ABSTRACT
Exosomes are 30-120nm bio particles transferred from donor to recipient cells leading to modification in their regulatory mechanisms depending upon the coded message in the form of loaded biomolecule. Cancer cells derived exosomes the true representatives of the parent cells have been found to modify the tumor surrounding/distinct regions and participate in metastasis, angiogenesis and immune suppression. Tis study was aimed to study the effects of tumor mice derived exosomes on the normal mice spleen isolated T cells by using co-culture experiments and flow cytometer analysis. We mainly focused on some of the T cells population and cytokines including IFN-γ, FOXP3+ regulatory T (Treg) cells and KI67 (proliferation marker). Overall results indicated random changes in different set of experiments, where the cancer derived exosomes reduced the IFN-γ expression in both CD4 and CD8 T cells, similarly the Treg cells were also found decreased in the presence of cancer exosomes. No significant changes were observed on the Ki67 marker expression. Such studies are helpful in understanding the role of cancer exosomes in immune cells suppression in tumor microenvironment. Cancer exosomes will need to be validated in vivo and in vitro on a molecular scale in detail for clinical applications.
Os exossomos são biopartículas de 30-120 nm transferidas de células doadoras para células receptoras, levando à modificação em seus mecanismos reguladores, dependendo da mensagem codificada na forma de biomolécula carregada. Verificou-se que exossomos derivados de células cancerosas os verdadeiros representantes das células-mãe modificam as regiões circundantes / distintas do tumor e participam da metástase, angiogênese e imunossupressão. Este estudo teve como objetivo estudar os efeitos de exossomos derivados de camundongos com tumor nas células T isoladas de baço de camundongos normais, usando experimentos de cocultura e análise de citômetro de fluxo. Concentrou-se, principalmente, em algumas populações de células T e citocinas, incluindo IFN-γ, células T reguladoras FOXP3 + (Treg) e KI67 (marcador de proliferação). Os resultados gerais indicaram mudanças aleatórias em diferentes conjuntos de experimentos, em que os exossomos derivados de câncer reduziram a expressão de IFN-γ em células T CD4 e CD8, da mesma forma que as células Treg também foram encontradas diminuídas na presença de exossomos de câncer. Nenhuma mudança significativa foi observada na expressão do marcador Ki67. Esses dados são úteis para a compreensão do papel dos exossomos do câncer na supressão de células do sistema imunológico no microambiente tumoral. Exossomos de câncer precisarão ser validados in vivo e in vitro em escala molecular com detalhes para aplicações clínicas.
Subject(s)
Animals , Mice , Exosomes , Tumor Microenvironment , Immune System , Neoplasm Metastasis , NeoplasmsABSTRACT
Introducción: El cáncer de próstata (CP) el segundo cáncer diagnosticado en hombres, con mayor incidencia a los 66 años. La obesidad, el tabaquismo, alcoholismo y antecedentes familiares de CP se han encontrado asociados al riesgo de metástasis. El objetivo del presente estudio fue medir la aso-ciación entre factores y el estado metastásico en pacientes con CP en un centro único de referencia en Ecuador. Metodología: El presente estudio analítico, se realizó en el Hospital "Teodoro Maldonado Carbo", en Guayaquil-Ecuador, en el período enero-diciembre del 2019. El cálculo muestral fue no probabilístico, tipo censo. Se incluyeron casos con CP. Las variables fueron: edad, PSA, escala de Gleason, presencia de metástasis, sintomatología, tabaquismo, obesidad y antecedentes. Se presenta Odds Ratio como medida de asociación con intervalo de confianza del 95% y valor P. Resultados: El estudio incluyó 363 pacientes, con edad promedio de 75.2 ± 9.6 años. El grupo con metástasis fue de 202 casos (55.65%). Metástasis ósea 32.5%, pulmonar 9.6%, ganglionar 8.8% y hepático 4.75%. En la sintomatología la más frecuente fue, disuria (44.4%); el 33.6% con polaquiuria, un 13.2% hematuria y 8.8% tenesmo. El estadio Gleason-9 OR=24.85 (IC 95% 1.47-419.8) P=0.0259. El nivel de PSA >19 ng/ml OR= 6.996 (IC 95% 2.68-18.29) P=0.0001. El tabaquismo OR=2.34 (IC 95% 1.52-3.60) P=0.0001. Fueron factores protectores el valor de PSA <19 ng/ml OR=0.082 (IC 95% 0.043-0.157) P<0.0001, acudir a consulta de Hipertensión arterial OR=0.33 (IC 95% 0.161-0.691) P=0.0032 y el estadío Gleason-6 OR=0.108 (IC 95% 0.0665-9.1736) P<0.0001. Conclusión: Los niveles de PSA >19 ng/ml y el estadio Gleason >9 se asocian a la presencia de metástasis en pacientes con CP.
