RESUMEN
BACKGROUND: Various functions in elderly patients with esophageal cancer deteriorate easily and their quality of life can be adversely affected by treatment. The age groups covered in previous studies are wide, and the impact on the elderly individuals is unknown. This study examined changes in quality of life scores after preoperative chemotherapy to clarify aspects of physical, psychological, and social quality of life in elderly patients with esophageal cancer. METHODS: Thirty-six patients aged over 65 years, who were scheduled to undergo preoperative chemotherapy for esophageal cancer surgery, were enrolled. The survey questionnaire comprised the EORTC QLQ-C30 Japanese Language Version, EORTC QLQ-OES 18 Japanese Language Version, and G8. The surveys were conducted before chemotherapy (pre-CT) and after chemotherapy (post-CT). RESULTS: In the functional scale of QLQ-C 30, physical functioning decreased significantly, while emotional functioning increased significantly post-CT (p = 0.021, p = 0.030, respectively). Global health status was not changed. In QLQ-OES18, the mean symptom scale score decreased significantly for dysphagia, trouble swallowing saliva, choking, eating, reflux, and pain post-CT (p = 0.014, p = 0.034, p = 0.033, p = 0.022, p = 0.026, p = 0.016, respectively). The mean G8 score decreased significantly from 11.7 to 10.7 (p = 0.022) post-CT, but the proportion of patients with dysfunction decreased. CONCLUSIONS: Quality of life scores of elderly patients with esophageal cancer who received preoperative chemotherapy decreased in terms of physical function but improved in terms of esophageal cancer symptoms and mental function. Our results suggest that alleviation of symptoms contributed to the improvements in mental health.
Asunto(s)
Neoplasias Esofágicas , Calidad de Vida , Anciano , Neoplasias Esofágicas/tratamiento farmacológico , Neoplasias Esofágicas/psicología , Neoplasias Esofágicas/cirugía , Humanos , Encuestas y CuestionariosAsunto(s)
Drenaje , Hepatectomía/efectos adversos , Laparoscopía/efectos adversos , Anciano , Femenino , Hepatectomía/métodos , Humanos , Laparoscopía/métodos , Tiempo de Internación/estadística & datos numéricos , Neoplasias Hepáticas/cirugía , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Resultado del TratamientoRESUMEN
BACKGROUND: The appropriate surgical procedure for patients with upper third early gastric cancer is controversial. We compared total gastrectomy (TG) with proximal gastrectomy (PG) in this patient population. METHODS: A multicenter, non-randomized trial was conducted, with patients treated with PG or TG. We compared short- and long-term outcomes between these procedures. RESULTS: Between 2009 and 2014, we enrolled 254 patients from 22 institutions; data from 252 were included in the analysis. These 252 patients were assigned to either the PG (n = 159) or TG (n = 93) group. Percentage of body weight loss (%BWL) at 1 year after surgery, i.e., the primary endpoint, in the PG group was significantly less than that of the TG group (- 12.8% versus - 16.9%; p = 0.0001). For short-term outcomes, operation time was significantly shorter for PG than TG (252 min versus 303 min; p < 0.0001), but there were no group-dependent differences in blood loss and postoperative complications. For long-term outcomes, incidence of reflux esophagitis in the PG group was significantly higher than that of the TG group (14.5% versus 5.4%; p = 0.02), while there were no differences in the incidence of anastomotic stenosis between the two (5.7% versus 5.4%; p = 0.92). Overall patient survival rates were similar between the two groups (3-year survival rates: 96% versus 92% in the PG and TG groups, respectively; p = 0.49). CONCLUSIONS: Patients who underwent PG were better able to control weight loss without worsening the prognosis, relative to those in the TG group. Optimization of a reconstruction method to reduce reflux in PG patients will be important.
