The Role of the Heat-Shock Proteins in Esophagogastric Cancer.

Heat-shock proteins (HSPs) are a family of proteins that have received considerable attention over the last several years. They have been classified into six prominent families: high-molecular-mass HSP, 90, 70, 60, 40, and small heat shock proteins. HSPs participate in protein folding, stability, and maturation of several proteins during stress, such as in heat, oxidative stress, fever, and inflammation. Due to the immunogenic host's role in the combat against cancer cells and the role of the inflammation in the cancer control or progression, abnormal expression of these proteins has been associated with many types of cancer, including esophagogastric cancer. This study aims to review all the evidence concerning the role of HSPs in the pathogenesis and prognosis of esophagogastric cancer and their potential role in future treatment options. This narrative review gathers scientific evidence concerning HSPs in relation to esophagus and gastric cancer. All esophagogastric cancer subtypes are included. The role of HSPs in carcinogenesis, prognostication, and therapy for esophagogastric cancer are discussed. The main topics covered are premalignant conditions for gastric cancer atrophic gastritis, Barrett esophagus, and some viral infections such as human papillomavirus (HPV) and Epstein-Barr virus (EBV). HSPs represent new perspectives on the development, prognostication, and treatment of esophagogastric cancer.

Is early extubation after esophagectomy safe? A systematic review and meta-analysis.

There is no consensus on the timing of extubation after esophagectomy. There is a fear that premature extubation may result in a high risk of urgent reintubation. On the other hand, there is a risk of lung damage in prolonged intubation. The present systematic review compares early and late extubation. Five articles were selected. Early extubation after esophagectomy does not increase the risk of reintubation, mortality, complications, and length of stay.

Consumo de erva-mate em altas temperaturas e sua possível relação com o Carcinoma Esofagiano de Células Escamosas / Consumption of yerba mate at high temperatures and its possible relationship with Esophageal Squamous Cell Carcinoma

Introdução: Em relação aos tipos histológicos do câncer de esôfago, podemos apresentar o adenocarcinoma e o carcinoma de células escamosas, sendo que 90% dos casos de câncer de esôfago em todo o mundo são do segundo tipo citado. Tem-se relatado uma associação entre o desenvolvimento de câncer de esôfago de células escamosas com o consumo de bebidas em altas temperaturas, mais especificamente em temperaturas igual ou superiores a 65ºC. O trabalho terá como objeto de estudo o consumo de mate por infusão de líquidos em altas temperaturas, presente nas tradições de diversas regiões, como no Sul do Brasil, Uruguai e Argentina, locais onde se concentraram os estudos dessa obra. Objetivo: O objetivo desse trabalho é apresentar os dados mais atuais no que abrange os assuntos relacionados à associação do câncer de esôfago com o consumo de bebidas em altas temperaturas. Metodologia: Trata-se de uma revisão bibliográfica, de caráter analítico comparativo, baseado em artigos científicos datados de 2000 a 2018. Discussão: Quase todos os autores concordam com a possível associação do consumo de bebidas em altas temperaturas com o desenvolvimento de câncer de esôfago de células escamosas, devido à injuria térmica ocasionada. Conclusão: Foi possível identificar uma relação positiva entre o consumo de bebidas quentes e o desenvolvimento de câncer de esôfago de células escamosas em animais experimentais, porem para humanos essa associação ainda não é bem documentada, mas já existem estudos recentes que fortificam essa relação positiva, fornecendo uma oportunidade para a realização de novos estudos na área.

Dissecção endoscópica submucosa com incisão circunferencial versus túnel submucoso no tratamento da neoplasia superficial do esôfago / Endoscopic submucosal dissection with circumferential incision versus tunneling method for treatment of superficial esophageal cancer

ABSTRACT BACKGROUND: Endoscopic submucosal dissection (ESD) of esophageal superficial neoplasm is associated with a high en bloc R0 resection rate and low recurrence. OBJECTIVE: We aim to compare the performance and clinical outcomes of ESD via ESD after circumferential incision (ESD-C) versus submucosal tunneling (ESD-T). METHODS: Single-center retrospective analysis of all consecutive patients who underwent ESD for superficial esophageal cancer, between 2009 and 2018. ESD-T was defined as the technique of making the mucosal incisions followed by submucosal tunneling in the oral to anal direction. ESD-C consisted of completing a circumferential incision followed by ESD. Main study outcomes included en bloc and R0 resection rates. Secondary outcomes included procedural characteristics, curative resection rate, local recurrence and adverse events. RESULTS: A total of 65 procedures (23 ESD-T and 42 ESD-C) were performed for ESCC (40; 61.5%) and BE-neoplasia (25; 38.5%). There were no statistically significant differences between patients who underwent ESD-T versus ESD-C in en bloc (91.3% vs 100%, P=0.12), R0 (65.2% vs 78.6%, P=0.24), curative resection rates (65.2% vs 73.8%, P=0.47) and mean procedure time (118.7 min with vs 102.4 min, P=0.35). Adverse events for ESD-T and ESD-C were as follows: bleeding (0 versus 2.4%; P=0.53), perforation (4.3% vs 0; P=0.61), esophageal stricture (8.7% versus 9.5%; P=0.31). Local recurrence was encountered in 8.7% after ESD-T and 2.4% after ESD-C (P=0.28) at a mean follow-up of 8 and 2.75 years, respectively (P=0.001). CONCLUSION: ESD-T and ESD-C appear to be equally effective with similar safety profiles for the management of superficial esophageal neoplasms.