Introduction: Prostate cancer (PC) is the second most common cancer diagnosed in men, with the highest incidence at 66 years of age. Obesity, smoking, alcoholism, and a family history of PC are associated with the risk of metastasis. This study aimed to measure the association between factors and the metastatic state in patients with PC in a single reference center in Ecuador. Methodology: This analytical study was conducted at the "Teodoro Maldonado Carbo" Hospital in Guayaquil-Ecuador, January-December 2019. The sample calculation was nonprobabilistic, census type, and cases with PC were included. The variables were age, PSA, Gleason score, presence of me-tastases, symptoms, smoking, obesity, and history. The odds ratio was used to measure the associa-tion with a 95% confidence interval and P value. Results: The study included 363 patients, with a mean age of 75.2 ± 9.6 years. The group with me-tastasis included 202 patients (55.65%). Bone metastasis 32.5%, lung 9.6%, lymph nodes 8.8%, and liver 4.75%. In the symptomatology, the most frequent were dysuria (44.4%), 33.6% with pollakiuria, 13.2% hematuria, and 8.8% tenesmus. Gleason stage-9 OR=24.85 (95% CI 1.47-419.8) P=0.0259. PSA level >19 ng/ml OR= 6.996 (95% CI 2.68-18.29) P =0.0001. Smoking OR=2.34 (95% CI 1.52-3.60) P=0.0001. Protective factors were PSA value <19 ng/ml OR=0.082 (95% CI 0.043-0.157) P<0.0001, arterial hypertension consultation OR=0.33 (95% CI 0.161-0.691) P=0.0032 and stage Gleason-6 OR=0.108 (95% CI 0.0665-9.1736) P<0.0001. Conclusión: PSA levels >19 ng/ml and Gleason stage > nine are associated with metastases in patients with PC.
Subject(s)
Humans , Prostatic Neoplasms , Prostate-Specific Antigen , Odds Ratio , Risk Factors , Neoplasm MetastasisABSTRACT
Os cordomas sacrais (CS) são tumores ósseos malignos primários da coluna vertebral de ocorrência rara, com incidência entre 0,000005-0,000027%. O objetivo deste estudo é relatar um caso de CS metastático. Homem de 41 anos, sem comorbidades, chega ao serviço de referência apresentando lesão sacral. Ressonância magnética mostrou tratar-se de tumor com 9,3 cm sugestivo de mieloma ou cordoma. Realizou-se biópsia e histopatológico, confirmando o diagnóstico de CS. O paciente submeteu-se à excisão cirúrgica do tumor. Seis meses após a cirurgia, evoluiu com recidiva e implantes metastáticos em coluna vertebral, partes moles da parede torácica, fígado e espa-ço pleural, evoluindo com paraplegia. Não havia indicação de radioterapia e/ou quimioterapia adjuvante. Não havia também possibilidade de liberação de imatinibe pelo Sistema Único de Saúde. Em cerca de 28 meses de seguimento clínico mensal, o paciente foi a óbito. O caso apresentado mostrou um CS sem sucesso cirúrgico, o que é associa-do a pior prognóstico. O paciente apresentou disseminação sistêmica do tumor e paraplegia poucos meses após a cirurgia, indo a óbito em 28 meses de seguimento. (AU)
Sacral chordomas (SC) are rare primary malignant bone tumors of the vertebral column, with an incidence between 0.000005-0.000027%. This study aims to describe a case of metastatic SC. A 42-year-old man without comorbid conditions, arrived at the referral center, presenting with a sacral lesion. MRI showed a tumor measuring 9.3 cm that was suggestive of myeloma or chordoma. A biopsy with histopathology study was performed, confirming the diagnosis of SC. The patient underwent surgical tumor excision. Six months after surgery, the tumor recurred with metastatic vertebral column implants, soft tissues of the chest wall, liver, and pleural space, and the patient developed paraplegia. There was no indication of adjuvant radiotherapy and/or chemotherapy. There was also no possibility that the Unified Health System would approve imatinib. At about 28 months of monthly clinical follow-up, the patient died. The case presented showed unsuccessful SC surgery, which is associated with a worse prognosis. The patient had systemic tumor dissemination and paraplegia a few months after surgery, dying at 28 months of follow-up. (AU)
Subject(s)
Humans , Male , Adult , Recurrence , Sacrum/pathology , Chordoma/diagnosis , Neoplasm MetastasisABSTRACT
RESUMEN Antecedentes: la biopsia del ganglio centinela (GC) es la técnica aceptada para determinar el pronóstico en estadios iniciales de melanoma cutáneo. La ventaja del vaciamiento ganglionar (VG) cuando el GC resulta positivo ha sido recientemente cuestionada. Objetivo: describir los porcentajes y factores asociados a metástasis en el GC, y en los ganglios no centinela (GnC) en los VG de pacientes con GC positivo. Material y métodos: se llevó a cabo un estudio retrospectivo de los registros clínicos y patológicos de 139 pacientes operados por melanoma cutáneo entre enero de 2012 y diciembre de 2019. Resultados: a 96 (69%) pacientes se les realizó biopsia de GC. El promedio de edad fue 61,7 años ± 17,5 (19-93); 53 (55,2%) fueron hombres. La lesión primaria estuvo ubicada en: extremidades 47 (49%), tronco 39 (40,6%), cabeza y cuello 10 (10,4%). El promedio de espesor de Breslow fue 5,01 mm (1,05- 50 mm) y se encontró ulceración en 35 casos (36,4%). El GC fue identificado en todas las oportunidades y en 39 (40,6%) fue positivo. Hubo asociación con el espesor ≥ 3 mm (p = 0,000017) y con la ulceración (p = 0,0011). A los pacientes con GC positivo se les efectuó el VG del territorio afectado: 23 axilar, 10 inguinal y 6 cervical. Veintitrés (59%) presentaron metástasis en GnC. Se asoció con el espesor (p = 0,022) y la ulceración (p = 0,019). Conclusión: existió un alto porcentaje de GnC positivos en la población estudiada, vinculado al espesor y la ulceración. Estas características, así como la dificultad de un estricto seguimiento, inducen a no abandonar el VG en pacientes con GC positivo.
