RESUMEN
Esophageal adenoid cystic carcinoma (EACC) is an exceedingly rare malignant tumor constituting only 0.2% of all esophageal tumors. The tumor exhibits aggressive behavior, composed histologically of ductal and modified myoepithelial cells. We report a case of a 69-year-old female with a diagnosis of an EACC by preoperative endoscopic biopsy. Thoracoscopy esophagectomy was carried out. However, pleural metastasis was found. Therefore, surgical resection of the esophageal tumor was not carried out. The patient underwent an uneventful recovery, followed by palliative treatment and ongoing chemoradiotherapy. EACC is uncommon but exhibits a more aggressive nature compared to its counterparts in the head and neck region. Dysphagia associated with gastroesophageal reflux disease is a common symptom. The duration from symptom onset to diagnosis is typically short. Treatment options include surgical resection, chemotherapy, and radiotherapy, with surgery being the preferred initial approach despite high operative mortality. Prognosis remains inconclusive, with some studies associating poor outcomes with lymph node metastasis and vascular invasion, while others report better survival rates. EACC presents diagnostic and therapeutic challenges due to its rarity and aggressive nature. Prognostic considerations remain unclear, emphasizing the need for further research and accumulated cases to delineate optimal treatment. The presented case demonstrates a 1-year survival with systemic palliative care, contributing to the evolving knowledge surrounding EACC.
El carcinoma adenoide quístico primario de esófago (EACC) es un tumor maligno excepcionalmente raro que constituye solo el 0.2% de todos los tumores esofágicos. El tumor exhibe un comportamiento agresivo, compuesto histológicamente por células ductales y mioepiteliales modificadas. Presentamos el caso de una mujer de 69 años con diagnóstico de un EACC mediante biopsia endoscópica preoperatoria. Se realizó una esofagectomía por toracoscopia. Sin embargo, se encontró metástasis pleural. Por lo tanto, no se llevó a cabo la resección quirúrgica del tumor esofágico. La paciente tuvo una recuperación sin complicaciones, seguida de tratamiento paliativo y radioquimioterapia continua. El EACC es poco común, pero exhibe una naturaleza más agresiva en comparación con sus contrapartes en la región de la cabeza y el cuello. La disfagia asociada con la enfermedad por reflujo gastroesofágico es un síntoma común. La duración desde el inicio de los síntomas hasta el diagnóstico suele ser corta. Las opciones de tratamiento incluyen la cirugía, quimio y radioterapia, siendo la cirugía la preferida a pesar de la alta mortalidad operatoria. El pronóstico es inconcluso, algunos estudios asocian resultados pobres con metástasis e invasión vascular, mientras que otros informan mejores tasas de supervivencia. El EACC presenta desafíos diagnósticos y terapéuticos debido a su rareza y naturaleza agresiva. El pronóstico sigue siendo poco claro, lo que enfatiza la necesidad de más investigación para delinear el tratamiento óptimo. El caso presentado demuestra una supervivencia de un año con cuidados paliativos sistémicos, contribuyendo al conocimiento en evolución sobre el EACC.
Asunto(s)
Carcinoma Adenoide Quístico , Neoplasias Esofágicas , Humanos , Carcinoma Adenoide Quístico/patología , Carcinoma Adenoide Quístico/terapia , Femenino , Anciano , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Esofagectomía , BiopsiaRESUMEN
BACKGROUND: Vulnerable populations potentially have a worse prognosis for cancer. The present study aimed to identify individual and municipal characteristics of access to health, including education, use of health insurance, gross domestic product per capita (GDPpc), and urban aspects, which could impact the prognosis of patients with esophageal cancer. METHODS: Data on urban concentration, administrative hierarchy, GDPpc, individual patient characteristics, and access to healthcare were collected from national and state public databases spanning between 2013 and 2022. The study included cities in the state of Sao Paulo, Brazil. Independent variables such as GDPpc, urban concentration, municipal administrative hierarchy, health insurance status, education level, and individual cancer and patient characteristics were evaluated against the outcomes of overall survival (OS), likelihood of undergoing surgical treatment, and time-to-treatment initiation. RESULTS: A total of 9280 patients with esophageal cancer (85% squamous cell carcinoma and 15% adenocarcinoma) treated in 42 cities were included in the study. In univariate analysis, higher education (hazard ratio [HR] = 0.6; P < .001), female gender (HR = 0.85; P < .001), and having private health insurance (HR = 0.65; P < .001) were identified as protective factors for OS in esophageal cancer. After adjusting for other variables in multivariate analysis, higher education (HR = 0.77; P = .009), female gender (HR = 0.82; P < .001), and private insurance (HR = 0.65; P < .001) remained protective factors. GDPpc was not associated with OS. Urban concentration and hierarchy influenced the likelihood of receiving surgical treatment. Patients from high urban concentrations had shorter time-to-treatment initiation intervals. CONCLUSION: Populations at risk, particularly those with limited access to education and healthcare, face a worse prognosis for esophageal cancer.
