatocellular Carcinoma, Lung Cancer, Neuroblastoma, Breast Cancer, Aplastic Hepatitis C, and HIV-1. Methods: A systematic review was conducted using databases (Elsevier, Google Scholar, PubMed) to compile documents published before December 2023. Results:Multiple pharmacological applications of arsenic trioxide have been reported to treat acute and chronic myeloid leukemia. Arsenic trioxide has been shown to inhibit angiogenesis, which helps treat multiple myeloma. Several studies have shown and suggested the effectiveness of arsenic trioxide as a treatment of hepatocellular carcinoma, lung cancer, neuroblastoma, prostate cancer, breast cancer, aplastic anemia, hepatitis C, and HIV-1. Conclusion: Despite potentially toxic effects, Arsenic compounds are therapeutic agents for multiple diseases, from syphilis to cancer. In recent years, more efficient ways have been investigated to deliver and find the specific dose to treat the disease, causing the fewest possible adverse effects.

Antecedentes: El trióxido de arsénico es un compuesto químico que se ha utilizado como tratamiento de diversas enfermedades. A pesar de ser potencialmente tóxico, este compuesto se ha utilizado como terapia para tratar la leucemia mieloide aguda y se está investigando como posible tratamiento para diferentes tipos de cáncer. Objetivos: La presente revisión pretende describir el uso del trióxido de arsénico como posible agente terapéutico para la leucemia mieloide aguda, la leucemia promielocítica aguda, la leucemia mieloide crónica, el mieloma múltiple, el síndrome mielodisplásico, el carcinoma hepatocelular, el cáncer de pulmón, el neuroblastoma, el cáncer de mama, la hepatitis C aplásica y el VIH-1. Métodos: Se realizó una revisión sistemática utilizando bases de datos (Elsevier, Google Scholar, PubMed) para recopilar documentos publicados antes de diciembre de 2023. Resultados: Se ha informado de múltiples aplicaciones farmacológicas del trióxido de arsénico para tratar la leucemia mieloide aguda y la leucemia mieloide crónica. Se ha demostrado que el trióxido de arsénico inhibe la angiogénesis, lo que resulta útil para el tratamiento del mieloma múltiple. Varios estudios han demostrado y sugerido la eficacia del trióxido de arsénico como tratamiento del carcinoma hepatocelular, el cáncer de pulmón, el neuroblastoma, el cáncer de próstata, el cáncer de mama, la anemia aplásica, la hepatitis C y el VIH-1. Conclusión: A pesar de tener un efecto potencialmente tóxico, los compuestos de arsénico destacan como agentes terapéuticos para múltiples enfermedades, desde la sífilis hasta el cáncer. En los últimos años, se han investigado formas más eficientes de administrar y encontrar la dosis específica para poder tratar la enfermedad, causando los menores efectos adversos posibles.

Salivary gland tumor: atypical presentation of breast cancer

Breast cancer is a heterogeneous disease with various histological and molecular subtypes. Among them, salivary gland tumors are rare and can be divided into three groups: pure myoepithelial differentiation, pure epithelial differentiation and myoepithelial with mixed epithelial differentiation. In the last group, adenoid cystic carcinoma stands out, a rare entity with low malignant potential. It represents less than 0.1­3% of breast cancer cases and has the most frequent clinical presentation as a palpable mass. The diagnosis is confirmed by histology and immunohistochemistry. Classically, they are low-aggressive triple-negative tumors, with overall survival and specific cancer survival at five and ten years greater than 95%. However, there are rare reports of aggressive variants with a risk of distant metastasis and death. Treatment is based on surgical resection with margins. Lymphatic dissemination is rare, and there is no consensus regarding the indication of an axillary approach. Adjuvant radiotherapy is indicated in cases of conservative surgery and should be discussed in other cases. The benefit of chemotherapy remains uncertain, as most tumors are indolent. We report a case that required individualized decisions based on its peculiarities of presentation, diagnosed in an asymptomatic elderly patient during screening, in which mammography showed heterogeneous gross calcifications clustered covering 1.6 cm. Stereotacticguided vacuum-assisted biopsy was performed, and the area was marked with a clip. The anatomopathological examination led to a diagnosis of salivary gland-type carcinoma, triple-negative. The patient underwent segmental resection of the right breast and sentinel lymph node biopsy. The final anatomopathological result was similar to that of the biopsy, with an immunohistochemicalprofile of the adenoid cystic type and two sentinel lymph nodes free of neoplasia. Considering age and histological subtype, adjuvant therapy was not indicated. Follow-up for three years showed no evidence of disease

Déterminants du carcinome photo-induit chez les sujets de phototype albinos aux Cliniques Universitaires de Kinshasa / Determinants of photo-induced carcinoma in albino phototype people at the Kinshasa University hospital

