ABSTRACT
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.
Subject(s)
Asthma/complications , Cough/etiology , Administration, Inhalation , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Anti-Asthmatic Agents/therapeutic use , Asthma/drug therapy , Cough/drug therapy , Drug Resistance , Female , Humans , Male , Middle Aged , Risk Factors , Severity of Illness Index , Time FactorsABSTRACT
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.
Subject(s)
ADAM Proteins , Asthma/blood , Asthma/genetics , Interleukin-4 Receptor alpha Subunit , ADAM Proteins/blood , ADAM Proteins/genetics , Adult , Aged , Asthma/drug therapy , Follow-Up Studies , Genetic Markers , Humans , Interleukin-4 Receptor alpha Subunit/blood , Interleukin-4 Receptor alpha Subunit/genetics , Middle Aged , Risk FactorsABSTRACT
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.
Subject(s)
Anti-Asthmatic Agents/therapeutic use , Asthma/blood , Asthma/drug therapy , Cell Adhesion Molecules/blood , Immunoglobulin E/blood , Omalizumab/therapeutic use , Adult , Aged , Anti-Asthmatic Agents/pharmacology , Asthma/diagnosis , Asthma/immunology , Biomarkers , Disease Progression , Female , Humans , Immunoglobulin E/immunology , Male , Middle Aged , Omalizumab/pharmacology , ROC Curve , Severity of Illness Index , Treatment OutcomeABSTRACT
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.
Subject(s)
Asthma/genetics , Asthma/physiopathology , Genetic Variation , Receptors, Glucocorticoid/genetics , Administration, Inhalation , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/therapeutic use , Aged , Asthma/drug therapy , Asthma/immunology , Cell Adhesion Molecules/blood , Eosinophils/immunology , Female , Forced Expiratory Volume , Genetic Association Studies , Heat-Shock Proteins/genetics , Humans , Leukocyte Count , Male , Middle Aged , Polymorphism, Single Nucleotide , Respiratory Function Tests , Risk FactorsABSTRACT
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.
Subject(s)
Eosinophils/immunology , Immunoglobulin E/immunology , Inflammation/immunology , Smoking , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , Asthma/immunology , Asthma/metabolism , Cross-Sectional Studies , Cytokines/metabolism , Exhalation , Female , Ferric Compounds/blood , Humans , Immunoglobulin E/blood , Inflammation/blood , Leukocyte Count , Male , Middle Aged , Nitrates/blood , Nitric Oxide , Sputum/metabolism , Young Adult , Thymic Stromal LymphopoietinABSTRACT
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.
Subject(s)
Dissection/instrumentation , Dissection/methods , Gastric Mucosa/surgery , Gastroscopy/methods , Stomach Neoplasms/surgery , Aged , Aged, 80 and over , Female , Gastroscopes , Humans , Male , Middle Aged , Treatment OutcomeABSTRACT
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.
Subject(s)
Dendritic Cells/transplantation , Gamma Rays/therapeutic use , Genetic Therapy/methods , Interferon-beta/genetics , Neuroblastoma/therapy , Animals , Combined Modality Therapy , Dendritic Cells/immunology , Disease Models, Animal , Female , Gene Transfer Techniques , Genetic Vectors , Interferon-beta/biosynthesis , Mice , Mice, Inbred A , Neuroblastoma/immunology , Neuroblastoma/pathology , Neuroblastoma/radiotherapy , Sendai virus/geneticsABSTRACT
INTRODUCTION: Laparoscopic surgery is unique and complex in nature, so the training is necessary before proceeding to operation room. Many computer aided simulators have been developed for the purpose. Our objective is to assess the improvement of basic laparoscopic skills after training in simulator. METHODS: The fifth year medical students underwent training of three laparoscopic skills using Promis2 simulator twice weekly for 4-6 weeks. The skills are laparoscopic orientation, target pointing and objects transferring. Time, path length of instruments and economy of movements were recorded. The comparisons were made for these parameters between session first and the last using a Mann-Whitney U test. RESULTS: Ten volunteers completed the exercises in less time (186.3 +/- 55.4 seconds) than the first exercise (215.7 +/- 57.4 seconds) (P=0.0027). Both the right and left hand instrument path lengths were also improved from 4425.8 +/- 1284.3 mm in the first exercise to 3925.3 +/- 1313.6 mm in the last exercise in the left side (P=0.0219) and likewise from 4273.8 +/- 1859.4 mm to 3831.3 +/- 1717.4 mm in the right side (P=0.0027). Economy of the movement in the left handed instrument improved from 1114.4 +/- 453.5 mm in the first exercise to 966.8 +/- 411.1 mm in the last (P=0.0443) and in the right handed instrument from 845 +/- 398.8 mm to 771.4 +/- 370.5 mm according to the software of Promis2 simulator (P >0.005). CONCLUSIONS: Training in Promis2 simulator improves the basic laparoscopic skills. The candidates become consistently faster with shorter path lengths and had smoother instruments movements. They also became significantly more consistent in their performance.
