Gastric adenocarcinoma of fundic gland type (chief cell predominant type) with unique endoscopic appearance curatively treated by endoscopic submucosal resection.

Gastric adenocarcinoma of fundic gland type [chief cell predominant type; (GA-FD-CCP)] is a rare gastric cancer variant arising from non-atrophic mucosa without Helicobacter pylori infection in the upper third portion of the stomach. GA-FD-CCP originates deep in the mucosal layer; hence, endoscopic lesion detection is often difficult at an early stage because of a minimal change in the mucosal surface. Here we present a 66-year-old man with an early stage of GA-FD-CCP showing characteristic endoscopic features. Esophagogastroduodenoscopy demonstrated a flat, slightly reddish area with black pigment dispersion and irregular micro-surface structure at the gastric fornix. The tumor was resected by endoscopic submucosal dissection and was pathologically diagnosed as GA-FD-CCP. Prussian blue staining revealed that the black pigment was a hemosiderin deposition. We reported a rare case of successfully treated GA-FD-CCP with black pigmentation that aided in early lesion detection.

Molecular targeting of CSN5 in human hepatocellular carcinoma: a mechanism of therapeutic response.

Development of targeted therapy for hepatocellular carcinoma (HCC) remains a major challenge. We have recently identified an elevated expression of the fifth subunit of COP9 signalosome (CSN5) in early HCC as compared with dysplastic stage. In the present study, we explored the possibility of CSN5 being a potential therapeutic target for HCC. Our results show that CSN5 knockdown by small-interfering (si) RNA caused a strong induction of apoptosis and inhibition of cell-cycle progression in HCC cells in vitro. The down-regulation of CSN5 was sufficient to interfere with CSN function as evidenced by the accumulation of neddylated Cullin 1 and changes in the protein levels of CSN-controlled substrates SKP2, p53, p27 and nuclear factor-κB, albeit to a different degree depending on the HCC cell line, which could account for the CSN5 knockdown phenotype. The transcriptomic analysis of CSN5 knockdown signature showed that the anti-proliferative effect was driven by a common subset of molecular alterations including down-regulation of cyclin-dependent kinase 6 (CDK6) and integrin ß1 (ITGB1), which were functionally interconnected with key oncogenic regulators MYC and TGFß1 involved in the control of proliferation, apoptotic cell death and HCC progression. Consistent with microarray analysis, western blotting revealed that CSN5 depletion increased phosphorylation of Smad 2/3, key mediators of TGFß1 signaling, decreased the protein levels of ITGB1, CDK6 and cyclin D1 and caused reduced expression of anti-apoptotic Bcl-2, while elevating the levels of pro-apoptotic Bak. A chemically modified variant of CSN5 siRNA was then selected for in vivo application based on the growth inhibitory effect and minimal induction of unwanted immune response. Systemic delivery of the CSN5 3/8 variant by stable-nucleic-acid-lipid particles significantly suppressed the tumor growth in Huh7-luc+ orthotopic xenograft model. Taken together, these results indicate that CSN5 has a pivotal role in HCC pathogenesis and maybe an attractive molecular target for systemic HCC therapy.

Angiopoietin 2 displays a vascular endothelial growth factor dependent synergistic effect in hepatocellular carcinoma development in mice.

BACKGROUND: Orchestration of two major classes of angiogenic factors-namely, vascular endothelial growth factor (VEGF) and angiopoietin 2 (Ang-2)-has been shown to play a pivotal role in tumour angiogenesis, including hepatocellular carcinoma (HCC). However, few studies have focused on the direct interaction of these factors on in vivo tumour development and angiogenesis. AIM: To examine the interaction between both factors in murine HCC. METHODS: We examined the combination effect of VEGF and Ang-2 overexpression by means of a combination of a retroviral tetracycline (tet) regulated gene manipulating system in vivo, by providing tet in the drinking water, and a conventional plasmid gene expression system. RESULTS: Neither Ang-2 nor VEGF overexpression induced proliferation of HCC cells in vitro. In vivo, although overexpression of Ang-2 did not increase tumour development, simultaneous expression of Ang-2 and VEGF synergistically augmented tumour growth and angiogenesis in murine HCC. Ang-2 plus VEGF induced tumour development was markedly attenuated by treatment with neutralising monoclonal antibodies against VEGF receptors. Ang-2 plus VEGF overexpression significantly increased the activities of matrix metalloproteinase (MMP)-2 and MMP-9 in the tumour. Suppression of intratumoral VEGF almost completely abolished this augmentation of MMPs. CONCLUSIONS: These results suggest that Ang-2 synergistically augments VEGF mediated HCC development and angiogenesis. This proangiogenic activity was exerted only in the presence of VEGF, at least partly mediated via induction of MMP-2 and MMP-9 in the tumour.