Contexte et objectif. Les rayonnements ultra-violets constituent un facteur connu de risque de carcinome photo-induit chez l'albinos en milieu à fort ensoleillement. La présente étude a évalué l'ampleur du carcinome photo induit et a recherché les principaux déterminants chez les sujets de phototype albinos à Kinshasa. Méthodes. Dans une étude transversale, des sujets de phototype albinos recrutés de manière consécutive, ont été examinés du 1er janvier 2020 au 30 septembre 2020 au Service de dermatologie des Cliniques Universitaires de Kinshasa. La fréquence du carcinome a été estimée et ses déterminants recherchés à l'aide d'une analyse de régression logistique. Résultats. Au total 100 albinos ont été inclus. Près d'un albinos sur deux (44 %) a développé un carcinome. En analyse multivariée, l'âge >30 ans (OR : 2,68 ; IC 95% :1,65-11,10 ; p=0,017), la présence des kératoses actiniques (OR: 3.80; IC 95%: 1.43-7.23; p=0.023), un antécédent familial de cancer non cutané (OR : 2,40 ; IC95% : 1,47-12,35 ; p=0,29), un antécédent familial de carcinome (OR : 4,99 ; IC95% :3,0-9,29 ;p=0,000) et un antécédent personnel de polytransfusion (OR :2,30 ; IC 95% :1,26-6,20 ;p=0,045) ont été identifiés comme les principaux déterminants du carcinome photo-induit. Conclusion. Près d'un albinos sur deux présente un carcinome photo-induit. Ceci justifie l'intensification des mesures comportementales et préventives contre le développement des cancers cutanés ciblant particulièrement les albinos âgés de moins de 30 ans, présentant des kératoses actiniques et ceux avec antécédents familiaux de cancer (carcinome et autres).

Nefroureterectomía radical lumboscópica con rodete vesical endoscópico, en cáncer urotelial de tracto urinario superior / Lumboscopic radical nephroureterectomy with endoscopic bladder cuff excision in an upper urinary tract urothelial tumor

Los carcinomas uroteliales son el 4to tumor más común. Pueden ubicarse en el tracto urinario inferior (vejiga y uretra) o en el tracto urinario superior (cavidades renales, pelvis renal y uréter). Presentamos una serie de 3 casos, con cuadro de hematuria macroscópica, documentando tumores uroteliales, realizándose en estos casos un abordaje lumboscópico de riñón y una resección endoscópica del rodete vesical. Se realiza nefroureterectomía lumboscópica con resección de rodete vesical endoscópica transuretral. Los 3 pacientes fueron egresados al segundo día posquirúrgico sin complicaciones y en los tres casos el rodete vesical sin evidencia de actividad tumoral, y actualmente en vigilancia con excelente resultados oncológicos. La nefroureterectomía lumboscópica con resección endoscópica del rodete vesical es una técnica reproducible en manos experimentadas, con iguales resultados oncológicos que el abordaje abierto.

Urothelial carcinomas are the 4th most common tumor. They can be located in the lower urinary tract (bladder and urethra) or in the upper urinary tract (renal cavities, renal pelvis, and ureter). We present a series of 3 cases, with a picture of macroscopic hematuria, documenting urothelial tumors, performing in these cases a lumboscopic approach to the kidney and an endoscopic resection of the bladder rim. Lumboscopic nephroureterectomy was performed with transurethral endoscopic bladder rump resection. The 3 patients were discharged on the second postoperative day without complications and in the three cases the bladder rim without evidence of tumor activity, and currently under surveillance with excellent oncological results. Lumboscopic nephroureterectomy with endoscopic resection of the bladder rim is a reproducible technique in experienced hands, with the same oncological results as the open approach.

The prognostic roles of PYCR2 and ZBTB18 expression in tissues of colorectal carcinoma and non-neoplastic tissues: an immunohistochemical study

Background: It is important to detect novel biomarkers responsible for the progression and spread of colorectal cancer (CRC) to better evaluate the prognosis of the patients, provide better management, and foster the development of therapeutic targets. In humans, pyrroline-5-carboxylate reductase 2 (PYCR2) is encoded on chromosome 1q42.12, and its metabolic activity has been linked to oncogenesis in many cancers. Zinc finger and broad-complex, tramtrack, and bric-à-brac (BTB) domain-containing protein 18 (ZBTB18), a zinc finger transcriptional repressor, has been found to have a tumor-suppressor role and to be methylated in CRCs. To date, the prognostic roles of PYCR2 and ZBTB18 in CRC patients have not been thoroughly studied. Objective: To evaluate the tissue protein expression of PYCR2 and ZBTB18 in CRC and adjacent non-neoplastic intestinal tissues, to detect their roles in CRC carcinogenesis, progression and metastases. Patients and methods: After applying the inclusion criteria, 60 CRC patients were included in the study. Tissue samples from the tumor and the adjacent non-neoplastic tissues were stained with PYCR2 and ZBTB18. The patients were followed up for about 30 months (range: 10 to 36 months). We performed a correlation regarding the expression of the markers, and clinicopathological and prognostic parameters. Results Upregulation of PYCR2 and downregulation of ZBTB18 were found to be higher in CRC tissue than in the adjacent non-neoplastic colonic mucosa (p = 0.026 and p < 0.001 respectively). High expression of PYCR2 and low expression of ZBTB18 were positively correlated with large tumor size, higher tumor grade, advanced tumor stage, presence of spread to lymph nodes, and presence of distant metastases (p < 0.001). High PYCR2 and low ZBTB18 expressions were significantly associated with poor response to therapy (p = 0.008 and 0.0.17 respectively), as well as high incidence of progression and recurrence (p = 0.005), and unfavorable overall survival (OS) rates (p = 0.001). Conclusion: High expression of PYCR2 and low expression of ZBTB18 were independent predictors of CRC, progression, poor prognosis and unfavorable patient OS and progression-free survival (PFS) rates. (AU)