RESUMO CONTEXTO: A dissecção endoscópica submucosa (DES) no tratamento da neoplasia superficial do esôfago está associada a uma alta taxa de ressecção R0 em bloco e baixa taxa de recorrência. OBJETIVO: O objetivo deste estudo é comparar o desempenho e os resultados clínicos da DES com incisão circunferencial (DES-C) versus com DES com túnel submucoso (DES-TS). MÉTODOS: Estudo retrospectivo de banco de dados coletados prospectivamente de um centro especializado em DES, investigando pacientes consecutivos submetidos à DES por câncer de esôfago superficial, entre 2009 e 2018. DES-TS foi definida como a técnica de realizar primeiro incisões na mucosa seguida de tunelamento submucoso no sentido oral para anal. DES-C consistiu em completar uma incisão circunferencial seguida da dissecção submucosa. As principais variáveis do estudo incluíram taxas de ressecção em bloco e R0. Os resultados secundários incluíram características do procedimento, taxa de ressecção curativa, recorrência local e eventos adversos. RESULTADOS: Um total de 65 procedimentos (23 DES-TS e 42 DES-C) foram realizados para CCE de esôfago (40; 61,5%) e neoplasia associada ao EB (25; 38,5%). Não houve diferenças estatisticamente significativas entre os pacientes submetidos a DES-TS versus DES-C nas taxas de ressecção em bloco (91,3% vs 100%, P=0,12), R0 (65,2% vs 78,6%, P=0,24), taxas de ressecção curativa (65,2% vs 73,8%, P=0,47) e tempo médio do procedimento (118,7 min com vs 102,4 min, P=0,35). Os eventos adversos para DES-TS e DES-C foram os seguintes: sangramento (0 vs 2,4%; P=0,53), perfuração (4,3% vs 0; P=0,61), estenose esofágica (8,7% vs 9,5%; P=0,31). A recorrência local foi encontrada em 8,7% após DES-TS e 2,4% após DES-C (P=0,28) em um seguimento médio de 8 e 2,75 anos, respectivamente (P=0,001). CONCLUSÃO: DES-TS e DES-C demostram ser igualmente eficazes com perfil de segurança semelhante para o tratamento das neoplasias superficiais do esôfago.

Neoadjuvant therapy or upfront surgery? A systematic review and meta-analysis of T2N0 esophageal cancer treatment options.

BACKGROUND: Esophageal carcinoma usually shows poor long-term survival rates, even when esophagectomy, the standard curative treatment is performed. As a result, there has been increasing interest in the neoadjuvant therapy, which could potentially downstage cancer, eliminate micrometastasis and ergo increase resectability and curative (R0) resection. Currently, for the earliest stage esophageal cancers, most guidelines point out to the role of endoscopic treatment, and for T1bN0 upfront surgery. For locally advanced cases, several studies have demonstrated the benefits of neoadjuvant therapy to increase resectability. For clinical stage T2N0 esophageal cancer, there is no consensus as to the optimal treatment strategy. METHODS: A systematic review and meta-analysis was performed to compare neoadjuvant therapy with surgery alone on clinical stage T2N0 esophageal cancer patients, concerning overall survival, recurrence, post-operative mortality, anastomotic leak, and R0 resection rate. RESULTS: For overall survival at the mean follow-up point, the neoadjuvant therapy was not associated to a higher probability of survival than upfront surgery in cT2N0 patients (risk difference: 0.00; 95% CI: -0.09, 0.09). There was no difference between neoadjuvant therapy and primary surgery concerning recurrence (risk difference: 0.21; 95% CI: -0.03, 0.45); perioperative mortality (risk difference: 0.00; 95% CI: -0.02, 0.01); and risk for anastomotic leak (risk difference: -0.08; 95% CI: -0.21, 0.05). Pooled data showed that neoadjuvant therapy was associated to a higher risk for positive margins after resection (risk difference: 0.04; 95% CI: 0.02, 0.06). CONCLUSIONS: This review showed that neoadjuvant therapy is not associated to better results than surgery alone, for the management of clinical stage T2N0 esophageal cancer patients, concerning overall survival, recurrence rate, perioperative mortality, anastomotic leak, and seems to be associated to a higher risk for resection with positive margins.

Narrow band imaging versus lugol chromoendoscopy to diagnose squamous cell carcinoma of the esophagus: a systematic review and meta-analysis.

