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

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

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

Advances of immunotherapy-related biomarker in esophageal carcinoma / 中华胃肠外科杂志

Esophageal carcinoma is one of the most common malignant tumors in the world, with incidence and mortality rankings of 7th and 6th, respectively. In recent years, immunotherapy represented by immune checkpoint inhibitors of programmed death-1 and programmed death ligand 1 (PD-L1) has been introduced into clinical practice and has changed the treatment status of esophageal cancer. Although immunotherapy has provided long-term survival benefits for patients with advanced esophageal cancer and high pathological response rates in the neoadjuvant therapy, only a few of the patients have satisfactory therapeutic outcomes. Therefore, effective biomarkers for predicting immunotherapeutic effects are urgently needed to identify those patients who could benefit from immunotherapy. In this paper, we mainly discuss recent research advances of biomarkers related to the immunotherapy of esophageal cancer and the clinical application prospects of these biomarkers.

Tumor antigen-loaded dendritic cells combined with cytokine-induced killer (CIK) enhance the killing activity of human esophageal cancer cells by promoting ASK1 activation / 细胞与分子免疫学杂志

Objective To clarify the effect and mechanism of tumor antigen-loaded dendritic cells (Ag-DCs) combined with cytokine-induced killers (CIKs) on the killing of esophageal cancer tumor cells. Methods Peripheral blood DCs and CIKs were induced and cultured, and the DCs were loaded with tumor antigen to obtain Ag-DCs, and Ag-DCs were co-cultured with CIKs. The experiment was divided into CIK group, DC combined with CIK group, Ag-DC combined with CIK group. Flow cytometry was used to detect the phenotype of cells. MTT assay was employed to determine the killing activity against EC9706 cells. Annexin V-FITC/PI double staining was used to detect the apoptosis rate of cells, immunofluorescence staining to detect the expression of phosphorylated apoptotic signal-regulated kinase 1 (p-ASK1) and Western blot analysis to detect the expression of ASK1 pathway related proteins. A nude mouse model of esophageal cancer transplantation tumor was constructed and divided into control group, DC combined with CIK group and Ag-DC combined with CIK group. The corresponding immune cells were injected into the tail vein for treatment and the tumor volume was measured every 2 days. After 21 days, all nude mice were sacrificed with the tumors taken out. HE staining was used to observe the tumor pathological changes and immunohistochemical staining was performed to detect the expression of ki67 and ASK1 in the tumor tissue. Results Comparedwith the CIK group alone and the DC combined with CIK group, the ratio of CD3+ CD8+ and CD3+ CD56+ in the cells significantly increased after Ag-DCs and CIKs co-culture, along with the increased killing rate of EC9706 cells, increased apoptosis rate of EC9706 cells, and the improved activation level of ASK1. Compared with the CIK group and the DC combined with CIK group, the growth of the transplanted tumor in nude mice treated with Ag-DCs combined with CIKs was significantly inhibited, and after 21 days, it was observed that the tumor tissue mass in this group was relatively smaller, with sparsely arranged cells in the tumor tissue and a decline in the positive rate of ki67 in tumor tissue, while the positive rate of ASK1 was significantly increased. Conclusion Co-cultivation of tumor antigen-loaded DCs with CIKs can significantly increase the killing activity of esophageal cancer tumor cells. The mechanism of action may be related to the activation of the ASK1 pathway.

Neoadjuvant chemoradiotherapy followed by transhital esophagectomy in locally advanced esophageal squamous cell carcinoma: impact of pathological complete response / Quimiorradioterapia neoadjuvante seguido de esofagectomia transhital no carcinoma espinocelular do esôfago avançado: impacto da resposta patológica completa

ABSTRACT Background Multimodal therapy with neoadjuvant chemoradiotherapy, followed by esophagectomy has offered better survival results, compared to isolated esophagectomy, in advanced esophageal cancer. In addition, patients who have a complete pathological response to neoadjuvant treatment presented greater overall survival and longer disease-free survival compared to those with incomplete response. Aim: To compare the results of overall survival and disease-free survival among patients with complete and incomplete response, submitted to neoadjuvant chemoradiotherapy, with two therapeutic regimens, followed by transhiatal esophagectomy. Methods: Retrospective study, approved by the Research Ethics Committee, analyzing the medical records of 56 patients with squamous cell carcinoma of the esophagus, divided into two groups, submitted to radiotherapy (5040 cGY) and chemotherapy (5-Fluorouracil + Cisplatin versus Paclitaxel + Carboplatin) neoadjuvants and subsequently to surgical treatment, in the period from 2005 to 2012, patients. Results The groups did not differ significantly in terms of gender, race, age, postoperative complications, disease-free survival and overall survival. The 5-year survival rate of patients with incomplete and complete response was 18.92% and 42.10%, respectively (p> 0.05). However, patients who received Paclitaxel + Carboplatin, had better complete pathological responses to neoadjuvant, compared to 5-Fluorouracil + Cisplatin (47.37% versus 21.62% - p = 0.0473, p <0.05). Conclusions There was no statistical difference in overall survival and disease-free survival for patients who had a complete pathological response to neoadjuvant. Patients submitted to the therapeutic regimen with Paclitaxel and Carboplastin, showed a significant difference with better complete pathological response and disease progression. New parameters are indicated to clarify the real value in survival, from the complete pathological response to neoadjuvant, in esophageal cancer.