Asunto(s)
Adenocarcinoma , Neoplasias Esofágicas , Accesibilidad a los Servicios de Salud , Disparidades en Atención de Salud , Seguro de Salud , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Masculino , Femenino , Persona de Mediana Edad , Disparidades en Atención de Salud/estadística & datos numéricos , Anciano , Accesibilidad a los Servicios de Salud/estadística & datos numéricos , Seguro de Salud/estadística & datos numéricos , Adenocarcinoma/terapia , Adenocarcinoma/mortalidad , Adenocarcinoma/cirugía , Brasil/epidemiología , Escolaridad , Tiempo de Tratamiento/estadística & datos numéricos , Producto Interno Bruto/estadística & datos numéricos , Pronóstico , Factores Sexuales , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/cirugía , Población Urbana/estadística & datos numéricosAsunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Esofagoscopía , Humanos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/diagnóstico por imagen , Carcinoma de Células Escamosas de Esófago/terapia , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/diagnóstico , Esofagoscopía/métodos , Carcinoma de Células Escamosas/terapia , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/patologíaRESUMEN
AIM: To assess the appropriateness of systemic oncological treatments (SOT) provided to patients diagnosed with advanced esophageal cancer (EC) across a group of participating hospitals. METHODS: Multicenter, retrospective cohort study in five Spanish hospitals including newly confirmed advanced EC cases between July 1, 2014, and June 30, 2016, with a 5-year follow-up. RESULTS: We identified 157 patients fulfilling the inclusion criteria (median age: 65 years, 85.9% males). Most patients, 125 (79.6%) were treated at least with one active treatment, and 33% received two or more lines of SOT. The 1-, 2- and 5-year overall survival rates were 30.3% [95%CI: 23.8, 38.7], 14.0% [95%CI: 9.3, 21.0], and 7.1% [95% CI: 3.8, 13.1] respectively, and the median survival time 8 months (95% CI: 6, 19) for stages IIIb IIIc and 7 months (95% CI: 5, 9) for stage IV. Clinical stage, receiving more than one line of SOT, and treatment with radiotherapy accelerated the time to death (0.4, 0.9-, and 0.8-times shorter survival respectively, p < 0.05). Better performance status (ECOG < 2) extended survival time by 2.2 times (p = 0.04). Age < 65 years (OR 9.4, 95% CI 3.2, 31.4, p < 0.001), and being treated in one particular hospital (OR 0.2, 95% CI 0.0, 0.8, p < 0.01) were associated with the administration of two or more lines of SOT. Altogether, 18.9% and 9.0% of patients received chemotherapy in the last four and two weeks of life, respectively. Moreover, 2.5% of patients were prescribed a new line of chemotherapy during the last month of life. The proportion of all patients who did not have access to palliative care reached 29.3%, and among those who had access to it, 34.2% initiated it in the last month of life. CONCLUSION: A high proportion of advanced EC patients receive many treatments not based on sound evidence and they do not benefit enough from palliative care services. The most accepted appropriateness indicators point out that some of the analyzed patients could have been overtreated. This study provides important insights into the quality of care provided to advanced EC, and furthermore, for giving valuable insight and opportunities for improvement.
Asunto(s)
Neoplasias Esofágicas , Humanos , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidad , Estudios Retrospectivos , Masculino , Femenino , Anciano , España , Persona de Mediana Edad , Tasa de Supervivencia , Anciano de 80 o más Años , Antineoplásicos/uso terapéutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Estadificación de Neoplasias , Adulto , Estudios de SeguimientoRESUMEN
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.
