Vigilancia activa en cáncer de próstata en un grupo de pacientes asistidos en el Centro Docente Asociado de Oncología Médica Rivera: Cooperativa Médica de Rivera (COMERI) / Active surveillance in prostate cancer in a group of patients assisted at the Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI) / Vigilância ativa do câncer de próstata em um grupo de pacientes atendidos no Rivera Associated Teaching Center for Medical Oncology: Rivera Medical Cooperative (COMERI)

Introducción: En Uruguay el cáncer de próstata ocupa el primer lugar en incidencia y el tercer lugar en mortalidad en el hombre. La mayoría de estos cánceres se diagnostican en estadios precoces. Hoy en día, para pacientes con adenocarcinoma de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, la vigilancia activa es una opción adecuada. Objetivos: Describir una población de pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, en vigilancia activa en COMERI. Material y métodos: Estudio descriptivo, observacional, retrospectivo. Se incluyeron pacientes con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, tratados entre 2010 y 2018 en COMERI. Se recopilaron datos en el sistema de registro clínico electrónico. Resultados: Se incluyeron 33 pacientes, la mediana de edad al diagnóstico fue de 74 años. Todos los pacientes fueron sometidos a controles clínicos y determinación de PSA cada 3 meses. El tacto rectal se realizó en forma anual. El tiempo mediano de vigilancia activa fue de 33 meses. Durante el seguimiento, se observaron pocas variaciones en los valores de PSA. El 21% de los pacientes fue sometido a una nueva biopsia durante el seguimiento activo, y en todos los casos, el Gleason se mantuvo incambiado. Ningún paciente abandonó la modalidad de vigilancia activa. Conclusión: En nuestro entorno, la vigilancia activa se considera una opción terapéutica válida para pacientes altamente seleccionados con cáncer de próstata de muy bajo riesgo, bajo riesgo o riesgo intermedio favorable, y es bien aceptada por ellos.

Introduction: In Uruguay, prostate cancer ranks first in incidence and third in mortality among men. The majority of these cancers are diagnosed at early stages. Nowadays, active surveillance is an appropriate option for patients with adenocarcinoma of very low risk, low risk, or favorable intermediate risk. Objectives: To describe a population of patients with prostate cancer of very low risk, low risk, or favorable intermediate risk under active surveillance at COMERI. Materials and Methods: Descriptive, observational, retrospective study. Patients with prostate cancer of very low risk, low risk, or favorable intermediate risk treated between 2010 and 2018 at COMERI were included. Data were collected from the electronic clinical registry system. Results: Thirty-three patients were included, with a median age at diagnosis of 74 years. All patients underwent clinical monitoring and PSA determination every 3 months. Digital rectal examination was performed annually. The median time of active surveillance was 33 months. During follow-up, there were few variations in PSA values. 21% of patients underwent a repeat biopsy during active surveillance, and in all cases, the Gleason score remained unchanged. No patient discontinued active surveillance. Conclusion: In our setting, active surveillance is considered a valid therapeutic option for highly selected patients with prostate cancer of very low risk, low risk, or favorable intermediate risk, and it is well accepted by them.

Introdução: No Uruguai, o câncer de próstata ocupa o primeiro lugar em incidência e o terceiro lugar em mortalidade entre os homens. A maioria desses cânceres é diagnosticada em estágios precoces. Atualmente, para pacientes com adenocarcinoma de risco muito baixo, baixo risco ou risco intermediário favorável, a vigilância ativa é uma opção adequada. Objetivos: Descrever uma população de pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável sob vigilância ativa em COMERI. Material e métodos: Estudo descritivo, observacional, retrospectivo. Foram incluídos pacientes com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, tratados entre 2010 e 2018 em COMERI. Os dados foram coletados no sistema de registro clínico eletrônico. Resultados: Foram incluídos 33 pacientes, com mediana de idade no diagnóstico de 74 anos. Todos os pacientes foram submetidos a controles clínicos e determinação de PSA a cada 3 meses. O toque retal foi realizado anualmente. O tempo médio de vigilância ativa foi de 33 meses. Durante o acompanhamento, houve poucas variações nos valores de PSA. 21% dos pacientes foram submetidos a uma nova biópsia durante a vigilância ativa, e em todos os casos, o Gleason permaneceu inalterado. Nenhum paciente abandonou a modalidade de vigilância ativa. Conclusão: Em nosso ambiente, a vigilância ativa é considerada uma opção terapêutica válida para pacientes altamente selecionados com câncer de próstata de risco muito baixo, baixo risco ou risco intermediário favorável, e é bem aceita por eles.

Meningeal Carcinomatosis for Prostate Adenocarcinoma Mimicking Chronic SubduralHematoma: Case Report and Literature Review

Introduction Cerebral metastases are the most common cancer of the central nervous system (CNS). Meningeal infiltration by neoplasms that did not originate in the CNS is a rare fact that is present in 0.02% of the autopsies. Epidemiologically, the radiological presentation mimicking a subdural hematoma is even more uncommon. We report a case of meningeal carcinomatosis by an adenocarcinoma of the prostate mimicking a chronic subdural hematoma. Case Report A 60-year-old male patient was diagnosed with prostate cancer in 2011. He underwent radical resection of the prostate, as well as adjuvant hormonal therapy and chemotherapy. Five years later, the patient presented peripheral facial paralysis that evolved with vomiting and mental confusion. Tomography and magnetic resonance imaging scans confirmed the subdural collection. At surgery, the dura was infiltrated by friable material of difficult hemostasis. The anatomicopathological examination showed atypical epithelial cells. The immunohistochemistry was positive for prostate-specific antigen (PSA) and other keymarkers, and it was conclusive for meningeal carcinomatosis by a prostate adenocarcinoma.

Role of heat-shock proteins in infection of human adenocarcinoma cell line MCF-7 by tumor-adapted rotavirus isolates / Papel de las proteínas de choque térmico en la infección de la línea celular de adenocarcinoma humano MCF-7 por aislados de rotavirus adaptados a tumores

Abstract Background: Viruses are being used as alternative and complementary tools for treating cancers. Oncolytic viruses exhibit tumor tropism, ability to enhance anti-tumor immunity and ability to be used in combination with conventional chemotherapy and radiotherapy. We have recently selected some rotavirus isolates which are adapted to efficiently infect and kill tumor cell lines. Aim: We tested five tumor cell-adapted rotavirus isolates for their ability to infect the human adenocarcinoma cell line MCF-7. Methods: Cell surface membrane-associated proteins mediating virus particle attachment were characterized using ELISA, immunoprecipitation, FACS analysis, and antibody blocking. Results: It was found that heat shock proteins (HSPs) such as Hsp90, Hsp70, Hsp60, and Hsp40 are expressed on the cell surface forming complexes with protein disulfide isomerase (PDI), integrin β3, and heat shock cognate protein 70 (Hsc70) in lipid raft microdomains. Interaction of rotavirus isolates with these cellular proteins was further confirmed by a competition assay and an inhibition assay involving the HSPs tested. Conclusion: Our findings suggest that the tumor cell-adapted rotavirus isolates studied here offer a promising tool for killing tumor cells, thus encouraging further research into this topic, including animal models.