RESUMO Racional: A terapia multimodal com quimioradioterapia neoadjuvantes, seguido de esofagectomia tem oferecido melhores resultados de sobrevida, em comparação à esofagectomia isolada, no câncer do esôfago avançado. Além disso, os doentes que apresentam resposta patológica completa ao tratamento neoadjuvante, têm evoluido com maior sobrevida global e maior sobrevida livre de doença em comparação aos que apresentam resposta incompleta. Objetivo: Comparar os resultados de sobrevida global e sobrevida livre de doença entre os doentes com resposta completa e incompleta, submetidos à quimioradioterapia neoadjuvante, com dois esquemas terapêuticos, seguidos de esofagectomia transhiatal. Métodos: Estudo retrospectivo, aprovado pelo Comitê de Ética em pesquisa, analisando os prontuários de 56 doentes, divididos em dois grupos de pacientes, submetidos a radioterapia (4400 a 5400 cGY) e quimioterapia (5-Fluorouracil+Cisplatina versus Paclitaxel+Carboplatina) neoadjuvantes e posteriormente a tratamento cirúrgico, no período de 2005 a 2012, portadores de carcinoma espinocelular do esôfago. Resultados: Os grupos não diferiram significativamente quanto ao gênero, raça, idade, complicações pós-operatórias, sobrevida livre de doença e sobrevida global. A sobrevida em 5 anos de doentes com resposta incompleta e completa foram, respectivamente, 18,92% e 42,10% (p>0,05). Entretanto, os doentes que receberam Paclitaxel+Carboplatina, tiveram melhores respostas patológicas completas à neoadjuvância, em comparação ao 5-Fluorouracil+Cisplatina (47,37% versus 21,62% - p=0,0473, p<0,05). Conclusões: Não houve diferença estatística na sobrevida global e na sobrevida livre de doença dos doentes que apresentaram resposta patológica completa à neoadjuvância. Os doentes submetidos ao esquema terapêutico com Paclitaxel e Carboplastina, mostraram diferença significativa com melhor resposta patológica completa e evolução da doença. Novos parâmetros são indicados para esclarecer o real valor na sobrevida, da resposta patológica completa à neoadjuvância, no câncer de esôfago.

Características e desfechos em curto prazo de pacientes com câncer esofágico em admissões não planejadas a unidades de terapia intensiva: um estudo de coorte retrospectiva / Characteristics and short-term outcomes of patients with esophageal cancer with unplanned intensive care unit admissions: a retrospective cohort study

RESUMO Objetivo: Mostrar o quadro clínico e os desfechos de uma coorte de pacientes críticos com câncer esofágico. Métodos: Conduzimos um estudo multicêntrico retrospectivo que incluiu pacientes com câncer esofágico admitidos a unidades de terapia intensiva em razão de doença aguda entre setembro de 2009 e dezembro de 2017. Colhemos os dados demográficos e as características clínicas de todos os pacientes incluídos, assim como as medidas de suporte a órgãos e os desfechos no hospital. Realizamos uma análise de regressão logística para identificar os fatores associados de forma independente com mortalidade hospitalar. Resultados: Dentre os 226 pacientes incluídos no estudo, 131 (58,0%) faleceram antes de receber alta hospitalar. O carcinoma espinocelular foi mais frequente do que o adenocarcinoma, e 124 (54,9%) pacientes tinham câncer metastático. As principais razões para admissão foram sepse/choque séptico e insuficiência respiratória aguda. Uso de ventilação mecânica (RC = 6,18; IC95% 2,86 - 13,35) e doença metastática (RC = 7,10; IC95% 3,35 - 15,05) tiveram associação independente com mortalidade hospitalar. Conclusão: Nesta coorte de pacientes com câncer esofágico admitidos à unidades de terapia intensiva em razão de doença aguda, a taxa de mortalidade hospitalar foi muito elevada. A necessidade de utilizar ventilação mecânica invasiva e a presença de doença metastática foram fatores independentes de prognóstico e devem ser levados em conta nas discussões a respeito dos desfechos destes pacientes em curto prazo.

ABSTRACT Objective: To depict the clinical presentation and outcomes of a cohort of critically ill patients with esophageal cancer. Methods: We carried out a multicenter retrospective study that included patients with esophageal cancer admitted to intensive care units with acute illness between September 2009 and December 2017. We collected the demographic and clinical characteristics of all included patients, as well as organ-support measures and hospital outcomes. We performed logistic regression analysis to identify independent factors associated with in-hospital mortality. Results: Of 226 patients included in the study, 131 (58.0%) patients died before hospital discharge. Squamous cell carcinoma was more frequent than adenocarcinoma, and 124 (54.9%) patients had metastatic cancer. The main reasons for admission were sepsis/septic shock and acute respiratory failure. Mechanical ventilation (OR = 6.18; 95%CI 2.86 - 13.35) and metastatic disease (OR = 7.10; 95%CI 3.35 - 15.05) were independently associated with in-hospital mortality. Conclusion: In this cohort of patients with esophageal cancer admitted to intensive care units with acute illness, the in-hospital mortality rate was very high. The requirement for invasive mechanical ventilation and metastatic disease were independent prognostic factors and should be considered in discussions about the short-term outcomes of these patients.