Asunto(s)
Gastrectomía/métodos , Neoplasias Gástricas/cirugía , Estómago/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Anastomosis Quirúrgica , Femenino , Gastrectomía/mortalidad , Humanos , Masculino , Persona de Mediana Edad , Estadificación de Neoplasias , Tempo Operativo , Pronóstico , Estudios Prospectivos , Estómago/patología , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Resultado del Tratamiento , Pérdida de PesoRESUMEN
Reflux following an esophagectomy with gastric conduit reconstruction in the posterior mediastinum is a clinically significant problem. In this study, we investigated the frequency and impact of reflux on the quality of life (QOL) among 158 patients who underwent an esophagectomy for esophageal cancer using an original questionnaire and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Version 3.0 (EORTC QLQ-C30). Reflux frequency was assessed using the original questionnaire. The number of patients who complained of reflux every day, two or three times a week, once a week, or less than once a week was 16 (10.1%), 21 (13.3%), 26 (16.5%), and 60 (38.0%), respectively. Out of 35 patients (22.2%) reported no reflux symptoms. Patients were divided into two groups: those with reflux ≥ once/week (63 patients) and those with low frequency of symptoms (95 patients). Time elapsed following surgery was the only factor to influence reflux frequency. Reflux frequency decreased within two years of surgery; however, the frequency plateaued after more than two years. QOL was assessed using the EORTC QLQ-C30. The ≥ once/week reflux group had a significantly lower global health status score than the low-frequency reflux group (59.6 ± 24.2 vs. 70.8 ± 20.7; P = 0.007). In addition, the ≥ once/week reflux group had a significantly lower social functioning score than the low-frequency reflux group (81.6 ± 24.1 vs. 88.4 ± 19.8; P = 0.035). Regarding symptoms, the ≥ once/week reflux group had significantly higher scores for fatigue, nausea, and vomiting, dyspnea and insomnia compared to the low-frequency reflux group (fatigue: 42.4 ± 21.9 vs. 28.9 ± 18.4, P < 0.001; nausea and vomiting: 17.3 ± 17.1 vs. 4.9 ± 10.6, P < 0. 001; dyspnea: 29.2 ± 26.0 vs. 21.7 ± 26.8, P = 0.043; insomnia: 22.2 ± 31.1 vs. 10.5 ± 21.7, P = 0.015). Thus, reflux after an esophagectomy was associated with a lower QOL.
Asunto(s)
Esofagectomía/efectos adversos , Reflujo Gastroesofágico/psicología , Procedimientos de Cirugía Plástica/efectos adversos , Complicaciones Posoperatorias/psicología , Calidad de Vida/psicología , Anciano , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Unión Esofagogástrica/cirugía , Femenino , Reflujo Gastroesofágico/epidemiología , Reflujo Gastroesofágico/etiología , Humanos , Masculino , Mediastino/cirugía , Persona de Mediana Edad , Complicaciones Posoperatorias/epidemiología , Complicaciones Posoperatorias/etiología , Periodo Posoperatorio , Procedimientos de Cirugía Plástica/métodos , Encuestas y Cuestionarios , Resultado del TratamientoRESUMEN
Although no consensus is available on the treatment of esophageal squamous cell carcinoma (ESCC) invading adjacent organs (T4), establishing effective induction treatments is crucial to altering an unresectable status and achieving curative resection. Here, we evaluated the efficacy of chemotherapy using 5-fluorouracil, cisplatin, and docetaxel (DCF) as the initial induction treatment for T4 ESCC. Fifty patients without distant metastasis who underwent initial induction chemotherapy using DCF for T4 ESCC were propensity score-matched with 50 patients who underwent radiotherapy concurrent with cisplatin and 5-fluorouracil (CRT). In the DCF group, 24 (48.0%) patients underwent surgery, achieving a 64% clinical response rate compared to 72.0% for induction CRT. CRT was also performed in another 24 (48.0%) patients in the DCF group in whom surgical resection was not indicated. The DCF group had significantly higher overall resectability than the CRT group (78.0% vs. 48.0%, P = 0.0017). The esophageal perforation rate during induction treatments was significantly lower in the DCF group than the CRT group (4.0% vs. 18.0%, P = 0.0205). Prognosis was significantly better in the DCF group than the CRT group (5-year cancer-specific survival 42.1% vs. 22.2%, P = 0.0146). Thus, induction DCF chemotherapy in patients with T4 ESCC reduced esophageal perforation and increased overall resectability, leading to better survival than CRT alone. Therefore, DCF chemotherapy may be an effective and safe option for initial induction treatment of T4 ESCC.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Carcinoma de Células Escamosas/terapia , Cisplatino/administración & dosificación , Neoplasias Esofágicas/terapia , Fluorouracilo/administración & dosificación , Quimioterapia de Inducción/métodos , Taxoides/administración & dosificación , Anciano , Carcinoma de Células Escamosas/patología , Quimioradioterapia/métodos , Docetaxel , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Esofagoscopía/estadística & datos numéricos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Resultado del TratamientoRESUMEN
