An operated case of lung cancer with pleural plaques: its asbestos bodies, fiber analysis and asbestos exposure

This case was a 79-year-old man with pleural plaques, which had been pointed out in the left lung field on chest X-ray six years ago. A new shadow in the right chest appeared in 1999 and was closely examined. Cytological class IV carcinoma was detected in his lung tissue obtained by broncho-fiberscope. Lobectomy of the right upper lobe was performed, and calcified pleural plaques were found on the chest wall. The clinical diagnosis was poorly differentiated squamous cell carcinoma, T1N0M0. In World War II when he was 26 years old, he had worked as a boiler man on a battle cruiser for one year. The amount of asbestos bodies (AB) was 3,348 per gram dry lung tissue. The cores of AB and asbestos fibers were examined and showed that amosite was the most prevalent and crocidolite, tremolite and chrysotile were present in that order. After leaving the navy, he had worked as a farmer throughout his life, suggesting that he had never contacted asbestos occupationally after being a boiler man. It is strongly suggested that he had been exposed to asbestos during his work as a boiler man and that produced pleural plaques and lung cancer 50 years' later.     

Directional preponderance in pitch circular vection

We used optokinetic stimulation (OKS) in eighteen normal adults aged 18-30 years to investigate vertical self-motion perception. In order to induce self-rotation, either a stripe pattern or a random dot pattern was projected onto the inner wall of a hemispherical dome with a diameter of 150 cm. The pattern was rotated either about the subject's vertical axis (yaw) or about the subject's interaural axis (pitch) for 80 s at a constant acceleration of 1 deg/s2. Stimuli were randomly repeated three to four times in each direction. The latency of onset as well as the perceived intensity of circular vection (CV) was measured for each stimulus presentation. CV latencies for upward rotational stimulation were significantly longer than those for downward rotational stimulation under both types of stimulus conditions. There was no significant difference in CV latency between rightward and leftward rotational stimulation. For most subjects, the magnitudes of the perceived CV for rightward rotational stimulation were equal to those for leftward rotational stimulation, whereas the magnitudes of the perceived CV for vertical stimulation showed large intersubject variability. These results provide additional evidence that fundamental differences exist between different types of self-motion. Possible explanations for the directional asymmetry in vertical perception of self-motion will also be discussed.     

Prevalence and clinical features of Paget's disease of bone in Japan

The present study aimed to evaluate the prevalence and clinical presentation of Paget's disease of bone (PDB) in Japan. As PDB is a very rare disease in Japan, a nationwide mail survey was conducted targeting doctors in the specialty most frequently diagnosing and treating PDB patients in Japan. First, the literature for all case reports in Japan published between January 1990 and December 2002 was reviewed to determine who was diagnosing and treating PDB in Japan. This literature review for all case reports in Japan revealed that 72.1% of cases in Japan were reported from departments of orthopedic surgery. A nationwide two-phase mail survey was conducted for the departments of orthopedic surgery of 2320 general hospitals accredited by the Japanese Orthopaedic Association. Phase 1 involved determining how many patients with PDB were followed at each hospital. If the answer was one or more, phase 2 of the survey gathered information on the clinical presentation of current patients. The mail survey yielded a final response rate of 75.4% for phase 1 and 87.6% for phase 2. Phase 1 indicated that the prevalence of PDB in Japan is about 2.8 cases per million capita. Phase 2 revealed a slight female predominance, lower frequency of familial clustering, higher frequency of femoral fracture in the affected femur, and a higher ratio of symptomatic PDB in Japan compared with findings in countries displaying a higher prevalence of PDB. The present epidemiological study revealed that the disorder is extremely rare in Japanese individuals, and that some differences exist with regard to the clinical features of PDB between Japanese patients and patients from high-prevalence countries.     

Aneurysm of a systemic artery supplying the normal basal segments of the left lower lobe

The case of an aneurysm of a systemic artery supplying otherwise normal basal segments of the left lower lobe is presented. The diagnosis was correctly made postprocessed with three-dimensional reformatting using a multidetector row CT (MDCT) scanner. Conventional angiography was obviated.     

