RESUMEN
BACKGROUND: Cough is a common feature of asthma, which is often resistant to inhaled corticosteroids (ICSs). The pathophysiology of this refractoriness may differ between daytime and nighttime asthmatic cough. We sought to identify factors contributing to ICS-refractory daytime and nighttime asthmatic cough. METHODS: Sixty-seven patients with asthma presenting solely or predominantly with chronic cough were prospectively enrolled from April 2012 to December 2014. At baseline and 12 weeks after ICS treatment, the capsaicin cough threshold (C2, C5) and methacholine airway sensitivity and reactivity were examined. A visual analog scale (VAS) and numeric scores were used to evaluate daytime and nighttime cough symptoms separately. The Japanese version of the Leicester Cough Questionnaire was also completed. When either the VAS or numeric scores showed an improvement of ≥50% or ≥2 points, patients were considered responders to ICS treatment. RESULTS: Fifty-five patients were eligible for evaluation. Subjective cough indices improved significantly at 12 weeks after ICS treatment (P<.001). Multivariate analysis revealed that lower C2 significantly contributed to residual daytime cough (P=.04). Meanwhile, methacholine hyperreactivity and lower IgE levels were predictors of the nighttime residual cough (P=.002 and P=.03, respectively). CONCLUSIONS: Heightened cough reflex sensitivity is an independent factor of daytime asthmatic cough that is refractory to ICSs. In contrast, airway hyperreactivity and less atopic status contribute to ICS-refractory nighttime cough.
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Asma/complicaciones , Tos/etiología , Administración por Inhalación , Corticoesteroides/uso terapéutico , Adulto , Anciano , Antiasmáticos/uso terapéutico , Asma/tratamiento farmacológico , Tos/tratamiento farmacológico , Resistencia a Medicamentos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Factores de Riesgo , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
BACKGROUND: Genetic markers of susceptibility to asthma exacerbations in adults remain unclear. OBJECTIVE: To identify genetic markers of asthma exacerbations, particularly in patients with type-2 inflammatory endotype. METHODS: In this observational study of patients enrolled in the Kinki Hokuriku Airway disease Conference multicenter study, frequency of exacerbations requiring systemic corticosteroids during 2 years after enrolment and associated risk factors was determined. For genetic marker analysis, interleukin-4 receptor α (IL4RA) rs8832 and a disintegrin and metalloprotease 33 (ADAM33) S_2 (rs528557), T_1 (rs2280091), T_2 (rs2280090), and V_4 (rs2787094) variants were included. Elevated serum periostin levels at enrolment (≥95 ng/mL, defined as type-2 inflammatory endotype) were considered in the analysis. RESULTS: Among 217 patients who were successfully followed up for 2 years after enrolment, 60 patients showed at least one asthma exacerbation during the 2 years. Airflow limitation (%FEV1 <80%) and recent exacerbations but not genetic variants were identified as risk markers of exacerbations. A total of 27 patients showed type-2 inflammatory endotype (serum periostin ≥95 ng/mL at enrolment) and subsequent exacerbations; risk factors in these patients were airflow limitation (odds ratio, 6.51; 95% confidence interval (CI): 2.37-18.6; P=.0003), GG genotype of IL4RA rs8832 (odds ratio, 4.01; 95% CI: 1.47-11.0; P=.007), and A allele of ADAM33 T_2 (odds ratio, 2.81; 95% CI: 1.05-7.67; P=.04) by multivariate analysis. In addition, GG genotype of IL4RA rs8832 was associated with type-2 endotype, whereas A allele of ADAM33 T_2 was associated with mixed type of eosinophilic/type-2 and neutrophilic inflammations. CONCLUSIONS AND CLINICAL RELEVANCE: IL4RA and ADAM33 variants may be risk markers of asthma exacerbations in type-2 inflammatory endotype. Precise endotyping may facilitate the identification of genetic risk markers of asthma exacerbations.