Desafios à Intervenção Interdisciplinar no Olhar da Equipe Multiprofissional em um Hospital de Referência em Tratamento de Câncer no Brasil / Challenges of the Interdisciplinary Approach under the Perspective of the Multidisciplinary Team in a Referral Hospital for Cancer Treatment in Brazil / Desafíos del Enfoque Interdisciplinario a los Ojos del Equipo Multidisciplinario en un Hospital de Referencia para el Tratamiento del Cáncer en Brasil

Introdução: A interdisciplinaridade é vista como uma alternativa que, somada ao desenvolvimento tecnológico, possa a contribuir para a melhoria do cuidado em saúde, mas cuja construção é cercada de desafios. O Grupo de Estudos e Tratamento do Câncer Gástrico e Esofágico de um hospital referência em tratamento de câncer, composto por equipe multiprofissional, foi criado no sentido de promover interação entre a equipe e a melhoria no atendimento ao paciente, mas ainda precisa avançar no sentido da interdisciplinaridade. Objetivo: Conhecer e analisar os desafios à intervenção interdisciplinar no olhar dos profissionais que integram a equipe. Método: Pesquisa qualitativa, cuja coleta de dados se deu por entrevista com profissionais das categorias inseridas no grupo e análise com base na hermenêutica-dialética. Resultados: O entendimento acerca do propósito do grupo e das temáticas integralidade e interdisciplinaridade, incluindo-se a percepção sobre a rede de cuidados ao paciente. Foram apresentados desafios objetivos e subjetivos, vinculados, respectivamente, à gestão e à relação entre a equipe e entre os profissionais e os pacientes, para os quais é fundamental destinar o cuidado. Foram ainda apresentados avanços e resultados positivos e a necessidade de se direcionar o olhar também à equipe e ao seu cuidado. Conclusão: Verifica-se a importância de levar os profissionais à reflexão acerca de sua intervenção, individual e coletiva, tendo em vista as possibilidades que estão ao alcance da equipe e de outras que poderiam ser alvo de pleitos e lutas para a efetiva implementação do Sistema Único de Saúde, como também valorizar as potencialidades e os ganhos já conquistados.

Introduction: The interdisciplinarity is seen as an alternative that, added to the technological development, could contribute to the improvement of healthcare, but whose construction faces challenges. The Gastric and Esophageal Cancer Study and Treatment Group of a referral cancer treatment hospital formed by a multi-professional team, was created to promote interaction between the team and the improvement of patient care; nevertheless, still needs to move towards interdisciplinarity. Objective: To know and analyze the challenges of interdisciplinary intervention through the vision of the professionals who belong to the team. Method: Qualitative approach, with data collected through interviews with professionals of the group's categories and analysis based on hermeneutic-dialectic. Results: One of the results was the understanding about the purpose of the group and the concepts of integrality and interdisciplinarity, including the perception about the patient care network. Other result was the presentation of objective and subjective challenges and their relation, respectively, to the management and relationship between the team, and between professionals and patients, for whom care is provided. In addition, it were presented positive results and progress, and the necessity to focus the attention to the team and its own care. Conclusion: It was verified the importance to encourage the professionals to think about their own individual and collective intervention, bearing in mind the possibilities that are within the scope of the team and others that could be the object of pledges and struggles for the effective implementation of National Health System and to value the potentialities and conquests already achieved.

Introducción: La interdisciplinariedad se considera una alternativa que, sumada al desarrollo tecnológico, puede contribuir a la mejora de la atención médica, pero cuya construcción está rodeada de desafíos El Grupo de Estudio y Tratamiento del Cáncer Gástrico y Esofágico de un hospital de referencia para el tratamiento del cáncer, compuesto por un equipo multiprofesional, fue creado para promover la interacción del equipo y mejorar la atención al paciente, pero aún necesita avanzar hacia la interdisciplinariedad. Objetivo: Conocer y analizar los desafíos de la intervención interdisciplinaria a los ojos de los profesionales que forman parte del equipo. Método: Investigación cualitativa, cuya recopilación de datos se realizó mediante entrevista con profesionales de las categorías incluidas en el grupo y el análisis basado en la dialéctica hermenéutica. Resultados: La comprensión sobre el propósito del grupo y los temas de integralidad e interdisciplinariedad, incluida la percepción sobre la red de atención al paciente. Se presentaron desafíos objetivos y subjetivos, vinculados, respectivamente, al manejo y la relación entre el equipo y entre profesionales y pacientes, para lo cual la atención es esencial. También se presentaron avances y resultados positivos, así como la necesidad de dirigir la mirada hacia el equipo y su cuidado. Conclusión: Existe la importancia de que los profesionales líderes reflexionen sobre su intervención individual y colectiva, considerando las posibilidades que están al alcance del equipo y otros que podrían ser el objetivo de reclamos y luchas para la implementación efectiva del Sistema Único de Salud, además de valorar el potencial y los logros ya alcanzados.

Pathologic complete response (ypt0 ypn0) after chemotherapy and radiotherapy neoadjuvant followed by esophagectomy in the squamous cell carcinoma of the esophagus / Resposta patológica completa (ypt0 ypn0) após quimioterapia e radioterapia neoadjuvantes seguido de esofagectomia no carcinoma epidermóide avançado do esôfago: resultados e sobrevida

ABSTRACT Background: Esophageal squamous cell carcinoma is an aggressive neoplasia that requires a multidisciplinary treatment in which survival and prognosis are still not satisfactory. The complete pathologic response to neoadjuvant chemotherapy and radiotherapy is considered a good prognosis factor, and esophagectomy is indicated. Aim: Survival analysis of cases with pathologic complete response (ypT0 ypN0) to neoadjuvant chemotherapy and/or radiotherapy, submmitted to esophagectomy. Methods: Between 1983-2014, 222 esophagectomies were performed, and 177 were conducted to neoadjuvant treatment. In 34 patients the pathologic response was considered complete. Medical records of the patients were retrospectively reviewed regarding type of chemotherapy applied, amount of radiotherapy, interval between the neoadjuvant therapy and the surgery, body mass index; postoperative complications; hospital admission time and survival. Results: The average age was 55.8 years. Twenty-five patients were subjected to chemotherapy and radiotherapy, and nine to neoadjuvant radiotherapy. The total radiation dose ranged from 4400 until 5400 cGy. The chemotherapy was performed with 5FU, cisplatin, and carbotaxol, concomitantly with the radiotherapy. The esophagectomy was transmediastinal, followed by the cervical esophagogastroplasty performed on a average of 49.4 days after the neoadjuvant therapy. The hospital admission time was an average of 14.8 days. During the follow-up period, 52% of the patients submitted to radiotherapy and chemotherapy were disease-free, with 23.6% of them presenting more than five years survival. Conclusions: The neoadjuvant treatment followed by esophagectomy in patients with pathologic complete response is beneficial for the survival of patients with esophageal squamous cell carcinoma.