Although 3-field lymph node dissection (3-FLD) is often performed for thoracic esophageal squamous cell carcinoma (ESCC), the clinical effects of cervical lymph node dissection in addition to mediastinal and abdominal dissections on postoperative complications remain unclear. A total of 367 ESCC patients who underwent curative esophagectomy for thoracic esophageal cancer in our hospital from 2010 to 2015 were included in the study: 157 patients who underwent 2-field lymph node dissection (2-FLD) and 210 patients who underwent 3-FLD. Clinicopathological parameters and postoperative complications based on the Clavien-Dindo classification were compared between the two groups. We performed propensity score matching (PSM) analyses to compare the groups with well-balanced backgrounds. In terms of patient background, clinical T (p < 0.001), N (p < 0.001), and M (p = 0.002) stage of tumor was significantly more advanced; therefore, preoperative treatment was more frequently performed in the 3-FLD group than in the 2-FLD group (91.0% vs. 79.0%, P< 0.001). However, perioperative parameters including operation time, blood loss, and the number of dissected mediastinal and abdominal lymph nodes did not differ between the groups. In terms of postoperative complications, the occurrence rate of pneumonia increased significantly in patients with 3-FLD compared to 2-FLD (grade III or higher: 10.5% vs. 3.2%, P= 0.025). Although the duration of systemic inflammatory response syndrome (SIRS) was longer in the 3-FLD group than in the 2-FLD group (median 3 days vs. 2 days, P= 0.025), other postoperative parameters (including the highest level of postoperative serum C-reactive protein, intensive care unit stay, re-operation rate, and postoperative hospital stay) were similar between the groups. After PSM, the differences in the background between the groups disappeared. PSM analysis showed that there was no significant difference in each complication between the groups. The duration of SIRS tended to be longer in the 3-FLD group than in the 2-FLD group, but the difference was not significant. The field of lymphadenectomy negatively impacted the short-term outcome in ESCC patients in terms of pneumonia and inflammatory response. However, because the results of the PSM analyses indicate that the short-term outcome was similar between the two groups, 3-FLD could be as feasible as 2-FLD in ESCC patients.
Asunto(s)
Carcinoma de Células Escamosas/cirugía , Neoplasias Esofágicas/cirugía , Esofagectomía/métodos , Escisión del Ganglio Linfático/métodos , Ganglios Linfáticos/cirugía , Complicaciones Posoperatorias/etiología , Abdomen , Adulto , Anciano , Anciano de 80 o más Años , Proteína C-Reactiva/análisis , Carcinoma de Células Escamosas/sangre , Carcinoma de Células Escamosas/patología , Neoplasias Esofágicas/sangre , Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago , Femenino , Humanos , Tiempo de Internación , Ganglios Linfáticos/patología , Masculino , Mediastino , Persona de Mediana Edad , Cuello , Tempo Operativo , Neumonía/etiología , Periodo Posoperatorio , Puntaje de Propensión , Estudios Prospectivos , Estudios Retrospectivos , Síndrome de Respuesta Inflamatoria Sistémica/etiología , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: This phase II trial evaluated the efficacy of cisplatin and fluorouracil (CF)-based combination neoadjuvant chemotherapy on the outcome of patients with resectable locally advanced esophageal squamous cell carcinoma (ESCC). We compared the recurrence-free survival (RFS) associated with CF plus Adriamycin (ACF) with that associated with CF plus docetaxel (DCF) to select an alternative regimen in a new phase III trial investigating the optimal neoadjuvant treatment of patients with ESCC. PATIENTS AND METHODS: Patients with resectable advanced ESCC were randomly assigned to either ACF (Adriamycin 35 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 7 days) every 4 weeks or DCF (docetaxel 70 mg/m2, cisplatin 70 mg/m2 i.v. on day 1, fluorouracil 700 mg/m2 continuous infusion for 5 days) every 3 weeks. Surgery was scheduled after completion of two cycles of chemotherapy. The primary end point was RFS, analyzed by the intention-to-treat. RESULTS: Between October 2011 and October 2013, 162 patients at 10 institutions were enrolled in the study, all of whom were eligible and randomly assigned to the two groups (81 to the ACF group and 81 to the DCF group). The R0 resection rates for the ACF and DCF groups were equivalent (95.9% versus 96.2%, P = 0.93). The 2-year RFS and overall survival rates for DCF versus ACF were 64.1% versus 42.9% (hazard ratio 0.53, 95% confidence interval 0.33-0.83, P = 0.0057) and 78.6% versus 65.4% (P = 0.08), respectively. CONCLUSION: Compared with ACF, DCF chemotherapy was associated with prolonged RFS for patients with resectable advanced ESCC. Thus, DCF chemotherapy has potential as a standard neoadjuvant therapy for resectable ESCC. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Clinical Trials Registry of Japan (identification number UMIN000004555/000004616).