Asunto(s)
Humanos , Neoplasias Esofágicas/terapia , Survivin , Carcinoma de Células Escamosas de Esófago/terapia , Fármacos Sensibilizantes a Radiaciones , Tolerancia a Radiación , ARN Mensajero , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/radioterapia , Transfección , Regulación hacia Abajo , Western Blotting , Apoptosis , Terapia Combinada , ARN Interferente Pequeño , Línea Celular Tumoral/efectos de la radiación , Proteína 1 de la Respuesta de Crecimiento Precoz , Caspasa 3 , Caspasa 9 , Reacción en Cadena en Tiempo Real de la Polimerasa , Citometría de Flujo , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/radioterapiaRESUMEN
El esófago de Barrett (EB) se define como la condición en la cual una mucosa columnar metaplásica predispuesta a neoplasia reemplaza la mucosa escamosa del esófago distal. La guías actuales recomiendan que el diagnóstico requiere el hallazgo de metaplasia intestinal (MI) con células caliciformes de al menos 1 cm de longitud. El EB afecta aproximadamente al 1% de la población general y hasta en 14% de los pacientes con enfermedad por reflujo gastroesofágico (ERGE). El EB es precursor del adenocarcinoma esofágico (ACE), neoplasia en aumento en países occidentales. Los principales factores de riesgo descritos para ACE asociado a EB son: sexo masculino, edad > 50 años, obesidad central y tabaquismo. El riesgo anual de ACE en EB sin displasia, displasia de bajo (DBG) y alto grado es 0,1-0,3%, 0,5% y 5-8%, respectivamente. El tratamiento del EB no displásico consiste en un cambio de estilo de vida saludable, quimioprevención mediante inhibidores de la bomba de protones y vigilancia endoscópica cada 3 a 5 años. Se recomienda que a partir de la presencia de DBG los pacientes sean referidos a un centro experto para la confirmación del diagnóstico, estadio y así definir su manejo. En pacientes con EB y displasia o cáncer incipiente, el tratamiento endoscópico consiste en la resección y ablación, con un éxito cercano al 90%. El principal evento adverso es la estenosis esofágica que es manejada endoscópicamente.
Barrett's esophagus (BE) is the condition in which a metaplastic columnar mucosa predisposed to neoplasia replaces the squamous mucosa of the distal esophagus. The current guidelines recommends that diagnosis requires the finding of intestinal metaplasia (IM) with goblet cells of at least 1 cm in length. BE affects approximately 1% of the general population and up to 14% of patients with gastroesophageal reflux disease (GERD). BE is a precursor of esophageal adenocarcinoma (EAC), which has increased in western countries. The main risk factors described for EAC associated with BE are male sex, age > 50 years, central obesity and tobacco use. Annual risk of EAC in patients with BE without dysplasia, low grade (LGD) and high-grade dysplasia is 0,1-0,3%, 0,5% y 5-8%, respectively. Treatment of non-dysplastic BE consists mainly of a healthy lifestyle change, chemoprevention with proton pump inhibitors and surveillance endoscopy every 3 to 5 years. It is recommended that from the presence of LGD patients are referred to an expert center for confirmation of the diagnosis, stage and thus define their management. In patients with BE and dysplasia or early-stage cancer, endoscopic therapy with resection and ablation is successful in about 90% of the patients. The main adverse event is esophageal stricture, which is managed endoscopically.
Asunto(s)
Humanos , Masculino , Esófago de Barrett/diagnóstico , Esófago de Barrett/etiología , Esófago de Barrett/terapia , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/terapia , Adenocarcinoma/diagnóstico , Adenocarcinoma/etiología , Adenocarcinoma/patología , Lesiones Precancerosas/diagnóstico , Lesiones Precancerosas/terapia , Factores de Riesgo , EsofagoscopíaRESUMEN
Self-expanding metallic stents (SEMS) are considered the treatment of choice for the palliation of dysphagia and fistulas in inoperable esophageal neoplasms. However, the safety of SEMSs in patients who received or who will be submitted to radiotherapy (RT) is uncertain. The study aimed to evaluate the impact of RT on adverse events (AEs) in patients with esophageal cancer with SEMSs. This is a retrospective study conducted at a tertiary cancer hospital from 2009 to 2018. We collected information regarding RT, the histological type of the tumor, the model of SEMSs and AEs after stent placement. Three hundred twenty-three patients with malignant stenosis or fistula were treated with SEMSs. The predominant histological type was squamous cell carcinoma (79.6%). A total of 282 partially covered and 41 fully covered SEMSs were inserted. Of the 323 patients, 182 did not received RT, 118 received RT before SEMS placement and 23 after. Comparing the group that received RT before stent insertion with the group that did not, the first one presented a higher frequency of severe pain (9/118 7.6% vs. 3/182 1.6%; P = 0.02). The group treated with RT after stent placement had a higher risk of global AEs (13/23 56.5% vs. 63/182 34.6%; P = 0.019), ingrowth/overgrowth (6/23 26.1% vs. 21/182 11.5%; P = 0.045) and gastroesophageal reflux (2/23 8.7% vs. 2/182 1.1%; P = 0.034). Treatment with RT before stent placement in patients with inoperable esophageal neoplasm prolongs survival and is associated with an increased risk of severe chest pain. Treatment with RT of patients with an esophageal stent increases the frequency of minor, not life-threatening AEs.