ABSTRACT Background: Sentinel lymph node (SLN) biopsy is the technique accepted to determine the prognosis of early cutaneous melanomas. The advantage of lymph node dissection (LND) when SLN biopsy is positive has recently been questioned. Objective: The aim of this study is to describe the percentages and factors associated with SLN and non-sentinel node (NSN) metastases in LNDs of SLN-positive patients. Material and methods: The clinical records and pathology reports of 139 patients undergoing surgery for cutaneous melanoma between January 2012 and December 2019 were retrospectively reviewed. Results: Ninety-six (69%) patients underwent SLN biopsy. Mean age was 61.7 ± 17.5 years (19-93) and 53 (55.2%) were men. The primary lesion was located in the extremities in 47 (49%) cases, in the trunk in 39 (40.6%), and in the head and neck in 10 (10.4%). Mean Breslow thickness was 5.01 mm (1.05-50 mm) and ulceration was found in 35 cases (36.4%). The SLN was identified in all the cases and was positive in 39 (40.6%). There was an association with thickness ≥ 3 mm (p = 0.000017) and ulceration (p = 0.0011). Those patients with positive SLN biopsy underwent LND of the territory involved: axillary in 23, inguinal in 10 and cervical in 6. Twenty-three (59%) presented NSLN metastases and were associated with thickness (p = 0.022) and ulceration (p = 0.019). Conclusion: There was a high percentage of positive NSLN in the population studied which was associated with thickness and ulceration. These characteristics and the difficulty to achieve strict follow-up are the reasons for completion LND in SLN-positive patients.
Subject(s)
Humans , Animals , Male , Adult , Middle Aged , Aged , Aged, 80 and over , Young Adult , Sentinel Lymph Node/surgery , Melanoma/diagnosis , Epidemiology, Descriptive , Retrospective Studies , Sentinel Lymph Node Biopsy , Sentinel Lymph Node Biopsy/statistics & numerical data , Sentinel Lymph Node/pathology , Lymph Node Excision , Neoplasm MetastasisABSTRACT
RESUMEN La impresión de modelos tridimensionales (M3D) implica obtener una estructura sólida y formada a partir de un modelo digital. Para la reconstrucción 3D se utilizó tomografía computarizada contrastada, realizándose impresión de modelos sobre la base de las principales estructuras anatómicas hepáticas. Se utilizaron M3D en dos pacientes con indicación quirúrgica, una mujer con trombocitopenia familiar y metástasis hepática de adenocarcinoma rectal, sin respuesta a quimioterapia, y un hombre con hepatopatía infecciosa crónica y diagnóstico de carcinoma hepatocelular. La aplicación de M3D resultó de gran utilidad, pues permitió un mejor entendimiento de la relación espacial de las estructuras anatómicas en ambos casos. En nuestra experiencia, la aplicación de M3D fue muy útil para planificar la cirugía y dar una aproximación más certera de los reparos anatómicos. El modelo se obtuvo en 7 días y costó 380 dólares, un valor elevado para nuestro medio.
ABSTRACT Three-dimensional (3D) printing is the construction of a solid structure from a digital model. 3D reconstruction was performed using contrast-enhanced computed tomography scan, and 3D-printed models were built based on the main anatomic structures of the liver. 3D-printed models were used in two patients with indication of surgery; one woman with inherited thrombocytopenia and liver metastases from colorectal adenocarcinoma with no response to chemotherapy, and one man with chronic liver infection and hepatocellular carcinoma. The implementation of 3D printing technology was very useful, as it facilitated the understanding of the spatial relationships among the anatomical structures in both cases. In our experience, the use of 3D-printed models was very useful for preoperative planning and for understanding the anatomic landmarks. The model was built in 7 days, with a cost of 380 dollars which is elevated in our environment.