BACKGROUND: In the early stage esophageal cancer, changes in the mucosa are subtle and pass unnoticed in endoscopic examinations using white light. To increase sensitivity, chromoscopy with Lugol's solution has been used. Technological advancements have led to the emergence of virtual methods of endoscopic chromoscopy, including narrow band imaging (NBI). NBI enhances the relief of the mucosa and the underlying vascular pattern, providing greater convenience without the risks inherent to the use of vital dye. The purpose of this systematic review and meta-analysis was to evaluate the ability of NBI to diagnose squamous cell carcinoma of the esophagus and to compare it to chromoscopy with Lugol's solution. METHODS: This systematic review included all studies comparing the diagnostic accuracy of NBI and Lugol chromoendoscopy performed to identify high-grade dysplasia and/or squamous cell carcinoma in the esophagus. In the meta-analysis, we calculated and demonstrated sensitivity, specificity, and positive and negative likelihood values in forest plots. We also determined summary receiver operating characteristic (sROC) curves and estimates of the areas under the curves for both per-patient and per-lesion analysis. RESULTS: The initial search identified 7079 articles. Of these, 18 studies were included in the systematic review and 12 were used in the meta-analysis, for a total of 1911 patients. In per-patient and per-lesion analysis, the sensitivity, specificity, and positive and negative likelihood values for Lugol chromoendoscopy were 92% and 98, 82 and 37%, 5.42 and 1.4, and 0.13 and 0.39, respectively, and for NBI were 88 and 94%, 88 and 65%, 8.32 and 2.62, and 0.16 and 0.12, respectively. There was a statistically significant difference in only specificity values, in which case NBI was superior to Lugol chromoendoscopy in both analyses. In the per-patient analysis, the area under the sROC curve for Lugol chromoendoscopy was 0.9559. In the case of NBI, this value was 0.9611; in the per-lesion analysis, this number was 0.9685 and 0.9587, respectively. CONCLUSIONS: NBI was adequate in evaluating the esophagus in order to diagnose high-grade dysplasia and squamous cell carcinoma. In the differentiation of those disorders from other esophageal mucosa alterations, the NBI was shown to be superior than Lugol.

Prognostic factors and survival analysis in esophageal carcinoma / Fatores prognósticos e análise de sobrevida no carcinoma esofágico

ABSTRACT Background: Despite recent advances in diagnosis and treatment, esophageal cancer still has high mortality. Prognostic factors associated with patient and with disease itself are multiple and poorly explored. Aim: Assess prognostic variables in esophageal cancer patients. Methods: Retrospective review of all patients with esophageal cancer in an oncology referral center. They were divided according to histological diagnosis (444 squamous cell carcinoma patients and 105 adenocarcinoma), and their demographic, pathological and clinical characteristics were analyzed and compared to clinical stage and overall survival. Results: No difference was noted between squamous cell carcinoma and esophageal adenocarcinoma overall survival curves. Squamous cell carcinoma presented 22.8% survival after five years against 20.2% for adenocarcinoma. When considering only patients treated with curative intent resection, after five years squamous cell carcinoma survival rate was 56.6 and adenocarcinoma, 58%. In patients with squamous cell carcinoma, poor differentiation histology and tumor size were associated with worse oncology stage, but this was not evidenced in adenocarcinoma. Conclusion: Weight loss (kg), BMI variation (kg/m²) and percentage of weight loss are factors that predict worse stage at diagnosis in the squamous cell carcinoma. In adenocarcinoma, these findings were not statistically significant.

RESUMO Racional: Apesar dos avanços recentes nos métodos diagnósticos e tratamento, o câncer de esôfago mantém alta mortalidade. Fatores prognósticos associados ao paciente e ao câncer propriamente dito são pouco conhecidos. Objetivo: Investigar variáveis prognósticas no câncer esofágico. Métodos: Pacientes diagnosticados entre 2009 e 2012 foram analisados e subdivididos de acordo com tipo histológico (444 carcinomas espinocelulares e 105 adenocarcinomas), e então características demográficas, anatomopatológicas e clínicas foram analisadas. Resultados: Não houve diferença entre os dois tipos histológicos na sobrevida global. Carcinoma espinocelular apresentou sobrevida de 22,8% em 5 anos, contra 20,2% de adenocarcinoma. Quando considerado somente os tratados com operação com intenção curativa, sobrevida em cinco anos foi de 56,6% para espinocelular e 58% para adenocarcinoma. Para o subtipo espinocelular, tumores pouco diferenciados e extensão tumoral mostraram associação com pior estadiamento oncológico, o que não foi verificado para adenocarcinoma. Conclusão: Perda de peso, variação de IMC e porcentagem de perda de peso foram fatores associados ao pior estadiamento oncológico para espinocelular, o que não se confirmou para adenocarcinoma.

Occult esophageal squamous cell carcinoma with metastases to the spine and central nervous system.