Asunto(s)
Trastornos de Deglución , Neoplasias Esofágicas , Estenosis Esofágica , Stents Metálicos Autoexpandibles , Humanos , Estudios Retrospectivos , Resultado del Tratamiento , Stents/efectos adversos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/complicaciones , Trastornos de Deglución/etiología , Trastornos de Deglución/terapia , Cuidados Paliativos , Stents Metálicos Autoexpandibles/efectos adversos , Estenosis Esofágica/terapiaRESUMEN
Esophageal squamous cell carcinoma (ESCC) is the most common type of esophageal cancer (EC) in Asia. It is a malignant digestive tract tumor with abundant gene mutations. Due to the lack of specific diagnostic markers and early cancer screening markers, most patients are diagnosed at an advanced stage. Genetic and epigenetic changes are closely related to the occurrence and development of ESCC. Here, We review the activation of proto-oncogenes into oncogenes through gene mutation and gene amplification in ESCC from a genetic and epigenetic genome perspective, We also discuss the specific regulatory mechanisms through which these oncogenes mainly affect the biological function and occurrence and development of ESCC through specific regulatory mechanisms. In addition, we summarize the clinical application value of these oncogenes is summarized, and it provides a feasible direction for clinical use as potential therapeutic and diagnostic markers.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Carcinoma de Células Escamosas de Esófago/genética , Carcinoma de Células Escamosas de Esófago/patología , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/metabolismo , Oncogenes , Mutación , Epigénesis Genética , Línea Celular Tumoral , Regulación Neoplásica de la Expresión GénicaRESUMEN
Barrett's esophagus (BE) is the condition in which a metaplastic columnar mucosa predisposed to neoplasia replaces the squamous mucosa of the distal esophagus. The current guidelines recommends that diagnosis requires the finding of intestinal metaplasia (IM) with goblet cells of at least 1 cm in length. BE affects approximately 1% of the general population and up to 14% of patients with gastroesophageal reflux disease (GERD). BE is a precursor of esophageal adenocarcinoma (EAC), which has increased in western countries. The main risk factors described for EAC associated with BE are male sex, age > 50 years, central obesity and tobacco use. Annual risk of EAC in patients with BE without dysplasia, low grade (LGD) and high-grade dysplasia is 0,1-0,3%, 0,5% y 5-8%, respectively. Treatment of non-dysplastic BE consists mainly of a healthy lifestyle change, chemoprevention with proton pump inhibitors and surveillance endoscopy every 3 to 5 years. It is recommended that from the presence of LGD patients are referred to an expert center for confirmation of the diagnosis, stage and thus define their management. In patients with BE and dysplasia or early-stage cancer, endoscopic therapy with resection and ablation is successful in about 90% of the patients. The main adverse event is esophageal stricture, which is managed endoscopically.