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Proteínas ADAM , Asma/sangre , Asma/genética , Subunidad alfa del Receptor de Interleucina-4 , Proteínas ADAM/sangre , Proteínas ADAM/genética , Adulto , Anciano , Asma/tratamiento farmacológico , Estudios de Seguimiento , Marcadores Genéticos , Humanos , Subunidad alfa del Receptor de Interleucina-4/sangre , Subunidad alfa del Receptor de Interleucina-4/genética , Persona de Mediana Edad , Factores de RiesgoRESUMEN
BACKGROUND: Omalizumab, a humanized anti-IgE monoclonal antibody, has demonstrated efficacy in patients with severe allergic asthma. However, treatment responses vary widely among individuals. Despite a lack of data, free serum IgE levels following omalizumab treatment have been proposed as a marker of treatment responsiveness. METHODS: In this prospective, observational study, we assessed the utility of biomarkers of type 2 inflammation in predicting omalizumab treatment responses, as determined by the absence of asthma exacerbation during the first year of treatment. Free serum IgE levels were monitored for 2 years to examine their association with baseline biomarker levels and the number of exacerbations. RESULTS: We enrolled thirty patients who had been treated with omalizumab for at least 1 year, of whom 27 were treated for 2 years. Baseline serum periostin levels and blood eosinophil counts were significantly higher in patients without exacerbations during the first year of treatment than in patients with exacerbations. Baseline serum periostin levels, but not eosinophil counts, were negatively associated with free serum IgE levels after 16 or 32 weeks of treatment. Reduced free serum IgE levels during treatment from those at baseline were associated with reduced exacerbation numbers at 2 years. In 14 patients who continued to have exacerbations during the first year of treatment, exacerbation numbers gradually and significantly decreased over the 2-year study period, with concurrent significant reductions in free serum IgE levels. CONCLUSION: Baseline serum periostin levels and serum free IgE levels during treatment follow-up may be useful in evaluating responses to omalizumab treatment.
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Antiasmáticos/uso terapéutico , Asma/sangre , Asma/tratamiento farmacológico , Moléculas de Adhesión Celular/sangre , Inmunoglobulina E/sangre , Omalizumab/uso terapéutico , Adulto , Anciano , Antiasmáticos/farmacología , Asma/diagnóstico , Asma/inmunología , Biomarcadores , Progresión de la Enfermedad , Femenino , Humanos , Inmunoglobulina E/inmunología , Masculino , Persona de Mediana Edad , Omalizumab/farmacología , Curva ROC , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
BACKGROUND: In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. METHODS: In this study, 224 patients with asthma receiving ICS treatment for at least 4 years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30 ml/year or greater were determined. RESULTS: Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95 ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30 ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/µl) in the high serum periostin group. CONCLUSIONS: A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.
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Asma/genética , Asma/fisiopatología , Variación Genética , Receptores de Glucocorticoides/genética , Administración por Inhalación , Corticoesteroides/administración & dosificación , Corticoesteroides/uso terapéutico , Anciano , Asma/tratamiento farmacológico , Asma/inmunología , Moléculas de Adhesión Celular/sangre , Eosinófilos/inmunología , Femenino , Volumen Espiratorio Forzado , Estudios de Asociación Genética , Proteínas de Choque Térmico/genética , Humanos , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Polimorfismo de Nucleótido Simple , Pruebas de Función Respiratoria , Factores de RiesgoRESUMEN
BACKGROUND: Epidemiological studies have shown that smoking increases the propensity for atopy and asthma. However, the effects of smoking on atopy and eosinophilic inflammation in asthmatics, including the elderly, remain unknown. OBJECTIVE: To determine the effects of smoking on serum immunoglobulin E (IgE) levels and eosinophilic inflammation in asthmatics of all ages. METHODS: The associations of serum IgE levels, blood eosinophil counts and fractional exhaled nitric oxide (FeNO) levels with smoking and age in steroid-naive asthmatics were cross-sectionally assessed (n = 307). Levels of sputum eosinophil and thymic stromal lymphopoietin (TSLP) that promotes Th2 inflammation were also analysed. Current smokers were excluded when analysing contributing factors of FeNO. RESULTS: Levels of serum IgE, blood eosinophil and FeNO decreased with increasing age in never-smokers, whereas decrease in serum IgE levels with increasing age was not observed in current smokers. In addition, current smoking was associated with higher blood eosinophil counts. In atopic asthmatics, age-related declines in serum IgE levels were less steep in ex-smokers than in never-smokers, and atopic ex-smokers with asthma showed higher blood eosinophil counts and higher FeNO irrespective of age. Lastly, sputum TSLP levels were associated with sputum eosinophil proportions and pack-years. Current and ex-smokers had higher TSLP levels than never-smokers. CONCLUSIONS AND CLINICAL RELEVANCE: In steroid-naive asthmatics, smoking may attenuate the age-related decrease in IgE levels and maintain eosinophilic inflammation, in which TSLP may be involved.