Successful treatment of acute Budd-Chiari syndrome with percutaneous transluminal angioplasty.

A 26-year-old man developed progressive, massive ascites and hematemesis due to rupture of esophageal varices. Combination diagnostic modalities of color doppler ultrasonography, enhanced computed tomography, and magnetic resonance imaging led to the case being diagnosed as acute Budd-Chiari syndrome with severe stricture of the intrahepatic inferior vena cava. Percutaneous transluminal angioplasty this resulted in great improvement of the clinical manifestations.

Two cases of colonic tuberculosis presenting with massive melena.

The clinical symptoms of colonic tuberculosis are variable, among which massive melena is extremely rare. Herein, we report two cases of colonic tuberculosis representing with massive melena, both of whom never had active pulmonary tuberculosis. The first case was a 55-year-old woman. Although her emergency colonoscopic setting suggested colonic tuberculosis, no evidence of tuberculosis could be found at that time. We performed a therapeutic trial and observed a drastic regression of the initial changes with 4-week treatment using antituberculous agents. The second case was a 37-year-old man. His emergency colonoscopy showed lesions mimicking colon carcinoma. However, the histological examinations did not indicate malignancy. The polymerase chain reaction of colonic biopsy specimen was positive for Mycobacterium tuberculosis. Similar to the first case, a significant improvement of the initial lesions was observed after 4-week treatment using antituberculous agents. Collectively, although the massive melena is a rare manifestation, tuberculosis of the colon should be suspected in the patients with such symptom.

[Effects of oxitropium bromide on exercise and lung function in patients with pulmonary emphysema].

Anticholinergic drugs have been reported to be effective in pulmonary emphysema. We studied the effects of the anticholinergic drug oxitropium bromide on exercise capacity and lung function in patients with this disease. We studied 11 men and 1 women, aged 69.3 +/- 4.5 yrs, in whom chest radiography showed pulmonary emphysema. Before and after the subjects inhaled two puffs of oxitropium bromide, they walked in a corridor for 12 minutes, and the distance they walked and spirometric data were recorded. FVC and FEV1 were significantly higher after inhalation of the drug. FEV1% did not change, and the distance walked increased slightly. We also studied symptoms and peak expiratory flow rate in 37 patients with pulmonary emphysema before and after the start of therapy with inhaled oxitropium bromide. Symptom scores of wheezing and sleep improved, and peak expiratory flows increased significantly. We conclude that inhaled oxitropium bromide can improve lung function and slightly increase exercise capacity in patients with pulmonary emphysema. These effects may be caused by bronchodilation-induced increases in FEV1 and FVC. Monitoring of peak expiratory flow in patients with pulmonary emphysema may be useful for evaluating the clinical effectiveness of oxitropium bromide.

[A case of cystic fibrosis in a Japanese student].

A 16-year-old boy was admitted to our hospital because of coughing, sputum, and exertional dyspnea. Seven months after birth cystic fibrosis had been diagnosed. The chest roentgenogram on admission showed diffuse reticulonodular shadows and overinflation. Pulmonary function tests revealed obstructive and restrictive impairment. Erythromycin and Lomefloxacin were administered by mouth, and aminoglycosides were administered by inhalation. His symptoms were alleviated, and he is now an outpatient. In Japan, cystic fibrosis is rare, and this patient is extremely rare because he has grown up to be a 16-year-old. In this case, low-dose and long-term erythromycin administration was very effective.

[Respiratory disease in the tertiary emergency hospital].

