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BACKGROUND: We suspected that fatty pancreas, accompanied with metabolic syndrome, may be associated with the incidence of postoperative pancreatic fistula (POPF) after radial gastrectomy. METHODS: Between February 2012 and March 2014, we reviewed consecutive 79 gastric cancer patients who underwent radical gastrectomy. To quantify the degree of fatty infiltration to pancreas by preoperative contrast-enhanced CT, we measured ratios and differences between pancreatic and splenic attenuation values (P/S and P-S, respectively). The optimal cut-off values of P/S and P-S for predicting POPF were determined using the receiver operating characteristic (ROC) curve analysis. Risk factors for POPF of International Study Group on Pancreatic Fistula grade B or higher were examined using univariate and multivariate analyses. RESULTS: POPF occurred in 6 patients (7.6%). ROC curve analyses revealed that the most optimal predictive values of P/S and P-S were 0.74 and -28.8, respectively. Univariate analysis demonstrated that high visceral fat area (p = 0.037), low P/S (p = 0.013), and low P-S (p = 0.006) were significant risk factors of POPF. Multivariate analysis demonstrated that low P/S (OR 10.2 [p = 0.046]) and low P-S (OR 13.2 [p = 0.023]) were significant risk factors of POPF. CONCLUSION: Fatty pancreas is a risk factor of POPF after radical gastrectomy.
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Adiposidad , Gastrectomía/efectos adversos , Grasa Intraabdominal/diagnóstico por imagen , Páncreas/diagnóstico por imagen , Fístula Pancreática/etiología , Adulto , Anciano , Anciano de 80 o más Años , Área Bajo la Curva , Femenino , Gastrectomía/métodos , Humanos , Masculino , Síndrome Metabólico/complicaciones , Persona de Mediana Edad , Complicaciones Posoperatorias/etiología , Periodo Preoperatorio , Curva ROC , Estudios Retrospectivos , Factores de Riesgo , Bazo/diagnóstico por imagen , Tomografía Computarizada por Rayos XRESUMEN
AIMS: p-21 activated kinase (PAK) 4, part of the six PAK families, plays an important role in growth factor signalling, cytoskeletal remodelling, gene transcription, cell proliferation and oncogenic transformation. However, the clinical significance of PAK4 in gastric cancer has yet to be fully elucidated. PAK4 expression was evaluated, and the correlations of PAK4 expression with clinicopathological features and outcomes in gastric cancer were examined. METHODS: Gastric adenocarcinomas obtained from 217 patients who underwent gastrectomy were analysed. PAK4 expression was evaluated using immunohistochemical staining. RESULTS: PAK4 overexpression was found in 95 (43.8%) of 217 tumours . High PAK4 expression was significantly correlated with clinicopathological variables related to tumour progression, including depth of invasion, metastatic lymph nodes, pathological stage, distant metastasis or recurrent disease. High PAK4 expression was significantly associated with poorer disease-specific survival (DSS) (p<0.001) and relapse-free survival (RFS) (p<0.001). On multivariable analysis, PAK4 was an independent prognostic factor for DSS (HR 2.5 (95% CI 1.4 to 4.7), p=0.003) and RFS (HR 2.8 (95% CI 1.4 to 5.6), p=0.004). Even in stage II and III disease, PAK4 was an independent prognostic factor for RFS (HR 2.2 (95% CI 1.1 to 4.5), p=0.029). CONCLUSIONS: PAK4 may become a new prognostic factor in patients with gastric cancer.