Incidence and characterization of colorectal adenomas in the area of influence of a specialized institution / Incidencia y caracterización de adenomas colorrectales en el área de influencia de una institución especializada

Abstract Aim: To locate and characterize colorectal adenomas endoscopically and histologically in a cohort of patients undergoing colonoscopy in Medellín, Colombia. Materials and methods: Descriptive cross-sectional study. We included patients older than 18 years who underwent colonoscopy between February and July 2020 at a specialized center in Medellín, Colombia. We determined the incidence of adenomas, their location in different segments of the colon, their endoscopic and histological characteristics, and cases of colorectal cancer (CRC) and high-grade dysplasia (HGD). Results: 992 colonoscopies were performed, finding colorectal polyps in 266 patients, of which 208 had adenomas. We resected 461 polyps, of which 336 were adenomas (72 %). The histological type with the highest representation was tubular (78 %). The location of adenomas was 37 % in the right colon, 25 % in the transverse colon, and 38 % in the left colon. CRC cases were nine per 1,000 patients, including advanced carcinoma and carcinoma in situ (HGD). Conclusions: Given the incidence of adenomas in the right and transverse colon, rectosigmoidoscopy is discouraged as a screening study for CRC. Tubular adenomas, sessile in appearance and tiny, predominated in the population studied. We recommend screening in the population over 40 years of age and the search for precursor lesions as strategies to reduce morbidity and mortality rates due to CRC.

Resumen Objetivo: localización y caracterización endoscópica e histológica de los adenomas colorrectales en una cohorte de pacientes sometidos a colonoscopia en Medellín, Colombia. Materiales y métodos: estudio descriptivo de corte transversal. Se incluyeron pacientes mayores de 18 años sometidos a colonoscopia entre febrero y julio de 2020 en un centro especializado de Medellín, Colombia. Se determinó la incidencia de adenomas, su localización en los diferentes segmentos del colon, sus características endoscópicas e histológicas, así como también los casos de cáncer colorrectal (CCR) y displasia de alto grado. Resultados: se realizaron 992 colonoscopias y se encontraron pólipos colorrectales en 266 pacientes, de los cuales 208 tenían adenomas. En total se resecaron 461 pólipos, de los cuales 336 fueron adenomas (72 %). El tipo histológico con mayor representación fue el tubular (78 %). La localización de adenomas fue del 37 % en el colon derecho, 25 % en el transverso y 38 % en el colon izquierdo. La cantidad de casos de CCR fue de 9 por 1000 pacientes, que incluyen carcinoma avanzado y carcinoma in situ (DAG). Conclusiones: dada la incidencia de adenomas en el colon derecho y transverso, no se recomienda la rectosigmoidoscopia como estudio de tamizaje para CCR. En la población estudiada fueron predominantes los adenomas tubulares, de aspecto sésil y tamaño diminuto. Se recomienda el tamizaje en la población mayor de 40 años y la búsqueda de lesiones precursoras como estrategias para disminuir las tasas de morbimortalidad por CCR.

Treatment of Metastasis in the Appendicular Skeleton / Tratamento das metástases no esqueleto apendicular

Abstract Bone metastases may evolve with events (pain, fractures and compression) that the orthopedic surgeon will encounter regardless of his subspecialty. Accumulated surgical knowledge is predictive for the prevention of impending fractures, as well as of pathological fractures. We will present a guide to properly evaluate and conduct a patient with bone implant for surgeons who are not specialists in this area.

Resumo As metástases ósseas podem evoluir com eventos (dor, fraturas e compressão) com os quais o cirurgião ortopédico irá se depararar independentemente da sua subespecialidade. Os conhecimentos cirúrgicos acumulados são predicativos para a prevenção de fraturas iminentes, assim como de fraturas patológicas. Apresentaremos um guia para avaliar e conduzir de forma adequada um paciente com implante ósseo para cirurgiões que não sejam especialistas na área.