Esophageal malignancy encompasses a group of diseases that are mostly represented by the squamous cell carcinoma and the adenocarcinoma. Quite frequently, these neoplasms present aggressive behavior; therefore, the diagnosis is often made when the condition is in advanced stages. Dysphagia is the typical clinical complaint, although it is present only when most of the lumen is obstructed. Therefore, quite often, the metastatic disease is first diagnosed, which contributes to the patient's poor survival expectancy. The authors report the case of a 58-year-old man who looked for medical care complaining of a long-term history of scapular pain. The diagnostic work-up disclosed a cervical spine lytic lesion surrounded by a tumoral mass shown by computed tomography. The cervical tumor was sampled by fine needle aspiration, revealing an undifferentiated carcinoma. The outcome was unfavorable and the patient died. The autopsy findings revealed metastatic disease to the spine and central nervous system, and the primary tumor was found to be an esophageal squamous cell carcinoma, which had progressed without typical dysphagia.

Impact of minimally invasive surgery in the treatment of esophageal cancer / Impacto da cirurgia minimamente invasiva no tratamento de câncer de esôfago

BACKGROUND: Surgical treatment of esophageal cancer is associated to a high morbidity and mortality rate. The open transthoracic or transhiatal esophagectomy are considerably invasive procedures and have been associated to high rates of complications and operative mortality. In this way, minimally invasive esophageal surgery has been suggested as an alternative to the classic procedures because would produce improvement in clinical longterm postoperative outcomes. AIM: To assess survival, mortality and morbidity results of esophagectomy due to esophageal cancer submitted to minimally invasive techniques and compare them to results published in international literature. METHOD: An observational, prospective study. Between 2003 and 2012, 69 patients were submitted to a minimally invasive esophagectomy due to cancer. It was recorded postoperative morbidity and mortality according to the Clavien-Dindo classification. The survival rate was analyzed with the Kaplan-Meier method. The number of lymph nodes obtained during the lymph node dissection, as an index of the quality of the surgical technique, was analysed. RESULTS: 63.7% of patients had minor complications (type I-II Clavien Dindo), while nine (13%) required surgical re-exploration. The most common postoperative complication corresponded to leak of the cervical anastomosis seen in 44 (63.7%) patients but without clinical repercusion, only two of them required reoperation. The mortality rate was 4.34%, and reoperation was necessary in nine (13%) cases. The average survival time was 22.59±25.38 months, with the probability of a 3-year survival rate estimated at 30%. The number of resected lymph nodes was 17.17±9.62. CONCLUSION: Minimally invasive techniques have lower morbidity and mortality rate, very satisfactory lymphnodes resection and similar long term outcomes in term of quality of life and survival compared to results observed after open surgery. .

RACIONAL: O tratamento cirúrgico do câncer de esôfago está associado com alta morbidade e mortalidade. Os acessos transtorácicos abertos ou os transmediastinais são considerados procedimentos invasivos e têm sido associados à altas taxas de complicações e de mortalidade operatória. Desta forma, a operação do esôfago minimamente invasiva tem sido sugerida como alternativa aos procedimentos clássicos, porque iria produzir melhora no desempenho pós-operatório a longo prazo. OBJETIVO: Avaliar a sobrevida, mortalidade e morbidade da esofagectomia por câncer de esôfago submetidos às técnicas minimamente invasivas e compará-los com os resultados publicados na literatura internacional. MÉTODO: Estudo observacional, prospectivo. Entre 2003 e 2012, 69 pacientes foram submetidos à esofagectomia minimamente invasiva devido ao câncer. Foram analisadas morbidade e mortalidade pós-operatória de acordo com a classificação Clavien-Dindo. A taxa de sobrevivência foi analisada pelo método de Kaplan-Meier. O número de nódulos linfáticos obtidos durante a dissecção do nódulo linfático foi analisado como um índice da qualidade da técnica cirúrgica. RESULTADOS: 63,7% dos pacientes tiveram complicações menores (tipo I-II Clavien Dindo), enquanto nove (13%) necessitaram de re-exploração cirúrgica. A complicação pós-operatória mais comum correspondeu a deiscência da anastomose cervical observada em 44 (63,7%) pacientes, mas sem suas repercussões clínicas, apenas dois deles necessitaram de reoperação. A taxa de mortalidade foi de 4,34%, e reoperação foi necessária em nove (13%) casos. O tempo médio de sobrevivência foi de 22,59±25,38 meses, com a probabilidade de uma taxa de sobrevida em três anos estimada em 30%. O número de linfonodos ressecados foi 17,17±9,62. CONCLUSÃO: As técnicas minimamente invasivas têm menor morbidade e mortalidade, satisfatório número de linfonodos ressecados e resultados a longo prazo semelhantes após operação aberta, em termos de qualidade ...