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Eosinófilos/inmunología , Inmunoglobulina E/inmunología , Inflamación/inmunología , Fumar , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Asma/inmunología , Asma/metabolismo , Estudios Transversales , Citocinas/metabolismo , Espiración , Femenino , Compuestos Férricos/sangre , Humanos , Inmunoglobulina E/sangre , Inflamación/sangre , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Nitratos/sangre , Óxido Nítrico , Esputo/metabolismo , Adulto Joven , Linfopoyetina del Estroma TímicoRESUMEN
Dendritic cell (DC)-based immunotherapy has been investigated as a new therapeutic approach to intractable neuroblastomas; however, only limited clinical effect has been reported. To overcome the relatively low sensitivity of neuroblastomas against immunotherapy, we undertook a preclinical efficacy study to examine murine models to assess the combined effects of gamma-irradiation pretreatment and recombinant Sendai virus (ts-rSeV/dF)-mediated murine interferon-beta (mIFN-beta) gene transfer to DCs using established c1300 neuroblastomas. Similar to intractable neuroblastomas in the clinic, established c1300 tumors were highly resistant to monotherapy with either gamma-irradiation or DCs activated by ts-rSeV/dF without transgene (ts-rSeV/dF-null) that has been shown to be effective against other murine tumors, including B16F10 melanoma. In contrast, immunotherapy using DCs expressing mIFN-beta through ts-rSeV/dF (ts-rSeV/dF-mIFNbeta-DCs) effectively reduced tumor size, and its combination with gamma-irradiation pretreatment dramatically enhanced its antitumor effect, resulting frequently in the complete elimination of established c1300 tumors 7-9 mm in diameter, in a high survival rate among mice, and in the development of protective immunity in the mice against rechallenge by the tumor cells. These results indicate that the combination of ts-rSeV/dF-mIFNbeta-DCs with gamma-irradiation is a hopeful strategy for the treatment of intractable neuroblastomas, warranting further investigation in the clinical setting.
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Células Dendríticas/trasplante , Rayos gamma/uso terapéutico , Terapia Genética/métodos , Interferón beta/genética , Neuroblastoma/terapia , Animales , Terapia Combinada , Células Dendríticas/inmunología , Modelos Animales de Enfermedad , Femenino , Técnicas de Transferencia de Gen , Vectores Genéticos , Interferón beta/biosíntesis , Ratones , Ratones Endogámicos A , Neuroblastoma/inmunología , Neuroblastoma/patología , Neuroblastoma/radioterapia , Virus Sendai/genéticaRESUMEN
BACKGROUND AND STUDY AIMS: In recent years, endoscopic submucosal dissection (ESD) has been applied for the treatment of gastric tumors, and the en-bloc resection rate of early gastric cancer has greatly improved. Herein, we introduce spring-assisted ESD, for quicker submucosal dissection. PATIENTS AND METHODS: ESD was carried out in 32 patients (20 men, 12 women; mean age 72.6 years, range 53 - 88 years) for early gastric cancer, with tumors over 10 mm in diameter. The patients were divided retrospectively into two groups (spring-assisted ESD, n = 20; conventional ESD, n = 12). To comparatively evaluate the performance speed of ESD, the circumferential length and the area of the resected specimen were calculated by the approximation formula for ellipse. Then, the circumferential cutting speed, the submucosal dissection speed, and the total ESD speed were calculated as index scores. The scores for spring-assisted ESD and conventional ESD were compared. RESULTS: The mean (+/-SD) circumferential cutting speeds in spring-assisted ESD and conventional ESD were 0.53 +/- 0.27 and 0.60 +/- 0.30 cm/minute, respectively ( P = 0.51). The mean submucosal dissection speeds in spring-assisted ESD and conventional ESD were 0.67 +/- 0.41 and 0.32 +/- 0.24 cm (2)/minute, respectively ( P = 0.005). The mean total ESD speeds in spring-assisted ESD and conventional ESD were 0.25 +/- 0.10 and 0.17 +/- 0.07 cm (2)/minute, respectively ( P = 0.015). The mean total ESD times were 57 and 75 minutes in the spring and conventional group, respectively ( P = 0.30). CONCLUSION: Using the aforementioned indices, we evaluated the performance speed of ESD. Spring-assisted ESD may allow faster submucosal dissection.
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Disección/instrumentación , Disección/métodos , Mucosa Gástrica/cirugía , Gastroscopía/métodos , Neoplasias Gástricas/cirugía , Anciano , Anciano de 80 o más Años , Femenino , Gastroscopios , Humanos , Masculino , Persona de Mediana Edad , Resultado del TratamientoRESUMEN
Tumour samples from 71 patients with stomach cancer, 41 patients with liver metastasis (group A) and 15 patients each in stages II-IV (group B) and stage I (group C) without liver metastasis were analysed. MAGE-A protein expression was evaluated by immunohistochemistry using a 6C1 monoclonal antibody and MAGE-A10 mRNA expression was detected by highly sensitive in situ hybridisation using a cRNA probe. Expressions of MAGE-A protein and MAGE-A10 mRNA in group A were detected in 65.9 and 80.5%, respectively. Both protein and gene showed significantly higher expression in group A than those in groups B (6.7, 26.7%) and C (0, 0%) (P=0.0003, P=<0.0001, respectively). MAGE-A10 mRNA expression in liver metastasis was found in eight (88.9%) out of nine patients. The concordant rate between MAGE-A family protein expression and MAGE-A10 mRNA expression in the primary sites was 81.7% (P<0.0001). MAGE-A10 gene expression was associated with reduced survival duration. The results of this study suggest that MAGE-A10 is a possible target in active immunotherapy for advanced stomach cancer.