RESUMO Racional: O carcinoma epidermoide do esôfago é neoplasia de natureza agressiva, que requer tratamento multidisciplinar e tem taxas de sobrevida e prognóstico ainda não satisfatórios. A resposta patológica completa à neoadjuvância com quimioterapia e radioterapia é considerada fator de bom prognóstico e a esofagectomia está indicada. Objetivo: Análise de sobrevida dos casos com resposta patológica completa (ypT0 ypN0) à neoadjuvância com quimioterapia e/ou radioterapia, submetidos à esofagectomia. Métodos: Entre 1983-2014, 222 esofagectomias foram realizadas e 177 foram submetidas ao tratamento neoadjuvante. Em 34 pacientes, a resposta patológica foi considerada completa. Os prontuários dos pacientes foram revisados retrospectivamente quanto ao tipo de quimioterapia aplicada, quantidade de radioterapia, intervalo entre a terapia neoadjuvante e a operação, índice de massa corporal (IMC), complicações pós-operatórias, tempo de internação hospitalar e sobrevida. Resultados: A idade média foi de 55,8 anos. Vinte e cinco pacientes foram submetidos a quimioterapia e radioterapia e nove à radioterapia neoadjuvante. A dose total de radiação variou de 4400 até 5400 cGy. A quimioterapia foi realizada com 5FU, cisplatina e carbotaxol, concomitantemente à radioterapia. A esofagectomia foi transmediastinal, seguida da esofagogastroplastia cervical realizada em média 49,4 dias após a terapia neoadjuvante. O tempo de internação hospitalar foi em média de 14,8 dias. Durante o período de seguimento, 52% dos pacientes submetidos a radioterapia e quimioterapia estavam livres de doença, com 23,6% apresentando sobrevida maior que cinco anos. Conclusão: O tratamento neoadjuvante seguido de esofagectomia, nos pacientes com resposta patológica completa, oferece benefícios na sobrevida de portadores de carcinoma epidermoide do esôfago.

Endoscopic Ultrasonography in the Diagnosis and Treatment Strategy Choice of Esophageal Leiomyoma

OBJECTIVES: Esophageal leiomyoma is the most common benign tumor of the esophagus, and it originates from mesenchymal tissue. This study analyzed the clinicopathological characteristics of esophageal leiomyoma and aimed to evaluate the role of endoscopic ultrasonography in the diagnosis and treatment selection for these lesions. METHODS: Two hundred and twenty-five patients who had suspected esophageal leiomyomas in endoscopic ultrasonography were enrolled at the Endoscopy Center of The First Affiliated Hospital, Zhejiang University from January 1st, 2009 to May 31th, 2015. The main outcomes included the demographic and morphological characteristics, symptoms, comparisons of diagnosis and treatment methods, adverse events, and prognosis. RESULTS: One hundred and sixty-seven patients were diagnosed as having an esophageal leiomyoma by pathological examination. The mean patient age was 50.57±9.983 years. In total, 62.9% of the lesions originated from the muscularis mucosa, and the others originated from the muscularis propria. The median distance to the incisors was 30±12 cm. The median diameter was 0.72±0.99 cm. As determined by endoscopic ultrasonography, most existing leiomyomas were homogeneous, endophytic, and spherical. The leiomyomas from the muscularis mucosa were smaller than those from the muscularis propria and much closer to the incisors (p<0.05). SMA (smooth muscle antibody) (97.2%) and desmin (94.5%) were positive in the majority of patients. In terms of treatments, patients preferred endoscopic therapies, which led to less adverse events (e.g., intraoperative bleeding, local infection, pleural effusion) than surgical operations (p<0.05). The superficial leiomyomas presented less adverse events and better recovery (p<0.05) than deep leiomyomas. CONCLUSION: Endoscopic ultrasonography has demonstrated high accuracy in the diagnosis of esophageal leiomyomas and provides great support in selecting treatments; however, EUS cannot completely avoid misdiagnosis, so combining it with other examinations may be a good strategy to solve this problem.

Primary neuroendocrine neoplasm of the esophagus – Report of 14 cases from a single institute and review of the literature / Neoplasia neuroendócrina primária de esôfago - Relato de 14 casos e revisão de literatura

ABSTRACT BACKGROUND Most prevalent esophageal neoplasm is squamous cell carcinoma and adenocarcinoma. Other tumors are uncommon and poorly studied. Primary neuroendocrine esophageal neoplasm is a rare carcinoma and most of its therapy management is based on lung neuroendocrine studies. Neuroendocrine tumors can be clustered in the following subtypes: high grade (small cell carcinoma or large cell carcinoma) and low grade (carcinoids). OBJECTIVE The present study aims to assess clinical and pathological neuroendocrine esophageal tumors in a single oncologic center. METHODS A retrospective analysis of patients and review of the literatures was performed. RESULTS Fourteen patients were identified as neuroendocrine tumors, 11 male and 3 female patients. Mean age was 67.3 years old. Ten patients were classified as small cell, 3 as large cell and 1 as carcinoid. Four patients presented squamous cell carcinoma simultaneously and 1 also presented adenocarcinoma. Main sites of metastasis were liver, peritoneum, lung and bones. Most patients died before 2 years of follow-up. Patient with longer survival died at 35 months after diagnosis. CONCLUSION Neuroendocrine esophageal tumors are rare; affect mainly men in their sixties or seventies. High grade tumors can be mixed to other subtypes neoplasms, such as adenocarcinoma and squamous cell carcinoma. Most of these patients have poor overall survival rates.