Resumen Antecedentes: Los virus se utilizan como herramientas alternativas y complementarias para el tratamiento del cáncer. Los virus oncolíticos exhiben tropismo por tumores, capacidad para intensificar la inmunidad antitumoral y la capacidad para utilizarse en combinación con quimioterapia y radioterapia convencionales. Recientemente, hemos seleccionado algunos aislamientos de rotavirus que están adaptados para infectar y eliminar de manera eficiente líneas de células tumorales. Objetivo: Se ensayaron cinco aislamientos de rotavirus adaptados a células tumorales para determinar su capacidad para infectar la línea celular de adenocarcinoma humano MCF-7. Métodos: Las proteínas asociadas a la membrana de la superficie celular que median la unión de partículas de virus se caracterizaron mediante ELISA, inmunoprecipitación, análisis FACS y bloqueo de anticuerpos. Resultados: Se encontró que las proteínas de choque térmico (HSPs) como Hsp90, Hsp70, Hsp60 y Hsp40 se expresan en la superficie celular formando complejos con la proteína disulfuro isomerasa (PDI), la integrina β3 y la proteína análoga de choque térmico 70 (Hsc70) en microdominios lipídicos (rafts). La interacción de los aislamientos de rotavirus con estas proteínas celulares se confirmó adicionalmente mediante un ensayo de competición y un ensayo de inhibición que incluía las HSP ensayadas. Conclusión: Nuestros hallazgos sugieren que los aislamientos de rotavirus adaptados a las células tumorales estudiados aquí ofrecen una herramienta prometedora para eliminar las células tumorales, lo que estimula más investigaciones sobre este tema, incluidos los modelos animales.

Neoadjuvant chemoradiotherapy combined with surgery versus direct surgery in the treatment of Siewert type II and III adenocarcinomas of the esophagogastric junction: long-term prognostic analysis of a prospective randomized controlled trial / 中华胃肠外科杂志

Objective: To investigate the effectiveness, safety, and prognosis of neoadjuvant chemoradiotherapy (nCRT) for Siewert type II and III adenocarcinomas of the esophagogastric junction (AEG). Methods: This study is a prospective randomized controlled clinical study (NCT01962246). AEG patients who were treated at the Third Department of Surgery of the Fourth Hospital of Hebei Medical University from February 2012 to June 2016 were included. All of the enrolled patients were diagnosed with type II or III locally advanced AEG gastric cancer (T2-4N0-3M0 or T1N1-3M0) by gastroscopy and CT before operation; the longitudinal axis of the lesion was ≤ 8 cm; no anti-tumor treatment was previously given and no contraindications of chemotherapy and surgery were found. Case exclusion criteria: serious diseases accompanied by liver and kidney, cardiovascular system and other vital organs; allergy to capecitabine or oxaliplatin drugs or excipients; receiving any form of chemotherapy or other research drugs; pregnant or lactating women; patients with diseases resulting in difficulty to take capecitabine or with concurrent tumors. Based on sample size estimation, a total of 150 AEG patients were enrolled. Using the random number table method, the enrolled patients were divided into the nCRT group and the direct operation group with 75 cases in each group. The nCRT group received XELOX chemotherapy (capecitabine+ oxaliplatin) before surgery and concurrent radiotherapy (45 Gy, 25 times, 1.8 Gy/d, 5 times/week). Clinical efficacy of the nCRT group was evaluated by the solid tumor efficacy evaluation standard (RECIST1.1) and the tumor volume reduction rate was measured on CT. After completing the preoperative examination in the direct operation group, and 8-10 weeks after the end of nCRT in the nCRT group, surgery was performed. Laparoscopic exploration was initially performed. According to the Japanese "Regulations for the Treatment of Gastric Cancer", a transabdominal radical total gastrectomy combined with perigastric lymph node dissection was performed. The primary outcome was the 3-year overall survival (OS) and disease-free survival rate (DFS); the secondary outcomes were R0 resection rate, the toxicity of chemotherapy, and surgical complications. The follow-up ended on December 31, 2019. The postoperative recurrence, metastasis and survival time of the two groups were collected. Results: After excluding patients with incomplete clinical data, patients or family members requesting to withdraw informed consent, and those failing to follow the treatment plan, 63 cases in the nCRT group and 69 cases in the direct operation group were finally enrolled in the study. There were no statistically significant differences in baseline characteristics of the two groups (all P>0.05). Sixty-three patients in the nCRT group were evaluated by RECIST1.1 after treatment, the image based effective rate was 42.9% (27/63), and the stable disease rate was 98.4% (62/63); the tumor volume before and after nCRT measured on CT was (58.8±24.4) cm(3) and (46.6±25.7) cm(3), respectively, the effective rate of tumor volume reduction measured by CT was 47.6% (30/63). Incidences of neutrophilopenia [65.1% (41/63) vs. 40.6% (28/69), χ(2)=7.923, P=0.005], nausea [81.0% (51/63) vs. 56.5% (39/69), χ(2)=9.060, P=0.003] and fatigue [74.6% (47/63) vs. 42.0% (29/69), χ(2)=14.306, P=0.001] in the nCRT group were significantly higher than those in the direct surgery group. Radiation gastritis/esophagitis and radiation pneumonia were unique adverse reactions in the nCRT group, with incidences of 52.4% (33/63) and 15.9%(10/63), respectively. The classification of tumor regression of 63 patients in nCRT group presented as 11 cases of grade 0 (17.5%), 20 cases of grade 1 (31.7%), 28 cases of grade 2 (44.4%), and 5 cases of grade 3 (7.9%). Eleven (17.5%) patients achieved pathologic complete response. Sixty-one (96.8%) patients in the nCRT group underwent R0 resection, which was higher than 87.0% (60/69) in the direct surgery group (χ(2)=4.199, P=0.040). The mean number of harvested lymph nodes in the specimens in the nCRT group and the direct operation group was 27.6±12.4 and 26.8±14.6, respectively, and the difference was not statistically significant (t=-0.015, P=0.976). The pathological lymph node metastasis rate and lymph node ratio in the two groups were 44.4% (28/63) vs. 76.8% (53/69), and 4.0% (70/1 739) vs. 21.9% (404/1 847), respectively with statistically significant differences (χ(2)=14.552, P<0.001, and χ(2)=248.736, P<0.001, respectively). During a median follow-up of 52 (27-77) months, the 3-year DFS rate in the nCRT group and the direct surgery group was 52.4% and 39.1% (P=0.049), and the 3-year OS rate was 63.4% and 52.2% (P=0.019), respectively. According to whether the tumor volume reduction rate measured by CT was ≥ 12.5%, 63 patients in the nCRT group were divided into the effective group (n=30) and the ineffective group (n=33). The 3-year DFS rate of these two subgracps was 56.6% and 45.5%, respectively without significant difference (P=0.098). The 3-year OS rate was 73.3% and 51.5%,respectively with significant difference (P=0.038). The 3-year DFS rate of patients with the tumor regression grades 0, 1, 2 and 3 was 81.8%, 70.0%, 44.4%, and 20.0%, repectively (P=0.024); the 3-year OS rate was 81.8%, 75.0%, 48.1% and 40.0%, repectively (P=0.048). Conclusion: nCRT improves treatment efficacy of Siewert type II and III AEG patients, and the long-term prognosis is good.