Asunto(s)
Adenocarcinoma , Esófago de Barrett , Neoplasias Esofágicas , Humanos , Esófago de Barrett/terapia , Esófago de Barrett/diagnóstico , Esófago de Barrett/etiología , Neoplasias Esofágicas/etiología , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/terapia , Factores de Riesgo , Adenocarcinoma/etiología , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Lesiones Precancerosas/terapia , Lesiones Precancerosas/diagnóstico , Masculino , EsofagoscopíaRESUMEN
BACKGROUND & AIMS: Despite the significant advances made in the diagnosis and treatment of Barrett's esophagus (BE), there is still a need for standardized definitions, appropriate recognition of endoscopic landmarks, and consistent use of classification systems. Current controversies in basic definitions of BE and the relative lack of anatomic knowledge are significant barriers to uniform documentation. We aimed to provide consensus-driven recommendations for uniform reporting and global application. METHODS: The World Endoscopy Organization Barrett's Esophagus Committee appointed leaders to develop an evidence-based Delphi study. A working group of 6 members identified and formulated 23 statements, and 30 internationally recognized experts from 18 countries participated in 3 rounds of voting. We defined consensus as agreement by ≥80% of experts for each statement and used the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) tool to assess the quality of evidence and the strength of recommendations. RESULTS: After 3 rounds of voting, experts achieved consensus on 6 endoscopic landmarks (palisade vessels, gastroesophageal junction, squamocolumnar junction, lesion location, extraluminal compressions, and quadrant orientation), 13 definitions (BE, hiatus hernia, squamous islands, columnar islands, Barrett's endoscopic therapy, endoscopic resection, endoscopic ablation, systematic inspection, complete eradication of intestinal metaplasia, complete eradication of dysplasia, residual disease, recurrent disease, and failure of endoscopic therapy), and 4 classification systems (Prague, Los Angeles, Paris, and Barrett's International NBI Group). In round 1, 18 statements (78%) reached consensus, with 12 (67%) receiving strong agreement from more than half of the experts. In round 2, 4 of the remaining statements (80%) reached consensus, with 1 statement receiving strong agreement from 50% of the experts. In the third round, a consensus was reached on the remaining statement. CONCLUSIONS: We developed evidence-based, consensus-driven statements on endoscopic landmarks, definitions, and classifications of BE. These recommendations may facilitate global uniform reporting in BE.
Asunto(s)
Esófago de Barrett , Neoplasias Esofágicas , Esófago de Barrett/diagnóstico , Esófago de Barrett/patología , Esófago de Barrett/terapia , Brasil , Consenso , Técnica Delphi , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Esofagoscopía , HumanosRESUMEN
Esophageal cancer is an aggressive tumor, and is the sixth-leading cause of death from cancer. Incidence is rising in Spain, particularly among men. Two main pathological different subtypes have been described: squamous cell carcinoma and adenocarcinoma. Growing evidence of their epidemiology and molecular differences explains their different response to novel treatments, and they are therefore likely to be treated as two separate entities in the near future. The best results are obtained with a multidisciplinary therapeutic strategy, and the introduction of immunotherapy is a promising new approach that will improve prognosis. In these guidelines, we review the evidence for the different methods of diagnosis and therapeutic strategies that form the basis of our standard of care.
Asunto(s)
Adenocarcinoma , Carcinoma de Células Escamosas , Neoplasias Esofágicas , Adenocarcinoma/diagnóstico , Adenocarcinoma/patología , Adenocarcinoma/terapia , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/terapia , Humanos , Inmunoterapia/efectos adversos , Masculino , PronósticoRESUMEN
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.
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Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Esofagectomía , Humanos , Terapia Neoadyuvante , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
Esophageal cancer is a complex gastrointestinal malignancy with an extremely poor outcome. Approximately 80% of cases of this malignancy in Asian countries including India are of squamous cell origin, termed Esophageal Squamous Cell Carcinoma (ESCC).The five-year survival rate in ESCC patients is less than 20%. Neo-adjuvant chemo-radiotherapy (NACRT) followed by surgical resection remains the major therapeutic strategy for patients with operable ESCC. However, resistance to NACRT and local recurrence after initial treatment are the leading cause of dismal outcomes in these patients. Therefore, an alternative strategy to promote response to the therapy and reduce the post-operative disease recurrence is highly needed. At the molecular level, wide variations have been observed in tumor characteristics among different populations, nevertheless, several common molecular features have been identified which orchestrate disease progression and clinical outcome in the malignancy. Therefore, determination of candidate molecular pathways for targeted therapy remains the mainstream idea of focus in ESCC research. In this review, we have discussed the key signaling pathways associated with ESCC, i.e., Notch, Wnt, and Nrf2 pathways, and their crosstalk during disease progression. We further discuss the recent developments of novel agents to target these pathways in the context of targeted cancer therapy. In-depth research of the signaling pathways, gene signatures, and a combinatorial approach may help in discovering targeted therapy for ESCC.