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Antígenos de Neoplasias/biosíntesis , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/secundario , Proteínas de Neoplasias/biosíntesis , Neoplasias Gástricas/metabolismo , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Monoclonales/química , Antígenos de Neoplasias/genética , Progresión de la Enfermedad , Femenino , Expresión Génica , Humanos , Inmunohistoquímica , Hibridación in Situ , Neoplasias Hepáticas/genética , Masculino , Antígenos Específicos del Melanoma , Persona de Mediana Edad , Proteínas de Neoplasias/genética , Sondas ARN , ARN Mensajero/biosíntesis , ARN Mensajero/genética , Neoplasias Gástricas/genética , Neoplasias Gástricas/patología , alfa-Fetoproteínas/biosíntesisRESUMEN
BACKGROUND: The use of intraoperative cholangiography (IOC), routinely rather than selectively, during laparoscopic cholecystectomy (LC) is controversial. Recent findings have shown laparoscopic ultrasound (LUS) to be safe, quick, and effective not only for screening of the bile duct for stones, but also for evaluating the biliary anatomy. This study aimed to evaluate, on the basis of the LC outcome and the cost of LUS and IOC, whether and how much the routine use of LUS would be able to reduce the need for IOC. METHODS: During LC, LUS was used routinely to screen the bile duct for stones and to evaluate the biliary anatomy, whereas IOC was used selectively only when LUS was unsatisfactory or unsuccessful. RESULTS: For 193 (96.5%) of 200 patients, LUS was completed successfully, whereas IOC was needed for 7 patients (3.5%). Bile duct stones were identified in 20 patients (10%). For the detection of bile duct stones, LUS yielded 19 true-positive, 175 true-negative, 0 false-positive, and 1 false-negative results. It had a sensitivity of 95%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 99.4%. The postoperative complications included bile leaks from the liver bed in two patients and a retained bile duct stone in one patient. If IOC had been used selectively in a traditional manner on the basis of preoperative risk factors, IOC would have been needed for 77 patients (38.5%). The total cost of LUS plus IOC for the current 200 patients was 26,256 dollars. The total estimated cost of selective IOC, if it had been performed for the 77 patients, would have been 31,416 dollars. CONCLUSIONS: Routine LUS accurately diagnosed bile duct stones and significantly reduced the need for selective IOC from a potential 38.5% to an actual 3.5% without adversely affecting the outcome of the LC or increasing the overall cost. The routine use of LUS during LC is accurate and cost effective.
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Colecistectomía Laparoscópica/métodos , Cálculos Biliares/diagnóstico por imagen , Cálculos Biliares/cirugía , Complicaciones Intraoperatorias/prevención & control , Adulto , Anciano , Colangiografía/métodos , Colangiografía/estadística & datos numéricos , Colecistectomía Laparoscópica/efectos adversos , Femenino , Humanos , Complicaciones Intraoperatorias/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Monitoreo Intraoperatorio/métodos , Valor Predictivo de las Pruebas , Medición de Riesgo , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Ultrasonografía Intervencional/métodosRESUMEN
Cases of acromegaly due to GHRHproducing pancreatic endocrine tumors have been reported. Here we present a case of a 31-yr-old nonacromegalic man with hyperparathyroidism and elevated serum IGF-I with normal serum GH levels. Serum GH was not suppressed below 1 ng/ml by the glucose tolerance test and increased in response to TR H and GHRH administration. Magnetic resonance imaging (MRI) revealed pituitary hyperplasia and an abdominal computed tomography (CT ) scan showed a tumor in the pancreatic tail. Plasma concentration of GHRH was elevated. Based on these clinical data, multiple endocrine neoplasia (MEN) type 1 was suspected. Three enlarged parathyroid glands were removed and a distal pancreatectomy was performed. Pathological examination of the parathyroid glands and pancreatic tumor showed nodular hyperplasia and a well-differentiated endocrine tumor, respectively, both compatible with MEN features. Immunohistochemistry revealed positive immunoreactivity for GHRH, SS , insulin, glucagon, chromogranin A, and pancreatic polypeptide in the pancreatic tumor. After pancreatic surgery, elevated levels of GHRH and IGF-I were normalized and pituitary hyperplasia definitely decreased in size. In cases of pituitary hyperplasia with elevated IGF-I, ectopic GHRH syndrome must be considered even if physical features of acromegaly are absent. It is also important to measure plasma GHRH concentrations in order to give a diagnosis.