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Doxorrubicina/administración & dosificación , Neoplasias Esofágicas/tratamiento farmacológico , Taxoides/administración & dosificación , Adulto , Anciano , Carcinoma de Células Escamosas/mortalidad , Quimioterapia Adyuvante , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Docetaxel , Doxorrubicina/efectos adversos , Neoplasias Esofágicas/mortalidad , Carcinoma de Células Escamosas de Esófago , Femenino , Fluorouracilo/administración & dosificación , Fluorouracilo/efectos adversos , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Terapia Neoadyuvante , Taxoides/efectos adversos , Resultado del TratamientoRESUMEN
BACKGROUND: [(18) F]fluorodeoxyglucose (FDG)-PET has been used to evaluate the response of primary tumours to neoadjuvant therapy for oesophageal cancer. The clinical significance of the number of PET-positive nodes before and after therapy has not been investigated previously. METHODS: [(18) F]FDG-PET was performed before and 2-3 weeks after completion of neoadjuvant chemotherapy to identify the number of PET-positive nodes, and these numbers were assessed in relation to metabolic changes in the primary tumour. RESULTS: Of 302 patients in total, 90 had no PET-positive nodes, 83 had one, 59 had two and 70 patients had three or more positive nodes before therapy. After treatment, the numbers were: none in 207 patients, one in 59, two in 20 and three or more in 16 patients. The number of PET-positive nodes after treatment was influenced by both the number of PET-positive nodes before therapy and the response to preoperative therapy, and correlated with the number of metastatic lymph nodes. Overall survival was longer in patients who had no PET-positive nodes after treatment than in those who had one or more. Multivariable analysis identified the numbers of PET-positive nodes before and after chemotherapy as independent prognostic factors, together with clinical response, tumour depth and lymph node involvement. CONCLUSION: The number of PET-positive nodes after treatment correlated with survival in patients with oesophageal cancer who underwent neoadjuvant chemotherapy.
Asunto(s)
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Células Escamosas/tratamiento farmacológico , Neoplasias Esofágicas/tratamiento farmacológico , Esofagectomía , Ganglios Linfáticos/diagnóstico por imagen , Tomografía de Emisión de Positrones , Adulto , Anciano , Antineoplásicos/administración & dosificación , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/mortalidad , Carcinoma de Células Escamosas/cirugía , Quimioterapia Adyuvante , Neoplasias Esofágicas/diagnóstico por imagen , Neoplasias Esofágicas/mortalidad , Neoplasias Esofágicas/cirugía , Femenino , Fluorodesoxiglucosa F18 , Humanos , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Radiofármacos , Resultado del TratamientoRESUMEN
BACKGROUND: Functional microRNAs (miRNAs) in exosomes have been recognised as potential stable biomarkers in cancers. The aim of this study is to identify specific miRNAs in exosome as serum biomarkers for the early detection of recurrence in human colorectal cancer (CRC). METHODS: Serum samples were sequentially obtained from six patients with and without recurrent CRC. The miRNAs were purified from exosomes, and miRNA microarray analysis was performed. The miRNA expression profiles and copy number aberrations were explored using microarray and array CGH analyses in 124 CRC tissues. Then, we validated exosomal miRNAs in 2 serum sample sets (90 and 209 CRC patients) by quantitative real-time RT-PCR. RESULTS: Exosomal miR-17-92a cluster expression level in serum was correlated with the recurrence of CRC. Exosomal miR-19a expression levels in serum were significantly increased in patients with CRC as compared with healthy individuals with gene amplification. The CRC patients with high exosomal miR-19a expression showed poorer prognoses than the low expression group (P<0.001). CONCLUSIONS: Abundant expression of exosomal miR-19a in serum was identified as a prognostic biomarker for recurrence in CRC patients.
