RESUMEN
BACKGROUND: With the aging of society and increasingly longer of life expectancy, elderly patients with esophageal cancer are more commonly encountered. This study aimed to identify the risk factors for operative mortality after esophagectomy in elderly patients. METHODS: We used data from the National Clinical Database of Japan. After cleaning the data, 10,633 records obtained from 861 hospitals were analyzed. A risk model for operative mortality was developed using risk factors from the entire study population. Then, odds ratios (OR) were compared between age categories using this risk model. RESULTS: In this study, 1959 (18.4%) patients were ≥ 75 years (defined as "elderly" in this study). Eighteen variables, including T4b, N2-N3, and M1 in the TNM classification, were included in the risk model for operative mortality. The ORs increased in age categories < 65, 65-74, and ≥ 75 years for N2-N3 (1.172, 1.200, and 1.588, respectively), and M1 (2.189, 3.164, and 4.430, respectively). Based on these results, we also focused on residual tumors, which are caused by extensive tumor development. The operative mortality in the elderly group with residual tumors increased to more than twice than that in the non-elderly groups (15.9 vs. 5.5 or 6.5%) and was much higher than that in elderly patients without residual tumors (15.9 vs. 4.6%). CONCLUSION: We should carefully select the treatment for elderly patients with highly advanced tumors, which result in N2-N3 and M1, to avoid unfavorable short-term outcomes. In addition, R0 resection is important in preventing operative mortality among elderly patients.
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Neoplasias Esofágicas , Complicaciones Posoperatorias , Humanos , Persona de Mediana Edad , Anciano , Japón/epidemiología , Neoplasia Residual , Factores de Edad , Complicaciones Posoperatorias/epidemiología , Factores de Riesgo , Neoplasias Esofágicas/patologíaRESUMEN
BACKGROUND: A multicenter phase 2 trial analysed chemoselection with docetaxel plus 5-fluorouracil and cisplatin (DCF) induction chemotherapy (ICT) and subsequent conversion surgery (CS) for locally advanced unresectable esophageal cancer. This study presents updated 3-year analyses to further characterize the impact of DCF-ICT followed by CS. METHODS: Esophageal cancer patients with clinical T4 disease, unresectable supraclavicular lymph node metastasis, or both were eligible for this study. The treatment starts with DCF-ICT, followed by CS if the cancer is resectable, or by concurrent chemoradiation if it is not resectable. This updated analysis presents 3-year overall survival (OS), 3-year progression-free survival (PFS), and pattern of relapse. RESULTS: The median follow-up period for the patients surviving without death was 39.3 months. The estimated 1-year OS was 66.7%, and the lower limit of the 80% confidence interval (CI) was 54.6%. The estimated 3-year OS was 46.6% (95% CI 34.2-63.5%). The OS for the patients who underwent R0 resection (n = 19) was significantly longer than for those who did not (3-year OS: 71.4% vs. 30.1%). The estimated 1-year PFS was 50.6%, and the 3-year PFS was 39.6%. The PFS for R0 was significantly longer than for non-R0 (3-year PFS: 61.3% vs 25.0%). Recurrence or progression at the primary site was observed in 31% of the non-R0 group. The rate of distant metastasis did not differ significantly between the non-R0 and R0 groups (21% vs 16%). CONCLUSIONS: Long-term follow-up evaluation confirmed that DCF chemoselection aimed at CS is feasible and promising in terms of survival for patients with locally advanced esophageal cancer.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Quimioradioterapia/mortalidad , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago/mortalidad , Esofagectomía/mortalidad , Quimioterapia de Inducción/mortalidad , Recurrencia Local de Neoplasia/mortalidad , Anciano , Cisplatino/administración & dosificación , Docetaxel/administración & dosificación , Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago/patología , Carcinoma de Células Escamosas de Esófago/terapia , Femenino , Fluorouracilo/administración & dosificación , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/patología , Recurrencia Local de Neoplasia/terapia , Pronóstico , Tasa de SupervivenciaRESUMEN
BACKGROUND: Although diffusion-weighted magnetic resonance imaging (DWI) for detecting lymph node (LN) metastasis is reported to be a successful modality for primary malignant tumors, there are few studies relating to esophageal cancer. This study aimed to clarify the diagnostic performance of DWI for assessing LN metastasis compared with positron emission tomography (PET) in patients with esophageal squamous cell cancer (eSCC). METHODS: Seventy-six patients with histologically proven eSCC who underwent curative esophagectomy without neoadjuvant treatment were reviewed retrospectively. Harvested LNs were divided into 1229 node stations with 94 metastases. Diagnostic abilities and prognostic significance were compared. RESULTS: In a station-by-station evaluation, the sensitivity was higher in DWI than PET (67% vs. 32%, P < 0.001). DWI showed more than 80% sensitivity for middle- and large-sized cancer nests and large area of cancer nests. The DWI-N0 group had a better 5-year relapse-free survival rate than the DWI-N+ group (78.5% vs. 34.2%, P < 0.001), as did the PET-N0 group. DWI-N status was an independent prognostic factor (hazard ratio [HR], 2.642; P = 0.048), as was PET-N status (HR 2.481; P = 0.033). CONCLUSIONS: DWI, which depends on cancer cell volume followed by elevated intranodal density, is a non-invasive modality and showed higher sensitivity than PET. It has clinical impact in predicting postoperative survival for patients with eSCC alongside its diagnostic ability and has significant performance in clinical practice.