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Hormona Liberadora de Hormona del Crecimiento/metabolismo , Neoplasia Endocrina Múltiple Tipo 1/complicaciones , Neoplasias Pancreáticas/complicaciones , Neoplasias Pancreáticas/metabolismo , Acromegalia , Adulto , Hormona de Crecimiento Humana/sangre , Humanos , Hiperplasia , Hipertiroidismo/complicaciones , Hipertiroidismo/patología , Factor I del Crecimiento Similar a la Insulina/metabolismo , Imagen por Resonancia Magnética , Masculino , Neoplasia Endocrina Múltiple Tipo 1/diagnóstico por imagen , Neoplasia Endocrina Múltiple Tipo 1/patología , Neoplasias Pancreáticas/diagnóstico por imagen , Enfermedades de la Hipófisis/patología , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND/PURPOSE: Mass screening (MS) for neuroblastoma (NB) at 6 months of age in Japan was discontinued in 2004. We have previously reported that the majority of NB detected by MS showed a good prognosis, with only a few cases demonstrating an unfavorable outcome (J Pediatr Surg 2002, Cancer 2001). This study aims to provide insights into infant NB by assessing the details of the clinical courses in patients treated with a standard regimen and the biological features of such cases using highly sensitive methods at one institution in Japan. METHODS: In 76 NB detected through MS treated at Kyushu University Hospital, the clinical features and MYCN amplification, 1p deletion, 17q gain, the expression level of TRKA using FISH and the quantitative PCR were analyzed. RESULTS: Of these 76 persons with NB treated at one institution, 97 % are still alive, while 2 cases died from other diseases. Three patients experienced a recurrence after complete remission (CR), and 2 patients demonstrated refractory disease since the initial diagnosis. Two of the 3 NB patients with recurrence have demonstrated a 2nd CR, while one case still has multiple active diseases. Regarding the findings of highly sensitive biological analyses, 5/74 (7 %) showed MYCN amplification, 2/24 (8 %) cases had a 1p deletion, 3/33 (9 %) cases had a 17q gain, 5/50 (10 %) cases had diploidy, 1/25 (4 %) cases had a low expression of TRKA, and 2/76 (3 %) cases had an unfavorable histology. Of the 76 NB, 13 tumors (17 %) had one or more unfavorable factors (UF). Of the 5 refractory NB, 1 case had 3 UF, 1 case had 2 UF, 1 case had 1 UF, and 2 cases had no UF. As a result, 60 % of the refractory NB had one or more UF. CONCLUSIONS: Of the NB detected by MS at one institution in Japan, 17 % had one or more unfavorable factors (UF) and might have a higher risk of recurrence than the patients with no UF, although the unfavorable biology of several refractory cases is still unclear even after highly sensitive analyses. At least one-fifth of the NB cases detected by MS are anticipated cases. In infantile neuroblastomas, it may therefore be most important to analyze biologically prognostic factors using highly sensitive methods followed by immediate surgical intervention. Since the MS program has been discontinued in Japan, it will be necessary in future to assess the mortality and characteristics of NB detected clinically.
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Neuroblastoma , Cromosomas Humanos Par 1 , Cromosomas Humanos Par 17 , Eliminación de Gen , Dosificación de Gen , Expresión Génica , Humanos , Lactante , Japón , Tamizaje Masivo , Proteína Proto-Oncogénica N-Myc , Neuroblastoma/diagnóstico , Neuroblastoma/genética , Neuroblastoma/terapia , Proteínas Nucleares/genética , Proteínas Oncogénicas/genética , Ploidias , Pronóstico , Receptor trkA/genéticaRESUMEN
BACKGROUND: This study assessed the safety and utility of preoperative splenic artery embolization before laparoscopic splenectomy in children. METHODS: Five young girls with a mean age of 13.2 years underwent laparoscopic splenectomies at the authors' institution from August 1998 to April 2003. Three of the patients had idiopathic thrombocytopenic purpura, and two had hereditary spherocytosis. Preoperative splenic artery embolization was performed the day before the surgery in all cases. The laparoscopic splenectomy was performed using traditional laparoscopic procedures and standard laparoscopic instruments with the patient in the right semilateral position. RESULTS: The mean spleen weight was 252.6 g, and the mean length was 11.6 cm. All the patients reported postembolic pain, but not to a level unmanageable by intravascular narcotics. There were no severe complications in the splenic artery embolization. The laparoscopic splenectomies were completed in a mean of 211 min, with a mean estimated blood loss of 9 ml. None of the operations required conversion to traditional open laparotomy, and none of the patients died or experienced operative complications. CONCLUSION: The authors concluded that splenic artery embolization is safe and useful as an adjuvant procedure performed before elective laparoscopic splenectomy in children.