HIF-1α Levels in patients receiving chemoradiotherapy for locally advanced non-small cell lung carcinoma

SUMMARY AIM To examine the relationship between treatment response and hypoxia-inducible factor-1 alpha (HIF-1α) levels in patients with locally advanced non-small cell lung cancer (NSCLC) who received chemoradiotherapy (CRT). METHODS Eighty patients with NSCLC were included in the study and treated at Acibadem Mehmet Ali Aydınlar University Medical Faculty. HIF-1 α levels were measured before and after CRT by the enzyme-linked immunosorbent assay (ELISA) method. RESULTS Patients' stages were as follows; stage IIIA (65%) and stage IIIB (35%). Squamous histology was 45%, adenocarcinoma was 44%, and others were 11%. Chemotherapy and radiotherapy were given concurrently to 80 patients. Forty-five (56%) patients received cisplatin-based chemotherapy, and 35 (44%) received carboplatin-based chemotherapy. Serum HIF-1α levels (42.90 ± 10.55 pg/mL) after CRT were significantly lower than the pretreatment levels (63.10 ± 10.22 pg/mL, p<0.001) in patients with locally advanced NSCLC. CONCLUSION The results of this study revealed that serum HIF-1α levels decreased after CRT. Decrease of HIF-1α levels after the initiation of CRT may be useful for predicting the efficacy of CRT.

RESUMO OBJETIVO Examinar a relação entre a resposta ao tratamento e os níveis de fator 1 induzida por hipóxia (HIF-1α) em pacientes com câncer de pulmão de células não pequenas localmente avançado (NSCLC) que receberam quimiorradioterapia (CRT). MÉTODO Oitenta pacientes com NSCLC foram incluídos no estudo e foram tratados na Faculdade de Medicina da Acibadem Mehmet Ali Aydınlar University. O nível de HIF-1α foi medido antes e depois da TRC pelo método de ensaio imunoenzimático (ELISA). RESULTADOS Os estágios dos pacientes foram os seguintes; estágio IIIA (65%) e estágio IIIB (35%). A histologia escamosa foi de 45%, o adenocarcinoma de 44% e o outro de 11%. Quimioterapia e radioterapia foram dadas simultaneamente a 80 pacientes. Quarenta e cinco (56%) pacientes receberam quimioterapia à base de cisplatina e 35 (44%) receberam quimioterapia à base de carboplatina. Os níveis séricos de HIF-1α (42,90 ± 10,55 pg / mL) após a TRC foram significativamente menores do que os níveis pré-tratamento (63,10 ± 10,22 pg / mL, p <0,001) em pacientes com NSCLC localmente avançado. CONCLUSÃO Os resultados deste estudo revelaram que os níveis séricos de HIF-1α diminuíram após a TRC. A diminuição dos níveis de HIF-1α após o início da TRC pode ser útil para prever a eficácia da TRC.

Conversion therapy for gastric cancer: expanding the treatment possibilities / Terapia de conversão no câncer gástrico: ampliando as possibilidades de tratamento

ABSTRACT Background: Conversion therapy in gastric cancer (GC) is defined as the use of chemotherapy/radiotherapy followed by surgical resection with curative intent of a tumor that was prior considered unresectable or oncologically incurable. Aim: To evaluate the results of conversion therapy in the treatment of GC. Methods: Retrospective analysis of all GC surgeries between 2009 and 2018. Patients who received any therapy before surgery were further identified to define the conversion group. Results: Out of 1003 surgeries performed for GC, 113 cases underwent neoadjuvant treatment and 16 (1.6%) were considered as conversion therapy. The main indication for treatment was: T4b lesions (n=10), lymph node metastasis (n=4), peritoneal carcinomatosis and hepatic metastasis in one case each. The diagnosis was made by imaging in 14 cases (75%) and during surgical procedure in four (25%). The most commonly used chemotherapy regimens were XP and mFLOX. Major surgical complications occurred in four cases (25%) and one (6.3%) died. After an average follow-up of 20 months, 11 patients (68.7%) had recurrence and nine (56.3%) died. Prolonged recurrence-free survival over 40 months occurred in two cases. Conclusion: Conversion therapy may offer the possibility of prolonged survival for a group of GC patients initially considered beyond therapeutic possibility.

RESUMO Racional : A terapia de conversão no câncer gástrico (CG) é definida como o uso de quimio/radioterapia seguida de ressecção cirúrgica com intenção curativa de um tumor que era considerado irressecável ou oncologicamente incurável. Objetivo : Avaliar os resultados da terapia de conversão no tratamento do CG. Métodos : Análise retrospectiva de todas as operações de CG entre 2009 e 2018. Os pacientes que receberam alguma terapia antes da operação foram também identificados para definir o grupo de conversão. Resultados : Entre 1003 operações realizadas para o CG, 113 foram submetidos ao tratamento neoadjuvante e 16 (1,6%) considerados como terapia de conversão. As principais indicações para o tratamento foram: lesões T4b (n=10), metástase linfonodal (n=4), carcinomatose peritoneal e metástase hepática em 1 caso cada. O diagnóstico foi feito por exame de imagem em 14 casos (75%) e durante o procedimento cirúrgico em 4 casos (25%). Os esquemas quimioterápicos mais utilizados foram XP e mFLOX. Complicações cirúrgicas maiores ocorreram em 4 casos (25%) e 1 (6,3%) foi a óbito. Após seguimento médio de 20 meses, 11 pacientes (68,7%) apresentaram recidiva e 9 (56,3%) morreram. Sobrevida livre de recidiva prolongada acima de 40 meses ocorreu em dois casos. Conclusão : A terapia de conversão pode oferecer possibilidade de sobrevida prolongada para um grupo de pacientes com CG considerados inicialmente fora das possibilidades terapêuticas.

Oncological outcomes in extended time intervals between preoperative chemoradiotherapy with capecitabine and surgery in operable rectal adenocarcinoma / Resultados oncológicos en intervalos extendidos de tiempo entre quimioradioterapia preoperatoria con capecitabina y cirugía en adenocarcinoma rectal operable

Objective: To assess whether extended time intervals (8-12, 13-20 and >20 weeks) between the end of neoadjuvant chemoradiotherapy and surgery affect overall survival, disease-free survival. Materials and methods: Retrospective study in 120 patients with rectal adenocarcinoma without evidence of metastasis (T1-4/N0-2/M0) at the time of diagnosis that underwent surgery with curative intent after neoadjuvant chemoradiotherapy with capecitabine and obtained R0 or R1 resection between January 2010 to December 2014 at the National Cancer Institute of Peru. Dates were evaluated by Kaplan-Meier method, log- rank test and Cox regression analysis. Results: Of the 120 patients, 70 were women (58%). The median age was 63(26-85) years. All received neoadjuvant chemoradiotherapy. No significant difference was found between the association of the median radial (0.6, 0.7 and 0.8 cm; p=0.826) and distal edge (3.0, 3.5 and 4.0 cm; p=0.606) with time interval groups and similarly the mean resected (18.8, 19.1 and 16.0; p=0.239) and infiltrated nodules (1.05, 1.29 and 0.41); p=0.585). The median follow-up time of overall survival and desease free survival was 40 and 37 months, respectively. No significant differences were observed in overall survival (79.0%, 74.6% and 71.1%; p=0.66) and disease-free survival (73.7%, 68.1% and 73.6%; p=0.922) according to the three groups studied at the 3-year of follow-up. Conclusions: We found that widening the time intervals between the end of neoadjuvant chemoradiotherapy and surgery at 24 weeks does not affect the overall survival, disease-free survival and pathological outcomes. It allows to extend the intervals of time for future studies that finally will define the best time interval for the surgery