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Imagen de Difusión por Resonancia Magnética/métodos , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/secundario , Metástasis Linfática/diagnóstico por imagen , Tomografía de Emisión de Positrones/métodos , Adulto , Anciano , Anciano de 80 o más Años , Recuento de Células/estadística & datos numéricos , Supervivencia sin Enfermedad , Carcinoma de Células Escamosas de Esófago/diagnóstico , Carcinoma de Células Escamosas de Esófago/mortalidad , Carcinoma de Células Escamosas de Esófago/cirugía , Esofagectomía/métodos , Femenino , Humanos , Ganglios Linfáticos/patología , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias/métodos , Periodo Posoperatorio , Pronóstico , Estudios Retrospectivos , Sensibilidad y Especificidad , Carga Tumoral/fisiologíaRESUMEN
Esophageal squamous cell carcinoma (ESCC) is an intractable digestive organ cancer that has proven difficult to treat despite multidisciplinary therapy, and a new treatment strategy is demanded. Metformin is used for type 2 diabetes mellitus and its antitumor effects have been reported recently. Metformin exerts antitumor effects in various respects, such as inhibiting inflammation, tumor growth and epithelial-mesenchymal transition (EMT). However, few reports have described the efficacy of metformin on ESCC, and their findings have been controversial. We analyzed the antitumor effects of metformin and clarified its effects on anti-inflammation, growth suppression and EMT inhibition. Activation of nuclear factor kappa B (NF-κB), the major transcription factor induced by inflammation, was investigated by immunostaining. We found that localization of NF-κB in the nucleus was reduced after metformin treatment. This suggests that metformin inhibited the activation of NF-κB. Metformin inhibited tumor growth and induced apoptosis in ESCC cell lines. Associated with EMT, we examined cell motility by a wound healing assay and the epithelial marker E-cadherin expression of various ESCC cell lines by western blotting. Metformin inhibited cell motility and induced E-cadherin expression. In conclusion, metformin showed multiple antitumor effects such as growth suppression, invasion inhibition, and control of EMT by inhibiting NF-κB localization on ESCC. Further exploration of the marker of treatment efficacy and combination therapy could result in the possibility for novel treatment to use metformin on ESCC.
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Antineoplásicos/farmacología , Núcleo Celular/efectos de los fármacos , Metformina/farmacología , FN-kappa B/metabolismo , Translocación Genética/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Cadherinas/metabolismo , Carcinoma de Células Escamosas , Línea Celular Tumoral , Linaje de la Célula/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Diabetes Mellitus Tipo 2/metabolismo , Neoplasias Esofágicas , Carcinoma de Células Escamosas de Esófago , Humanos , Inflamación/metabolismo , Ratones , Ratones Endogámicos BALB C , Ratones DesnudosRESUMEN
OBJECTIVE: ZNF750, a transcriptional regulator of epidermal differentiation, has been identified as a tumor suppressor in esophageal squamous cell carcinoma (ESCC). The aim of the present study was to investigate the clinical and prognostic significance of ZNF750 expression and to evaluate the effect of ZNF750 knockdown on cell proliferation, migration, and invasion in ESCC. METHODS: A total of 124 patients with ESCC who underwent curative esophagectomy were evaluated in this study. The expression of ZNF750 in surgical specimens was immunohistochemically assessed and used in the analysis of clinicopathological features and overall survival (OS). The molecular role of ZNF750 was investigated by ZNF750 knockdown using small interfering RNA (siRNA) in ESCC cell lines. RESULTS: Low ZNF750 expression had a significant correlation with positive lymph node metastasis (p = 0.028). Furthermore, there was a significant relationship between low expression of ZNF750 in ESCC and a poor OS, and a multivariate analysis showed that low ZNF750 expression was an independent prognostic factor (p = 0.020). The cell growth, migration, and invasion were significantly increased by downregulation of ZNF750. CONCLUSIONS: The low expression of ZNF750 was significantly associated with a poor prognosis, and ZNF750 expression may, therefore, be a reliable prognostic biomarker in ESCC.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/patología , Factores de Transcripción/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Movimiento Celular/fisiología , Proliferación Celular/fisiología , Regulación hacia Abajo/fisiología , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Metástasis Linfática/patología , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Supresoras de TumorRESUMEN