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Embolización Terapéutica , Laparoscopía , Cuidados Preoperatorios , Esplenectomía/métodos , Arteria Esplénica , Adolescente , Niño , Femenino , HumanosRESUMEN
Cytochrome P4502E1 (CYP2E1) activates carcinogenic N-nitrosamines, benzene, urethane and other low molecular weight compounds. This enzyme is also inducible by ethanol, and metabolizes alcohol. A restriction fragment length polymorphism (RFLP) using the Rsa I restriction enzyme has been identified in the CYP2E1 transcription regulatory region; recent studies suggest that this polymorphism may affect gene expression. We investigated the frequency of the Rsa I RFLP in a Japanese population in relation to gastric cancer and liver disease susceptibility. The frequency of this polymorphism was determined in 150 gastric cancer, 16 hepatocellular cancer, 48 liver cirrhosis and 203 benign gastric disease (controls) patients. This preliminary study shows no association of the specific genotype with gastric cancer in all subjects (odds ratio = 1.04, 95% CI = 0.74-3.08 for the heterozygote and 0.57, 95% CI = 0.22-1.50 for the homozygous rare allele, respectively). To further confirm this lack of association, an age and gender matched case-control study should be performed. Separately, there was no association of the Rsa I RFLP with hepatocellular carcinoma (p = 0.911), but there was a suggested difference between the non-viral associated liver cirrhosis patients and control patients. Thus, this polymorphism may be related to ethanol metabolism and consequential liver diseases in a Japanese population.
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Carcinoma Hepatocelular/genética , Sistema Enzimático del Citocromo P-450/genética , Cirrosis Hepática/genética , Neoplasias Hepáticas/genética , Oxidorreductasas N-Desmetilantes/genética , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , Neoplasias Gástricas/genética , Secuencia de Bases , Carcinoma Hepatocelular/enzimología , Citocromo P-450 CYP2E1 , Sistema Enzimático del Citocromo P-450/biosíntesis , Cartilla de ADN , Femenino , Regulación Enzimológica de la Expresión Génica , Tamización de Portadores Genéticos , Genotipo , Homocigoto , Humanos , Cirrosis Hepática/enzimología , Neoplasias Hepáticas/enzimología , Masculino , Datos de Secuencia Molecular , Oportunidad Relativa , Oxidorreductasas N-Desmetilantes/biosíntesis , Reacción en Cadena de la Polimerasa , Valores de Referencia , Secuencias Reguladoras de Ácidos Nucleicos , Caracteres Sexuales , Gastropatías/enzimología , Gastropatías/genética , Neoplasias Gástricas/enzimología , Transcripción GenéticaRESUMEN
The amplification of the N-myc gene and a gain of the chromosome 17q arm correlate with an unfavorable outcome in patients with neuroblastoma. In this study, we determined the gene dosage of the N-myc gene (located at 2p24) and Survivin gene (located at 17q25) using the p53 gene (located at 17p13) as the internal control gene by the TaqMan polymerase chain reaction (PCR)-based gene dosage analysis in 25 neuroblastoma samples. Based on the assumption that the gene dosages of each gene of a normal individual lymphocytes are 1.0, 11 of the 25 cases with a corrected gene dosage of N-myc (N-myc/p53) of more than 2.0 had a more unfavorable prognosis than the 14 cases with a N-myc gene dosage of less than 2.0 (5-year survival rate: 18 vs. 71%, P<0.01). Ten of 25 cases with a corrected Survivin gene dosage (Survivin/p53) of more than 2.0 had a more unfavorable prognosis than the 15 cases with a Survivin gene dosage of less than 2.0 (5-year survival rate: 10 vs. 67%, P<0.01). This quantitative PCR system is considered to be useful for quickly and accurately evaluating the degree of malignancy of neuroblastoma in order to select the optimal treatment.
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Cromosomas Humanos Par 17 , Dosificación de Gen , Genes myc , Proteínas Asociadas a Microtúbulos , Neuroblastoma/genética , Neuroblastoma/mortalidad , Niño , Preescolar , Genes p53 , Humanos , Lactante , Proteínas Inhibidoras de la Apoptosis , Proteínas de Neoplasias , Reacción en Cadena de la Polimerasa , Pronóstico , Proteínas/genética , Tasa de Supervivencia , SurvivinRESUMEN
It has recently been reported that mismatch repair enzymes, which are one type of DNA repair enzymes, are the causative genes for a major group of hereditary non-polyposis colon cancers (HNPCC). Abnormalities in the mismatch repair system can be monitored by observing instability at the microsatellite loci (MSI) in cancer cells. MSI has been reported not only in tumors associated with hereditary non-polyposis colorectal cancer but also in sporadic forms of various tumors. No correlation between pediatric malignant tumors and the mismatch repair system has yet been reported. In the present study, we examined the frequency of MSI in 21 neuroblastomas, which are the most common solid tumors in childhood, using a high resolution fluorescent microsatellite analysis. MSI on five microsatellite loci was detected in none of the 21 samples. Other mechanisms independent of mismatch repair deficiency may thus play a role in both tumorigenesis and the development of neuroblastoma.