Frecuencia de virus papiloma humano en tumores no ginecológicos de la Región de la Araucanía, Chile / Human papilloma virus frequency in non-gynecological tumors in the Araucanía Region, Chile

El Virus Papiloma Humano (HPV por sus siglas en inglés) es una de las infecciones de transmisión sexual más frecuentes del mundo y se encuentra presente en la mayoría de los cánceres de cuello uterino. Se ha descrito su presencia en otros tipos de cáncer no ginecológicos como lo son esófago y próstata. Sin embargo, las frecuencias de HPV descritas hasta el momento para estos tipos de cáncer son muy variables, y no hay artículos donde se muestren la presencia de HPV en estas neoplasias en Chile. El objetivo de este estudio fue determinar la frecuencia de HPV en muestras de biopsias de tumores no ginecológicos y tejido inflamatorio de pacientes de la región de La Araucanía. Se extrajo DNA desde un total de 47 biopsias de pacientes con esofagitis, 25 con carcinoma escamoso esofágico, 20 con hiperplasia nodular de la próstata y 39 con adenocarcinoma prostático. Estas fueron analizadas por PCR de la región L1 del virus y posterior genotipificación por reverse line blot. Se detectó HPV en el 53,2% de las muestras de esofagitis, 48% en muestras de carcinoma escamoso esofágico, 15% en hiperplasia nodular de la próstata y un 15,4% en los casos de adenocarcinoma prostático. Siendo los más frecuentes los genotipos de HPV 16 y 18, ya sea en infecciones simples o junto con otros genotipos, en lesiones preneoplásicas y neoplásicas de los tejidos estudiados. Existe una alta frecuencia de infección por HPV en biopsias de esofagitis y tejido inflamatorio esofágico de pacientes de la región de la Araucanía. En los casos de adenocarcinoma prostático e hiperplasia nodular de la próstata se observa una baja frecuencia de HPV.

Human Papilloma Virus (HPV) is the most common sexually transmitted disease in the world and it is present in practically all cervical cancers. Its presence was described in other types of non-gynecologic cancer such as esophageal and prostate. However, HPV frequency described for these cancers is highly variable, and there are no articles describing the presence of HPV in these tumors in Chile. To determine HPV frequency in samples from biopsies of non-gynecological tumors and inflammatory tissue from patients in the Araucanía region, DNA was extracted from a total of 47 biopsies from patients with esophagitis, 25 with esophageal squamous cell carcinoma, 20 with prostate nodular hyperplasia and 39 with prostate adenocarcinoma. These were analyzed by PCR of HPV L1 region and subsequent genotyping by reverse line blot. HPV was detected in 53.2% of esophagitis samples, 48% in esophageal squamous cell carcinoma, 15% in prostatitis and 15.4% in cases of prostatic adenocarcinoma. The most frequent HPV genotypes were 16 and 18, either single or in combination with other genotype infections, in inflammatory tissue and neoplastic lesions. In patients of the Araucanía region, there is a high rate of HPV infection in biopsies obtained in esophagitis and esophageal inflammatory tissue. In cases of prostatic adenocarcinoma and prostate nodular hyperplasia a low rate of HPV was observed.

Maté consumption and the risk of esophageal squamous cell carcinoma: a meta-analysis.

Maté, a tea-like infusion of Ilex paraguariensis, is suspected to be a risk factor for esophageal squamous cell carcinoma; however, no meta-analysis on the subject has been performed to date. A meta-analysis of studies reporting the consumption of maté in patients with esophageal squamous cell carcinoma was conducted to provide a quantitative estimate of the risk of esophageal squamous cell carcinoma associated with maté consumption. A search was conducted through MEDLINE, PubMed, EMBASE, and Current Contents Connect to April 5, 2012. We calculated pooled odds ratios (ORs) and 95% confidence intervals (CIs) using a random effects model for the risk of esophageal squamous cell carcinoma associated with exposure to maté (ever- vs. never-drinkers), as well as for the dose-dependent risk of esophageal squamous cell carcinoma associated with different levels of maté consumption (highest vs. lowest intake). Nine studies, with 1565 esophageal squamous cell carcinoma cases, met our inclusion criteria. Esophageal squamous cell carcinoma was associated with exposure to maté drink, with an OR of 2.57 and a 95% CI of 1.66-3.98. There was an increased risk of esophageal squamous cell carcinoma associated with a higher consumption of maté versus low consumption (OR 2.76, 95% CI 1.33-5.73 vs. OR 1.84, 95% CI 1.12-3.00). Heterogeneity was observed in the ever versus never and the high-consumption analyses but not in the low-consumption analysis. Publication bias was present. Maté consumption was associated with an increased risk of esophageal squamous cell carcinoma.