Avaliação do efeito carcinogênico do bromazepam em Drosophila melanogaster / Evaluation of carcinogen bromazepam effect in Drosophila melanogaster

Introdução: embora o câncer seja um dos maiores problemas de saúde pública enfrentados mundialmente, diversas substâncias presentes no meio, como os fármacos, não estão muito bem elucidadas sobre seu possível potencial carcinogênico. Entre eles, estão os benzodiazepínicos, fármacos que possuem crescente aumento do consumo desde o século XX e, principalmente, na segunda década do século XXI, por suas ações ansiolíticas, sedativas e anticonvulsivantes. Objetivo: avaliar o efeito carcinogênico do bromazepam por meio do teste para detecção de tumores epiteliais (ETT) em Drosophila melanogaster. Metodologia: para realização do ETT foram utilizadas duas linhagens mutantes de D. melanogaster: wts (fêmeas) e mwh (machos). As larvas descendentes desse cruzamento foram tratadas isoladamente com cinco concentrações de bromazepam, sendo elas: 0,0375; 0,075; 0,15; 0,30 e 0,60 mM. A Doxorrubicina foi utilizada como controle positivo e a água ultrapura como controle negativo. Após tratamento, coleta e armazenamento, as moscas foram analisadas, identificando-se as frequências tumorais, por região corporal, em cada concentração testada. Resultados: o bromazepam não apresentou efeito carcinogênico em nenhuma das concentrações experimentadas neste estudo, não havendo diferença estatisticamente significativa nas frequências tumorais observadas nos indivíduos tratados com bromazepam quando comparadas à frequência obtida nos indivíduos tratados com o controle negativo. Conclusão: Nas presentes condições experimentais, o bromazepam não apresentou atividade carcinogênica, no entanto, há a necessidade de novos estudos, com diferentes metodologias e diferentes organismos testes, para a maior compreensão da ação do bromazepam no organismo.

Introduction: although cancer is one of the biggest public health problems faced worldwide, several substances present in the environment, such as drugs are not very well understood about its possible carcinogenic potential. Among them are benzodiazepines, drugs that have increased their consumption since the 20th century and, mainly, in the second decade of the 21st century, due to their anxiolytic, sedative and anticonvulsant actions. Objective: Evaluate the carcinogenic effect of bromazepam through the test to detect epithelial tumor clones (ETT) in Drosophila melanogaster. Methodology: to perform the ETT, two mutant strains of D. melanogaster were used: wts (female) and mwh (male). The descending larves of this cross were treated separately with five concentrations of bromazepam, namely: 0.0375; 0.075; 0.15; 0.30 and 0.60 mM. Doxorubicin was used as a positive control and ultrapure water as a negative control. After treatment, collection and storage, the flies were analyzed, identifying the tumor frequencies, by body region, at each concentration tested. Results: bromazepam did not have a carcinogenic effect at any of the concentrations experienced in this study, with no statistically significant difference in tumor frequencies observed in individuals treated with bromazepam when compared to the frequency obtained in individuals treated with the negative control. Conclusion: In the present experimental conditions, bromazepam did not show carcinogenic activity, however, there is a need for further studies with different methodologies and different test organisms to better understand the action of bromazepam in the body.

Cushing's syndrome due to ectopic adrenocorticotropin secretion by a parotid carcinoma

SUMMARY We report a rare case of Cushing's syndrome in a 37-year-old female who initially presented with localized acinic cell carcinoma of the parotid gland. In January 2014, she underwent a right parotidectomy with facial nerve preservation and adjuvant radiotherapy. In August 2018, she presented a histologically-proven local regional relapse. The patient was considered for salvage surgery with facial nerve sacrifice and remained with no evidence of disease. One year later the patient developed pulmonary dissemination and started to gain weight and developed facial plethora and acne on the face and upper trunk. In a physical examination, the patient presented moon face, buffalo hump, acne and stage 2 hypertension. Biochemical evaluation confirmed ACTH-dependent Cushing's syndrome. IHC for ACTH in the lung biopsy revealed strong positive staining for ACTH confirming a diagnosis of ectopic ACTH secretion by a metastatic parotid acinic cell carcinoma. Ketoconazole (600 mg/d) was started to treat the CS. In addition, as chemotherapy was initiated to treat the metastatic disease. After the fifth cycle of chemotherapy, ketoconazole was suspended and the patient remained in remission of CS for four months, when CS recurred. A unique feature of this case is related to the clinical CS relapse associated with disease progression, which needed prompt treatment with ketoconazole, resulting in a significant improvement in the patient's condition. Although rare, should be attentive for possible CS features in patients with high-grade salivary gland carcinomas, since the diagnosis of ectopic secretion of ACTH may significantly impact their management and outcomes.