PURPOSE: Oral mucositis (OM) is one of the most uncomfortable adverse events experienced by cancer patients undergoing chemotherapy. Previous reports have revealed that the oral administration of an elemental diet (ED) may prevent OM. However, the incidence of OM has not been accurately determined by specialized diagnostic methods and the effects of an ED on OM remain unclear. We investigated the dose that could feasibly be administered and its effects with regard to the suppression of OM in esophageal cancer patients undergoing chemotherapy. METHODS: We performed a prospective multi-center feasibility study of the administration of an ED (160 g/day) with 2 cycles of docetaxel/cisplatin/5-FU (DCF) chemotherapy. We assessed compliance to the ED for 49 days and the incidence of OM according to the amount of the ED that was orally administered. The incidence of OM was graded by a dental specialist who was experienced in dental oncology using a central OM review system. RESULTS: Fourteen of 20 patients (70%) were able to complete the orally administered ED (160 g/day) during the course of chemotherapy. Three patients (15%) could not take the ED orally for 9, 14, and 21 days, respectively, while 1 patient (5%) took the ED orally at an average dose of 80 g/day for 35 days. The remaining 2 patients (10%) could not take the 80 g/day dose for 11 and 12 days, respectively. The incidence of grade ≥ 2 OM in the ED completion group (15.4%, 2 of 13 patients) was significantly lower than that in the non-completion group (66.7%, 4 of 6 patients) (p = 0.046). CONCLUSIONS: An ED might be a one of the test treatment to reduce the incidence of OM in esophageal cancer patients treated with DCF and should be evaluated in further randomized study. CLINICAL TRIAL: The date of submission: Dec 08th, 2017.
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Neoplasias Esofágicas/tratamiento farmacológico , Alimentos Formulados/normas , Estomatitis/dietoterapia , Estomatitis/prevención & control , Adulto , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Neoplasias Esofágicas/patología , Estudios de Factibilidad , Femenino , Alimentos Formulados/estadística & datos numéricos , Humanos , Incidencia , Masculino , Cumplimiento de la Medicación/estadística & datos numéricos , Persona de Mediana Edad , Estadificación de Neoplasias , Estudios Prospectivos , Estomatitis/inducido químicamente , Estomatitis/epidemiologíaRESUMEN
BACKGROUND: We determined the serum concentrations of Programmed cell death-1 (PD-1) and its ligands (PD-L1 and PD-L2) in patients with esophageal squamous cell carcinoma (ESCC). METHODS: Blood samples were collected from 85 patients with histologically proved ESCC. Serum levels of PD-1, PD-L1, and PD-L2 were measured using enzyme linked immunosorbent assays. Correlations between serum PD-1, PD-L1, and PD-L2 concentration and tumor depth, number of lymph node metastases, organ metastasis status, or disease stage were assessed and five-year survival rates according to clinicopathological characteristics were calculated. RESULTS: The concentration of PD-1 was not differed according to tumor progression. On the other hand, the average concentration of PD-L1 in patients with T3/T4 disease was 15.6 (12.2-18.3) pg/mL (25-75%), and this was significantly higher than that in patients with Tis/T1/T2 disease (p = 0.020). Similarly, PD-L1 levels were significantly higher in patients with positive lymph nodes than in cases with negative lymph node involvement (p = 0.006) and were higher in patients with organ metastasis (p = 0.123) and in more advanced stage (p = 0.006). Similar tendency was observed regarding PD-L2 concentrations. PD-L2 concentration was higher in T3, T4 cases (p = 0.008), in LN positive cases (p = 0.032), and in more advanced stage (p = 0.024). CONCLUSION: Our data showed that a concentration of PD-L1 in peripheral blood was high in advanced cancer and high concentration of PD-L1 predicted disease progression and also poor survival in patients with ESCC.