Objetivo: Evaluar si los intervalos de tiempo extendidos (8-12, 13-20 y >20 semanas) entre el fin de la quimioradioterapia neoadyuvante y la cirugía afectan la sobrevida global, y la sobrevida libre de enfermedad. Material y métodos: Estudio retrospectivo de 120 pacientes con adenocarcinoma rectal sin evidencia de metástasis (T1-4/N0-2/M0) al momento del diagnóstico que se sometieron a cirugía con intención curativa luego de quimioradioterapia neoadyuvante con capecitabina y tuvieron resección R0 o R1 entre enero 2010 y diciembre 2014 en el Instituto Nacioanal de Enfermedades Neoplásicas de Perú. El análisis se hizo con el método de Kaplan-Meier, la prueba log-rank y la regresión de Cox. Resultados: De 120 pacientes, 70 fueron mujeres (58%). La mediana de la edad fue 63 años (26-85 años). Todos recibieron quimioradioterapia neoadyuvante. No hubo diferencia significativa entre la asociación de las medianas de los bordes radial (0,6, 0.7 y 0,8 cm; p=0,826) y distal (3,0, 3,5 y 4,0 cm; p=0,606) con los intervalos de tiempo de los grupos y similarmente con la media de los ganglios resecados (18,8, 19,1 y 16,0; p=0,239) e infiltrados (1,05, 1,29 y 0,41; p=0,585). No se observaron diferencias significativas en sobrevida global (79,0%, 74,6% y 71,1%; p=0,66) y sobrevida libre de enfermedad (73,7%, 68,1% y 73,6%; p=0,922), en los tres grupos estudiados a 3 años de seguimiento. Conclusiones: Encontramos que aumentar los intervalos de tiempo entre el fin de la quimioradioterapia neoadyuvante y la cirugía hasta 24 semanas no afecta la sobrevida global, sobrevida libre de enfermedad ni los desenlaces patológicos. Esto permitiría extender los intervalos de tiempo en estudios futuros para definir el mejor intervalo de tiempo para la cirugía

Individualized threshold for tumor segmentation in 18F-FDG PET/CT imaging: The key for response evaluation of neoadjuvant chemoradiation therapy in patients with rectal cancer? / Individualização na segmentação tumoral de imagens de 18F-FDG PET/CT: a chave para avaliação de resposta terapêutica neoadjuvante em pacientes com câncer retal?

Summary Introduction: The standard treatment for locally advanced rectal cancer (RC) consists of neoadjuvant chemoradiation followed by radical surgery. Regardless the extensive use of SUVmax in 18F-FDG PET tumor uptake as representation of tumor glycolytic consumption, there is a trend to apply metabolic volume instead. Thus, the aim of the present study was to evaluate a noninvasive method for tumor segmentation using the 18F-FDG PET imaging in order to predict response to neoadjuvant chemoradiation therapy in patients with rectal cancer. Method: The sample consisted of stage II and III rectal cancer patients undergoing 18F-FDG PET/CT examination before and eight weeks after neoadjuvant therapy. An individualized tumor segmentation methodology was applied to generate tumor volumes (SUV2SD) and compare with standard SUVmax and fixed threshold (SUV40%, SUV50% and SUV60%) pre- and post-therapy. Therapeutic response was assessed in the resected specimens using Dworak's protocol recommendations. Several variables were generated and compared with the histopathological results. Results: Seventeen (17) patients were included and analyzed. Significant differences were observed between responders (Dworak 3 and 4) and non-responders for SUVmax-2 (p<0.01), SUV2SD-2 (p<0.05), SUV40%-2 (p<0.05), SUV50%-2 (p<0.05) and SUV60%-2 (p<0.05). ROC analyses showed significant areas under the curve (p<0.01) for the proposed methodology with sensitivity and specificity varying from 60% to 83% and 73% to 82%, respectively. Conclusion: The present study confirmed the predictive power of the variables using a noninvasive individualized methodology for tumor segmentation based on 18F-FDG PET/CT imaging for response evaluation in patients with rectal cancer after neoadjuvant chemoradiation therapy.

Resumo Introdução: O câncer retal (RC) é uma doença de importância global, e o tratamento padrão para o câncer retal localmente avançado compreende quimiorradiação neoadjuvante seguida de cirurgia radical. Independentemente do uso extensivo da captação tumoral mais intensa do 18F-FDG (conhecida como SUVmax) como representativo do consumo glicolítico do tumor nas imagens de PET, há uma tendência para aplicar volume metabólico. Dessa forma, o objetivo do presente estudo foi avaliar um método não invasivo de segmentação tumoral utilizando a 18F-FDG PET para predizer a resposta à quimiorradioterapia neoadjuvante em pacientes com câncer de reto. Método: A amostra consistiu em pacientes com câncer retal em estádios II e III submetidos ao exame de 18F-FDG PET/CT antes e oito semanas após a terapia neoadjuvante. Foi aplicada uma metodologia de segmentação tumoral individualizada para gerar volumes tumorais (SUV2SD). A resposta terapêutica foi avaliada nos espécimes ressecados utilizando as recomendações do protocolo de Dworak. Várias variáveis foram geradas e comparadas com os resultados histopatológicos. Resultados: Dezessete (17) pacientes foram incluídos e analisados. Foram observadas diferenças significativas entre os respondedores (Dworak 3 e 4) e não respondedores para SUVmax-2 (p<0,01), SUV2SD-2 (p<0,05), SUV40%-2 (p<0,05), SUV50%-2 (p<0,05) e SUV60%-2 (p< 0,05). As análises ROC mostraram áreas significativas sob a curva (p<0,01) para a metodologia proposta, com sensibilidade e especificidade variando de 60% a 83% e 73% a 82%, respectivamente. Conclusão: O presente estudo confirmou o poder preditivo das variáveis utilizando uma metodologia não invasiva individualizada para segmentação tumoral baseada em imagens 18F-FDG PET/CT para avaliação da resposta em pacientes com câncer retal após tratamento com quimiorradiação neoadjuvante.

Manejo Nutricional em Paciente com Metástase Gástrica de Câncer de Mama: um Relato de Caso / Nutritional Management in a Patient with Breast Cancer Metastasis to the Stomach: a Case Report / Manejo Nutricional en Paciente con Metástasis Gástrica del Cáncer de Mama: un Informe de Caso

Introdução: O surgimento de metástase gástrica oriunda de neoplasia da mama é raro. Entretanto, o suporte nutricional nesses casos é imprescindível, já que tumores gástricos estão relacionados a complicações nutricionais, favorecendo desfechos clínicos negativos. Relato do caso: Paciente com diagnóstico de adenocarcinoma de mama, com progressão para ossos, ovário e estômago, internada em razão das complicações clínicas. Apresentou perda de peso grave durante a internação, além de diagnóstico de risco de desnutrição pela avaliação subjetiva global produzida pelo paciente. Em virtude do quadro de odinofagia severa, a alimentação via oral tornou-se impossibilitada, sendo optado pelo uso de sonda nasoentérica após discussão com equipe interdisciplinar. Conclusão: A terapia nutricional em pacientes com câncer avançado ainda é um dilema entre os profissionais e sua execução deve ser discutida e decidida por uma equipe interdisciplinar, com participação indispensável do nutricionista, do paciente e de seus familiares. Para isso, os serviços de saúde devem estar preparados para o correto manejo da conduta nutricional, a fim de promover qualidade de vida para esses pacientes.