Preliminary experience of transoral robotic surgery for oropharyngeal carcinoma / 中华耳鼻咽喉头颈外科杂志

Objective: To investigate the oncological and functional efficacy and safety of transoral robotic surgery (TORS) in the treatment of oropharyngeal carcinoma. Methods: Twenty-six patients with oropharyngeal cancer were enrolled who underwent TORS at Beijing United Hospital from June 1, 2017 to December 31, 2020. Among them, 22 patients were males and 4 were females, aged 39 to 76 years old. T1-2 patients accounted for 88.5% (23/26). Clinicopathological data including the time of removal of gastric and endotracheal tube were collected. The SPSS software package was used for survival analysis, and the overall survival rate and disease-free survival rate were calculated. Results: All the 26 patients with oropharyngeal cancer received TORS without conversion to open surgery, and 20 of them underwent simultaneous cervical lymph node dissection. TORS operation time ranged from 65 to 360 minutes with an average of 215 minutes. Intraoperative blood loss ranged from 5 to 600 ml with an average of 70 ml. Four patients (15.4%) underwent tracheotomy, of whom 3 patients had the removals of tracheal tubes within 1 month after surgery and 1 case remained to wear a tube by the end of follow-up. Twelve patients (46.2%) underwent gastric tube implantation, among them, 11 patients had removals of gastric tubes within 1 month after surgery and 1 patient died of oropharyngeal hemorrhage 13 days after operation. One patient (3.8%) had a positive surgical margin and others had pathologically negative surgical margins. Sixteen patients (61.5%) received postoperative radiotherapy, of whom 11 patients (42.3%) received platinum-based concurrent chemotherapy. The median follow-up time was 21.5 months (0.4 to 45 months). The overall survival and the disease-free survival rates were 83.0% and 75.8%, respectively. Conclusion: The application of TORS in treatment of oropharyngeal cancer can achieve good oncological and functional outcomes in selected patients.

Development of novel mucoadhesive gels containing nanoparticle for buccal administration of dexamethasone

Abstract This study aimed to develop promising and innovative mucoadhesive gel systems containing dexamethasone-loaded nanoparticle to increase the effectiveness of treatment for oral precancerous lesions and to reduce side effects. In this respect, a dexamethasone-loaded nanoparticle formulation was prepared by using emulsification/solvent evaporation method. The nanoparticle has high zeta potential (-10.3±0.5 mV), low particle size (218.42±2.1), low polydispersity index (0.070±0.014) and high encapsulation efficiency (95.018±2.982%). To improve the mucosal retention time, the dexamethasone-loaded nanoparticle was dispersed in mucoadhesive gel using gellan gum. The developed gels offered appropriate pH value, high drug content, suitable mechanical and mucoadhesive performance and appropriate viscosity for mucosal administration. All formulations exhibited plastic flow and typical gel-type mechanical spectra after the determined frequency value. The developed formulations exhibited extended drug release as intended for these systems. Cytotoxicity was tested by MTT assay in human epithelioid carcinoma cell (HeLa) in vitro. The MTT assay showed that the blank formulations were non-toxic to cells. It was observed that the bioactivity of the free dexamethasone was potentiated by mucoadhesive gels containing dexamethasone-loaded nanoparticle in HeLa cells. Results from this study indicate that mucoadhesive gels are effective for the local treatment of precancerous lesions. Our findings showed that the developed formulations were worthy of further studies.

Mammary analogue secretory carcinoma in minor salivary gland

ABSTRACT Mammary analogue secretory carcinoma is a rare neoplasm usually confused with other neoplasms in the salivary glands region. It has great similarity with the breast carcinoma. We report a case of a patient who presented with gingival submucosal bleeding and lesion, with the initial histopathological examination revealing salivary gland neoplasm of low crane. Computed tomography revealed the lesion near the tooth 27, with extension to the floor of the left maxillary sinus and to the palate mucosa. Resection of the infra-structure was performed, with a diagnosis of breast cancer secretory carcinoma in the minor salivary gland.

Influence of nicotine dependence, current smoking status and gender on CYP1A1, CYP1B1 and CYP2A6 expression in oral squamous cell carcinoma / Influência da dependência nicotínica, parâmetros de consumo de tabaco e gênero na expressão de CYP1A1, CYP1B1 e CYP2A6 em carcinoma de células escamosas oral

Objective: Tobacco smoke is composed of cancer-causing chemicals referred to as carcinogens. These carcinogens are metabolized by the enzymes of the cytochrome P450 (CYP) family. Our objective was to evaluate the correlation of tobacco consumption parameters with CYP1A1, CYP1B1 and CYP2A6 expression using qRT-PCR in samples of oral squamous cell carcinoma (OSCC). Material and Methods: The sample was divided into 2 groups: Cancer (36 subjects) and non-Cancer (12 subjects). The smokers' participants (36) were evaluated regarding their Nicotine dependence (ND) was assessed by the Fagerström test for cigarette dependence (FTCD). Questions regarding tobacco consumption like the number of cigarettes/day (CPD), duration of use, and pack-years were also evaluated. The Mann-Whitney and Spearman correlation tests were used at a significance level of 5%. Results: 48 participants were included, 32 men (66.7%), 36 smokers (75%) and 27 smokers with OSCC (56.3%). Samples of OSCC expressed more CYP1A1, CYP1B1, and CYP2A6. Especially, the CYP1B1 gene was significantly expressed in OSCC samples, regardless gender or tobacco use. No women expressed CYP2A6, as well as, non-smokers did not express the CYP1A1 and CYP2A6 genes. CYP1A1 gene was higher among men (P = 0.021). Conclusion: Lack of exposure to tobacco may justify the absence of CYP1A1 and CYP2A6 expression in non-smokers. The CYP1B1 gene was significantly expressed in the cancer presence despite gender or tobacco use. The assessment of ND and quantification of tobacco consumption are important instruments in monitoring smokers with benign oral lesions and, especially, in the presence of cancer.(AU)