Subject(s)
Clinical Competence , Computer Simulation , Laparoscopy/standards , Functional Laterality , Humans , Inservice Training , Psychomotor Performance , Statistics, Nonparametric , User-Computer InterfaceABSTRACT
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.
Subject(s)
Antigens, Neoplasm/biosynthesis , Liver Neoplasms/metabolism , Liver Neoplasms/secondary , Neoplasm Proteins/biosynthesis , Stomach Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Antibodies, Monoclonal/chemistry , Antigens, Neoplasm/genetics , Disease Progression , Female , Gene Expression , Humans , Immunohistochemistry , In Situ Hybridization , Liver Neoplasms/genetics , Male , Melanoma-Specific Antigens , Middle Aged , Neoplasm Proteins/genetics , RNA Probes , RNA, Messenger/biosynthesis , RNA, Messenger/genetics , Stomach Neoplasms/genetics , Stomach Neoplasms/pathology , alpha-Fetoproteins/biosynthesisABSTRACT
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.
Subject(s)
Growth Hormone-Releasing Hormone/metabolism , Multiple Endocrine Neoplasia Type 1/complications , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/metabolism , Acromegaly , Adult , Human Growth Hormone/blood , Humans , Hyperplasia , Hyperthyroidism/complications , Hyperthyroidism/pathology , Insulin-Like Growth Factor I/metabolism , Magnetic Resonance Imaging , Male , Multiple Endocrine Neoplasia Type 1/diagnostic imaging , Multiple Endocrine Neoplasia Type 1/pathology , Pancreatic Neoplasms/diagnostic imaging , Pituitary Diseases/pathology , Tomography, X-Ray ComputedABSTRACT
AIM: To assess haemodynamic changes in the liver under temporary occlusion of an intrahepatic portal vein. MATERIALS AND METHODS: Between February 2000 and October 2004, 16 patients with hepatobiliary disease underwent single-level dynamic computed tomography during hepatic arteriography (SLD-CTHA) under temporary balloon occlusion of an intrahepatic portal vein. All patients needed percutaneous transhepatic portography for therapy of their disease. SLD-CTHA was undertaken to clarify the time-attenuation curve influenced by portal vein occlusion, and it was performed continuously over a period of 30s. The difference in absolute attenuation of the liver parenchyma in segments with occluded and non-occluded portal vein branches was determined by means of the CT number, and the difference in absolute attenuation of the occluded and non-occluded portal veins themselves was also evaluated. RESULTS: SLD-CTHA demonstrated a demarcated hyperattenuation area in the corresponding distribution of the occluded portal vein branch. The attenuation of the liver parenchyma supplied by the occluded portal vein was significantly higher than that in the non-occluded area (p<0.01). The balloon-occluded portal branch enhancement in 15 of 16 cases (94%) appears due to arterio-portal communications. Failure to evaluate a remaining case for portal branch enhancement was due to absence of a visualized portal branch in the section. CONCLUSION: Under temporary occlusion of an intrahepatic portal vein, hepatic angiography produced enhancement of the occluded portal branches and their corresponding parenchymal distribution; this finding is considered consistent with the presence of arterio-portal communications.