RESUMO CONTEXTO As neoplasias esofágicas mais prevalentes são o adenocarcinoma e o carcinoma espinocelular. Outros subtipos histológicos são incomuns e pouco estudados. Neoplasia neuroendócrina esofágica é uma patologia rara e seu manejo atualmente se baseia nos conhecimentos prévios de tumores neuroendócrinos de pulmão. Tumores neuroendócrinos podem ser divididos nas seguintes formas: alto grau (pequenas células ou grandes célula) e baixo grau (carcinoides). OBJETIVO Avaliar clínica e patologicamente os tumores de esôfago em um centro oncológico referenciado. MÉTODOS Foi realizada análise retrospectiva e revisão da literatura de neoplasias neuroendócrinas de esôfago. RESULTADOS Foram identificados 14 pacientes com tumores neuroendócrino, sendo 11 homens, 3 mulheres. Idade média foi de 67,3 anos de idade. Desses pacientes, 10 foram classificados como pequenas células, 3 como grandes células e 1 como carcinoide. Foram encontrados quatro casos de tumor misto neuroendócrino e carcinoma espinocelular, e um caso de tumor misto adenoneuroendócrino. Principal sítio de metástases foi fígado, peritônio, pulmão e ossos. A maioria dos pacientes foi a óbito em até 2 anos de seguimento. Paciente com sobrevida mais longa foi a óbito após 35 meses do diagnóstico. CONCLUSÃO Neoplasias neuroendócrinas de esôfago são raras, afetam principalmente o sexo masculino na 7ª ou 8ª década de vida. A maioria dos pacientes com tumores de alto grau tem sobrevida curta.

Soporte nutricional y calidad de vida en pacientes con cáncer de esófago y cardias / Nutritional support and quality of life in patients with esophageal cancer and cardias

Introducción: el cáncer de esófago es la neoplasia del tubo digestivo de peor pronóstico. Su tratamiento constituye un desafío al tratarse de pacientes con deterioro nutricional con incapacidad de ingerir alimentos. La mayoría son tributarios de tratamiento paliativo. Objetivo: describir la experiencia en la atención nutricional de los pacientes con cáncer de esófago y cardias con la introducción del grupo de apoyo nutricional en el Hospital Universitario Comandante Manuel Fajardo. Método: se presentan 126 enfermos con cáncer de esófago y cardias, 51 de ellos con lesiones resecables a los que se realizó esofagectomía y 75 enfermos con cáncer avanzado e intervenciones paliativas, atendidos desde 2006 hasta 2015, según los protocolos de actuación del grupo de apoyo nutricional. Resultados: todos los pacientes se encontraban entre 46 y 76 años, 69 por ciento mayor de 60 años, 87,3 port ciento del sexo masculino, 90 por ciento con antecedentes de tabaquismo y 80 por ciento de alcoholismo. La localización del tumor predominó en el un tercio inferior del esófago y cardias, seguido por tercio medio y el tercio superior. Presentaron desnutrición leve 4,1 por ciento, 53,9 por ciento moderada y 42 por ciento grave. Todos presentaron disminución de la albúmina y 57,9 por ciento, la capacidad funcional disminuida. Todos recibieron consejería dietética y dietoterapia orientada. Se incrementó la supervivencia en 14 meses en los casos paliativos y a 39 meses en los resectivos, comparado con un periodo anterior sin la presencia del grupo de apoyo nutricional. Conclusiones: la valoración nutricional debe ser parte de la evaluación clínica de los pacientes con cáncer de esófago desde el momento del diagnóstico y durante la enfermedad, para identificar y corregir el déficit nutricional, mantener y preservar el peso. Esto mejora la respuesta a los distintos tratamientos oncológicos, aumenta la supervivencia y mejora la calidad de vida(AU)

Introduction: esophageal cancer is a malignancy of the digestive tract with the worst prognosis. Its treatment constitutes a challenge in the case of patients with nutritional deterioration and inability to ingest food. Most of them are candidates for palliative treatment. Objective: to describe the experience regarding the nutritional care of patients with esophageal cancer and cardias, with the introduction of the nutritional support group at Comandante Manuel Fajardo University Hospital. Method: 126 patients with esophageal cancer and cardia presented: 51 of them with resectable lesions and who underwent esophagectomy, and 75 with advanced cancer and palliative interventions, treated from 2006 to 2015, according to the performance protocols of the nutritional support group. Results: all patients were at age 46-76 years (69 percent over 60 years), 87.3 percent were male, 90 percent had a history of smoking and 80 percent of alcohol. The predominant location of the tumor was the third-lower esophagus and the cardia, followed by the middle and upper thirds. They had mild malnutrition (4,1 percent), 53,9 percent had moderate and 42 percent, severe malnutrition. All of them showed decreased albumin and 57,9 percent showed decreased functional capacity. All of them received dietary counseling and oriented diet therapy. Survival after 14 months was increased in the palliative cases and after 39 months in respective cases, compared with a previous period without the presence of the nutritional support group. Conclusions: nutritional assessment should be part of the clinical evaluation of patients with esophageal cancer from the time of diagnosis and during illness, in order to identify and correct nutritional deficit, maintain and preserve the weight, thus improving response to cancer treatments, and increasing survival, which improves quality of life(AU)

Surgery versus endoscopic therapies for early cancer and high-grade dysplasia in the esophagus: a systematic review