Objetivo: A fumaça do tabaco é composta de substâncias químicas cancerígenas conhecidas como carcinógenos. Esses carcinógenos são metabolizados pelas enzimas da família do citocromo P450 (CYP). Nosso objetivo foi avaliar a correlação dos parâmetros do consumo de tabaco com a expressão de CYP1A1, CYP1B1 e CYP2A6 por qRT-PCR em amostras de carcinoma de células escamosas bucal (CCEB). Material e Métodos: A amostra foi dividida em 2 grupos: Câncer (36 indivíduos) e sem Câncer (12 indivíduos). Os participantes fumantes (36) foram avaliados quanto à dependência nicotínica (DN) pelo teste de Fagerström para dependência de cigarro (TFDC). Questões relacionadas ao consumo de tabaco como número de cigarros / dia (CPD), tempo de uso e anos-maço também foram avaliadas. Os testes de correlação de Mann-Whitney e Spearman foram utilizados com nível de significância de 5%. Resultados: foram incluídos 48 participantes, 32 homens (66,7%), 36 fumantes (75%) e 27 fumantes com CCEB (56,3%). Amostras de CCEB expressaram mais CYP1A1, CYP1B1 e CYP2A6. Especialmente, o gene CYP1B1 foi significativamente expresso em amostras de CCEB, apesar do sexo ou uso de tabaco. Nenhuma mulher expressou CYP2A6, assim como, não fumantes não expressaram os genes CYP1A1 e CYP2A6. O gene CYP1A1 foi maior entre os homens (P = 0,021). Conclusão: A falta de exposição pode justificar a ausência da expressão dos genes CYP1A1 e CYP2A6 entre não fumantes. O gene CYP1B1 foi significativamente expresso na presença de câncer, independentemente do sexo ou do uso de tabaco. A avaliação da DN e a quantificação do consumo de tabaco são importantes instrumentos no acompanhamento de fumantes com lesões bucais benignas e, principalmente, na presença de câncer (AU)

Comparación histopatológica entre biopsia preoperatoria y debulking luego de la cirugía micrográfica de Mohs en carcinomas cutáneos / Histopathological comparison between preoperative biopsy and debulking after Mohs micrographic surgery in cutaneous carcinomas / Comparação histopatológica entre biópsia pré-operatória e citorredução após cirurgia micrográfica de Mohs em carcinomas cutâneos

Resumen: Introducción: el subtipo histopatológico es uno de los determinantes fundamentales en la clasificación de riesgo de los carcinomas cutáneos. Surge de una biopsia incisional que representa solo un porcentaje de la masa tumoral, siendo la principal preocupación la no detección de un subtipo agresivo. De ahí nace el interés de comparar la similitud entre ésta y la pieza de escisión quirúrgica (debulking) de la cirugía micrográfica de Mohs (CMM). Objetivos: comparar los resultados histopatológicos entre la biopsia incisional y el debulking en los carcinomas cutáneos tratados con CMM en el Servicio de Dermatología del Hospital de Clínicas en el período de noviembre de 2013 a marzo de 2019. Metodología: estudio retrospectivo descriptivo, se analizaron 202 pacientes con carcinomas de piel no melanoma (CPNM) sometidos a CMM en el servicio de Cirugía Dermatológica del Hospital de Clínicas "Dr. Manuel Quintela" entre noviembre de 2013 y marzo de 2019. Resultados: únicamente se consideran los casos donde en el debulking se halló tumor. Del total, la biopsia coincidió con el debulking en 61,39% de los casos. El debulking mostró un subtipo agresivo que no fue detectado en la biopsia en 8,41% de los casos. Conclusiones: el estudio histopatológico del debulking ha demostrado ser relevante, siendo la biopsia incisional parcialmente representativa para determinar el subtipo histopatológico de un CPNM, ya que aproximadamente 1 de cada 10 carcinomas podrían ser subdiagnosticados y tratados de manera insuficiente.