Subject(s)
Balloon Occlusion/methods , Liver Circulation/physiology , Liver/physiopathology , Portal Vein/physiopathology , Adult , Aged , Female , Hepatic Artery/diagnostic imaging , Humans , Liver/diagnostic imaging , Liver Cirrhosis/diagnostic imaging , Liver Cirrhosis/physiopathology , Male , Middle Aged , Portal Vein/diagnostic imaging , Tomography, X-Ray Computed/methods , UltrasonographyABSTRACT
It is reported that surveillance of serum p53 antibody (Ab) is a useful marker in detecting esophageal squamous cell carcinoma (ESCC). But there is little reported about prognostic significance of serum p53-Ab in postoperative patients with ESCC. The aim of this study is to evaluate the significance of preoperative serum p53-Ab as a marker of early recurrence after curative resection for ESCC. Enzyme-linked immunosorvent assay (ELISA) was used to analyze serum p53-Ab before treatment in 44 patients with ESCC. Carcinoembryonic antigen (CEA) and squamous cell carcinoma antigen (SCC-Ag) were examined by immunoradiometric assay. The patients who were strongly positive and positive in serum p53-Ab were more likely to have early recurrence after curative resection than seronegative patients. There were no significant correlations between CEA, SCC-Ag positivity and early recurrence. We found that serum p53-Ab was useful to predict a risk of early recurrence after curative surgical resection for ESCC.
Subject(s)
Carcinoma, Squamous Cell/surgery , Esophageal Neoplasms/surgery , Neoplasm Recurrence, Local/blood , Tumor Suppressor Protein p53/blood , Aged , Aged, 80 and over , Antigens, Neoplasm/blood , Biomarkers, Tumor/blood , Carcinoembryonic Antigen/blood , Carcinoma, Squamous Cell/pathology , Esophageal Neoplasms/pathology , Female , Follow-Up Studies , Humans , Lymph Node Excision , Male , Middle Aged , PrognosisABSTRACT
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.
Subject(s)
Neuroblastoma , Chromosomes, Human, Pair 1 , Chromosomes, Human, Pair 17 , Gene Deletion , Gene Dosage , Gene Expression , Humans , Infant , Japan , Mass Screening , N-Myc Proto-Oncogene Protein , Neuroblastoma/diagnosis , Neuroblastoma/genetics , Neuroblastoma/therapy , Nuclear Proteins/genetics , Oncogene Proteins/genetics , Ploidies , Prognosis , Receptor, trkA/geneticsABSTRACT
We herein describe a 4-year-old boy who after being treated for pneumonia showed an abnormal shadow at the hilus of the right lung on chest X-rays with continued inflammatory findings in his laboratory data. CT and MR investigations suggested the existence of a neoplasm at that site. An open biopsy was thus performed for a definite diagnosis. The histological findings and the expression of TPM3-ALK fusion gene confirmed a diagnosis of an inflammatory myofibroblastic tumor. A right upper and middle lobectomy including the tumor was thus performed for a complete resection. In addition to the histological diagnosis, the detection of the tumor specific fusion gene provided objective evidence in making a diagnosis.
Subject(s)
Lung Neoplasms/genetics , Neoplasms, Muscle Tissue/genetics , Oncogene Proteins, Fusion/genetics , Protein-Tyrosine Kinases/genetics , Tropomyosin/genetics , Anaplastic Lymphoma Kinase , Child, Preschool , Humans , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Male , Neoplasms, Muscle Tissue/pathology , Neoplasms, Muscle Tissue/surgery , RNA, Neoplasm/genetics , Receptor Protein-Tyrosine KinasesABSTRACT
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.