ABSTRACT Background Esophageal cancer occurs as a local disease in 22% of cases, and a minority of this disease is limited to the mucosa or submucosa (early lesions). Endoscopic mucosal resection, endoscopic submucosal dissection, photodynamic therapy, laser therapy, and argon plasma coagulation have emerged as alternatives to surgical resection for early lesions. Objective The aim of this systematic review is to identify studies that statistically compare survival, disease-free survival, morbidity and mortality associated with the procedure, and mortality associated with cancer in the endoscopic versus surgical therapies. Data sources A systematic review using MEDLINE, COCHRANE, EMBASE, EBSCO, LILACS, Library University of Sao Paulo, BVS, and SCOPE. Study selection Randomized controlled trial, controlled clinical trial, clinical trial, and cohort study. Criteria - Studies that statistically compare survival, disease-free survival, morbidity and mortality associated with the procedure, and mortality associated with cancer in patients who underwent endoscopic and surgical therapy for early lesions of esophageal cancer. Data extraction Independent extraction of the articles by two authors using predefined data fields, including study quality indicators. Limitation Only retrosprospective cohort studies comparing the endoscopic and surgical therapies were recovered. Results The survival rates after 3 and 5 years were different and exhibited superiority with the surgical therapies over time. Endoscopy is superior in the control of mortality related to cancer with a high rate of disease recurrence. With regard to the comorbidity and the mortality associated with the procedure, endoscopy is superior. Conclusion There is no evidence from clinical trials. In this systematic review, surgical therapies showed superiority for survival, and endoscopic therapies showed superiority in the control of mortality related to cancer with a high rate of disease recurrence; also, for the comorbidity and the mortality associated with the procedure, endoscopy is superior. Prospective, controlled trials with large sample sizes are necessary to confirm the results of the current analysis.

RESUMO Contexto Cerca de 22% dos casos de câncer esofágico ocorrem como uma doença local e uma minoria é considerada lesão precoce, isto é, está limitada à mucosa ou submucosa. A ressecção endoscópica da mucosa, dissecção endoscópica da submucosa, a terapia fotodinâmica, a terapia laser e coagulação com plasma de argônio se desenvolveram como alternativas à ressecção cirúrgica para lesões precoces. Objetivo O objetivo desta revisão sistemática é identificar estudos que comparam terapia endoscópica com terapia cirúrgica, quanto à sobrevivência, à sobrevivência livre de doença, à morbidade e a mortalidade associada ao procedimento e a mortalidade associada ao câncer. Fontes de dados - Revisão sistemática utilizando MEDLINE, COCHRANE, EMBASE, EBSCO, LILACS, Biblioteca da Universidade de São Paulo, BVS e ESCOPE. Seleção de estudo Estudo randomizado controlado, ensaio clínico e estudo de coorte. Critérios Estudos que comparam a sobrevivência, a sobrevivência livre de doença, a morbidade e a mortalidade associadas ao procedimento e mortalidade associada ao câncer na endoscópica e terapia cirúrgica para lesões precoces de câncer de esôfago. Extração de dados Extração independente de artigos com dois autores usando campos de dados pré-definidos, incluindo indicadores de qualidade do estudo. Limitação Somente estudos de coorte retrospectivos comparando endoscopia e a cirurgia foram recuperados. Resultados As taxas de sobrevida após 3 e 5 anos foram diferentes e mostrou-se superioridade das terapias cirúrgicas em relação às endoscópicas ao longo do tempo. A endoscopia é superior no controle da mortalidade relacionada ao câncer com alta taxa de recorrência da doença. Em relação à morbidade e mortalidade associadas ao procedimento, a endoscopia é superior. Conclusão Não há evidências de ensaios clínicos. Esta revisão sistemática mostrou superioridade na sobrevivência das terapias cirúrgicas. As terapias endoscópicas evidenciam superioridade no controle da mortalidade relacionada ao câncer com uma alta taxa de recorrência da doença. Além disso, a endoscopia correlaciona-se com menor morbidade e mortalidade associadas à intervenção. Ensaios controlados com grandes amostras são necessários para confirmar os resultados da análise atual.

Quality of life after oesophagectomy in patients with carcinoma of oesophagus: A prospective study.

Background: The present study was done to see if quality of life improves following oesophagectomy for carcinoma of oesophagus. Materials and Methods: This was a prospective study done from June 2007 to July 2009. All patients undergoing oesophagectomy and cervical anastomoses for squamous cell carcinoma and adenocarcinoma of oesophagus were included in the study. Quality of life assessment was done using EORTC QLQ C-30 and its oesophagus specific module (OES-18) before surgery and at 3, 6, 9 and 12 months. Results: There were 55 patients who underwent oesophagectomy for carcinoma of oesophagus. On the EORTC functional scale it was noted that patients undergoing transhiatal oesophagectomy showed significant improvement of emotional function only. Patients undergoing transthoracic oesophagectomy showed a decrease in functional scores in the first three months which improved later but this change was not significant. On the EORTC symptom scale, patients undergoing transhiatal oesophagectomy showed significant improvement of constipation but not in other symptoms. Patients undergoing transthoracic oesophagectomy showed an increase in symptoms for the first three months followed by a decrease which was significant with respect to scores for constipation and pain. On the EORTC oesophagus specific symptom scores, patients in both groups showed significant improvement of dysphagia and eating. Conclusion: Patients with carcinoma of oesophagus undergoing transhiatal oesophagectomy may not show significant improvement in quality of life. However there will be significant improvement in dysphagia and eating. Patients undergoing transthoracic oesophagectomy may show an initial decrease in the quality of life.