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Adenocarcinoma/metabolismo , Biomarcadores de Tumor/metabolismo , Recurrencia Local de Neoplasia/metabolismo , Neoplasias Gástricas/metabolismo , Quinasas p21 Activadas/metabolismo , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Anciano , Biomarcadores de Tumor/genética , Proliferación Celular/genética , Progresión de la Enfermedad , Femenino , Humanos , Metástasis Linfática/genética , Metástasis Linfática/patología , Masculino , Recurrencia Local de Neoplasia/genética , Recurrencia Local de Neoplasia/mortalidad , Recurrencia Local de Neoplasia/patología , Pronóstico , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Tasa de Supervivencia , Quinasas p21 Activadas/genéticaRESUMEN
Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 or vascular endothelial growth factor receptor 2 have become standard therapy for GC. Hepatocyte growth factor and its receptor, c-MET (MET), play key roles in tumor growth through activated signaling pathways from receptor in GC cells. Genomic amplification of MET leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical significance of MET in GC and examines MET as a potential therapeutic target in patients with GC. Preclinical studies in animal models have shown that MET antibodies or small-molecule MET inhibitors suppress tumor-cell proliferation and tumor progression in MET-amplified GC cells. These drugs are now being evaluated in clinical trials as treatments for metastatic or unresectable GC.
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AIM: To investigate the anastomotic complications of esophagojejunostomy (EJS) after laparoscopic total gastrectomy (LTG), we reviewed retrospective studies. METHODS: A literature search was conducted in PubMed for studies published from January 1, 1994 through January 31, 2015. The search terms included "laparoscopic," "total gastrectomy," and "gastric cancer." First, we selected 16 non-randomized controlled trials (RCTs) comparing LTG with open total gastrectomy (OTG) and conducted an updated meta-analysis of anastomotic complications after total gastrectomy. The Newcastle-Ottawa scoring system (NOS) was used to assess the quality of the non-RCTs included in this study. Next, we reviewed anastomotic complications in 46 case studies of LTG to compare the various procedures for EJS. RESULTS: The overall incidence of anastomotic leakage associated with EJS was 3.0% (30 of 984 patients) among LTG procedures and 2.1% (31 of 1500 patients) among OTG procedures in the 16 non-RCTs. The incidence of anastomotic leakage did not differ significantly between LTG and OTG (odds OR = 1.42, 95%CI: 0.86-2.33, P = 0.17, I(2) = 0%). Anastomotic stenosis related to EJS was reported in 72 (2.9%) of 2484 patients, and the incidence was 3.2% among LTG procedures and 2.7% among OTG procedures. The incidence of anastomotic stenosis related to EJS was slightly, but not significantly, higher in LTG than in OTG (OR = 1.55, 95%CI: 0.94-2.54, P = 0.08, I(2) = 0%). The various procedures for LTG were classified into six categories in the review of case studies of LTG. The incidence of EJS leakage was similar (1.1% to 3.2%), although the incidence of EJS stenosis was relatively high when the OrVil™ device was used (8.8%) compared with other procedures (1.0% to 3.6%). CONCLUSION: The incidence of anastomotic complications associated with EJS was not different between LTG and OTG. Anastomotic stenosis was relatively common when the OrVil™ device was used.
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Fuga Anastomótica/epidemiología , Esofagostomía/efectos adversos , Gastrectomía/métodos , Yeyunostomía/efectos adversos , Laparoscopía , Neoplasias Gástricas/cirugía , Fuga Anastomótica/diagnóstico , Distribución de Chi-Cuadrado , Constricción Patológica , Esofagostomía/instrumentación , Gastrectomía/efectos adversos , Humanos , Incidencia , Yeyunostomía/instrumentación , Laparoscopía/efectos adversos , Oportunidad Relativa , Factores de Riesgo , Resultado del TratamientoRESUMEN
AIMS: Insulin-like growth factor binding protein 7 (IGFBP7) is reported to have tumour suppressor function through an IGF-dependent pathway in various malignant tumours. However, the expression of IGFBP7 in adenocarcinoma and its relationship with tumour progression and survival differs among studies. Our aims were to investigate the relationship between the expression of IGFBP7 and clinicopathological variables and outcomes of patients with gastric cancer. METHODS: Tumour samples were obtained from 219 patients with gastric cancer who underwent gastrectomy. The expression of IGFBP7 protein was examined by immunohistochemical staining. IGFBP7 mRNA levels were analysed using real-time quantitative reverse-transcriptase PCR in 24 of the gastric cancer tumours and in adjacent non-tumour tissues. Correlation of IGFBP7 expression with clinicopathological features was analysed. RESULTS: The protein expression of IGFBP7 was positively correlated with depth of invasion, lymph node metastasis, distant metastasis or recurrence and pathological stage. High expression of IGFBP7 protein was associated with a significantly worse disease-specific survival (p<0.001) and was an independent prognostic factor in multivariable analysis (HR, 4.8; 95% CI 2.1 to 10.6; p<0.001). The IGFBP7 mRNA level was significantly higher in advanced gastric cancer than in early gastric cancer, in tumours with lymph node metastasis than in tumours without lymph node metastasis, and in tumours with distant metastasis or recurrence than in tumours without distant metastasis or recurrence. CONCLUSIONS: Overexpression of IGFBP7 was associated with tumour progression and poor survival in gastric cancer. IGFBP7 may play a role in tumour progression in gastric cancer.