Subject(s)
Humans , Male , Female , Adult , Middle Aged , Printing, Three-Dimensional , Hepatectomy/methods , Liver Neoplasms/surgery , Image Processing, Computer-Assisted , Tomography, X-Ray Computed , Liver Neoplasms/diagnostic imaging , Neoplasm Metastasis/diagnostic imagingSubject(s)
Humans , Female , Middle Aged , Carcinoma, Small Cell , Neoplasm Metastasis , Bone Marrow Diseases , Adaptation, BiologicalSubject(s)
Humans , Uterine Neoplasms , Neoplasm Metastasis , General Surgery , Abdominal Wall , Abdominal NeoplasmsABSTRACT
In troducción:La mortalidad de los pacientes con cáncer,ingresados en unaunidad de terapia intensiva puede ser estimada usando las escalas de sepsis. El objetivo del presente estudio fue realizar una prueba diagnóstica entre las principales escalas en un grupo de pacientes oncológicos de un centro de referencia de Guayaquil-Ecuador.Met odología: Se realizó un estudio transversal, en la unidad de terapia intensiva del Instituto Oncológico Nacional "Dr Juan Tanca Marengo" de SOLCA-Guayaquil, en el período octubre 2019a noviembre del 2020. La muestrafue probabilística, de pacientes con diagnóstico oncológicos clínicos ingresado en UCI. Se registró edad, tipo de cáncer, antecedentes familiares, mortalidad y las escalas SOFA y APACHE II. Se utiliza estadística descriptiva, se realiza una prueba diagnóstica y un análisis de supervivencia.R esultados: Se analizan 99 casos, de 57 ± 16 añosde edad, 37 hombres (37.4%). Con Hipertensión arte-rial (39.4%) y diabetes mellitus tipo 2 (17.1%). 12.1 %casos de linfoma no Hodgkiny cáncer intestinal 11.1%; 17 fallecimientos (17.2%). La puntuación global SOFA fue de 6.8 ± 3.0. La puntuación global APACHE II de 18.6 ± 7.0. El riesgo de mortalidad fue estadísticamente significativo a partir del 5to día. La puntuación SOFA >6 tuvo una sensibilidad del 88.24 %, valor predictivo (VP) positivo fue muy bajo, así como la especificidad; el VP negativo fue de 97%. La escala APACHE II, tuvo una sensibilidad del 94.12 %, con una especificidad de 96.34 %; VP positivo, comparada a la escala SOFA fue el doble.Co nclusión: La escala APACHE II en pacientes oncológicos clínicos ingresados en UCI predice de la ma-nera más exacta la mortalidad cuando la puntuación es mayor a 18
Subject(s)
Neoplasms , Survival Analysis , Mortality , Hospital Mortality , Critical Care , Neoplasm MetastasisABSTRACT
Introducción: El cáncer anal es el de menor incidencia del tubo digestivo, pero en los últimos años ha presentado un discreto incremento. Objetivo: Identificar los resultados del tratamiento empleado para el cáncer anal en el Servicio de Coloproctología del Hospital Universitario Clínico Quirúrgico "Comandante Manuel Fajardo". Métodos: Se realizó un estudio descriptivo y observacional con pacientes diagnosticados y tratados por cáncer anal en el período 2014-2019. Se estudiaron variables como antecedentes patológicos, factores de riesgo, síntomas, estadio de la enfermedad, tratamientos, entre otras. Resultados: La media de edad fue 58,4±14,7 años y el 75,3 por ciento fueron mujeres. El 52,1 por ciento presentaban antecedentes patológicos y el factor de riesgo más frecuente fue la edad (> 50 años: 80,8 por ciento). La localización más usual fue en el conducto anal y los estadios II y III. El sangrado se manifestó en el 58,9 por ciento de los pacientes. Se aplicó como tratamiento quimiorradioterapia (87,7 por ciento), exéresis local (17,8 por ciento) y cirugía abdominoperineal (8,2 por ciento). Se realizó colostomía al 14 por ciento de los individuos y el 72,6 por ciento estuvieron libres de colostomía más de un año. El tiempo libre de colostomía fue de 87,5 por ciento, con tratamiento de 5 años y más. De los pacientes fallecidos (24,7 por ciento), en el 55,6 por ciento la causa fue progresión de la enfermedad y la metástasis más frecuente fue la hepática. Conclusiones: La quimiorradioterapia fue el principal tratamiento con el que se obtuvo una aceptable tasa de sobrevida en los pacientes con cáncer anal(AU)
Introduction: Anal cancer is the one with the lowest incidence of the digestive tract, but in recent years it has slightly increased. Objective: To identify the results of the treatment used for anal cancer in the Coloproctology Service of Comandante Manuel Fajardo Surgical Clinical University Hospital. Methods: A descriptive and observational study was carried out with patients diagnosed and treated for anal cancer in the 2014-2019 period. Variables such as pathological history, risk factors, symptoms, stage of the disease, treatments, among others, were studied. Results: The mean age was 58.4 ± 14.7 years and 75.3 percent were women. 52.1 percent had pathological antecedents and the most frequent risk factor was age (> 50 years: 80.8 percent). The most usual location was in the anal canal and stages II and III. Bleeding appeared in 58.9 percent of the patients. Chemoradiation therapy (87.7 percent), local exeresis (17.8 percent) and abdominoperineal surgery (8.2 percent) were applied. Colostomy was performed in 14 percent of individuals; 72.6 percent were free of colostomy for more than one year. The colostomy-free time was 87.5 percent, with treatment of 5 years and more. 24.7 percent died, the disease progression was the cause of death in 55.6 percent of the diseased subjects, while the most frequent cause was liver metastasis. Conclusions: Chemoradiotherapy was the main treatment with which an acceptable survival rate was obtained in patients with anal cancer(AU)
Subject(s)
Humans , Female , Middle Aged , Anus Neoplasms/epidemiology , Risk Factors , Disease Progression , Neoplasm Metastasis/diagnosis , Epidemiology, Descriptive , Survival Rate , Observational Studies as TopicSubject(s)
Humans , Umbilicus , Neoplasms , Pathology , Carcinoma, Squamous Cell , Neoplasm MetastasisABSTRACT
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.