Introduction: It is uncommon for breast cancer to metastasize to the stomach. However, when it does occur, nutritional support is indispensable, because gastric tumors are associated with nutritional complications, which worsen clinical outcomes. Case report: We report the case of a female patient diagnosed with breast adenocarcinoma that had metastasized to the bones, ovary, and stomach, who was hospitalized because of clinical complications. During hospitalization, she presented severe weight loss and was classified as being at nutritional risk, as determined by the Patient-Generated Subjective Global Assessment. Due to severe odynophagia, oral intake was not possible. Therefore, after consultation with the multidisciplinary team, the decision was made to insert a nasogastric tube. Conclusion: Nutritional therapy in patients with advanced cancer still constitutes a dilemma facing professionals and needs to be discussed by a multidisciplinary team, the participation of the nutritionist, patient, and family being indispensable. Therefore, health care services must be prepared to manage nutritional therapy correctly, in order to promote better quality of life for such patients.

Introducción: El surgimiento de metástasis gástrica proveniente de neoplasia de mama es raro. Sin embargo, el soporte nutricional en estos casos es imprescindible, ya que los tumores gástricos están relacionados a complicaciones nutricionales, favoreciendo los resultados clínicos negativos. Informe de caso: Paciente con diagnóstico de adenocarcinoma de mama, con progresión para huesos, ovario y estómago, internada debido a complicaciones clínicas. Se presentó una pérdida de peso grave durante la internación, además de diagnóstico de riesgo de desnutrición por la evaluación subjetiva global producida por el paciente. Debido a un cuadro de odinofagia severa, la alimentación oral se volvió imposibilitada, siendo optado por el uso de sonda nasoentérica después de la discusión con el equipo interdisciplinario. Conclusión: La terapia nutricional en pacientes con cáncer avanzado sigue siendo un dilema entre los profesionales y su ejecución debe ser discutida y decidida por un equipo interdisciplinario, con participación indispensable del nutricionista, del paciente y de sus familiares. Para ello, los servicios de salud deben estar preparados para el correcto manejo de la co

Current status of the multidisciplinary treatment of gastric adenocarcinoma / Estado atual do tratamento multidisciplinar do adenocarcinoma gástrico

ABSTRACT Background: The complexity of the management of gastric cancer requires a multidisciplinary evaluation of patients with this tumor. Several treatments have been employed, associated to the surgical resection. Objective: To review the available therapeutic alternatives for the treatment of gastric adenocarcinoma. Methods : A review of selected articles on multidisciplinary treatment of gastric adenocarcinoma in the Pubmed and Medline databases between 2000 and 2017 was carried out. The following headings were related: stomach cancer, treatment, chemotherapy and radiotherapy. Results : There are several valid alternatives, with good results for the treatment of gastric cancer: chemoradiotherapy or chemotherapy in the adjuvant scenario; perioperative chemotherapy; and chemoradiotherapy after neoadjuvance with isolated chemotherapy. Conclusion : Current evidences suggest that combined multidisciplinary treatment is superior to surgery alone. However, the optimal treatment regimen is not yet established, and depends on a number of factors, especially the type of surgical resection employed. Therefore, the therapeutic decision should be made by a multidisciplinary team, assessing patient's personal characteristics, biology of the tumor, residual disease, risks and side effects.

RESUMO Introdução : A complexidade do manejo do câncer gástrico torna necessária a avaliação multidisciplinar dos pacientes com esse tumor. Diversas alternativas de tratamento têm sido empregadas, associadas com a ressecção cirúrgica. Objetivo: Analisar as alternativas disponíveis para o tratamento do adenocarcinoma gástrico. Método : Foi realizada revisão de artigos selecionados sobre tratamento multidisciplinar do adenocarcinoma gástrico nas bases de dados Pubmed e Medline entre 2000 e 2017. Os seguintes descritores foram relacionados: câncer de estômago, tratamento, quimioterapia e radioterapia. Resultados : Existem várias alternativas válidas, com bons resultados para o tratamento do câncer gástrico: adjuvância com químio e radioterapia ou quimioterapia isolada; quimioterapia perioperatória; e químio e radioterapia após neoadjuvância com quimioterapia isolada. Conclusão : As evidências sugerem que o tratamento combinado é superior ao da cirurgia isolada. Entretanto, o esquema ideal de tratamento ainda não está estabelecido e depende de uma série de fatores, principalmente o tipo de ressecção cirúrgica empregada. Portanto, a decisão terapêutica deve ser tomada por equipe multidisciplinar, avaliando características pessoais do paciente, biologia do tumor, possibilidade de doença residual, riscos e a capacidade do paciente de tolerar tratamentos não isentos de efeitos colaterais.

Recomendaciones sobre el manejo del cáncer de páncreas tipo adenocarcinoma en Latinoamérica: Reunión del Consenso del Simposio Latinoamericano de Gastroenterología Oncológica (SLAGO) y de la Asociación Ibero Latinoamericana de Terapia Radiante (ALATRO), Viña del Mar, Chile 2015 / Recommendations for the management of pancreatic cancer type adenocarcinoma: A consensus statement reached during the 2015 Latin American Symposium on Gastroenterological Oncology

Pancreatic cancer is a malignancy of great impact in developed countries and is having an increasing impact in Latin America. Incidence and mortality rates are similar for this cancer. This is an important reason to offer to the patients the best treatments available. During the Latin American Symposium of Gastroenterology Oncology (SLAGO) held in Viña del Mar, Chile, in April 2015, a multidisciplinary group of specialists in the field met to discuss about this disease. The main conclusions of this meeting, where practitioners from most of Latin American countries participated, are listed in this consensus that seek to serve as a guide for better decision making for patients with pancreatic cancer in Latin America.

Neoadjuvant therapy and surgery for rectal cancer. Comparative study between partial and complete pathological response / Terapia neoadjuvante e cirurgia para câncer do reto. Estudo comparativo entre resposta patológica parcial e completa

ABSTRACT Background The approach of locally advanced extra-peritoneal rectal adenocarcinoma implies a treatment with neoadjuvant chemoradiotherapy associated with total mesorectal excision surgery. However, the tumors respond variably to this neoadjuvant therapy, and the mechanisms for response are not completely understood. Objective Evaluate the variables related to the complete tumor response and the outcomes of patients who underwent surgery, comparing those with partial tumor regression and those with total remission of rectal lesion, at the pathological examination. Methods Retrospective analysis of medical records of 212 patients operated between 2000 and 2010, in which 182 (85.9%) obtained partial remission at neoadjuvant therapy (Group 1) and 30 (14.1%), total remission (Group 2). Results No difference was found between the groups in relation to gender, ethnicity, age, tumor distance from the anal verge, occurrence of metastases and synchronous lesions on preoperative staging, dose of radiotherapy and performed surgery. In Group 2, was verified high rate of complete remission when the time to surgery after neoadjuvant therapy was equal or less than 8 weeks (P=0.027), and a tendency of lower levels of pretreatment carcinoembryonic antigen (P=0.067). In pathological analysis, the Group 1 presented in relation to Group 2, more affected lymph nodes (average 1.9 and 0.5 respectively; P=0.003), more angiolymphatic (19.2% and 3.3%; P=0.032) and perineural involvement (15.4% and 0%; P=0.017) and greater number of lymph nodes examined (16.3 and 13.6; P=0.023). In the late follow-up, Group 1 also had lower overall survival than Group 2 (94.1 months and 136.4 months respectively; P=0.02) and disease-free survival (85.5 months and 134.6 months; P=0.004). There was no statistical difference between Group 2 and Group 1 in local recurrence (15% and 3.4%, respectively) and distant metastasis (28% and 13.8%, respectively). Conclusion In this study, the only factor associated with complete remission of rectal adenocarcinoma was the time between neoadjuvant therapy and surgery. This group of patients had less affected lymph nodes, less angiolymphatic and perineural involvement, a longer overall and disease-free survival, but no significant statistical difference was observed in local recurrence and distant metastasis. Although the complete pathologic remission was associated with better prognosis, this not implied in the cure of the disease for all patients.