Subject(s)
Cholecystectomy, Laparoscopic/methods , Gallstones/diagnostic imaging , Gallstones/surgery , Intraoperative Complications/prevention & control , Adult , Aged , Cholangiography/methods , Cholangiography/statistics & numerical data , Cholecystectomy, Laparoscopic/adverse effects , Female , Humans , Intraoperative Complications/diagnostic imaging , Male , Middle Aged , Monitoring, Intraoperative/methods , Predictive Value of Tests , Risk Assessment , Sensitivity and Specificity , Severity of Illness Index , Treatment Outcome , Ultrasonography, Interventional/methodsABSTRACT
Human epidermal growth factor receptors (HER) play a critical role in the branching morphogenesis of renal tubules. In the current study, we analyzed the expression of HER2 in Wilms tumor and assessed the role of this gene in the tumorgenesis of Wilms tumor. During the period from 1960 to 2005, 40 patients with Wilms tumor were treated in our department. Twenty-four of those patients (except those with clear cell sarcoma of the kidney and malignant rhabdoid tumor of the kidney) were collected and assessed. The histological component of each Wilms tumor was divided into three categories (epithelial, blastemal, and mesenchymal) and the extent of HER2 protein expression was analyzed immunohistochemically. The normal kidney tissue accompanied with 12 cases of Wilms tumor was also examined. In the normal kidney, HER2 showed a strong immunoreactivity in the cell membranes of the collecting tubules and in the endothelial cells. Of 24 cases, 15 cases showed an epithelial component, while 24 cases had a blastemal component and 21 cases had a mesenchymal component, respectively. Among the 15 specimens with epithelial cell differentiation, eight (53.3%) showed HER2 immunoreactive epithelial cells. HER2 immunoreactive blastemal cells were present in 11 (45.8%) of 24 specimens with blastemal cells. On the other hand, only 3 (14.3%) of 21 specimens containing mesenchymal cells showed HER2 immunoreactivity. These results suggest that the extent of HER2 expression is associated with epithelial differentiation in Wilms tumor. These histological findings may therefore help to explain the development of Wilms tumor from the standpoint of histological differentiation.
Subject(s)
Gene Expression Regulation, Neoplastic , Genes, erbB-2/genetics , Kidney Neoplasms/genetics , Kidney Neoplasms/pathology , Wilms Tumor/genetics , Wilms Tumor/pathology , Child , Humans , Kidney Neoplasms/etiology , Wilms Tumor/etiologyABSTRACT
MYCN is the most powerful prognostic factor in cases of older children. However, how MYCN is related to the prognosis of infantile cases is not clear. A mass screening program was carried out by measuring urinary catecholamine metabolites (VMA and HVA) from 6-month-old infants. Of 2084 cases detected by the screening program, MYCN amplification (MNA) was examined by Southern blot analyses in 1533 cases from 1987 to 2000. Of the 1533 cases examined, 1500 (97.8%) showed no MNA, 20 cases (1.3%) showed MNA from three to nine copies, and 13 (0.8%) cases showed more than 10 copies. The 4-year overall survival rates of these three groups (99, 89 and 53%, respectively) were significantly different (P<0.001), indicating that MYCN copy number correlates with the prognosis. Cases with MNA more than 10 copies were more advanced than those without amplification (stage III, IV vs I, II, IVs; P<0.001). Patients with MNA more than 10 copies had significantly higher serum levels of neuron-specific-enolase (NSE) and ferritin than non-amplified patients (P=0.049, P=0.025, respectively). MYCN amplification was strongly correlated with a poor prognosis in infantile neuroblastoma cases. Therefore, for the selection of appropriate treatment, an accurate determination of MNA is indispensable.
Subject(s)
Gene Amplification/genetics , Genes, myc/genetics , Neuroblastoma/genetics , Biomarkers, Tumor/blood , Catecholamines/urine , Female , Humans , Infant , Male , Mass Screening , Neoplasm Staging , Neuroblastoma/blood , Neuroblastoma/pathology , Prognosis , Survival RateABSTRACT
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.
Subject(s)
Embolization, Therapeutic , Laparoscopy , Preoperative Care , Splenectomy/methods , Splenic Artery , Adolescent , Child , Female , HumansABSTRACT
To find new genes involved in esophageal squamous cell carcinogenesis, we constructed custom cDNA arrays and used the arrays to compare gene expression profiles of 12 matched normal and malignant esophageal samples including seven superficial cancer tissues. The arrays represented nearly 4000 genes, including 1728 that were specifically selected based on pilot studies to find genes that were differentially expressed in esophageal cancers. Expression values for all genes were normalized for each sample and were compared in normal versus tumor tissues. There was a marked decrease in the levels of the transcriptional elongation factor A gene in all 12 of the squamous cell cancer samples compared to matched normal samples. Because the transcription elongation factor A gene has not been previously reported to be involved in cancer development, our results suggest that further investigation of its role in esophageal carcinogenesis is warranted.
Subject(s)
Carcinoma, Squamous Cell/genetics , DNA-Binding Proteins/genetics , Esophageal Neoplasms/genetics , Transcription Factors/genetics , Adult , Aged , Cell Transformation, Neoplastic/genetics , Female , Gene Expression Profiling , Humans , Male , Middle Aged , Oligonucleotide Array Sequence AnalysisABSTRACT
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.