Subject(s)
Humans , Bone Neoplasms/therapy , Carcinoma/therapy , Fractures, Bone/prevention & control , Fractures, Bone/therapy , Neoplasm Metastasis/therapyABSTRACT
Objectives The present study aims to categorize the prevalence of intracranial tumors surgically treated at the neurosurgery service of Hospital Universitário Evangélico Mackenzie (HUEM) between 2016 and 2018. Material and Methods This survey included patients surgically treated due to primary or metastatic intracranial neoplasia between 2016 and 2018 at a referral center in the city of Curitiba. These patients were analyzed for epidemiological, histopathological, and topographic data, and they underwent an assessment of the outcome at the time of hospital discharge. Results Atotal of 96patientsmet the inclusion criteria. Themost prevalent tumorwas the glioma, with 39.6% of the sample, with glioblastoma being themost prevalent histological type. Brainmetastases andmeningiomas represented, respectively, 21.9%and 18.8%of the total. There was a predominance of supratentorial and intra-axial tumors in our sample. Conclusion Glioma was the most commonly found tumor, directly associated with high morbidity and mortality. The development of new and more effective drugs with action directed at themolecular level of intracranial tumorsmay be the path to a longer survival and improvement in the quality of life of these patients.
Subject(s)
Skull Neoplasms/epidemiology , Supratentorial Neoplasms/epidemiology , Glioblastoma/epidemiology , Neoplasm Metastasis/diagnosis , Skull Neoplasms/surgery , Skull Neoplasms/physiopathology , Health Profile , Medical Records , Retrospective Studies , Data Interpretation, Statistical , Glioblastoma/mortalityABSTRACT
El angiosarcoma es un tumor vascular maligno poco frecuente. Constituye menos del 2% de todos los sarcomas. Existen varias formas clínicas, una es la producida después de radioterapia, en pacientes que fueron tratadas por un cáncer de mama, con cirugía conservadora y radioterapia. Se presenta como un sarcoma de alto grado, localizado en la piel o en el tejido subcutáneo y, ocasionalmente, el parénquima mamario. El único tratamiento curativo es la cirugía, con tendencia a la recurrencia y a hacer metástasis hematógena, el pronóstico es malo, con alta tasa de mortalidad.
Angiosarcoma is a rare malignant vascular tumor. It constitutes less than 2% of all sarcomas. There are several clinical forms; the one produced after radiation therapy is that associated with patients who were treated for breast cancer with conservative surgery and radiation therapy. It presents as a high-grade sarcoma located on the skin or the subcutaneous tissue and, occasionally, the breast parenchyma. The only curative treatment is surgery, with a tendency to recurrence and visceral hematogenous metastasis, with a poor prognosis and a high mortality rate.
El angiossarcoma é um tumor vascular maligno pouco frequente. Constitui menos de 2% de todos os sarcomas. Existem várias formas clínicas, uma é a produzida depois da radioterapia, em pacientes que foram tratadas por um câncer de mama, com cirurgia conservadora e radioterapia. Se apresenta como um sarcoma de alto grau, localizado na pele ou no tecido subcutâneo e, ocasionalmente, o parênquima mamário. O único tratamento curativo é a cirurgia, com tendência à recorrência e a fazer metástasehematogênica, o prognóstico é mau, com alta taxa de mortalidade.
Subject(s)
Humans , Female , Breast Neoplasms , Radiotherapy , Breast , Subcutaneous Tissue , Parenchymal Tissue , Neoplasm MetastasisABSTRACT
Introduction: The gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract. Even though it can be found in any location of the digestive tract, the colorectal GIST is rare. With this study, we aim to review the current knowledge regarding the prognosis and management of colorectal GIST. Methods: A literature search was conducted in PubMed, and 717 articles were collected. After analyzing these studies, 60 articles were selected to use in this review. Results: The mitotic index, as well as tumor size and location were identified as good discriminators of prognosis in various studies. Surgery remains the only curative therapy for potentially resectable tumors. However, even after surgical resection, some patients develop disease recurrence and metastasis, especially those with highrisk tumors. Therefore, surgical resection alone might be inadequate for the management of all colorectal GISTs. The discovery of GIST's molecular pathway led to a shift in its therapy, insofar as tyrosine kinase inhibitors became part of the treatment schemes for this tumor, revolutionizing the treatment's outcome and prognosis. Discussion/Conclusion: The controversy concerning colorectal GIST prognosis and treatment can be, in part, attributed to the limited number of studies in the literature. In this review, we gathered the most recent knowledge about the prognosis and management of GIST in this rare location and propose two algorithms for its approach. Lastly, we highlight the importance of an individualized approach in the setting of a multidisciplinary team. (AU)
Subject(s)
Humans , Rectum , Colon , Gastrointestinal Stromal Tumors/therapy , Gastrointestinal Neoplasms/secondary , Prognosis , Gastrointestinal Stromal Tumors/surgery , Neoplasm MetastasisABSTRACT
Solo imágenes
Subject(s)
Humans , Tomography, X-Ray Computed/methods , Hemangiosarcoma/diagnosis , Neoplasm Metastasis/diagnostic imagingABSTRACT
Abstract Introduction: We describe the case of a patient with appendiceal metastasis as the first manifestation of a cholangiocarcinoma. Main symptoms: Abdominal pain, jaundice, hyporexia, and choluria. Methods and results: We documented an appendiceal plastron histologically compatible with metastatic appendiceal adenocarcinoma, common hepatic duct stricture, and a suspected cholangiocarcinoma, later corroborated by endoscopic retrograde cholangiopancreatography. Conclusions: Metastatic appendiceal tumors are an infrequent and poorly studied manifestation, whereas those secondary to bile duct neoplasia have rarely been reported in the literature.