RESUMO Contexto A abordagem do câncer retal extra-peritoneal localmente avançado implica em um tratamento com quimio e radioterapia neoadjuvante associada com a cirurgia de excisão total do mesorreto. Entretanto, os tumores respondem de maneiras variadas a esta terapia neoadjuvante, não se conhecendo completamente os mecanismos envolvidos nesta resposta. Objetivo Avaliar os fatores relacionados à resposta tumoral completa e o seguimento de pacientes operados, comparando o grupo com regressão parcial com aqueles em que se evidenciou remissão total da lesão no reto, pelo estudo anatomopatológico. Métodos Análise retrospectiva de prontuários médicos de 212 pacientes operados entre 2000 e 2010, sendo que 182 (85,9%) apresentaram remissão parcial a neoadjuvância (Grupo 1) e 30 (14,1%), remissão total (Grupo 2). Resultados Não foi encontrada diferença entre os grupos em relação a gênero, etnia, idade, distância do tumor a margem anal, ocorrência de metástases e lesões sincrônicas no estadiamento pré-operatório, dose de radioterapia e tipo de cirurgia realizada. No Grupo 2, foi verificada alta taxa de remissão completa quando o paciente foi operado com intervalo menor ou igual a 8 semanas após a terapia neoadjuvante (P=0,027), e uma tendência a menor valor de antígeno carcinoembrionário pré-tratamento (P=0,067). Na análise patológica, o Grupo 1 apresentou em relação ao Grupo 2, mais linfonodos acometidos (média de 1,9 e 0,5 respectivamente; P=0,003), mais invasão angiolinfática (19,2% e 3,3%; P=0,032) e perineural (15,4% e 0%; P=0,017), e maior número de linfonodos examinados (16,3 e 13,6; P=0,023). No seguimento tardio, o Grupo 1 também apresentou menor sobrevida global do que o Grupo 2 (94,1 e 136,4 meses, respectivamente; P=0,02) e sobrevida livre de doença (85,5 e 134,6 meses; P=0,004). Não houve diferença estatística entre os Grupo 1 e Grupo 2 na ocorrência de recidiva local (3,4% e 15%, respectivamente; P=0,32) e metástases à distância (13,8 e 28%; P=0,26). Conclusão Neste estudo, o único fator que foi associado à remissão completa do adenocarcimona retal, foi o tempo entre neoadjuvância e a cirurgia. Este grupo de pacientes apresentou menos linfonodos acometidos, menor invasão angiolinfática e perineural, maior sobrevida global e livre de doença, porém não apresentou diferença estatística significativa com relação à recorrência local e metástases à distância. Embora a remissão completa fosse associada com melhor prognóstico, não implicou na cura da doença em todos os pacientes.

Clinical factors of post-chemoradiotherapy as valuable indicators for pathological complete response in locally advanced rectal cancer

OBJECTIVES: Pathological complete response has shown a better prognosis for patients with locally advanced rectal cancer after preoperative chemoradiotherapy. However, correlations between post-chemoradiotherapy clinical factors and pathologic complete response are not well confirmed. The aim of the current study was to identify post-chemoradiotherapy clinical factors that could serve as indicators of pathologic complete response in locally advanced rectal cancer. METHODS: This study retrospectively analyzed 544 consecutive patients with locally advanced rectal cancer treated at Sun Yat-sen University Cancer Center from December 2003 to June 2014. All patients received preoperative chemoradiotherapy followed by surgery. Univariate and multivariate regression analyses were performed to identify post-chemoradiotherapy clinical factors that are significant indicators of pathologic complete response. RESULTS: In this study, 126 of 544 patients (23.2%) achieved pathological complete response. In multivariate analyses, increased pathological complete response rate was significantly associated with the following factors: post-chemoradiotherapy clinical T stage 0-2 (odds ratio=2.098, 95% confidence interval=1.023-4.304, p=0.043), post-chemoradiotherapy clinical N stage 0 (odds ratio=2.011, 95% confidence interval=1.264-3.201, p=0.003), interval from completion of preoperative chemoradiotherapy to surgery of >7 weeks (odds ratio=1.795, 95% confidence interval=1.151-2.801, p=0.010) and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml (odds ratio=1.579, 95% confidence interval=1.026-2.432, p=0.038). CONCLUSIONS: Post-chemoradiotherapy clinical T stage 0-2, post-chemoradiotherapy clinical N stage 0, interval from completion of chemoradiotherapy to surgery of >7 weeks and post-chemoradiotherapy carcinoembryonic antigen ≤2 ng/ml were independent clinical indicators for pathological complete response. These findings demonstrate that post-chemoradiotherapy clinical factors could be valuable for post-operative assessment of pathological complete response.

Mixed adenoneuroendocrine carcinoma of the gastric stump following Billroth II gastrectomy: case report and review of the literature / Adenocarcinoma neuroendócrino misto do coto gástrico após gastrectomia à Billroth II: relato de caso e revisão de literatura

CONTEXT: Gastric stump cancer after gastric resection is a well-known disease. It may be a newly developed cancer after resection due to benign disease, or recurrent or residual disease after oncological surgery. The predominant histological type is usually adenocarcinoma. This study aimed to report on a rare occurrence of a mixed adenoneuroendocrine carcinoma (MANEC) on the gastric stump. CASE REPORT: The case of an 83-year-old female who presented a locally aggressive gastric stump MANEC, 35 years after Billroth II gastrectomy to treat a peptic ulcer, is reported. The patient underwent resection and adjuvant therapy. She has been followed up for one year without signs of recurrence. CONCLUSION: MANEC is a rare type of gastrointestinal neoplasm. The classification, histopathology, clinical features, treatment issues and prognosis are discussed along with a brief review of the literature.

CONTEXTO: O câncer de coto gástrico após gastrectomia é uma condição extensamente documentada. Pode se tratar de doença desenvolvida após a ressecção por doença benigna, ou ainda doença recorrente ou residual após cirurgia oncológica. Geralmente, o tipo histológico predominante é o adenocarcinoma. Este estudo tem como propósito relatar a rara ocorrência de um adenocarcinoma neuroendócrino misto (MANEC) no coto gástrico. RELATO DE CASO: É relatado o caso de uma mulher de 83 anos que apresentou um MANEC localmente agressivo 35 anos após uma gastrectomia à Billroth II devido a úlcera péptica. Foi submetida a ressecção e terapia adjuvante e foi seguida por 12 meses sem sinais de recorrência. CONCLUSÃO: Os MANECs constituem raro tipo de neoplasia gastrointestinal. Sua classificação, histopatologia, aspectos clínicos, tratamento e prognóstico são discutidos junto com uma breve revisão de literatura.