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Antígeno B7-H1/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/secundario , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/patología , Anciano , Biomarcadores/sangre , Progresión de la Enfermedad , Femenino , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Proteína 2 Ligando de Muerte Celular Programada 1/sangre , Receptor de Muerte Celular Programada 1/sangre , Tasa de SupervivenciaRESUMEN
BACKGROUND: The expression of Fos-related antigen 1 (Fra-1) affects tumor progression, migration, and invasion. In this study, we identified the genes regulated by Fra-1 in esophageal squamous cell carcinoma (ESCC). METHODS: We constructed Fra-1 knockdown models via the transfection of small interfering RNA (siRNA) into ESCC cell lines (TE10, TE11). The expression levels of the genes in the knockdown models were analyzed using a microarray and a Biobase Upstream Analysis, while the expression levels of the candidate genes in the primary tumors of surgical specimens obtained from ESCC patients were determined using real-time polymerase chain reaction (PCR) and immunohistochemical staining. The clinicopathological features were then analyzed. RESULTS: The Biobase Upstream Analysis showed the high-mobility-group protein-1 (HMGA1) to be a significant gene regulated by Fra-1. Actual binding of Fra-1 to the promotor region of HMGA1 was revealed in subsequent chromatin immunoprecipitation PCR experiments. Patients with a positive HMGA1 expression had a poor prognosis, and a multivariate analysis demonstrated a positive HMGA1 expression to be a significant independent prognostic factor. CONCLUSION: HMGA1 is regulated by Fra-1 in ESCC, and the HMGA1 expression is significantly associated with a poor prognosis in ESCC patients. Downregulation of the HMGA1 expression may become a practical treatment strategy against ESCC in the future.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/secundario , Neoplasias Esofágicas/patología , Regulación Neoplásica de la Expresión Génica , Proteína HMGA1a/metabolismo , Proteínas Proto-Oncogénicas c-fos/metabolismo , Biomarcadores de Tumor/genética , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/cirugía , Movimiento Celular , Proliferación Celular , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/cirugía , Proteína HMGA1a/genética , Humanos , Metástasis Linfática , Invasividad Neoplásica , Pronóstico , Proteínas Proto-Oncogénicas c-fos/genética , Células Tumorales CultivadasRESUMEN
OBJECTIVE: ZNF750, an epidermal differentiation regulator, has been suggested to act as a tumor suppressor of esophageal squamous cell carcinoma (ESCC). Although a correlation between the epidermal differentiation gene and resistance to chemoradiotherapy (CRT) has been posited, no data regarding the ZNF750 status in ESCC have been reported. The aim of the present study was to evaluate the relationship between ZNF750 expression and response to CRT in ESCC. METHODS: Eighty-seven patients who had been pathologically diagnosed with ESCC were evaluated in the present study. All patients underwent neoadjuvant CRT, followed by curative esophagectomy. The expression of ZNF750 in pretreatment biopsy samples was immunohistochemically investigated and compared to the histopathological effectiveness of CRT in surgical specimens. RESULTS: High expression of ZNF750 was closely correlated with good sensitivity to CRT (p = 0.016). A univariate analysis showed that high/intermediate expression of ZNF750 was a significant predictive factor for good sensitivity to CRT (p = 0.006). High/intermediate expression of ZNF750 (30% or more) remained an independent predictive factor for sensitivity to CRT in a multivariate analysis (p = 0.033). CONCLUSIONS: ZNF750 expression predicts sensitivity to CRT and can be a biomarker that reliably predicts the response of ESCC to CRT.
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Carcinoma de Células Escamosas/patología , Quimioradioterapia , Neoplasias Esofágicas/patología , Esofagectomía , Terapia Neoadyuvante , Factores de Transcripción/sangre , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/terapia , Carcinoma de Células Escamosas de Esófago , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Resultado del Tratamiento , Proteínas Supresoras de TumorRESUMEN
BACKGROUND: Intratumoral heterogeneity is a well-recognized characteristic feature of cancer. The purpose of this study is to assess the heterogeneity of the intratumoral glucose metabolism using fractal analysis, and evaluate its prognostic value in patients with esophageal squamous cell carcinoma (ESCC). METHODS: 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) studies of 79 patients who received curative surgery were evaluated. FDG-PET images were analyzed using fractal analysis software, where differential box-counting method was employed to calculate the fractal dimension (FD) of the tumor lesion. Maximum standardized uptake value (SUVmax) and FD were compared with overall survival (OS). RESULTS: The median SUVmax and FD of ESCCs in this cohort were 13.8 and 1.95, respectively. In univariate analysis performed using Cox's proportional hazard model, T stage and FD showed significant associations with OS (p = 0.04, p < 0.0001, respectively), while SUVmax did not (p = 0.1). In Kaplan-Meier analysis, the low FD tumor (<1.95) showed a significant association with favorable OS (p < 0.0001). In wthe multivariate analysis among TNM staging, serum tumor markers, FD, and SUVmax, the FD was identified as the only independent prognostic factor for OS (p = 0.0006; hazards ratio 0.251, 95% CI 0.104-0.562). CONCLUSION: Metabolic heterogeneity measured by fractal analysis can be a novel imaging biomarker for survival in patients with ESCC.