Resumen Introducción: se describe el caso de una paciente con una metástasis apendicular como primera manifestación encontrada de un colangiocarcinoma. Síntomas principales: expresado con dolor abdominal, ictericia, hiporexia y coluria. Métodos y resultados: se documentó un plastrón apendicular histológicamente compatible con adenocarcinoma apendicular metastásico, estrechez del conducto hepático común, con alta sospecha de colangiocarcinoma, corroborado luego con la realización de una colangiopancreatografía retrógrada endoscópica. Conclusiones: los tumores apendiculares metastásicos son una presentación infrecuente y poco estudiada, donde los secundarios a neoplasia de vía biliar se han reportados de forma muy escasa en la literatura.
Subject(s)
Appendicitis , Cholangiopancreatography, Endoscopic Retrograde , Cholangiocarcinoma , Signs and Symptoms , Biliary Tract Neoplasms , Abdominal Pain , Jaundice , Neoplasm MetastasisABSTRACT
Resumen El cáncer de cuello uterino ocupa el cuarto lugar dentro de las neoplasias de origen ginecológico a nivel global, representando un 85% de los casos en países en vías de desarrollo. Las metástasis cutáneas de origen ginecológico son altamente infrecuentes, observándose con mayor frecuencia en las neoplasias malignas de ovario, seguidas del adenocarcinoma endometrial y de cuello uterino y, menos frecuentemente, las de subtipo escamocelular. En la actualidad, existen alrededor de 80 reportes de casos citados en la literatura de metástasis cutáneas secundarias a un carcinoma de cuello uterino; sin embargo, ninguno con localización en la piel del cuello que se origine de un subtipo histológico escamocelular. En Colombia, no hay casos reportados hasta la fecha. Se presenta el caso de una paciente de 43 años que consulta por sangrado vaginal, dolor abdominal y una extensa placa tumoral exofítica de aspecto metastásico en la piel del cuello y del hombro izquierdo, encontrando al examen clínico inicial una masa tumoral en el cuello uterino con confirmación histológica de un carcinoma escamocelular como neoplasia primaria. Se hace diagnóstico de Carcinoma de cuello uterino estadio IVB y se inicia un tratamiento con intención paliativa con radioterapia y posterior quimioterapia sistémica. La enfermedad metastásica de origen ginecológico a nivel cutáneo confiere un mal pronóstico, con una supervivencia reportada de 1 a 37 meses después de su diagnóstico, por lo cual se deduce que la prevención y el diagnóstico temprano, particularmente en cáncer de cuello uterino, es de vital importancia en la población general.
Abstract Cervical cancer is the fourth most common cancer among gynecological neoplasms globally, representing 85% of cases in developing countries. Cutaneous metastases of gynecological origin are very rare, observed more frequently in ovarian malignancies, followed by endometrial and cervical adenocarcinoma and less frequently those of the squamous cell subtype. Currently there are about 80 case reports cited in the literature of cutaneous metastases secondary to cervical carcinoma, however, none with localization in the skin of the neck originated from a squamous cell histological subtype. In Colombia, there are no reported cases to date. We present the case of a 43-year-old patient who consulted for abdominal pain, vaginal bleeding and an extensive exophytic tumor plaque of metastatic appearance in the skin of the neck and left shoulder, finding a tumor mass in the cervix with histological confirmation of a squamous cell carcinoma as primary tumor. A diagnosis of stage IVB cervical carcinoma is made, and treatment is initiated with palliative intention with radiotherapy and subsequent systemic chemotherapy. Cutaneous metastatic disease of gynecological origin confers a poor prognosis, with a reported survival of 1 to 37 months after its diagnosis, for which prevention and early diagnosis, particularly in cervical cancer, is of vital importance in the general population.