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Neoplasias Colorrectales/diagnóstico , Exosomas , MicroARNs/sangre , Recurrencia Local de Neoplasia/diagnóstico , Biomarcadores de Tumor/sangre , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Humanos , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/patología , Pronóstico , ARN Largo no CodificanteRESUMEN
BACKGROUND: SIRT4, which is localised in the mitochondria, is one of the least characterised members of the sirtuin family of nicotinamide adenine dinucleotide-dependent enzymes that play key roles in multiple cellular processes such as metabolism, stress response and longevity. There are only a few studies that have characterised its function and assessed its clinical significance in human cancers. METHODS: We established colorectal cancer cell lines (SW480, HCT116, and HT29) overexpressing SIRT4 and investigated their effects on proliferation, migration and invasion, as well as E-cadherin expression, that negatively regulates tumour invasion and metastases. The associations between SIRT4 expression in colorectal cancer specimens and clinicopathological features including prognosis were assessed by immunohistochemistry. RESULTS: SIRT4 upregulated E-cadherin expression and suppressed proliferation, migration and invasion through inhibition of glutamine metabolism in colorectal cancer cells. Moreover, SIRT4 expression in colorectal cancer decreased with the progression of invasion and metastasis, and a low expression level of SIRT4 was correlated with a worse prognosis. CONCLUSIONS: SIRT4 has a tumour-suppressive function and may serve as a novel therapeutic target in colorectal cancer.
Asunto(s)
Neoplasias Colorrectales/genética , Genes Supresores de Tumor , Proteínas Mitocondriales/fisiología , Sirtuinas/fisiología , Movimiento Celular/genética , Proliferación Celular/genética , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/patología , Progresión de la Enfermedad , Glutamina/metabolismo , Células HCT116 , Células HT29 , Humanos , Invasividad Neoplásica , Pronóstico , Células Tumorales CultivadasRESUMEN
BACKGROUND: Long-term immunosuppression is associated with an increased risk of cancer. Especially, the immunosuppression in pancreas transplantation is more intensive than that in other organ transplantation because of its strong immunogenicity. Therefore, it suggests that the risk of post-transplant de novo malignancy might increase in pancreas transplantation. However, there have been few studies of de novo malignancy after pancreas transplantation. The aim of this study was to analyze the incidence of de novo malignancy after pancreas transplantation in Japan. METHODS: Post-transplant patients with de novo malignancy were surveyed and characterized in Japan. RESULTS: Among 107 cases receiving pancreas transplantation in Japan between 2001 and 2010, de novo malignancy developed in 9 cases (8.4%): post-transplant lymphoproliferative disorders in 6 cases, colon cancer in 1 case, renal cancer in 1 case, and brain tumor in 1 case. CONCLUSIONS: We clarified the incidence of de novo malignancy after pancreas transplantation in Japan.
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Neoplasias Encefálicas/etiología , Carcinoma de Células Renales/etiología , Neoplasias del Colon/etiología , Glioblastoma/etiología , Neoplasias Renales/etiología , Trasplante de Páncreas , Complicaciones Posoperatorias , Adulto , Anciano , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/epidemiología , Carcinoma de Células Renales/diagnóstico , Carcinoma de Células Renales/epidemiología , Neoplasias del Colon/diagnóstico , Neoplasias del Colon/epidemiología , Femenino , Glioblastoma/diagnóstico , Glioblastoma/epidemiología , Humanos , Incidencia , Japón , Neoplasias Renales/diagnóstico , Neoplasias Renales/epidemiología , Masculino , Persona de Mediana Edad , Evaluación de Resultado en la Atención de Salud , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/epidemiología , RiesgoRESUMEN
BACKGROUND: The MYC oncogene has long been established as a central driver in many types of human cancers including colorectal cancer. However, the realization of MYC-targeting therapies remains elusive; as a result, synthetic lethal therapeutic approaches are alternatively being explored. A synthetic lethal therapeutic approach aims to kill MYC-driven tumors by targeting a certain co-regulator on the MYC pathway. PATIENTS AND METHODS: We analyzed copy number and expression profiles from 130 colorectal cancer tumors together with publicly available datasets to identify co-regulators on the MYC pathway. Candidates were functionally tested by in vitro assays using colorectal cancer and normal fibroblast cell lines. Additionally, survival analyses were carried out on another 159 colorectal cancer patients and public datasets. RESULTS: Our in silico screening identified two MYC co-regulator candidates, AURKA and TPX2, which are interacting mitotic regulators located on chromosome 20q. We found the two candidates showed frequent co-amplification with the MYC locus while expression levels of MYC and the two genes were positively correlated with those of MYC downstream target genes across multiple cancer types. In vitro, the aberrant expression of MYC, AURKA and TPX2 resulted in more aggressive anchorage-independent growth in normal fibroblast cells. Furthermore, knockdown of AURKA or TPX2, or treatment with an AURKA-specific inhibitor effectively suppressed the proliferation of MYC-expressing colorectal cancer cells. Additionally, combined high expression of MYC, AURKA and TPX2 proved to be a poor prognostic indicator of colorectal cancer patient survival. CONCLUSIONS: Through bioinformatic analyses and experiments, we proposed TPX2 and AURKA as novel co-regulators on the MYC pathway. Inhibiting the AURKA/TPX2 axis would be a novel synthetic lethal therapeutic approach for MYC-driven cancers.