Comparação dos tratamentos do carcinoma espinocelular avançado do esofago pela teleterapia exclusiva e pela teleterapia associada à braquiterapia / Comparison of treatment using teletherapy (external beam radiation) alone versus teletherapy combined with brachytherapy for advanced squamous cell carcinoma of the esophagus

RACIONAL: O câncer do esôfago ainda constitui neoplasia de difícil tratamento e de prognóstico muito ruim. OBJETIVO: Comparar a resposta do tratamento exclusivo com teleterapia isolada versus teleterapia associada à braquiterapia endoluminal de doentes portadores de carcinoma espinocelular avançado do esôfago. MÉTODO: Foram estudados 49 doentes portadores de carcinoma espinocelular avançado do esôfago médio em estádio clínico III (TNM). Os doentes foram divididos em dois grupos de doentes. O primeiro grupo foi submetido à teleterapia exclusiva com acelerador linear de partículas, dose média de 6000 cGy e o segundo à teleterapia na dose de 5040 cGy associada à braquiterapia endoluminal com Iridium 192 na dose de 1500 cGy. A braquiterapia foi iniciada uma a duas semanas após o término da teleterapia e dividida em três aplicações semanais de 500 cGy. Foram avaliadas as variáveis idade, sexo, raça, hábitos (tabagismo e etilismo), índice de massa corpórea (IMC), complicações com o tratamento, benefícios (melhora da dor e satisfação alimentar) e sobrevivência. RESULTADOS: Os resultados quanto a qualidade de vida (satisfação alimentar, paliação da disfagia e dor) foram melhores no grupo submetido à teleterapia associada a braquiterapia. A sobrevivência foi maior no grupo de teleterapia associada a braquiterapia. CONCLUSÃO: Apesar do índice de cura do câncer espinocelular do esôfago ser quase nulo quando tratado com irradiação isolada, esta terapêutica constitui-se em uma forma de tratamento paliativo para grande parte dos doentes em que existe contra-indicação cirúrgica.

BACKGROUND: Squamous cell carcinoma of the esophagus is still a difficult tumor to treat with very poor prognosis. AIM: To compare the response to teletherapy treatment (external beam radiotherapy) alone versus teletherapy combined with brachytherapy for patients with advanced squamous cell carcinoma of the esophagus. METHODS: Were studied 49 patients with advanced squamous cell carcinoma of the esophagus on clinical stage III (TNM-1999). They were separated into two groups. The first, underwent radiation therapy alone with linear accelerator of particles, average dose of 6000 cGy and the second to external beam radiation therapy at a dose of 5040 cGy combined with brachytherapy with Iridium 192 at a dose of 1500 cGy. Brachytherapy started one to two weeks after the end of teletherapy, and it was divided into three weekly applications of 500 cGy. Age, gender, race, habits (smoking and drinking), body mass index (BMI), complications with treatment benefits (pain relief and food satisfaction) and survival were analyzed. RESULTS: The quality of life (food satisfaction, and pain palliation of dysphagia) were better in the group treated with external beam radiation therapy combined with brachytherapy. Survival was higher in the brachytherapy combined with external beam radiation therapy alone. CONCLUSION: Although the cure rate of squamous cell cancer of the esophagus is almost nil when treated with irradiation alone, this therapy is a form of palliative treatment for most patients in whom surgical contraindication exists.

Avaliação da expressão imunoistoquímica da proteína p16INK4a no adenocarcinoma de esôfago / Protein p16INK4a immunohistochemical expression in adenocarcinoma of the esophagus

INTRODUÇÃO: O adenocarcinoma de esôfago apresenta aumento de frequência nas últimas décadas, particularmente em países desenvolvidos. O esôfago de Barrett é reconhecido como a principal lesão precursora e o estudo da sequência metaplasia-displasia-adenocarcinoma mostra a ocorrência de alterações genéticas desde suas fases mais incipientes. As alterações no p16INK4a são relatadas como frequentes no esôfago de Barrett e no carcinoma de esôfago. OBJETIVO: Verificar a prevalência da expressão imunoistoquímica da proteína p16INK4a em exames anatomopatológicos de pacientes com adenocarcinoma de esôfago. MÉTODO: A população do estudo foi constituída de 37 pacientes com adenocarcinoma de esôfago. A expressão da proteína p16 foi detectada por meio de análise imunoistoquímica, com anticorpo primário p16INK4aAb-7, clone 16P07, NeoMarkers e avaliada de acordo com o Sistema de Escore de Imunorreatividade (Immunoreactive scoring system - IRS) modificado. RESULTADOS: No grupo houve predominância de pacientes do sexo masculino (86,5 por cento) e a maioria dos casos correspondia a estádios avançados (III e IV = 67,5 por cento). Em 12 casos (32,4 por cento) foi identificada expressão imunoistoquímica da proteína p16INK4a. Não foi observada relação significativa entre a perda da expressão da proteína p16INK4a e o grau de diferenciação histológica (p=0,81) nem com o estadiamento da doença (p=0,485). CONCLUSÃO: Ocorre perda da expressão imunoistoquímica da proteína p16INK4a, corroborando as informações de que a inativação do gene p16 é um evento frequente e que pode exercer papel importante na carcinogênese do adenocarcinoma de esôfago.