Abstract: Introduction: histological subtype is a vital element in determining the risk of skin cancer. It may be determined by an incisional biopsy which represents just a percentage of the tumor mass, the main concern lying in its potential failure to detect an agressive subtype. Therefore, comparing the results of biopsies with the surgically obtained piece with Mohs micrographic surgery is significantly relevant. Objective: to compare histopathologic evaluation results of incisional biospy and debulking in skin cancer treated with Mohs micrographic surgery at the Dermatology Service of the Clinicas University Hospital, between November, 2013 and March, 2019. Methodology: retrospective, descriptive study analysing 202 non-melanoma carcinomas which were treated with Mohs micrographic surgery the Dermatology Service of the "Dr. Manuel Quintela" Clinicas Hospital, between November, 2013 and March, 2019. Results: the study only considered the cases where bulking identified the tumor. Biopsy matched debulking in 61.39% of cases. Debulking detected an agressive subtype that was not detected in the biopsy in 8.41% of the cases. Conclusions: the hystopathological study of debulking has proved to be relevant, and the incisional biopsy was found to be partially representative in determining the histopathological subtype of non-melanoma carcinomas, since approximately 1 out of 10 carcinomas could be underdiagnosed and not appropriately treated.

Resumo: Introdução: o subtipo histopatológico é um dos determinantes fundamentais na classificação de risco dos carcinomas cutâneos. Identifica-se na biópsia incisional que representa apenas uma porcentagem da massa tumoral, sendo a principal preocupação a não detecção de um subtipo agressivo. Daí o interesse de comparar a semelhança entre esta e o material de excisão cirúrgica (citorreduçao - debulking) da Cirurgia Micrográfica de Mohs (CMM). Objetivos: comparar os resultados histopatológicos entre biópsia incisional e citorredução em carcinomas de pele tratados com CTM no serviço de Dermatologia do Hospital de Clínicas de novembro de 2013 a março de 2019. Metodologia: estudo descritivo retrospectivo onde foram analisados 202 carcinomas de pele não melanoma (NSCLC) submetidos a CCM no serviço de Cirurgia Dermatológica do Hospital de Clínicas "Dr. Manuel Quintela" entre novembro de 2013 e março de 2019. Resultados: foram considerados somente os casos em que um tumor foi encontrado em citorredução. Do total, a biópsia coincidiu com a cirurgia citorredutora em 61,39% dos casos. A citorredução mostrou um subtipo agressivo que não foi detectado na biópsia em 8,41% dos casos.

Carcinoma adrenal virilizante en una adolescente: reporte de caso / Virilizing adrenal carcinoma in an adolescent: case report

Los tumores suprarrenales virilizante son infrecuentes y representan 5-6% de los tumores de esas glándulas1. Pueden secretar diferentes andrógenos como dehidroepiandrosterona sulfato (DHEAS), androstenediona y testosterona. Las características clínicas dependen de la edad de presentación; en niños pueden determinar pubertad precoz y en mujeres en edad fértil ocasionar hirsutismo, amenorrea o ciclos oligomenorreicos y diversos grados de virilización2. Los carcinomas adrenocorticales son tumores raros y la incidencia es aproximadamente uno a dos por millón de habitantes/año3,4. Los exámenes de imagen como la tomografía o la resonancia confirman el origen suprarrenal, valoran la presencia de metástasis y definen la conducta terapéutica5. La presentación inicial en pacientes pediátricos mayoritariamente es con virilización6 y aproximadamente el 50% de los pacientes adultos con carcinoma adrenal tienen un estadio de la enfermedad relativamente avanzado7. El tratamiento de elección es la cirugía y sigue siendo la mejor esperanza para la supervivencia a largo plazo8. El pronóstico habitual para el carcinoma adrenocortical es generalmente malo con una supervivencia global a 5 años de 20 a 25%5 en adultos, pero en niños y adolescentes la supervivencia puede llegar al 100%9. Se presenta el caso de una paciente con fenotipo totalmente masculino con diagnóstico de carcinoma adrenal virilizante que comienza en la infancia y se diagnostica en la adolescencia.

Virilizing adrenal tumors are uncommon and represent 5-6% on tumors of these glands1. They can secrete different androgens such as dehydroepiandrosterone sulfate (DHEAS), androstenedione, and testosterone. Clinical features depend on the age of presentation; in children they can determine precocious puberty and in women of childbearing age cause hirsutism, amenorrhea or oligomenorrheic cycles and various degrees of virilization2. Diagnosis consists of clinical evidence of hyperandrogenism, accompanied by an increase in androgens in the blood, especially DHEAS, whose origin is mainly adrenal. Adrenocortical carcinomas are rare and the incidence is approximately one to two per million inhabitants/year3,4. Imaging tests such as tomography or resonance confirm the adrenal origin, assess the presence of metastases and define the therapeutic approach5. In initial presentation in most pediatric patients is with virilization6 and approximately 50% adult's patients with adrenal carcinoma have a relatively advanced stage of the disease7. The treatment of choice is surgery and is the best hope for long-term survival. The usual prognosis for adrenocortical carcinoma is generally poor with a 5-year overall survival of 20 to 25%5 in adults, but in children and adolescent's survival can reach 100%9. We present the case of a patient with a totally male phenotype diagnosed with virilizing adrenal carcinoma that begins in childhood and is diagnosed in adolescence.