Asunto(s)
ADN de Neoplasias/análisis , ADN Satélite/análisis , Repeticiones de Microsatélite , Neuroblastoma/genética , Niño , Preescolar , Cartilla de ADN , Reparación del ADN , ADN de Neoplasias/genética , ADN Satélite/genética , Colorantes Fluorescentes , Humanos , Lactante , Reacción en Cadena de la Polimerasa/métodos , Espectrometría de FluorescenciaRESUMEN
We performed molecular analysis of a germline interstitial deletion of chromosome 4 [del(4)(q21.22q23)], which had been observed in a male infant manifesting early-onset hepatoblastoma (HBL). The chromosomal anomaly in this child was associated with a unique congenital syndrome including HBL, atrial septal defect, ventricular septal defect, patent ductus arteriosus, mental retardation, and seizures. However, the patient did not exhibit a megalencephaly typical of 4q21-22 deletions. His HBL was associated with an increasing serum alpha-fetoprotein level and rapid growth. To define the chromosomal deletion at the molecular level in this child, we analyzed his lymphoblasts with fluorescence in situ hybridization, using as probes a panel of BAC/PAC genomic clones containing STS markers covering the 4q12-27 region. The analysis revealed that the affected chromosome had an 8-cM deletion within 4q21-q22, flanked by markers D4S2964 and D4S2966. This microdeletion overlaps with the commonly deleted region at 4q21-q22 that was recently defined in adult hepatocellular carcinomas.
Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 4/genética , ADN de Neoplasias/genética , Hepatoblastoma/genética , Neoplasias Hepáticas/genética , Adulto , Bandeo Cromosómico , Resultado Fatal , Hepatoblastoma/patología , Humanos , Hibridación Fluorescente in Situ , Lactante , Neoplasias Hepáticas/patología , Masculino , Repeticiones de MicrosatéliteRESUMEN
BACKGROUND: Diagnosis of Helicobacter pylori infection in the remnant stomach has not been established. AIMS: To investigate the diagnostic value of culture, histology, PCR and serum IgG against H. pylori (ELISA) with and without eradication therapy in the remnant stomach, compared with the unoperated stomach. METHODS: Biopsy samples for bacterial culture and histological diagnosis of H. pylori were taken from the stoma and upper corpus of the remnant stomach and gastric juice was used for PCR assay. RESULTS: Bacterial culture-based diagnosis in the remnant stomach, sensitivity and specificity of culture were 95.1%, 100%; histology 89%, 92.3%; PCR 66%, 89.7%; and ELISA 100%, 50%, respectively, in cases without H. pylori eradication therapy. In assessment of the results of therapy for the remnant stomach, sensitivity and specificity of culture were 100%, 100%; histology 80%, 96.8%; PCR 80%, 91.7%; and ELISA 100%, 0%, respectively. CONCLUSION: Bacterial culture had the highest diagnostic value in the remnant stomach as well as unoperated stomach. Sensitivity by histology and PCR was lower in the remnant stomach than the unoperated stomach, but specificity values were equal. Serum ELISA assay was not suitable for the remnant stomach.
Asunto(s)
Infecciones por Helicobacter/patología , Helicobacter pylori , Complicaciones Posoperatorias/patología , Neoplasias Gástricas/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Técnicas Bacteriológicas/normas , Biopsia , Endoscopía Gastrointestinal , Ensayo de Inmunoadsorción Enzimática/normas , Femenino , Jugo Gástrico/microbiología , Humanos , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/normas , Complicaciones Posoperatorias/microbiología , Sensibilidad y Especificidad , Estómago/patología , Neoplasias Gástricas/microbiología , Neoplasias Gástricas/patologíaRESUMEN
BACKGROUND: Gastric cancer incidence in men is almost double that in women. We investigated mucosal responses in the stomach against Helicobacter pylori (H. pylori) infections to elucidate the interindividual or sex-related differences, which may in turn be associated with gastric cancer incidence, mucosal changes of stomach as measured by the Sydney System, and interleukin-8, cyclooxygenase-2 and trefoil factor family 1 (TFF1) gene expression. METHODS: An age-, sex-, H. pylori status- and disease-matched case-control study was performed in 574 H. pylori-positive and 225 H. pylori-negative patients selected from 4125 patients with a diagnosis of benign disease of the stomach. Levels of acute and chronic inflammations, atrophy and intestinal metaplasia scored according to the Sydney System were compared by stomach site and by sex. Two biopsy specimens (antral and corpus gastric mucosa) from patients with benign gastric diseases (142 patients; 72 men, 70 women) were analysed for interleukin-8, cyclooxygenase-2 and TFF1 mRNA expression as measured by real-time PCR. RESULTS: Inflammation and activity scores in antrum with H. pylori infection were higher in men, but scores declined according to age. Atrophy and intestinal metaplasia scores in corpus with H. pylori infection appeared more severe in men than in women, especially in older patients. In women, atrophy score increased with increasing age, particularly in postmenopausal H. pylori-negative patients. Interleukin-8 mRNA induction was detected in both antrum and corpus mucosa in H. pylori infection, but sex differences were not found. Response of cyclooxygenase-2 mRNA expression against H. pylori infection in the mucosa was higher in men than women. In H. pylori-negative patients, TFF1 mRNA levels in women were significantly higher than in men, and TFF1 mRNA was significantly lower in positive than negative women. CONCLUSIONS: Sex differences in mucosal responses to H. pylori infection in the stomach may be correlated with sex differences in the incidence of stomach cancer.