Asunto(s)
Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Línea Celular Tumoral , Progresión de la Enfermedad , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/genética , Humanos , Recurrencia Local de Neoplasia , Transducción de SeñalRESUMEN
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.
Asunto(s)
Humanos , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/terapia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Tasa de Supervivencia , Estudios Retrospectivos , Resultado del Tratamiento , Esofagectomía , Terapia NeoadyuvanteRESUMEN
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.
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Enfermedad Crítica , Neoplasias Esofágicas/terapia , Unidades de Cuidados Intensivos/estadística & datos numéricos , Enfermedad Aguda , Anciano , Estudios de Cohortes , Neoplasias Esofágicas/mortalidad , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Respiración Artificial/estadística & datos numéricos , Insuficiencia Respiratoria/epidemiología , Estudios Retrospectivos , Sepsis/epidemiología , Choque Séptico/epidemiologíaRESUMEN
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.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Anciano , Neoplasias Esofágicas/terapia , Enfermedad Crítica , Unidades de Cuidados Intensivos/estadística & datos numéricos , Pronóstico , Respiración Artificial/estadística & datos numéricos , Insuficiencia Respiratoria/epidemiología , Choque Séptico/epidemiología , Neoplasias Esofágicas/mortalidad , Enfermedad Aguda , Estudios Retrospectivos , Estudios de Cohortes , Mortalidad Hospitalaria , Sepsis/epidemiologíaRESUMEN
PURPOSE: Basaloid squamous cell carcinoma (BSCC) of the head and neck is an aggressive and highly malignant variant of squamous cell carcinoma that accounts for 2% of head and neck cancers. Previous studies have not analyzed the significance of adjuvant chemoradiation and anatomical site within BSCC subtype and its impact on survival. METHODS: A cohort of 1999 patients with BSCC of the head and neck was formed from the National Cancer Database and analyzed with descriptive studies, median survival and 5- and 10-year survival. A multivariable Cox hazard regression was performed to determine the prognostic significance of anatomical site and adjuvant therapy. RESULTS: The most common primary anatomical site was the oropharynx (71.9%) followed by oral cavity (11.5%), larynx (10.1%), hypopharynx (3.5%), esophagus (1.9%), and nasopharynx (1.1%). The presence of metastasis increased the risk of mortality (HR = 2.14; 95% CI 1.40-3.26). Tumors localized to the oropharynx demonstrated better survival compared to all sites except nasopharynx, including the oral cavity (HR = 2.45; 95% CI 1.83-3.29), hypopharynx (HR = 2.58; 95% CI:1.64-4.05), and larynx (HR = 2.89; 95% CI:2.25-3.73). Adjuvant chemoradiation (HR = 0.36; 95% CI 0.23-0.58) and adjuvant radiation (HR = 0.38; 95% CI 0.23-0.64) had better survival outcomes compared to adjuvant chemotherapy. Patients with microscopic margins had better survival outcomes when compared to no surgery (HR = 0.38, 98% Cl 0.23-0.64) while there were no better survival outcomes of patients with macroscopic margins compared to no surgery. CONCLUSION: This study illustrated that tumors in the oropharynx, lower age, adjuvant chemoradiation and radiation, and microscopic margins were associated with greater survival.