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Aurora Quinasa A/metabolismo , Proteínas de Ciclo Celular/metabolismo , Neoplasias Colorrectales/enzimología , Proteínas Asociadas a Microtúbulos/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Proto-Oncogénicas c-myc/metabolismo , Transducción de Señal , Antineoplásicos/uso terapéutico , Aurora Quinasa A/antagonistas & inhibidores , Aurora Quinasa A/genética , Proteínas de Ciclo Celular/genética , Proliferación Celular , Supervivencia Celular , Cromosomas Humanos Par 20 , Cromosomas Humanos Par 8 , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/mortalidad , Neoplasias Colorrectales/patología , Biología Computacional , Amplificación de Genes , Dosificación de Gen , Perfilación de la Expresión Génica , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Células HCT116 , Humanos , Proteínas Asociadas a Microtúbulos/genética , Proteínas Nucleares/genética , Pronóstico , Inhibidores de Proteínas Quinasas/farmacología , Proteínas Proto-Oncogénicas c-myc/genética , Interferencia de ARN , Transducción de Señal/efectos de los fármacos , Análisis de Supervivencia , Factores de Tiempo , TransfecciónRESUMEN
PURPOSE: Recent advances in laparoscopic surgical technology have made it possible to perform advanced high-level surgery, such as lymph node dissection for malignancy. Grasping the anatomy during such procedures is important for a safe operation. We have developed a new image information system that provides three-dimensional (3D) reconstructed CT images synchronized with the motion of the laparoscope. This study assesses this new navigation system. METHODS: Enhanced CT using a custom-made software program can provide 3D angiography images reconstructed as a laparoscopic view. A motion sensor mounted on the laparoscope can detect the direction angle of the laparoscope. The real-time rendered 3D CT images are synchronized with the laparoscopic video images according to the motion of the scope. These 3D CT images are projected on another monitor close to the laparoscopic video monitor. Lymph node dissection can be performed with the help of the real-time navigation system that provides a detailed 3D view of the vasculature. RESULTS: Ten laparoscopic gastrectomies were performed using this navigation system. Real-time intraoperative navigation of the vasculature was available, allowing for an excellent surgical outcome. No complications occurred in this series. CONCLUSION: Our intraoperative navigation system allows for safe laparoscopic gastric lymph node dissection.
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Gastrectomía/métodos , Imagenología Tridimensional/métodos , Laparoscopía/métodos , Escisión del Ganglio Linfático/métodos , Neoplasias Gástricas/diagnóstico por imagen , Neoplasias Gástricas/cirugía , Cirugía Asistida por Computador/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Programas Informáticos , Resultado del TratamientoRESUMEN
BACKGROUND: Circulating tumour DNA (ctDNA) is an emerging candidate biomarker for malignancies and may be useful for monitoring the disease status of gastric cancer. METHODS: We performed targeted deep sequencing of plasma cell-free DNA (cfDNA) by massively parallel sequencing in patients with tumours harbouring TP53 mutations. The quantitative values of TP53-ctDNA during the clinical course were compared with the tumour status. RESULTS: Three out of ten patients with TP53 mutations in primary tumours showed detectable TP53 mutation levels in preoperative cfDNA. Although the cfDNA concentrations were not always reflective of the disease course, the ctDNA fraction correlated with the disease status. CONCLUSIONS: ctDNA may serve as a useful biomarker to monitor gastric cancer progression and residual disease.