Asunto(s)
Gastritis Atrófica/microbiología , Infecciones por Helicobacter/metabolismo , Helicobacter pylori , Isoenzimas/metabolismo , Prostaglandina-Endoperóxido Sintasas/metabolismo , Proteínas/metabolismo , Caracteres Sexuales , Anciano , Estudios de Casos y Controles , Ciclooxigenasa 2 , Femenino , Mucosa Gástrica/metabolismo , Mucosa Gástrica/microbiología , Gastritis Atrófica/metabolismo , Humanos , Masculino , Proteínas de la Membrana , Persona de Mediana Edad , ARN Mensajero/metabolismo , Factor Trefoil-1 , Proteínas Supresoras de TumorRESUMEN
Malignant rhabdoid tumor of the kidney (MRTK) is a highly aggressive tumor which occurs in childhood and which is histologically characterized by the existence of eosinophilic intracytoplasmic inclusions. We established and characterized a cell line from this tumor with histological, immunohistochemical and cytogenetical analysis. Histologically, the tumor cells demonstrate typical eosinophilic inclusions, while immunohistochemically the cells demonstrate common mesenchymal and epithelial differentiation. Although the conventional karyotyping of this tumor lacked the abnormalities of 22q chromosome, Southern blot analysis and microsatellite analysis verified abnormalities of the BCR gene and of the hSNF5/INI1 gene. Despite the variety of locations, these common genetic abnormalities appear to contribute to distinguish rhabdoid tumor from such other small round cell tumors as primitive neuroectodermal tumor, rhabdomyosarcoma, poorly differentiated synovial sarcoma and desmoplastic small round cell tumor.
Asunto(s)
Neoplasias Renales/patología , Proteínas de la Membrana , Tumor Rabdoide/patología , Células Tumorales Cultivadas , Animales , Southern Blotting , Diferenciación Celular , Proteínas Cromosómicas no Histona , Proteínas de Unión al ADN/genética , Humanos , Cuerpos de Inclusión/ultraestructura , Lactante , Cariotipificación , Queratinas/análisis , Neoplasias Renales/genética , Pérdida de Heterocigocidad , Masculino , Ratones , Ratones Desnudos , Repeticiones de Microsatélite , Mucina-1/análisis , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/genética , Trasplante de Neoplasias , Fosfopiruvato Hidratasa/análisis , Reacción en Cadena de la Polimerasa , Proteínas Protozoarias/análisis , Tumor Rabdoide/genética , Proteínas S100/análisis , Proteína SMARCB1 , Factores de Transcripción , Trasplante Heterólogo , Células Tumorales Cultivadas/química , Células Tumorales Cultivadas/patología , Células Tumorales Cultivadas/trasplante , Proteína p53 Supresora de Tumor/análisis , Vimentina/análisisRESUMEN
BACKGROUND: Reconstruction of the portal vein with autologous veins requires extra incisions. Prosthetic material is associated with an increased risk of infection. We therefore created an animal model of portal vein reconstruction using the peritoneum. METHODS: A 2.5 x 2.5 cm piece of the peritoneum was resected from Landrace pigs weighing 30 to 40 kg and was dipped in 100% alcohol for 10 minutes. The anterior wall of the portal vein measuring 1.2 x 0.6 cm was resected. The peritoneal patch-graft fitting the defect of the portal vein was used to repair it. RESULTS: All 7 pigs survived the surgery, and were killed at 2, 7, 7, 14, 21, 35 and 49 days, respectively, after surgery. There was no evidence of thrombosis or obstruction of the reconstructed portal vein or any other complications. Complete endothelialization of the patches were noted at day 14. CONCLUSIONS: Our patch-graft technique using the peritoneum is considered to be a good and safe alternative for reconstruction after partial resection of the portal vein in clinical surgery.