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Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/terapia , Neoplasias Esofágicas/metabolismo , Neoplasias Esofágicas/terapia , Glucosa/metabolismo , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/sangre , Carcinoma de Células Escamosas/patología , Quimioradioterapia Adyuvante , Quimioterapia Adyuvante , Neoplasias Esofágicas/patología , Esofagectomía , Femenino , Fluorodesoxiglucosa F18/metabolismo , Fractales , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Estadificación de Neoplasias , Tomografía de Emisión de Positrones , Modelos de Riesgos Proporcionales , Radiofármacos/metabolismo , Estudios Retrospectivos , Tasa de SupervivenciaRESUMEN
Postoperative anastomotic leaks and subsequent mediastinal abscess are serious complications. The purpose of this study was to assess the efficacy of naso-esophageal extraluminal drainage after thoracic esophagectomy with gastric conduit reconstruction using a posterior mediastinal route. About 50 of 365 patients (13.7%) with esophageal cancer and postoperative anastomotic leak after curative esophagectomy was investigated. Beginning in June 2009, naso-esophageal extraluminal drainage by inserting a naso-esophageal aspiration tube into the abscess cavity when percutaneous abscess drainage was introduced which was ineffective or technically impossible. Twenty-five patients underwent naso-esophageal extraluminal drainage concomitantly with enteral nutrition. Twenty-one (84%) patients had major leaks, one (4%) minor leak and three (12%) had endoscopically proven conduit necrosis. None of the naso-esophageal extraluminal drainage cases (100%) required reintervention or reoperation and all experienced complete cure (100%) during hospitalization. Endoscopic balloon dilatation was performed for four patients after discharge because of anastomotic stricture. Patients with leaks were divided into two groups: current group (n = 32), treated after June 2009, and preceding group (n = 18), treated prior to the introduction of naso-esophageal extraluminal drainage. Significantly more patients in the preceding group suffered respiratory failure (28% vs. 61%, p = 0.024), and higher reoperation rate (0% vs. 17%, p = 0.042) and hospital mortality (0% vs. 22%, p = 0.013). In the current group, 31 (97%) patients experienced complete cure during hospitalization. Naso-esophageal extraluminal drainage and concomitant enteral nutritional support are less invasive, and effective and powerful methods to treat even major leakage after esophagectomy. These methods may be an alternative management to improve mortality for patients with esophageal cancer.
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Fuga Anastomótica/cirugía , Drenaje/métodos , Neoplasias Esofágicas/cirugía , Esofagectomía/efectos adversos , Reoperación/métodos , Adulto , Anciano , Fuga Anastomótica/etiología , Fuga Anastomótica/mortalidad , Drenaje/mortalidad , Nutrición Enteral/métodos , Neoplasias Esofágicas/mortalidad , Esofagectomía/métodos , Esofagectomía/mortalidad , Esófago/cirugía , Femenino , Mortalidad Hospitalaria , Humanos , Masculino , Persona de Mediana Edad , Nariz/cirugía , Reoperación/mortalidad , Estudios Retrospectivos , Cavidad Torácica/cirugía , Resultado del TratamientoRESUMEN
BACKGROUND: The standard treatment for locally advanced unresectable squamous cell carcinoma (SCC) of the oesophagus is chemoradiation with cisplatin and 5-fluorouracil (CF-RT). This multicentre phase II trial assessed the safety and efficacy of chemoselection with docetaxel plus cisplatin and 5-fluorouracil (DCF) induction chemotherapy (ICT) and subsequent conversion surgery (CS) for initially unresectable locally advanced SCC of the oesophagus. METHODS: Patients with clinical T4 and/or unresectable supraclavicular lymph node metastasis were eligible. Treatment started with three cycles of DCF-ICT, followed by CS if resectable, or by CF-RT if unresectable. The resectability was re-evaluated at 30-40 Gy of CF-RT, followed by CS if resectable, or by completion of 60 Gy of CF-RT. If resectable after CF-RT, CS was performed. The primary end point was 1-year overall survival (OS). RESULTS: From April 2013 to July 2014, 48 patients were enrolled. CS was performed in 41.7% (n=20), including DCF-CS (n=18), DCF-CF-RT40Gy-CS (n=1), and DCF-CF-RT60Gy-CS (n=1). R0 resection was confirmed in 19 patients (39.6%). Grade ⩾3 postoperative complications included one event each of recurrent laryngeal nerve palsy, lung infection, wound infection, pulmonary fistula, and dysphagia; but no serious postoperative complications were observed in patients undergoing CS. Clinical complete response after CF-RT was confirmed in 4 patients (8.3%). The estimated 1-year OS was 67.9% and lower limit of 80% confidence interval was 59.7%. There was one treatment-related death in patient receiving DCF-CF-RT60Gy. CONCLUSIONS: Chemoselection with DCF-ICT followed by CS as a multidisciplinary treatment strategy showed promising signs of tolerability and efficacy in patients with locally advanced unresectable SCC of the oesophagus.