Marcadores e mecanismos de resistência à terapia neoadjuvante e o papel das vesículas extracelulares secretadas pelas células tumorais no câncer de reto / Biomarkers and mechanisms of resistance to neoadjuvnat therapy and the role of extracelular vesicles secreted by tumor cells in rectal cancer

O câncer de reto é o segundo tumor mais comum no intestino grosso correspondendo a um terço do total de casos de câncer colorretal (CCR). Pacientes com câncer de reto em estádios II e III são tratados com radioquimioterapia neoadjuvante seguida de ressecção cirúrgica do tumor. Análises das peças cirúrgicas ressecadas mostraram que apenas 10-45% dos pacientes obtém resposta patológica completa (RCp) à terapia neoadjuvante, estando essa associada com uma diminuição da recorrência local, melhora da sobrevida livre de doença e aumento na preservação esfincteriana. Apesar da melhora na sobrevida nas últimas décadas, a resposta à terapia neoadjuvante continua variável e imprevisível e não é possível identificar e separar clinicamente os grupos de pacientes que terão ou não resposta completa ao tratamento neoadjuvante. Além disso, os mecanismos de resistência à radioquimioterapia nos tumores de reto são pouco compreendidos. Dessa forma, o objetivo principal deste estudo foi identificar marcadores e mecanismos celulares relacionados à resistência à terapia neoadjuvante em adenocarcinoma de reto e o papel das vesículas extracelulares (VEs) nesse processo. O estudo proteômico comparativo entre biópsias obtidas de tumores pré-tratamento com o tumor residual removido cirurgicamente pós-tratamento radioquimioterápico mostrou uma importante alteração no perfil de expressão proteica. Entre as proteínas que aumentam a expressão após a neoadjuvância estão as proteínas de reparo de dano de DNA, Ku70 e Ku80, e a proteína de tráfego intracelular Rab5C. Em um modelo in vitro, foi demonstrado que Rab5C orquestra um mecanismo de resistência à radioterapia nos tumores de reto através da modulação da internalização de EGFR promovida por radiação ionizante (RI). O EGRF intracelular por sua vez é essencial para regular a expressão de Ku70 e Ku80 e a resistência celular à RI. Estes dados apontam Rab5C e EGFR como potenciais alvos terapêuticos para sensibilizar células de câncer de reto resistentes ao tratamento neoadjuvante. Também foi observado que a RI promove alterações epigenéticas predominantemente de hipometilação, e entre os genes alterados estão SPG20 e TBC1D16, sendo o primeiro importante para a internalização de EGFR e o segundo para a regulação de Rab5C e modulação de EGFR. O perfil de expressão proteica foi ainda comparado entre biópsias pré-tratamento de pacientes com RCp e sem resposta patológica, e o resultado mostrou que esses dois grupos de pacientes apresentam um diferente perfil de expressão proteica. Nos pacientes com RCp as proteínas com aumento da expressão estão atuando em vias que favorecem a resposta à terapia, como a detoxificação de glutationa e degradação de glicogênio, enquanto as proteínas com aumento da expressão em pacientes sem RCp estão envolvidas em vias do metabolismo energético do tumor as quais contribuem para a resistência tumoral à terapia. As diferenças observadas nestes grupos devem ser amplamente exploradas uma vez que podem ser marcadores preditivos de resposta ao tratamento radioquimioterápico. A realização de estudos funcionais foi viabilizada pela geração de um modelo celular de tumor de reto resistente à radioterapia. Ao analisar as VEs secretadas por estas células foi observado que a RI não altera a quantidade e o tamanho médio das VEs secretadas, porém é capaz de alterar o carregamento proteico das mesmas. De fato, as VEs de células irradiadas apresentam um perfil proteico diferente quando comparadas as VEs de células não irradiadas, onde encontramos aumento da expressão de Ku70, Ku80 e Rab5C, além das metiltransferases NSUN2 e GLYM nas VEs de células pós RI. Interessantemente, as VEs secretadas por células irradiadas são capazes de transmitir a resistência à RI às células não irradiadas. Além disso os resultados mostraram que o tratamento com VEs de células irradiadas promove metilação em 98% do DNA avaliado em células SW837 em comparação ao tratamento com VEs de células não irradiadas. Os genes hipermetilados estão envolvidos em vias relacionadas ao sistema imune, como a apresentação de antígeno, sinalização de imunodeficiência primária e maturação de células dendríticas. Por fim, foi identificado que a expressão da proteína A33 está relacionada ao grau de diferenciação dos tumores colorretais, e que essa proteína está presente em VEs secretadas por células de adenocarcinoma de reto, indicando que a mesma pode ser usada para isolar VEs específicas do tecido colorretal. Os dados obtidos neste trabalho apontam mecanismos relacionados à resistência à terapia neoadjuvante no adenocarcinoma de reto e que em conjunto permitirão identificar novos alvos terapêuticos com potencial de melhorar a resposta à radioquimioterapia, além de identificar marcadores de resposta à terapia neoadjuvante antes do tratamento e dessa forma, poupar os pacientes não respondedores de terapias tóxicas e melhorar a sustentabilidade na saúde poupando os custos com drogas não eficientes para um grupo de pacientes.

Rectal cancer is the second most common cancer in large intestine, corresponding to one third of total cases of colorectal cancer (CRC). Patients with rectal cancer in stage II and III are treated with neoadjuvant chemoradiation followed by surgical resection. Analyzes of the resected tumor demonstrated that only 10-45% of the patients achieve pathological complete response (pCR) after neoadjuvant therapy, which is associated with a decrease in local recurrence, improvement of disease free survival and increase in sphincter preservation. Despite the improvement in survival in the last decades, the response to neoadjuvant therapy is still variable and unpredictable, and before the surgery it is not possible to identify and separate clinically the group of patients that will or will not have complete response to neoadjuvant treatment. Moreover, the mechanisms of resistance of rectal tumors to chemoradiation are poorly understood. Thus, the main objective of this work was to identify biomarkers and cellular mechanisms related to the resistance to neoadjuvant therapy in rectal adenocarcinomas and the role of extracellular vesicles (EVs) in this process. The comparative proteomic study between biopsy obtained from tumors pretreatment with residual tumor, post chemoradiation treatment, removed by surgery showed an important alteration in the protein expression profile. Among the proteins with increased expression after neoadjuvant therapy are the DNA repair proteins Ku70 and Ku80, and the protein involved in the intracellular trafficking, Rab5C. It was demonstrated in vitro that Rab5C orchestrates a mechanism of radioresistance in rectal tumors by modulating the EGFR internalization promoted by ionizing radiation (IR). The intracellular EGFR is essential to regulate Ku70 and Ku80 expression and the cell resistance to IR. These data pointed Rab5C and EGFR as potential therapeutic targets to sensitize rectal cancer cells resistant to neoadjuvant treatment. It was also observed that IR promotes epigenetic alterations, predominantly hypomethylation, and between the altered genes are SPG20 and TBC1D16, the first is important to EGFR internalization, while the second regulates Rab5C and modulates EGFR. The protein expression profile was further compared between biopsy pretreatment of patients with and without pCR, and the results showed that these two groups of patients present a different protein expression profile. In patients with pCR the proteins with increased expression are involved in pathways favoring the response to therapy, as glutathione-mediated detoxification and glycogen degradation, while the proteins with increased expression in patients without pCR are involved in tumor energetic metabolism pathways that contribute to tumor resistance to therapy. The observed differences in these groups should be widely explored since they may be predictive markers of response to chemoradiation treatment. The performance of functional studies was possible by generation of a cellular model of rectal tumor resistant to radiotherapy. The analysis of the EVs secreted by these cells showed that IR does not alter the amount and the medium size of secreted EVs, but is able to change their protein content. EVs from irradiated cells presented a different protein profile when compared to EVs from non-irradiated cells, where it was found the increased expression of Ku70, Ku80 and Rab5C, besides the methyltransferases NSUN2 and GLYM in EVs after irradiation. Interestingly, the EVs secreted by irradiated cells are capable of transfering resistance to IR to non-irradiated cells. Moreover, the results showed that the treatment of SW837 cells with EVs from irradiated cells promoted methylation in 98% of the analyzed DNA in comparison with the treatment with EVs from non-irradiated cells. The hypermethylated genes are involved in pathways related to immune system, as antigen presentation, primary immunodeficiency signaling and dendritic cells maturation. Lastly, it was identified that the A33 expression is related to the colorectal tumors differentiation degree, and this protein is present in EVs secreted by rectal adenocarcinoma, indicating that it may be used to isolate EVs specific from colorectal tissues. The data obtained in this work pointed to mechanisms related to resistance to neoadjuvant therapy in rectal adenocarcinoma that together will allow to identify new therapeutic targets with the potential to improve the response to chemoradiation, as well as to identify markers of response to neoadjuvant therapy before the treatment, and, in this way, avoid the non-responder patients to receive toxic therapies and improve health sustainability, sparing cost with non-efficient drugs for a group of patients.