Asunto(s)
Biomarcadores de Tumor/sangre , ADN de Neoplasias/sangre , Neoplasias Gástricas/sangre , Anciano , Anciano de 80 o más Años , Análisis Mutacional de ADN , Progresión de la Enfermedad , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Metástasis Linfática , Masculino , Neoplasia Residual , Estudios Prospectivos , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Proteína p53 Supresora de Tumor/genéticaRESUMEN
BACKGROUND: Pancreatic cancer has a poor prognosis because of its high refractoriness to chemotherapy and tumour recurrence, and these properties have been attributed to cancer stem cells (CSCs). MicroRNA (miRNA) regulates various molecular mechanisms of cancer progression associated with CSCs. This study aimed to identify the candidate miRNA and to characterise the clinical significance. METHODS: We established gemcitabine-resistant Panc1 cells, and induced CSC-like properties through sphere formation. Candidate miRNAs were selected through microarray analysis. The overexpression and knockdown experiments were performed by evaluating the in vitro cell growth and in vivo tumourigenicity. The expression was studied in 24 pancreatic cancer samples after laser captured microdissection and by immunohistochemical staining. RESULTS: The in vitro drug sensitivity of pancreatic cancer cells was altered according to the miR-1246 expression via CCNG2. In vivo, we found that miR-1246 could increase tumour-initiating potential and induced drug resistance. A high expression level of miR-1246 was correlated with a worse prognosis and CCNG2 expression was significantly lower in those patients. CONCLUSIONS: miR-1246 expression was associated with chemoresistance and CSC-like properties via CCNG2, and could predict worse prognosis in pancreatic cancer patients.
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Ciclina G2/fisiología , Desoxicitidina/análogos & derivados , MicroARNs/metabolismo , Células Madre Neoplásicas/patología , Neoplasias Pancreáticas/tratamiento farmacológico , Animales , Antimetabolitos Antineoplásicos , Línea Celular Tumoral , Desoxicitidina/uso terapéutico , Resistencia a Antineoplásicos , Femenino , Humanos , Ratones , Neoplasias Pancreáticas/patología , GemcitabinaRESUMEN
BACKGROUND: Cancer stem cells (CSCs) are responsible for treatment failure. However, their identification and roles in resistance are not well established in head and neck squamous cell carcinoma (HNSCC). METHODS: Three HNSCC cell lines (FaDu, Detroit562 and BICR6) were treated with cisplatin or radiation. Cell surface antigens were analysed by LyoPlate, a novel cell surface antigen array. The expression levels of antigens highly expressed after treatments were further compared between cisplatin-resistant Detroit562 cells and its parental line. Association of the candidate antigen with CSCs properties, namely sphere formation and in vivo tumourigenicity, was also examined. RESULTS: CD10, CD15s, CD146 and CD282 were upregulated across the treated cell lines, while the increased expression of CD10 was prominent in the cisplatin-resistant cell line. Isolation mediated by FACS revealed that the CD10-positive subpopulation was more refractory to cisplatin, fluorouracil and radiation than the CD10-negative subpopulation. It also showed an increased ability to form spheres in vitro and tumours in vivo. Moreover, the CD10-positive subpopulation expressed the CSC marker OCT3/4 at a higher level than that in the CD10-negative subpopulation. CONCLUSIONS: CD10 is associated with therapeutic resistance and CSC-like properties of HNSCC. CD10 may serve as a target molecule in the treatment of refractory HNSCC.
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Biomarcadores de Tumor/metabolismo , Carcinoma de Células Escamosas/metabolismo , Resistencia a Antineoplásicos , Neoplasias de Cabeza y Cuello/metabolismo , Células Madre Neoplásicas/metabolismo , Neprilisina/metabolismo , Animales , Antineoplásicos/farmacología , Carcinoma de Células Escamosas/tratamiento farmacológico , Carcinoma de Células Escamosas/radioterapia , Línea Celular Tumoral , Cisplatino/farmacología , Puntos de Control de la Fase G1 del Ciclo Celular , Regulación Neoplásica de la Expresión Génica , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/radioterapia , Humanos , Ratones , Ratones Endogámicos NOD , Ratones SCID , Células Madre Neoplásicas/efectos de los fármacos , Células Madre Neoplásicas/efectos de la radiación , Factor 3 de Transcripción de Unión a Octámeros/genética , Factor 3 de Transcripción de Unión a Octámeros/metabolismo , Tolerancia a Radiación , Carcinoma de Células Escamosas de Cabeza y Cuello , Regulación hacia Arriba , Ensayos Antitumor por Modelo de XenoinjertoRESUMEN
In Japan, absolute shortage of donors still continues even after the law allowing organ transplantation from deceased donors came into force in 1997. With the passage of the waiting period after registration for pancreas transplantation (PTx), both deaths and serious cases of diabetic complications necessitating withdrawal of the registration have undoubtedly increased. Therefore, so-called "marginal donor" (MD) has been considered as a potential solution for shortage of donors in Japan. The aim of the present study is to evaluate feasibility of MD in terms of post-PTx outcomes using data from Japan Organ Transplantation Network. A total of 148 PTx were performed from deceased donors in Japan from 2000 to 2012. MD was defined as follows: (1) >45 years old; (2) hemodynamically unstable at harvest using a high-dose dopamine or more than 2 vasopressors; or (3) non-heart-beating status. Postoperative outcomes after PTx were compared between the MD group and the non-MD group. Among the 148 PTx donors, 108 donors (73.0%) satisfied the criteria of MD. Early graft loss of pancreas graft during 3 months post-transplant was observed in 15 patients (10.1%), and the marginality (MD vs non-MD) was not significantly correlated with the early loss of pancreas graft. The overall patient survival of the MD group (1, 3, 5 years: 94.7%, 94.7%, 94.7%) was not significantly different from that of the non-MD group (1, 3, 5 years: 95.0%, 95.0%, 95.0%). Pancreas graft survival in the MD group (1, 3, 5 years: 80.9%, 73.2%, 66.0%) seemed to be slightly lower than that in the non-MD group (1, 3, 5 years: 92.5%, 85.2%, 77.4%), but no statistically significant differences were found between the 2 groups. These results suggest the feasibility of the use of MD for PTx.