BACKGROUND: The esophageal adenocarcinoma shows an increasing frequence in the last decades, specially in the developed countries. The Barrett´s esophagus is accepted as the major premalignant lesion and the metaplasia-dysplasia-adenocarcinoma sequence presents a lot of genetic changes since its early events. The alterations in p16INK4a are frequent in Barrett´s esophagus and esophageal carcinoma. AIM: To verify the prevalence of the immunohistochemical expression of the p16INK4a protein in patients with esophageal adenocarcinoma. METHODS: The study population consisted of 37 patients with resected esophageal adenocarcinoma. The p16INK4a protein expression was determined by immunohistochemistry using primary antibody p16INK4aAb-7, clone 16P07 NeoMarkers and assessed according to the Immunoreactive scoring system (IRS). RESULTS: Of 37 analyzed patients, the most were male (86,5 percent) and the advanced disease was predominant (stages III and IV = 67,5 percent). In 12 (32,4 percent) the immunohistochemistry was positive for p16INK4a.There was no significative relation between the protein expression and the degrees of histological differentiation of the biopsies and surgical especimens (p=0,81) neither with the staging (p=0,485). CONCLUSION: The lost of the immunohistochemical expression of the p16INK4a protein in this study suggests that p16 is enroled in the carcinogenesis of the adenocarcinoma of esophagus.

Estudo comparativo entre as anastomoses cervicais esofagogástrica término-terminal com e sem invaginação após esofagectomia para câncer / Comparative study of end-to-end cervical esophagogastric anastomosis with or without invagination after esophagectomy for cancer

OBJETIVO: Avaliar a incidência de fístula e estenose da anastomose esofagogástrica cervical com invaginação do coto esofágico no interior do estômago na esofagectomia para tratamento do carcinoma do esôfago. MÉTODOS: Foram estudados dois grupos de doentes com carcinoma do esôfago torácico ou abdominal submetidos à esofagectomia subtotal e esofagogastroplastia. O grupo I (estudo) foi constituído por 29 doentes operados no período de 1998 a 2007, no qual foi realizada a anastomose esofagogástrica cervical com invaginação de segmento do coto esofágico no interior do estômago. O grupo II (controle) foi constituído por 36 doentes operados no período de 1989 a 1997 submetidos à anastomose esfagogástrica cervical término-terminal sem invaginação. RESULTADOS: No grupo I, 3 (10,3 por cento) doentes apresentaram fístula da anastomose esofagogástrica com repercussão clínica mínima. No grupo II observou-se fístula com franca saída de saliva em 11 (30,5 por cento) doentes. A freqüência de fístula nos doentes do grupo I foi significantemente menor (p=0,04) do que nos do grupo II. No grupo I, estenose fibrótica da anastomose ocorreu em 7 (24,1 por cento) enfermos, ao passo que no grupo II 10 (27,7 por cento) evoluíram com estenose, não se constatando diferença significante (p=0,72) entre esses grupos. CONCLUSÃO: No tratamento do carcinoma do esôfago, a esofagectomia com anastomose esofagogástrica cervical com invaginação do coto esofágico no interior do estômago determina menor ocorrência de fístula esofagogástrica quando comparado à anastomose sem invaginação. A incidência de estenose da anastomose esofagogástrica não diferiu em ambos os grupos.

OBJECTIVE: To assess the incidence of fistula and stenosis of cervical esophagogastric anastomosis with invagination of the esophageal stump into the gastric tube in esophagectomy for esophagus cancer. METHODS: Two groups of patients with thoracic and abdominal esophagus cancer undergoing esophagectomy and esophagogastroplasty were studied. Group I comprised 29 patients who underwent cervical esophagogastric anastomosis with invagination of the proximal esophageal stump segment within the stomach, in the period of 1998 to 2007 while Group II was composed of 36 patients submitted to end-to-end cervical esophago-gastric anastomosis without invagination during the period of 1989 to 1997. RESULTS: In Group I, esophagogastric anastomosis by invagination presented fistula with mild clinical implications in 3 (10.3 percent) patients, whereas in Group II, fistulas with heavy saliva leaks were observed in 11 (30.5 percent) patients. The frequency of fistulas was significantly lower in Group I patients (p=0.04) than in Group II. In Group I, fibrotic stenosis of anastomoses occurred in 7 (24.1 percent) subjects, and 10 patients (27.7 percent) in Group II evolved with stenosis, while no significant difference (p=0.72) was found between the two groups. CONCLUSION: In esophagectomy for esophagus cancer, cervical esophagogastric anastomosis with invagination presented a lower rate of esophagogastric fistula versus anastomosis without invagination. Stenosis rates in esophagogastric anastomosis proved similar in both approach with or without invagination.

Fístula cervical pós-anastomose esofagogástrica: é possível diminuir a ocorrência? / Is it possible to reduce the fistula rate of the cervical esophagogastric anastomosis after oesophagectomy?