Adenocarcinoma pulmonar metastásico con evolución favorable al tratamiento con ITK-EGFR en un paciente fumador / Metastatic lung adenocarcinoma favorable outcome with ITK-EGFR treatment in a smoker

El cáncer de pulmón es el cáncer con mayor mortalidad en ambos sexos. El esquema de manejo actual del adenocarcinoma pulmonar incluye determinar el estado mutacional del receptor del factor de crecimiento epidérmico (EGFR), por ser la diana para el erlotinib, una terapia biológica. Caso clínico: Varón de 62 años, con hábito tabáquico de alto riesgo oncológico, que debuta con un cuadro de cefalea de un mes de evolución, objetivándose por resonancia magnética tumor cerebral. El diagnóstico inmunohistoquímico post quirúrgico fue adenocarcinoma pulmonar metastásico (TTF-1 (+)). La tomografía identificó una lesión en el lóbulo superior derecho del pulmón; no presentaba clínica respiratoria. Al ser positivo para la mutación en el exón 21 del gen EGFR, se inició terapia con erlotinib, siendo bien tolerada por el paciente y manteniendo su estabilidad clínica. El paciente sobrevivió por el lapso de 31 meses posterior a su diagnóstico. Discusión: El tratamiento con erlotinib fue inicialmente indicado en el perfil de una paciente mujer, asiática y no fumadora. La eficacia en los estudios en pacientes con cáncer de pulmón de células no pequeñas evidencia que la sobrevida global es 15,9 meses, muy por debajo del visto en el presente caso...

Lung cancer has highest mortality in both sexes. Current management of lung adenocarcinoma includes determining epidermal growth factor receptor (EGFR) mutational status as this is the target of erlotinib, a biologic therapy. Case report: A 62 yearold male with high smoking cancer risk presented chronic headache for a month, and magnetic resonance showed a brain tumor. Surgical specimen diagnosis was metastatic pulmonary adenocarcinoma by immunohistochemistry (TTF-1 (+)). An asymptomatic lesion in the right upper lobe of the lung was identified by tomography. Due to positivity to EGFR gene exon 21 mutation erlotinib was started; it was well tolerated by the patient. The patient died 31 months after diagnosis. Discussion: Treatment with erlotinib was initially indicated in the profile of an Asian and non-smoker woman patient. The overall survival rate with erlotinib in patients with non-small cell lung cancer is reported as 15.9 months, less time than with our patient, even considering his heavy smoker condition which should have decreased both the chance of having EGFR mutation and response to treatment...

Leprosy: type 1 reaction precipitated by doxorubicin and cisplatin

Type 1 reaction [T1R] in leprosy is common and characterized by increased inflammation in skin lesions or nerve. Besides antileprotic therapy, T1Rs are associated with intercurrent infection, pregnancy and drugs. Also, T1Rs may be a presenting feature of leprosy. We report a case of T1R in leprosy presenting as drug reaction during cancer chemotherapy with doxorubicin and cisplatin. We propose to explain this unusual occurrence by highlighting the increased production and expression of TNF-alpha by these drugs. Thus, physicians using these drugs should keep this unusual adverse effect in mind

Carcinoma de osso temporal sem foco metastático primário: relato de caso e revisão de literatura / Carcinoma temporal bone unfocused metastatic primary: case report and literature review

Os tumores do osso temporal são raros e geralmente apresentam sintomas como otorreia, otalgia e hipoacusia, por isso podem ser facilmente confundidos com um processo infeccioso, retardando o diagnóstico e piorando o prognóstico do paciente. KS, 7 anos, masculino. Estado geral: regular. Ao exame: consciente; linfonodos cervicais palpáveis, móveis; massa palpável, imóvel e indolor em topografia retroauricular esquerda; surdez à esquerda e paralisia facial esquerda. Tomografia computadorizada de crânio evidenciou lesão expansiva do osso temporal captante de contraste com extensão para fossa média e posterior do crânio. Realizada complementação radiológica com ressonância de encéfalo, a qual apresentou imagem hipercaptante em T1 contrastado. Nas incidências T2, observa-se edema lobotemporal adjacente à lesão. Exame angiográfico cerebral apresentou obstrução tumoral do seio sigmoide esquerdo. Paciente submetido à mastoidectomia radical esquerda com ligadura e ressecçãodo seio sigmoide esquerdo resultando em ressecção completa lesional. Anatomopatológico e exame imunoistoquímico compatíveis com adenocarcinoma. Encaminhado para terapia oncológica com quimioterapia e radioterapia. Óbito após quatro meses do tratamento neurocirúrgico. O diagnóstico precoce associado com a extensão do tumor acarreta melhor ou pior prognóstico para os pacientes acometidos por essa moléstia.

Tumors of the temporal bone are rare and usually have symptoms such as otorrhea, otalgia and hearing loss and, therefore, can be easily confused with an infectious process delaying diagnosis and worse prognosis. KS, age 7, male. General condition: regular. On examination: conscious, palpable cervical lymph nodes, mobile; palpable mass, painless and property surveying retroauricular left, left deafness and facial paralysis left. Cranial computed tomography showed a lesion of the temporal bone with extensionto the middle fossa and posterior skull that enhance with contrast. Performed complementation with radiological MRI brain image which showed uptake, in contrast T1. Incidences in T2, there is edema temporal lobe adjacent to the lesion. Cerebral angiography showed a tumor obstructing the left sigmoidsinus. Patient underwent left radical mastoidectomy with ligation and resection of the left sigmoid sinus resulting in complete lesional resection. Histopathological and immunohistochemical examination compatible with adenocarcinoma. Referred for cancer therapy with chemotherapy and radiation. Death within four months after neurosurgical treatment. Early diagnosis associated with tumor extension carries a better or worse prognosis for patients affected by this disease.