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Trasplante de Páncreas , Donantes de Tejidos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
BACKGROUND: S-1, an oral fluoropyrimidine, plus cisplatin (SP) is a standard regimen for advanced gastric cancer (AGC) in East Asia. To date, no studies have evaluated the efficacy and safety of trastuzumab combined with SP in patients with human epidermal growth factor receptor type 2 (HER2)-positive AGC. METHODS: Patients with HER2-positive AGC received S-1 (80-120 mg per day) orally on days 1-14, cisplatin (60 mg m(-2)) intravenously on day 1, and trastuzumab (course 1, 8 mg kg(-1); course 2 onward, 6 mg kg(-1)) intravenously on day 1 of a 21-day cycle. The primary end point was response rate (RR); secondary end points included overall survival (OS), progression-free survival (PFS), time to treatment failure (TTF), and adverse events. RESULTS: A total of 56 patients were enrolled. In the full analysis set of 53 patients, the confirmed RR was 68% (95% confidence interval (CI)=54-80%), and the disease control rate was 94% (95% CI=84-99%). Median OS, PFS, and TTF were estimated as 16.0, 7.8, and 5.7 months, respectively. Major grade 3 or 4 adverse events included neutropaenia (36%), anorexia (23%), and anaemia (15%). CONCLUSIONS: Trastuzumab in combination with SP showed promising antitumour activity and manageable toxic effects in patients with HER2-positive AGC.
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Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Receptor ErbB-2/biosíntesis , Neoplasias Gástricas/tratamiento farmacológico , Adulto , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Cisplatino/administración & dosificación , Cisplatino/efectos adversos , Supervivencia sin Enfermedad , Combinación de Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ácido Oxónico/administración & dosificación , Ácido Oxónico/efectos adversos , Receptor ErbB-2/genética , Neoplasias Gástricas/enzimología , Tegafur/administración & dosificación , Tegafur/efectos adversos , TrastuzumabRESUMEN
BACKGROUND: We previously conducted gene expression microarray analyses to identify novel indicators for colorectal cancer (CRC) metastasis and prognosis from which we identified PVT-1 as a candidate gene. PVT-1, which encodes a long noncoding RNA, mapped to chromosome 8q24 whose copy-number amplification is one of the most frequent events in a wide variety of malignant diseases. However, PVT-1 molecular mechanism of action remains unclear. METHODS: We conducted cell proliferation and invasion assays using colorectal cancer cell lines transfected with PVT-1siRNA or negative control siRNA. Gene expression microarray analyses on these cell lines were also carried out to investigate the molecular function of PVT-1. Further, we investigated the impact of PVT-1 expression on the prognosis of 164 colorectal cancer patients by qRT-PCR. RESULTS: CRC cells transfected with PVT-1 siRNA exhibited significant loss of their proliferation and invasion capabilities. In these cells, the TGF-ß signalling pathway and apoptotic signals were significantly activated. In addition, univariate and multivariate analysis revealed that PVT-1 expression level was an independent risk factor for overall survival of colorectal cancer patients. CONCLUSION: PVT-1, which maps to 8q24, generates antiapoptotic activity in CRC, and abnormal expression of PVT-1 was a prognostic indicator for CRC patients.