Presentaciones infrecuentes y atípicas del carcinoma hepatocelular en tomografía computarizada y resonancia magnética / Rare and atypical presentations of hepatocellular carcinoma on CT and MRI

Resumen La apariencia en imágenes típicas del carcinoma hepatocelular (HCC) es ampliamente reconocida y consiste en hiperrealce en fase arterial con lavado en las fases venosa portal y tardía, tanto en tomografía computada como en resonancia magnética. Este patrón se observa en el 60% de los casos y se ha incorporado en las directrices diagnósticas de las diferentes organizaciones que participan en el estudio de las enfermedades hepáticas y su presencia evita la necesidad de una biopsia. Además, son signos auxiliares útiles en el diagnóstico del HCC la hiperintensidad en secuencias ponderadas en T2, la presencia de grasa, la trombosis tumoral venosa y el crecimiento entre intervalos en los estudios de seguimiento. Sin embargo, no todos los pacientes con HCC presentan estas características y en el 40% de los casos las presentaciones atípicas plantean un reto diagnóstico y de manejo de los pacientes.

Abstract The typical imaging appearance of hepatocellular carcinoma (HCC) is widely recognized and consists in hyper enhancement in the arterial phase with lavage in the portal and late venous phases, as on computed tomography (CT) as on magnetic resonance imaging (MRI). This pattern is observed in 60% of cases and has been incorporated into the diagnostics directives of the different organizations which participates in the hepatic diseases studies and its presence avoid the necessity of a biopsy. Besides, are auxiliar signs useful on the HCC diagnostic, T2 hyperintensity, presence of grease, venous tumor thrombosis and the growth between intervals in follow up studies. However, not all HCC patients harbor these characteristics and in 40% of cases the atypical introduction proposes a diagnostic and handling challenge of patients.

Zofenopril antitumor activity in mice bearing Ehrlich solid carcinoma: Modulation of PI3K/AKT signaling pathway

Angiotensin-II (AgII) is thought to be crucial for tumor growth and progression. Moreover, hydrogen sulfide (H2S) performs a controversial action in cancer pathology. Zofenopril (ZF) is an angiotensin-converting enzyme (ACE) inhibitor with H2S donating properties. Hence, this study aims at investigating the tumor suppressor activity of ZF and elucidating the involved trajectories in Ehrlich's solid tumor (EST)-bearing mice. EST was induced by the intradermal injection of Ehrlich's ascites carcinoma cells into femoral region. All parameters were assessed after 28 days post-inoculation or one-week thereafter. ZF treatment resulted in significant reduction of tumor weights with marked decrease in IL-6 and VEGF levels in serum, and tumor Ag II and CEA contents. Additionally, the administration of ZF downregulated the tumor gene expression of cyclin-D, ACE-1, and Bcl2 and upregulated the proapoptotic gene, BAX. Moreover, ZF increased CBS gene expression, which is a major contributor to cellular H2S production. In addition, ZF was able to reduce the protein expression of PI3K, pAKT, pGSK-3ß, and NFκB. Our study has provided novel insights into the possible mechanisms by which ZF may produce its tumor defeating properties. These intersecting trajectories involve the interference between PI3K/Akt and CBS signaling pathways

Facteurs pronostiques des carcinomes épidermoïdes non métastatiques du larynx

Etudier les facteurs influençant le pronostic des carcinomes épidermoïdes du larynx. Méthodes: Etude rétrospective analytique menée sur 100 patients présentant un carcinome épidermoïde primitif du larynx, durant une période de 24 ans (1992­2015). Résultats: La survie globale à 1 an, à 3 ans et à 5 ans a été respectivement de 99 %, de 77 % et de 63 %. La survie sans maladie à 1 an, à 3 ans et à 5 ans a été respectivement de 88 %, de 76 % et de 63 %. L'étude univariée de la survie globale et la survie sans maladie a montré un impact péjoratif de l'atteinte ganglionnaire histologique, de l'engainement péri-nerveux et des limites chirurgicales tumorales (facteurs histo-pronostiques). Dans l'étude multivariée, seuls le stade T, le stade N, l'atteinte sous-glottique, l'atteinte du cartilage thyroïde et le délai de la radiothérapie postopératoire ont présenté un impact significatif sur la survie sans maladie. Aucun facteur n'a présenté d'impact significatif sur la survie globale, en analyse multivariée. L'étude statistique de la récidive n'a montré aucun facteur prédictif. Conclusion: Le stade tumoral et les facteurs histo-pronostiques sont les 2 facteurs pronostiques majeurs. Dans la littérature, Les principaux facteurs prédictifs de récidive sont: le stade tumoral, les limites chirurgicales tumorales et l'extension extra-nodale. Dans notre étude, aucun facteur prédictif n'a été trouvé.