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Neoplasias Esofágicas/terapia , Anciano , Quimioradioterapia , Cisplatino/administración & dosificación , Terapia Combinada , Docetaxel , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/cirugía , Femenino , Fluorouracilo/administración & dosificación , Humanos , Masculino , Persona de Mediana Edad , Tasa de Supervivencia , Taxoides/administración & dosificaciónRESUMEN
OBJECTIVE: To evaluate the sites and frequencies of overall and initial lymph node (LN) metastases (LNMs) of clinical T1N0 esophageal cancer. BACKGROUND: The sites and frequencies of initial LNMs and sentinel LNs (SLNs) of esophageal cancer remain unclear. METHODS: The Japan Clinical Oncology Group JCOG0502 trial was a 4-arm prospective study that compared esophagectomy with chemoradiotherapy for clinical T1N0 esophageal cancer in both randomized and patient-preference arms. The preoperative diagnostic accuracy was evaluated for patients assigned to the surgery arm. Patients who withdrew consent and who were not treated were excluded. All patients underwent esophagectomy with D2 or greater LN dissection. From the pathologic findings, sites and frequencies of LNMs and SLNs were assessed and the frequency of skip LNMs was calculated. RESULTS: In total, 211 patients underwent LNM and SLN analysis. Regarding N-factor accuracy, 57 (27.0%) of 211 clinical N0 cases had pathologic LNMs. The upper mediastinal and mediastinal/abdominal regions were frequent sites of LNMs in upper and lower thoracic cases, respectively. However, in middle thoracic cases, LNMs were observed in the neck, mediastinal, and abdominal regions, and pathologic SLN spread to all 3 fields. The frequency of skip LNMs was 36.7%. CONCLUSIONS: A clinical diagnosis of T1N0 is not sufficiently accurate, and therefore, it is unacceptable to omit LN dissection or minimize the prophylactic radiation field. SLNs, which are not location restricted, should be surveyed in all 3 fields.
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Neoplasias Esofágicas/patología , Neoplasias Esofágicas/terapia , Metástasis Linfática/patología , Adulto , Anciano , Quimioradioterapia , Esofagectomía , Femenino , Humanos , Japón/epidemiología , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Estadificación de Neoplasias , Prevalencia , Estudios Prospectivos , Análisis de SupervivenciaRESUMEN
BACKGROUND: The expression of genes can be influenced by the balance of histone acetylation and/or histone demethylation, with an imbalance of these processes possibly observed in many cancers. The histone demethylase LSD1 inhibitor activity is associated with selective transcriptional regulation and alterations in the gene expression. However, the exact mechanisms underlying the antitumor effects of LSD1 inhibitors are not fully understood. METHODS: The antitumor effects of NCL1, an LSD1 inhibitor, in esophageal squamous cell cancer (ESCC) cell lines were evaluated. A comprehensive analysis of the changes in the gene expression in ESCC cell lines induced by NCL1 was carried out using a microarray analysis. A loss-of-function assay using a siRNA analysis was performed to examine the oncogenic function of the gene. RESULTS: NCL1 strongly inhibited the cell growth of T.Tn and TE2 ESCC cells and induced apoptosis. According to the microarray analysis, 81 genes in the T.Tn cells and 149 genes in the TE2 cells were up- or down-regulated 2-fold or more by NCL1 exposure. Among these genes, 27 were contained in both cell lines and exhibited similar expression patterns. PHLDB2, one of the genes down-regulated by NCL1, was overexpressed in the ESCC tumor tissues. Moreover, a high expression level of PHLDB2 was found to be significantly correlated with poor prognosis. CONCLUSIONS: The present observations of the comprehensive analysis of the gene expression levels provide insight into the mechanisms underlying the antitumor effects of LSD1 inhibitors in ESCC patients.