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Quimioradioterapia Adyuvante , Neoplasias de Cabeza y Cuello/patología , Neoplasias de Cabeza y Cuello/terapia , Carcinoma de Células Escamosas de Cabeza y Cuello/patología , Carcinoma de Células Escamosas de Cabeza y Cuello/terapia , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Quimioradioterapia Adyuvante/mortalidad , Niño , Preescolar , Bases de Datos Factuales , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Femenino , Neoplasias de Cabeza y Cuello/mortalidad , Humanos , Neoplasias Hipofaríngeas/mortalidad , Neoplasias Hipofaríngeas/patología , Neoplasias Hipofaríngeas/terapia , Lactante , Recién Nacido , Estimación de Kaplan-Meier , Neoplasias Laríngeas/mortalidad , Neoplasias Laríngeas/patología , Neoplasias Laríngeas/terapia , Masculino , Persona de Mediana Edad , Neoplasias de la Boca/mortalidad , Neoplasias de la Boca/patología , Neoplasias de la Boca/terapia , Neoplasias Nasofaríngeas/mortalidad , Neoplasias Nasofaríngeas/patología , Neoplasias Nasofaríngeas/terapia , Neoplasias Orofaríngeas/mortalidad , Neoplasias Orofaríngeas/patología , Neoplasias Orofaríngeas/terapia , Pronóstico , Modelos de Riesgos Proporcionales , Radioterapia Adyuvante/mortalidad , Carcinoma de Células Escamosas de Cabeza y Cuello/mortalidad , Adulto JovenRESUMEN
OBJECTIVE: Diffusion-weighted magnetic resonance imaging (DWI) is part of clinical practice. The aim of this study was to evaluate the role of apparent diffusion coefficient (ADC) as a predictor of pathologic response to neoadjuvant therapy (nCRT) in patients with esophageal cancer (EC). METHODS: The MEDLINE, Embase, and Google Scholar databases were systematically searched for studies using ADC to evaluate response to neoadjuvant therapy in patients with EC. Methodological quality of the studies was evaluated with the QUADAS tool. Data from eligible studies were extracted and evaluated by two independent reviewers. Meta-analyses were performed comparing mean ADC values between responders and non-responders to nCRT in three different scenarios: baseline (BL) absolute values; percent change between intermediate (IM) values and BL; and percent change between final follow-up (FU) value and baseline BL. RESULTS: Seven studies (n = 158 patients) were included. Responders exhibited a statistically significant percent increase in ADC during nCRT (mean difference [MD] 21.06%, 95%CI = 13.04-29.09; I2 = 49%; p = 0.12). A similar increase was identified in the complete pathologic response (pCR) versus non-complete pathologic response (npCR) subgroup (MD = 25.68%, 95%CI = 18.87-32.48; I2 = 0%; p = 0.60). At the end of treatment, responders also exhibited a statistically significant percent increase in ADC (MD = 22.49%, 95%CI = 9.94-35.05; I2 = 0%; p = 0.46). BL ADC was not associated with any definition of pathologic response (MD = 0.11%, 95%CI = - 0.21-0.42; I2 = 85%; p < 0.01). CONCLUSION: These results suggest that ADC can be used as a predictor of pathologic response, with a statistically significant association between percent ADC increase during and after treatment and pCR. ADC may serve as a tool to help in guiding clinical decisions. KEY POINTS: ⢠DWI is routinely included in MRI oncological protocols. ⢠ADC can be used as a predictor of pathologic response, with a statistically significant association between percent ADC increase during and after treatment and pCR.
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Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/diagnóstico , Humanos , Terapia Neoadyuvante/métodos , Resultado del TratamientoRESUMEN
OBJECTIVE: A recent meta-analysis of 3 randomized controlled trials reported reduced incidence and severity of postesophagectomy anastomotic dehiscence with anastomotic omentoplasty. Unfortunately, these trials excluded neoadjuvant patients who received chemoradiation. We aimed to determine whether anastomotic omentoplasty was associated with differential postesophagectomy anastomotic complications after neoadjuvant chemoradiotherapy. METHODS: Data for patients who underwent minimally invasive esophagectomy following neoadjuvant chemoradiotherapy were abstracted (n = 245; 2001-2016; omentoplasty = 147 [60%]). Propensity for omentoplasty was estimated on 21 pretreatment variables, using augmented inverse probability of treatment weights, and used to determine the adjusted proportion of adverse anastomotic outcomes, major morbidity, and 30-day/in-hospital mortality. RESULTS: Overall, anastomotic leak rate was 15%; leak-associated mortality was 13% (n = 5 out of 37). Leak rates (omentoplasty n = 24 [16%] vs no omentoplasty n = 13 [13%]; P = .512) and incidence of any major complications (48% vs 48%; P = .958) were similar. Leaks requiring surgical intervention occurred in 12 patients (5% vs 5%; P = .904). Propensity weighting achieved excellent balance across all 21 pretreatment variables (before weighting, standardized differences ranged from -0.23 to 0.35; postweighting standardized differences ranged from -0.09 to 0.07). In propensity-weighted data, omentoplasty was not associated with differential adjusted risk of anastomotic leak (13.2% vs 14.3%; P = .83), major morbidity (27.9% vs 32.6%; P = .44), or mortality (6.7% vs 4.8%; P = .61). CONCLUSIONS: Within the limits of our sample size and statistical approach, our study failed to find evidence that anastomotic omentoplasty during esophagectomy after neoadjuvant chemoradiation reduced anastomotic leak rate or need for leak-related reoperation.