Subject(s)
Humans , Female , Adult , Carcinoma, Squamous Cell , Uterine Cervical Neoplasms , Cervix Uteri , Adenocarcinoma , Neoplasm MetastasisABSTRACT
Melanoma accounts for 3% of skin neoplasms and is the leading cause of death from skin disorders worldwide. The high mortality rate associated with this disease stems from the high capacity of melanoma patients to develop metastases and treatment relapse with inhibitors of the MAPK signaling pathway (such as BRAF inhibitors), commonly used in melanoma therapy. Thus, the investigation of genes involved in the mechanisms of melanoma development is essential for new and more effective therapeutic strategies. Hence, we describe in this thesis two projects involving the genes SIN3B and IRF4 as possible biomarkers for cutaneous melanoma. Initially, through bioinformatics analyses performed by our group, an upregulation of SIN3B was found in metastatic melanomas. This result together with the understanding of SIN3B role in regulating gene expression and oncogenic transformation, prompted us to describe in this thesis some mechanisms by which SIN3B may influence melanoma development. We then sought to characterize the gene function using SIN3B-deleted cells, generated by the CRISPR-Cas9 methodology. Initially, we observed increased SIN3B expression in BRAF-mutant metastatic melanomas, where we noted that the long splicing variant of the gene (NM_001297595.1) was effectively prevalent in melanomas. Subsequently, we designed gRNAs between the exons 2 and 3 of the human SIN3B gene and engineered three knockout clones and three control clones (containing empty lentiCRISPRv2 plasmid) from different melanoma cell lines (SKMEL28, A2058, and A375). Through functional analyses, it was observed that the absence of the gene did not interfere in the proliferation of tumor cells; however, it led to a decrease in invasive properties. These results were verified by Boyden chamber assays and transcriptome analysis (total RNA sequencing of deleted cells), where a decrease in migration and motility pathways was observed. Additionally, a screening of synthetically lethal genes with SIN3B was performed with a genome wide CRISPR library. These results showed that USP7 and STK11 genes, which belong to the FoxO signaling pathway, were essential in SIN3B-depleted melanoma cells. Finally, through a collaborative project with the Wellcome Trust Sanger Institute, previous large-scale sequencing analyses demonstrated that deletion of the IRF4 gene was lethal for melanoma cells. Accordingly, we performed IRF4 silencing in vitro and noticed that the lack of IRF4 promotes cell death and apoptosis, independently of MYC and MITF, known in the literature to be downstream targets of this gene. Therefore, these data suggest that IRF4 plays a vital role in melanoma cell survival. Taken together, both works herein described in this thesis demonstrate how CRISPR-Cas9 can be applied to study the functions and mechanisms of genes involved in melanoma progression, collectively helping in the development of more effective therapeutic strategies for this tumor
O melanoma representa 3% dos tipos de neoplasias cutâneas e é a maior causa das mortes por distúrbios de pele no mundo. A alta taxa de mortalidade associada à essa doença advém da alta capacidade de pacientes com melanoma desenvolverem metástases, e apresentarem recidiva após tratamento com inibidores da via de sinalização MAPK (como da proteína BRAF), comumente utilizados no tratamento de pacientes metastáticos. Assim, a investigação de genes envolvidos nos mecanismos de desenvolvimento do melanoma é primordial para novas estratégias terapêuticas mais efetivas. Dessa forma, descrevemos no presente trabalho dois projetos envolvendo os genes SIN3B e IRF4 como possíveis biomarcadores para melanoma cutâneo. Em análises prévias de bioinformática realizados pelo nosso grupo, SIN3B foi identificado tendo maior expressão em melanomas metastáticos. Além disso, diversos estudos mostraram que o gene está envolvido na regulação da expressão gênica e transformação oncogênica. Dessa forma, descrevemos nessa tese alguns mecanismos pelos quais SIN3B pode influenciar no desenvolvimento do melanoma, através da caracterização funcional de células SIN3B-deletadas pela metodologia CRISPR-Cas9. Inicialmente, observamos aumento na expressão de SIN3B em melanomas metastáticos BRAF-mutados, onde notamos que a variante de splicing longa do gene (NM_001297595.1), era efetivamente prevalente em melanomas. Assim, desenhamos sequências de RNA guias entre os éxons 2 e 3 do gene SIN3B humano e, obtivemos três clones knockout e outros três clones controle (contendo plasmídeo vazio) em diferentes linhagens de melanoma (SKMEL28, A2058 e A375), para caracterização funcional. Observou-se que a ausência do gene não interferiu na proliferação das células tumorais, contudo, acarretou na diminuição de processos invasivos. Esses resultados foram averiguados através de ensaios em câmara de Boyden e análises de transcriptoma (sequenciamento de RNA total das células deletadas), onde notou-se diminuição das vias de migração e motilidade. Adicionalmente, um rastreamento de genes sinteticamente letais com SIN3B foi realizado com uma biblioteca de CRISPR capaz de silenciar todo o genoma. Esses resultados mostraram que os genes USP7 e STK11, ambos pertencentes à via de sinalização de FoxO, são essenciais nas células SIN3B deletadas. Por fim, através de um projeto colaborativo com o Wellcome Trust Sanger Institute, análises prévias de sequenciamento de larga escala demonstraram que a deleção do gene IRF4 era letal para células de melanoma. Dessa forma, realizamos o silenciamento de IRF4 in vitro e notamos que a ausência do gene promove morte celular e apoptose, independentemente de MYC e MITF, conhecidos na literatura por serem alvos downstream do gene. Portanto, esses dados sugerem que IRF4 tem um papel importante na sobrevivência de células de melanoma. Em conjunto, ambos trabalhos descritos nessa tese, demonstram como a metodologia CRISPR-Cas9 pode auxiliar no entendimento de processos importantes para a malignidade do melanoma e contribuir para estratégias terapêuticas mais efetivas para esse tumor