Asunto(s)
Apoptosis/efectos de los fármacos , Carcinoma de Células Escamosas/prevención & control , Proliferación Celular/efectos de los fármacos , Neoplasias Esofágicas/prevención & control , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Inhibidores de Histona Desacetilasas/farmacología , Histona Demetilasas/antagonistas & inhibidores , Biomarcadores de Tumor/genética , Western Blotting , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patología , Movimiento Celular/efectos de los fármacos , Neoplasias Esofágicas/genética , Neoplasias Esofágicas/patología , Perfilación de la Expresión Génica , Histona Demetilasas/genética , Histona Demetilasas/metabolismo , Humanos , Técnicas para Inmunoenzimas , Análisis de Secuencia por Matrices de Oligonucleótidos , ARN Mensajero/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales CultivadasRESUMEN
OBJECTIVE: There is little information about the patterns of care for elderly esophageal squamous cell carcinoma patients, and a standardized strategy has not been established. Therefore, we conducted a questionnaire survey about the patterns of care for these patients. METHODS: On September 2014, the questionnaires were sent to all 43 institutions of the Japan Esophageal Oncology Group, which comprised five parts: (i) definition of 'elderly' (age, method), (ii) basic treatment strategy according to stage and elderly status (fit/vulnerable/frail), (iii) patterns of care in each stage, (iv) considerations about conducting future clinical trials and (v) other information about geriatric oncology concerning esophageal squamous cell carcinoma. RESULTS: All answers were obtained by January 2015. Nearly half institutions (47%) considered the chronological definition of elderly to be over 80 years old. Among 43 institutions, 36 (84%) reported that the type of comorbidity and performance status were important factors for decision-making; no institution selected geriatric scale as an indicator. The most selected treatment strategy in fit healthy elderly patients was the same as the standard treatment of non-elderly patients. Radiation alone was considered the main treatment for vulnerable and frail esophageal squamous cell carcinoma patients. Most of the institutions answered that clinical trials for the elderly are warranted. Most institutions (70%) chose Stage II/III (non-T4) esophageal squamous cell carcinoma as an important investigational target. CONCLUSIONS: Fit healthy elderly were considered the same as non-elderly patients, although there are no established treatment selection criteria. Radiation alone plays most important role in the treatment for vulnerable and frail esophageal squamous cell carcinoma patients. Stage II/III (non-T4) disease is attractive and warranted for future investigations.
Asunto(s)
Carcinoma de Células Escamosas , Atención a la Salud/organización & administración , Neoplasias Esofágicas , Anciano , Atención a la Salud/normas , Atención a la Salud/tendencias , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Japón , Masculino , Encuestas y CuestionariosRESUMEN
Esophageal cancer is thought to be the most malignant neoplasm due to its biological aggressiveness. The most effective treatment modality for esophageal cancer, particularly T4 esophageal cancer, is chemoradiotherapy (CRT). Some T4 patients show long-term survival after receiving CRT, suggesting that even T4 esophageal cancer can be cured with this modality. Although surgery is performed after CRT in some T4 cases, its prognostic benefit is controversial. In this paper, we review the status of CRT and conversion surgery as well as the development of new regimens and discuss the future prospects of CRT in the treatment of T4 esophageal cancer in Japan.
Asunto(s)
Quimioradioterapia , Neoplasias Esofágicas/terapia , Esofagectomía , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Cisplatino/administración & dosificación , Terapia Combinada , Neoplasias Esofágicas/patología , Fluorouracilo/administración & dosificación , Humanos , Japón , Estadificación de Neoplasias , Dosificación Radioterapéutica , Resultado del TratamientoRESUMEN
Gastrointestinal stromal tumors (GISTs) rarely arise in the esophagus, where carcinoma is the most common malignant neoplasm and leiomyoma is the most common benign tumor. Because of their rarity, the clinical course and treatment of esophageal GISTs are poorly understood. These lesions are generally thought to carry a poor prognosis, making the differential diagnosis of other common mesenchymal neoplasms essential, for both prognostic and therapeutic reasons. We report a case of successfully resected giant esophageal GIST, thought to be the largest resected GIST reported in Japan. The patient was a 65-year-old woman, in whom upper gastrointestinal endoscopy found a 180-mm submucosal tumor in the lower thoracic esophagus, extending just below the aortic arch. We diagnosed esophageal GIST, and the patient underwent middle and lower esophagectomy via left thoracotomy, followed by gastric tube reconstruction. The tumor was resected completely. Histopathological and immunohistochemical staining confirmed that the tumor was a high-risk lesion, and treatment with imatinib was initiated. Computed tomography showed liver metastasis 5 months later, but the patient is doing well 24 months after surgery.
Asunto(s)
Neoplasias Esofágicas/cirugía , Tumores del Estroma Gastrointestinal/cirugía , Anciano , Benzamidas/administración & dosificación , Endoscopía Gastrointestinal , Neoplasias Esofágicas/diagnóstico , Neoplasias Esofágicas/patología , Esofagectomía , Femenino , Tumores del Estroma Gastrointestinal/patología , Humanos , Mesilato de Imatinib , Neoplasias Hepáticas/secundario , Piperazinas/administración & dosificación , Pirimidinas/administración & dosificación , Procedimientos de Cirugía Plástica , Toracotomía , Resultado del TratamientoRESUMEN
OBJECTIVE: The aim of this study was to identify alternative compounds to the tumor suppressor miR-375 using the connectivity map (CMAP) and to validate the antitumor effects of the identified drugs in esophageal squamous cell carcinoma (ESCC). METHODS: Gene profiling of miR-375-treated TE2 and T.Tn cells was applied in order to search the CMAP database. Among the compounds identified using the CMAP, we focused on 8 drugs [(-)-epigallocatechin-3-gallate, metformin, rosiglitazone among others], excluding 2 drugs among the top 10 compounds. We evaluated whether these compounds possess tumor-suppressive functions in ESCC. RESULTS: A cytotoxicity assay showed that the sensitivity of TE2 and T.Tn cells treated with the 8 compounds was evaluated based on IC50 values of 42.9 µM to 3.8 mM. A cell cycle analysis revealed that the percentage of TE2 and T.Tn cells incubated with 6 compounds in the G0/G1 phase or the G2/M phase increased by approximately 40-80%. A TUNEL assay showed that the percentages of apoptotic cells treated with almost all compounds were significantly increased (p < 0.05) compared with the control cells. CONCLUSION: The CMAP database is a useful tool for identifying compounds affecting the same molecular pathways, particularly products that are difficult to apply via practical approaches, such as microRNAs.