RACIONAL: O câncer de esôfago é a sexta causa de morte relacionada à neoplasia no Brasil, e a esofagectomia quando factível é um dos pilares do tratamento, tanto com intento curativo quanto paliativo. A fístula cervical é complicação comum do procedimento e tem incidência entre 0,8 e 47, 6 por cento. OBJETIVO: Testar a eficiência de uma alternativa técnica para a diminuição desta ocorrência. MÉTODOS: Análise prospectiva de 126 pacientes alocados em dois grupos de acordo com a técnica utilizada para a anastomose esofagogástrica cervical. O grupo A, composto por 96 pacientes, teve a anastomose cervical realizada em dois planos, camadas mucosa com sutura contínua de fio categute cromado 3-0 ou caprofyl 3-0 e seromuscular com pontos separados de seda 3-0 agulhada, de forma tradicional, após ressecção prévia das extremidades redundantes do esôfago e tubo gástrico. O grupo B, composto por 25 pacientes, foi submetido a uma variação técnica para esta anastomose, inicialmente sem a abertura da camada mucosa da extremidade redundante do tubo gástrico e coto esofágico. RESULTADOS: O grupo no qual foi efetuada a nova alternativa técnica de esofagogastroanastomose cervical apresentou incidência nula de deiscência de sutura cervical. CONCLUSÃO: A alternativa técnica proposta foi eficiente no quesito fístula por otimizar a apresentação dos planos de sutura, facilitando a confecção da anastomose, diminuindo assim as taxas desta complicação na esofagectomia.

BACKGROUND: The esophageal cancer is the 6th cause of cancer-related death in Brazil, and esophagectomy is the cornerstone of the treatment, not only for the curative cases, but with palliative intent as well. The cervical fistula is a very frequent complication of the procedure with a related incidence between 0,8 and 47,8 percent. AIM: Prospective analysis to determine the success of a new alternative technique of cervical anastomosis. METHODS: Prospective analysis of 126 patients, distributed in two groups accordingly to the cervical anastomosis technique. Group A (n=96) had cervical anastomosis in two layers, the inner continuous type and outer isolated, followed by redundant tissue. Group B (n=25) had a technical variation with suture done without mucosa opening at first. RESULTS: This alternative technique for the cervical esophagogastric anastomosis presented zero fistulas. CONCLUSION: This alternative was efficient in decrease fistula rate because it allow best exposition and visualization of the anastomosis, facilitating the suture lines.

Novas perspectivas no estadiamento e tratamento do câncer de esôfago / New perspectives in esophageal cancer staging and treatment

INTRODUÇÃO: O câncer de esôfago apresenta-se como uma das neoplasias mais freqüentes e letais. O acometimento linfático aparece como principal fator individual de pior prognóstico, sendo a esofagectomia com linfadenectomia extensa ainda seu tratamento de escolha. Ressecções mais extensas através da toracotomia estão associadas com maior sobrevida, mas apresentam altas taxas de morbimortalidade. O conceito de micrometástases pode nos trazer avaliação mais acurada do estadiamento dos tumores operados, com detecção através de imunoistoquímica ou reação em cadeia de polimerase de metástases não diagnosticadas pelos métodos convencionais. MÉTODOS: Realizou-se revisão bibliográfica de artigos científicos publicados e disponíveis no PubMed, através do site www.pubmed.gov. cruzando-se os descritores neoplasias esofágicas, biologia molecular, estadiamento de neoplasias, linfonodo sentinela, metástase linfática. REVISÃO DA LITERATURA: O conceito do linfonodo sentinela, onde se pesquisa durante a cirurgia os possíveis primeiros sítios de metástases, direcionando desta maneira a rota da ressecção linfática no intuito de permitir ressecções completas não necessariamente extensas, possibilita diminuir a morbimortalidade e restringir as indicações de procedimentos muitas vezes super-dimensionados que podem não trazer benefício aos pacientes. CONCLUSÃO: O estadiamento preciso através da procura de micrometástase e o tratamento mais regrado pelo método do linfonodo sentinela, podem trazer novas perspectivas no tratamento do câncer de esôfago, principalmente em casos de tumores precoces.

BACKGROUND: The esophageal cancer presents as one of the most frequent and lethal neoplasia. Lymphatic involvement appears to be the principal individual factor for poor prognosis, thus esophagectomy with extensive lymphadenectomy still is the choice treatment. Thoracotomy for extensive resection is related to higher survival rate, as well as higher morbid-mortality rates. Micrometastasis concept involves a more accurate staging method for resected tumors, using immunohistochemistry or polymerase chain reaction techniques, which were not diagnosed by conventional methods. METHODS: A literature review was made over scientific articles published and available at PubMed site (www.pubmed.gov), crossing the following headings: esophageal neoplasm, molecular biology, neoplasm staging, sentinel lymph node, lymphatic metastasis. LITERATURE REVIEW: Sentinel lymph node concept consist of intraoperative identification of possible primary dissemination metastasis sites, thus guiding to a more complete and not so extensively lymphatic resection, decreasing morbid-mortality and restraining an over-dimensioned procedure that may not benefit the patient. CONCLUSION: Accurate staging by micrometastasis identification and precise treatment using sentinel lymph node method may bring new perspectives in the esophageal cancer treatment, especially on early-stages tumors.