Neoadjuvant cheooradiotherapy and surgery compaed with surgery alone in squamoous cell carcinoma of the esophagus / Radioterapia e quimioterapia neoadjuvantes e cirurgia comparado com a cirurgia no tratamento do carcinoma epidermoide do esofago

Context Despite progress in recent years in methods of diagnosis and surgical treatment of esophageal cancer, there is still controversy about the benefits from neoadjuvant chemoradiotherapy. Objective To analise the survival of patients submitted to esophagectomy for squamous cell carcinoma of the esophagus with or without neoadjuvant chemoradiotherapy. Method A retrospective, non-randomized study conducted using the medical charts of patients operated for squamous cell carcinoma of the esophagus at the School of Medical Sciences, University of Campinas (UNICAMP), Campinas, São Paulo, Brazil between 1979 and 2006. The Kaplan-Meier analysis was used to calculate survival curves and the log-rank test to compare data in each group. The significance level was settled as 5%. Results A total of 123 patients were evaluated in this study, divided into three groups: I - 26 (21.2%) patients submitted to esophagectomy alone; II - 81 (65.8%) patients submitted to neoadjuvant radiotherapy plus esophagectomy and III - 16 (13%) patients submitted to neoadjuvant chemoradiotherapy plus esophagectomy. A statistically significant survival was recorded between the groups (log rank = 6.007; P = 0.05), survival being greatest in the group submitted to neoadjuvant chemoradiotherapy, followed by the group submitted to neoadjuvant radiotherapy compared to the group submitted to esophagectomy alone as the initial treatment of choice. Conclusion Radiotherapy and chemotherapy neoadjuvants in patients with squamous cell carcinoma of the esophagus offers benefits and increases survival. .

Contexto Apesar dos progressos realizados nos últimos anos em métodos de diagnóstico e tratamento cirúrgico do câncer de esôfago, ainda há controvérsias sobre os benefícios reais da quimioradioterapia neoadjuvante. Objetivo Avaliar o tempo de sobrevida em pacientes operados de carcinoma de células escamosas do esôfago com ou sem quimioradioterapia neoadjuvante. Método Estudo retrospectivo, não randomizado, realizado com os prontuários dos pacientes submetidos a esofagectomia por carcinoma de células escamosas do esôfago na Faculdade de Ciências Médicas da Universidade de Campinas (UNICAMP), Campinas, São Paulo, Brasil, entre 1979 e 2006. Na análise estatística, o estimador de Kaplan-Meier foi utilizado para calcular as curvas de sobrevivência e do teste log-rank para comparar a sobrevivência em cada grupo. O nível de significância foi estabelecido em 5%. Resultados O total de 123 pacientes foi avaliado neste estudo, dividido em três grupos: I - 26 (21,2%) pacientes submetidos a esofagectomia, II - 81 (65,8%) pacientes submetidos a radioterapia neoadjuvante seguido de esofagectomia e III - 16 (13%) submetidos a quimioradioterapia neoadjuvante seguido de esofagectomia. Diferença estatisticamente significativa na sobrevida foi registrado entre os grupos (log rank = 6,007, P = 0,05), tendo maior sobrevida o grupo submetido a quimioradioterapia neoadjuvante, seguida pelo grupo submetido a radioterapia neoadjuvante em comparação com o grupo submetido a esofagectomia apenas como o tratamento inicial de escolha. Conclusão A radioterapia e a quimioterapia neoadjuvantes em pacientes com carcinoma de células escamosas do esôfago oferecem benefícios e aumenta a sobrevida. .

Efeitos da intervenção nutricional pós-operatória com vitaminas do complexo B sobre os indicadores metabólicos da via sulfurada e a sobrevida de pacientes com câncer de esôfago / Effects of postoperative with vitamins nutritional intervention B on metabolic indicators of sulfur via the survival of patients with esophageal cancer

Em cada célula existe uma batalha entre a produção de componentes oxidantes provenientes do metabolismo aeróbico e antioxidantes enzimáticos e não enzimáticos naturais. Entre eles, há os compostos sulfurados. O estresse oxidativo desenvolve um papel chave na produção de processos patológicos crônicos como câncer oral. Em uma revisão não sistemática da literatura disponível nós verificamos que o câncer de esôfago é conhecido por sua marcada variação por regiões geográficas e etnia racial e diferenças dietéticas o que poderia contribuir com algumas destas disparidades. Deficiências nutricionais de frutas frescas, vegetais e fibras dietéticas são comumente referidas associadas com a presença de câncer de esôfago. Alem disso, consumo pesado de bebidas alcoólicas de tabaco, e outros riscos de câncer podem interferir no consumo de vitaminas lipossolúveis e hidrossolúveis e componentes dietéticos com potencial efeito anticancerígeno...

In every cell, there is an ongoing battle between the production of oxidants components from the aerobic metabolism and the antioxidants of enzymatic and nonenzymatic nature. Among the later are the sulfur-containing compounds. The oxidative stress plays a key role in production of chronic pathological processes such as oral cancer. In a non-systematic review of the available literature we found that esophageal cancer is known for its marked variation by geographic regions and race ethnicity and the dietary differences may account for at least some of these disparities. Nutritional deficits in fresh fruits, vegetables and dietary fiber are commonly referred as associated with the presence of esophagus cancer. Moreover heavy consumption of alcoholic beverages and tobacco, the other risk factors for the cancer, can interfere with the consumption of liposoluble and hydrosoluble vitamins and dietary components with potential anti-carcinogenic effects...