Subject(s)
Skin Neoplasms/complications , Methodology as a Subject , Melanoma/pathology , Neoplasm Metastasis , Neoplasms , Patients/classification , Skin , In Vitro Techniques/methods , Biomarkers/analysis , Gene Expression , Cell Survival , Sequence Analysis, RNA/instrumentation , Computational Biology/methods , Absenteeism , Clustered Regularly Interspaced Short Palindromic RepeatsABSTRACT
Introdução: Pacientes com câncer em estádios avançados e metástases ósseas frequentemente não apresentam condições clínicas para a realização de esquemas quimioterápicos convencionais subsequentes, restringindo as opções de tratamento. Anteriormente, demonstramos que nanopartículas artificiais lipídicas (LDE), semelhantes à lipoproteína de baixa densidade (LDL) rica em colesterol, são captadas por tecidos malignos, e quando associadas aos quimioterápicos, após injeção pela via endovenosa, reduz drasticamente a toxicidade do tratamento. Os objetivos deste presente estudo foram avaliar a resposta clínica ao tratamento quimioterápico com paclitaxel (PTX) associado à LDE; avaliar as toxicidades clínicas e laboratorial, e a capacidade da associação LDE-PTX em reduzir a dor oncológica relacionada às metástases ósseas em pacientes com carcinoma de mama, próstata e pulmão, previamente tratados e não elegíveis para tratamento quimioterápico convencional subsequente. Métodos: Dezoito pacientes (8 com câncer de mama, 5 de próstata e 5 de pulmão) com metástases ósseas foram incluídos. O tratamento consistiu no esquema LDE-PTX na dose convencional do PTX (175 mg/m2 de superfície corpórea de 3/3 semanas) e os pacientes foram avaliados por resposta clínica, redução da dor óssea, uso de medicamentos opióides, e ocorrência de fraturas ósseas patológicas. Resultados: No total, 104 ciclos de quimioterapia foram realizados, e nenhum paciente apresentou toxicidade clínica, laboratorial, assim como não houve fraturas patológicas. Dos 18 pacientes incluídos, 9 tiveram sobrevida livre de progressão de doença 6 meses. Houve em todos os pacientes redução da dor óssea, permitindo substituição da medicação opióide por analgésico não opióide. Conclusão: A melhora significativa na dor óssea sem que tenha ocorrido toxicidade do tratamento, e o tempo de não progressão de doença 6 meses na metade dos pacientes sugere que esses pacientes tenham se beneficiado consistentemente do tratamento com a LDE-PTX. Portanto, a LDE-PTX pode tornar- se uma opção terapêutica interessante em pacientes com carcinomas de próstata, mama ou pulmão em estágios avançados e sem condições clínicas de se submeterem a outros esquemas quimioterápicos convencionais
Introduction: Patients with advanced cancer and bone metastases usually do not have clinical conditions to perform additional conventional chemotherapy regimens, restricting treatment options. Previously, we showed that lipid core nanoparticles (LDE), similar to cholesterol-rich low-density lipoprotein (LDL), are taken up by malignant tissues, and when associated to chemotherapy, after endovenous injection, it drastically decreases the toxicity of the treatment. The objectives of this study were to evaluate the clinical response to chemotherapy treatment with paclitaxel (PTX) associated with LDE; to evaluate the clinical and laboratorial toxicities, and the ability of the LDE-PTX to reduce cancer pain related to bone metastases in patients with breast, prostate or lung carcinoma, previously treated and not eligible for subsequent conventional chemotherapy treatment. Methods: Eighteen patients (8 with breast cancer, 5 with prostate and 5 with lung) with bone metastases were included. Treatment consisted of the LDE-PTX regimen at a conventional dose of PTX (175 mg/m2 body surface area, 3/3 weeks) and patients were evaluated for clinical response, reduction in bone pain, use of opioid medications, and the occurrence of pathological bone fractures. Results: In total, 104 chemotherapy cycles were performed, and none of the patients showed clinical or laboratorial toxicities, as well as there were no pathological fractures. Of the 18 patients evaluated, 9 had progression-fee survival 6 months. Patients had decrease in bone pain allowing replacement of opioid medication by another non-opioid analgesic. Conclusion: Significant improvement in bone pain without treatment toxicity, and time to disease progression of 6 months in half of the patients suggest that these patients have consistently benefited with LDE-PTX treatment. Therefore, LDE-PTX may become an interesting therapeutic option in patients with advanced stage of prostate, breast or lung carcinomas and without clinical conditions to undergo other conventional chemotherapy regimens