We studied treatment for respiratory emergencies over the past 11 years at our hospital, a tertiary emergency center. We supply intermediate management services to a general hospital. A total of 13,667 patients received tertiary emergency medical care (annual mean: 1243). Of these, 1592 had severe respiratory disturbances (11.5% of the total; 971 males, 621 females; annual mean: 143). The most frequently seen conditions were COPD, respiratory failure due to old pulmonary tuberculosis) 35.2%, mortality failure due to old pulmonary tuberculosis (35.2%, mortality rate: 29.7%), bronchial asthma (26.0%, mortality rate 9.6%), pneumonia (19.0%, mortality rate 20.4%), and pneumothorax (10.3%). Very few of the patients with bronchial asthma who arrived in cardiopulmonary arrest survived. Patients with interstitial pneumonia, paraquat lung, pulmonary obstruction, adult respiratory distress syndrome, and near-drowning all had poor prognoses, as did victims of attempted suicide by hanging and attempted murder by strangulation. About 25% of the patients required mechanical ventilation, and about half of those patients died. Changes in prehospital care and in care given after critical care is no longer needed are important in improving the prognoses for patients with respiratory emergencies.

Mixed tumor of salivary gland type arising in the bronchus.

During bronchoscopy for atelectasis of the middle lobe, a 61-year-old man was found to have a polypoid mass obstructing the bronchus. Right middle and lower lobectomy disclosed a tumor growing into the lumen of the middle lobe bronchus. The histological features of the tumor were indistinguishable from those of the mixed tumor of the salivary gland. A review of the literature reveals only 7 cases of this extremely rare tumor.

[CEA and CA19-9 in BALF from patients with idiopathic interstitial pneumonia].

Carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA19-9) were measured in bronchoalveolar lavage fluid (BALF) in 21 patients with idiopathic interstitial pneumonia (IIP) and 7 healthy volunteers. The concentrations of both CEA and CA19-9 in the BALF were significantly higher in patients with IIP than those in healthy subjects. Significant correlations were present between the concentration of CEA and neutrophil percentage of the total BALF cells and between the concentration of CA19-9 and neutrophil percentage of the total BALF cells in the patients with IIP. Immunohistochemical study of tissue CEA and CA19-9 in the postmortem lungs of patients with IIP showed that CEA staining was present in the epithelia of respiratory bronchioles and alveoli, and it was especially increased in the region of alveoli where type II pneumocytes proliferate. CA19-9 staining was present in the epithelia of the respiratory bronchioles but absent in the epithelia of alveoli. It seems that assay of CEA in BALF may be useful to estimate the degree of pathological change and the activity of IIP.

Tuberculous mediastinal lymphadenitis in an adult patient.

A 40-year-old woman was presented with a fever, which proved to be due to mediastinal tuberculous lymphadenitis. Up to 1988, 149 cases of tuberculous mediastinal lymphadenitis have been reported in the literature in Japan. This case was very rare because a chest plain film revealed neither mediastinal widening nor lung parenchymal involvement. On the other hand, a CT scan of the chest was very useful because it showed unsuspected mediastinal lymph nodes enlargement. The diagnosis of tuberculous mediastinal lymphadenitis was made by the findings of a supraclavocular lymph node biopsy, which showed granulomas, compatible with tuberculosis. A good response from the patient to antituberculous therapy confirmed this diagnosis.

A case of intralobar pulmonary sequestration with high serum CA19-9 levels.

A 38-year-old female presented with cough and fever. A chest X-ray examination revealed an abnormal shadow in the posteroinferior portion of the left hemithorax, and a laboratory examination showed that the serum carbohydrate antigen 19-9 (CA19-9) level was markedly high (1000 U/ml). A left thoracotomy showed an intralobar pulmonary sequestration of the left lower lobe, and after a left lower lobe lobectomy, the serum level of CA19-9 decreased to normal. Increased CA19-9 activity was detected by immunohistochemistry in the epithelia of bronchioles in the pulmonary sequestration. This communication is the first to report a case of increased activity of CA19-9 in pulmonary sequestration.

The oral administration of stannous chloride to rats.

The dose-effect of inorganic tin (Sn) was examined in rats given 6 oral doses of stannous chloride at 12-h intervals. Of the biochemical indices for the toxicity of Sn reported previously, i.e. gastric acid secretion, duodenal alkaline phosphatase and hepatic phosphorylase activities, serum calcium (Ca) concentration, and femoral calcium content, significant decreases were found, except in gastric acid secretion (6X10 mg/kg). Sn, 6X3 mg/kg, decreased significantly the calcium content in the epiphysis of the femur but the decrease was not significant at 6X1 mg/kg. These results suggest that the critical organ in inorganic Sn toxicity is bone and that the oral no-effect dose level is 6X3 mg/kg.