Asunto(s)
Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Citotoxinas/farmacología , Neoplasias Esofágicas/tratamiento farmacológico , MicroARNs/efectos de los fármacos , Proteínas Supresoras de Tumor/efectos de los fármacos , Apoptosis/efectos de los fármacos , Benzocaína/farmacología , Betazol/farmacología , Catequina/análogos & derivados , Catequina/farmacología , Línea Celular Tumoral/efectos de los fármacos , Ácido Quenodesoxicólico/farmacología , Cartilla de ADN , Humanos , Etiquetado Corte-Fin in Situ , Metformina/farmacología , MicroARNs/metabolismo , Nizatidina/farmacología , Organofosfatos/farmacología , Prolina/análogos & derivados , Prolina/farmacología , Análisis por Matrices de Proteínas , Reacción en Cadena en Tiempo Real de la Polimerasa , Rosiglitazona , Tiazolidinedionas/farmacología , Transcriptoma , Transfección , Proteínas Supresoras de Tumor/genéticaRESUMEN
BACKGROUND: Among patients with T4 thoracic esophageal squamous cell carcinoma (TESCC), it is unclear whether the outcomes of late responders who undergo high-dose chemoradiotherapy (CRT) followed by salvage esophagectomy differs from those of early responders who undergo low-dose CRT followed by esophagectomy. METHODS: A total of 153 patients with T4 TESCC were treated with CRT. The first evaluation was performed after 40 Gy of CRT for downstaging. Of these, 28 patients could be downstaged, and underwent subsequent surgery (early responders). For the remaining patients, additional CRT was administered, and patients were re-evaluated after treatment and underwent salvage surgery. In total, 40 patients (early + late responders) were analyzed. RESULTS: The primary tumors exhibited a grade 3 response in six (21.4 %) of the early responders and two (16.7 %) of the late responders (p = 1.000). The rate of residual tumor in the primary tumor was 80 % (32/40 patients). The proportions of resected lymph nodes and positive metastatic nodes were similar between early and late responders (p = 0.406 and p = 0.859, respectively). The 5-year overall survival rates among the early and late responders were 25.9 and 36.5 %, respectively, and the median survival times were 24.8 and 24.3 months (p = 0.925), respectively. The 5-year cause-specific survival rates in the early and late responder groups were 61.5 and 72.9 % (p = 0.425), respectively. CONCLUSION: The outcomes of both early and late responders to CRT were similar, and salvage surgery for T4 TESCC outweighs the risks in patients with T4 TESCC.
Asunto(s)
Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/cirugía , Carcinoma de Células Escamosas/terapia , Quimioradioterapia , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Neoplasias Esofágicas/terapia , Esofagectomía , Terapia Recuperativa , Adulto , Anciano , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Masculino , Persona de Mediana Edad , Dosificación Radioterapéutica , Estudios Retrospectivos , Tasa de Supervivencia , Resultado del TratamientoRESUMEN
We investigated the usefulness of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) for superficial esophageal squamous cell carcinoma after resection via endoscopic submucosal dissection (ESD). Our case study included 37 patients and 49 tumors resected via ESD in our hospital between January 2012 and December 2013. Histopathological diagnosis confirmed squamous cell carcinoma in all cases. Tumors located near the esophago cardiac junction were excluded. We investigated retrospectively whether the standardized uptake value (SUV) obtained by using FDG-PET could be the criterion to decide whether to perform ESD. At first, the tumor was examined via endoscopy. If tumor depth (T status)was less than cSM1, we performed ESD. When the tumor depth was less than pSM1, no infiltration of the vessel or lymph duct was observed, and the surgical margin was free; therefore, we did not perform any further therapy. On the other hand, we measured the SUV obtained via FDG-PET. The cut-off value was set as 3.0 based on the correlation between the SUV and tumor depth. We investigated if SUV<.0 could be the criterion for further therapy after ESD. In our results, the sensitivity was 95%, specificity was 67%, and accuracy was 90%. The SUV also helped to identify the malignancy of the superficial esophageal cancer and could help to decide whether ESD should be undertaken.