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Adenocarcinoma/química , Biomarcadores de Tumor/análisis , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/análisis , Neoplasias Gástricas/química , Adenocarcinoma/genética , Adenocarcinoma/mortalidad , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores de Tumor/genética , Biopsia , Distribución de Chi-Cuadrado , Femenino , Gastrectomía , Humanos , Inmunohistoquímica , Proteínas de Unión a Factor de Crecimiento Similar a la Insulina/genética , Estimación de Kaplan-Meier , Modelos Lineales , Metástasis Linfática , Masculino , Persona de Mediana Edad , Análisis Multivariante , Invasividad Neoplásica , Recurrencia Local de Neoplasia , Estadificación de Neoplasias , Valor Predictivo de las Pruebas , Modelos de Riesgos Proporcionales , ARN Mensajero/análisis , Reacción en Cadena en Tiempo Real de la Polimerasa , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Factores de Riesgo , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugía , Factores de Tiempo , Resultado del Tratamiento , Regulación hacia Arriba , Adulto JovenRESUMEN
Chemotherapy has become the global standard treatment for patients with metastatic or unresectable gastric cancer (GC), although outcomes remain unfavorable. Many molecular-targeted therapies inhibiting signaling pathways of various tyrosine kinase receptors have been developed, and monoclonal antibodies targeting human epidermal growth factor receptor 2 (HER2) have become standard therapy for HER2-positive GC. An inhibitor of vascular endothelial growth factor receptor 2 or MET has also produced promising results in patients with GC. Fibroblast growth factor receptors (FGFR) play key roles in tumor growth via activated signaling pathways in GC. Genomic amplification of FGFR2 leads to the aberrant activation found in GC tumors and is related to survival in patients with GC. This review discusses the clinical relevance of FGFR in GC and examines FGFR as a potential therapeutic target in patients with GC. Preclinical studies in animal models suggest that multitargeted tyrosine kinase inhibitors (TKIs), including FGFR inhibitor, suppress tumor cell proliferation and delay tumor progression. Several TKIs are now being evaluated in clinical trials as treatment for metastatic or unresectable GC harboring FGFR2 amplification.
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BACKGROUND: The mitogen-activated protein kinase (MAPK) signaling pathway participates in several steps of tumour development and is considered a prominent therapeutic target for the design of chemotherapeutic agents. We evaluated the expressions of extracellular signal-regulated kinase (ERK), mitogen-activated protein kinase (MEK), an upstream regulator of ERK, and Raf kinase inhibitor protein (RKIP), and investigated correlations of these expressions with clinicopathological features and outcomes in gastric cancer. METHODS: Tumour samples were obtained from 105 patients with gastric adenocarcinomas who underwent radical gastrectomy. The expressions of phosphorylated ERK (p-ERK), phosphorylated MEK (p-MEK), and RKIP were analysed by immunohistochemical staining. RESULTS: Expression of RKIP, p-MEK, and p-ERK was found in 69 (66%), 54 (51%), and 64 (61%) of all tumours, respectively. RKIP expression negatively correlated with the depth of invasion (p < 0.001), lymph node involvement (p = 0.028), and Union for International Cancer Control (UICC) stage (p = 0.007). RKIP expression was associated with significantly longer relapse-free survival (RFS) (p = 0.0033), whereas p-MEK was not (p = 0.79). Patients with p-ERK expression had slightly, but not significantly shorter RFS than those without such expression (p = 0.054). Patients with positive p-ERK and negative RKIP expression had significantly shorter RFS than the other patients (p < 0.001). The combination of RKIP and p-ERK expression was an independent prognostic factor (hazard ratio, 2.4; 95% confidence interval, 1.3 - 4.6; p = 0.008). CONCLUSIONS: Our results demonstrated that loss of RKIP was associated with tumour progression and poor survival. Negative RKIP expression combined with positive p-ERK expression was an independent predictor of poor outcomes in patients with gastric cancer.