Prótesis Choostent como método de paliación de la disfagia secundaria a patología maligna / Use of Choostent prosthetic device for palliation of dysphagia secondary to esophageal cancer

Background: Esophageal cancer causes disabling dysphagia and swallowing problems. Aim: To prospectively analyze the outcome of the insertion of a covered self-expanding metallic Choostent type prosthesis as a method of palliation of dysphagia, esophageal fistula or leak secondary to malignant disease of the esophagus or cardia. Material and Methods: A total of 30 consecutive patients aged 75 +/- 8.8 years (63 percent males) with malignant disease of the esophagus or cardia were studied. Results: In 27 patients (90 percent) the stenosis was located in the esophagus, in two (6.7 percent) at the gastroesophageal junction and in one (3.3 percent) at the esophago - jejunal anastomosis due to tumor recurrence. In 24 cases (80 percent), the indication of the prosthesis was dysphagia, in three (10 percent) the presence of a tracheo-esophageal fistula and in the remaining three (10 percent), the suspicion of a perforation. Patients were followed until death. The prosthesis was inserted without incidents in 29 patients (96.6 percent). One patient had a pneumomediastinum, which evolved favorably. Dysphagia subsided in all patients. Early evolution was satisfactory in 12 patients (66.7 percent). The most common early complication was a transient chest pain in 3 cases (10 percent). Four patients (13.3 percent) died within 30 days post procedure. Of the remaining 26 patients, 14 (53.8 percent) had late complications (recurrence of dysphagia in 42 percent and hemorrhage in 11 percent). The mean interval between stent insertion and death was 169 +/- 142.5 days. Conclusions: The Choostent esophageal prosthesis improves dysphagia immediately and safely. However, its use is associated with a high rate of late complications, directly related to prosthetic dysfunction.

Objetivo: Analizar en forma prospectiva los resultados de la inserción de una prótesis metálica autoexpandible cubierta tipo Choostent como método de paliación de la disfagia, fístulas o fugas esofágicas secundarias a patología maligna del esófago o cardias. Material y Método: Se estudiaron un total de 30 pacientes consecutivos portadores de patología maligna del esófago o de cardias. La edad promedio fue de 75 +/- 8,8 años. 19 (63,3 por ciento) eran del género masculino. En 27 pacientes (90 por ciento) la estenosis comprometía el esófago, en 2 (6,7 por ciento) la unión gastroesofágica y en 1 (3,3 por ciento) la anastomosis esófago yeyunal por recidiva tumoral. En 24/30 casos (80 por ciento), la indicación de la prótesis fue la disfagia, en 3 (10 por ciento) la presencia de fístula esófago-traqueal y en los 3 restantes (10 por ciento), la sospecha de perforación. Los pacientes fueron controlados hasta su fallecimiento. Resultados: La prótesis se insertó sin incidentes en 29/30 pacientes (96,7 por ciento). Un caso (3 por ciento) presentó neumo-mediastino, que evolucionó favorablemente. La disfagia cedió en la totalidad de los enfermos. La evolución precoz fue satisfactoria en 12/30 pacientes (40 por ciento), siendo la complicación precoz más frecuente el dolor torácico transitorio en 3 casos (10 por ciento). Fallecieron precozmente 4 enfermos (13,3 por ciento). De los 26 restantes, en 14 (53,8 por ciento) se presentaron complicaciones tardías, siendo las más frecuentes la recidiva de la disfagia (42,3 por ciento) y la hemorragia (11,5 por ciento). Conclusión: Las prótesis Choostent mejoran la disfagia en forma inmediata y segura. Son efectivas en el manejo de las fístulas traqueo-esofágicas y perforaciones. Sin embargo, su uso se asocia a una alta tasa de morbilidad tardía directamente relacionada a la disfunción protésica.

Esofagectomía transhiatal y ascenso gástrico en el tratamiento de las neoplasias malignas esofágicas / Transhiatal esophagectomy and gastric elevation in the treatment of malignat neoplasm of esophagus

Se evalúa la esofagectomía transhiatal y el ascenso gástrico como alternativa terapéutica en veintiún pacientes concarcinoma de esófago. La edad promedio fue de 60,52 ± 9,64 años, de los cuales catorce pacientes (66,66%)pertenecieron al sexo masculino y siete pacientes al sexo femenino (33,33%). En los pacientes sometidos a ascensogástrico la complicación peroperatoria más frecuente fue la ruptura unilateral y bilateral de la pleura, y las complicaciones posoperatorias más frecuentes la presencia de estenosis de la anastomosis cervical (23,80%) la fístula cervical (14,28%), con una mortalidad de 19,04% asociadasa complicaciones infecciosas en tres pacientes (14,28%). La esofagectomía transhiatal es una de las técnicas quirúrgicas en el tratamiento de las neoplasias esofágicas; sin embargo, no está exenta de complicaciones tales como estenosis de la anastomosis y fístula cervical, es necesaria una adecuada preparación nutricional preoperatoria para disminuir la presencia de complicaciones posoperatorias

In this study the transhiatal esophagectomy is evaluated as therapeutic alternative in twenty-one patients with esophagus carcinoma. The average age of the patients was 60,52 ± 9,64 years, fourteen patients (66.66%) were male and seven patients female. In the patients with transhiatal esophagectomy the peroperative complication more frequent was the unilateral and bilateral rupture of the pleura, and the most frequent postoperatory complications was the cervical anastomosis stenosis (23.80%) and the cervical leakage (14.28%), with a mortality of 19.04%associated with infectious complications in three patients (14.28%). The transhiatal esophagectomy is one of the surgical procedures in the treatment esophageal neoplasm but is important consider the possibility of complications as cervical stenosis and cervical leakage and is necessary and adequate nutritional preoperative preparation to avoid complications as cervical stenosis and anastomosis leakage and is required an adequate preoperatory preparation to reduce the incidence of postoperative complications

Photodynamic Therapy: Establishing Its Role in Palliation of Advanced Esophageal Cancer

No abstract available.