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Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Proteínas de Unión a Fosfatidiletanolamina/metabolismo , Neoplasias Gástricas/metabolismo , Humanos , Estimación de Kaplan-Meier , Fosforilación , Pronóstico , Transducción de Señal , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patologíaRESUMEN
We report a case of rectal cancer with unresectable multiple liver metastases, which was worried about the transition from liver dysfunction to liver failure. The male patient in his 70s was diagnosed as advanced rectal cancer with severe liver dysfunction because of multiple liver metastases. Hepatic arterial infusion (HAI) chemotherapy, which was effective to reduce the size of metastatic liver tumors, was initially started. During HAI chemotherapy, sigmoid colostomy was performed. He recovered from liver dysfunction after he had been treated with 13th cycle HAI chemotherapy. He was treated with the modified FOLFOX6 regimen following a resection of rectal cancer. Although the standard therapy for colorectal cancer with unresectable liver metastases is firstly systemic chemotherapy such as FOLFOX or FOLFIRI, it might be better to control the liver metastases by HAI chemotherapy when a liver function is severely damaged by extensive liver tumors.
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Hepatopatías/etiología , Neoplasias Hepáticas/complicaciones , Neoplasias Hepáticas/secundario , Neoplasias del Recto/patología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/administración & dosificación , Fluorouracilo/administración & dosificación , Arteria Hepática , Humanos , Infusiones Intraarteriales , Leucovorina/administración & dosificación , Neoplasias Hepáticas/tratamiento farmacológico , Masculino , Compuestos Organoplatinos/administración & dosificación , Neoplasias del Recto/cirugíaRESUMEN
An indwelling catheter was dislocated into the duodenum during the course of hepatic arterial infusion for multiple metastases of colon cancer to the liver. A possible cause of extravascular dislocation includes an exposure to highly concentrated anticancer due to defective positioning of the catheter side hole and bending of the catheter. A dislocation of the hepatic arterial infusion catheter into the digestive tract is a serious complication and accounts for 10% of all dislocations. Although countermeasures consisting of monitoring progress, laparotic catheter extraction and endoscopic catheter extraction, a monitoring process is selected in nearly all cases. Even though hepatic arterial infusion has established as being effective against liver tumors, there is a possibility of encountering more of these cases in the future along with an increase in the number of cases and a prolongation of treatment that improves prognoses. In the case, a catheter extravascular dislocation has occurred in addition to complications stemming from the dislocation itself. There was also a risk of exacerbation of prognosis resulting from being forced to discontinue the treatment. It is therefore necessary to pay close attention to positioning of the catheter side hole and its immobilization.
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Catéteres de Permanencia/efectos adversos , Duodeno , Infusiones Intraarteriales/instrumentación , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias del Colon/patología , Falla de Equipo , Arteria Hepática , Humanos , Neoplasias Hepáticas/secundario , Masculino , Persona de Mediana EdadRESUMEN
The case reported here was a 80-year-old male who was presented with a diffuse type of hepatocellular carcinoma accompanied by thrombosis of the main trunk of the portal vein. The primary focus and portal vein thrombosis improved considerably following repeated transcatheter arterial chemoembolization using DSM (DSM-TACE). DSM-TACE was suggested to have the potential for becoming a new treatment method for advanced hepatocellular carcinoma, for which conventional transcatheter arterial embolization (TAE) using Lipiodol and so forth is contraindicated tue to thrombosis of the main trunk of the portal vein.