Management of febrile neutropenic patients

Infection is the most common complication of febrile neutropenia. Bacterial infections predominate during the early stages of a neutropenic episode,whereas invasive fungal infections tend to occur later. Prompt initiation of antimicrobial agents remains the gold standard. The recent cumulative data indicate a low-risk group that is unlikely to progress to a grave clinical condition. In the Japanese guideline updated in 2003, the patients at low risk of complications are determined initially, and the patients at low risk can receive oral fluoroquinolones with or without amoxicillin/clavulanate. A high-risk group, however,must be given vigorous parenteral treatment with 4 th-generation cephalosporins or carbapenems with or without an aminoglycoside. Initial empirical therapy should be based on local epidemiology and drug-susceptibility patterns. Antimicrobial coverage against Pseudomonas species is necessary. If defervescence occurs in 3-5 days or fever persists with a stable condition, the same agents could be continued. If fever persists with no improvement in conditions, an aminoglycoside is added to patients on monotherapy as an initial therapy. Changing the Beta-lactams is considered for patients on combination therapy with Beta-lactams plus an aminoglycoside. Fungal cultures and serological test are performed. After 48 hours of observation on the treatment, antifungals are then started depending on the results of culture and serological tests. Chemoprophylaxis should be considered for patients at high risk.     

Significance of glucose intolerance and SHIP2 expression in hepatocellular carcinoma patients with HCV infection

Glucose intolerance frequently is found in hepatocellular carcinoma (HCC) patients with hepatitis C virus (HCV) infection; however, the significance of glucose intolerance remains unclear. In addition, SH2 domain-containing inositol phosphatase (SHIP) 2 is a negative regulator of intracellular insulin signaling; however, changes in SHIP2 expression have not been investigated in HCC. To assess the significance of glucose intolerance, we analyzed 118 HCC patients with HCV infection. Twenty HCC specimens were used for immunoblotting and immunostaining for SHIP2. Patients were classified into two groups: a glucose intolerance group (n=39) and a normal glucose tolerance group (n=79). There was no significant difference in the disease-free survival (P=0.838) or long-term survival (P=0.091) between the groups. However, for males, the cumulative survival rate was significantly lower in the glucose intolerance group (n=22) than that in the normal glucose tolerance group (n=52) (P=0.036). In multivariate analysis, Child-Pugh class (P=0.0003) and glucose intolerance (P=0.036) were identified as statistically significant and independent prognostic factors in males. SHIP2 expression level decreased in HCC compared to that in nontumor tissues. In conclusion, this study is the first to demonstrate the significance of glucose intolerance in prognosis of male HCC patients and down-regulation of SHIP2 expression in HCC.     

Activation of downstream epidermal growth factor receptor (EGFR) signaling provides gefitinib-resistance in cells carrying EGFR mutation

Patients with pulmonary adenocarcinoma carrying the epidermal growth factor receptor (EGFR) mutation tend to display dramatic clinical response to treatment with the EGFR tyrosine kinase inhibitor gefitinib. Unfortunately, in many cases the cancer cells eventually acquire resistance, and this limits the duration of efficacy. To gain insight into these acquired resistance mechanisms, we first prepared HEK293T cell line stably transfected with either wild-type (WT) or mutant (L858R) EGFR, and then expressed oncogenic K-Ras12V mutant in the latter transfectant. Although 293T cells expressing wild-type EGFR did not show any growth inhibition by gefitinib treatment similarly to the non-transfected cells, the cells expressing the EGFR-L858R were exquisitely sensitive. Consistently, phospho-Akt levels were decreased in response to gefitinib in cells expressing EGFR-L858R but not in cells with EGFR-WT. In contrast, 293T cells expressing both EGFR-L858R and oncogenic K-Ras were able to proliferate even in the presence of high concentration of gefitinib probably by inducing Erk1/2 activation. We also expressed K-Ras12V in the gefitinib-sensitive pulmonary adenocarcinoma cell line PC-9, which harbors an in-frame deletion in the EGFR gene. The activated K-Ras inhibited the effects of gefitinib treatment on cell growth, cell death induction and levels of phospho-Akt, as well as phospho-Erk. These data indicate that activated Ras could substitute most of the upstream EGFR signal, and are consistent with the hypothesis that mutational activation of targets immediately downstream from the EGFR could induce the secondary resistance to gefitinib in patients with lung cancer carrying EGFR mutation.     

Validation study of the prediction system for clinical response of M-VAC neoadjuvant chemotherapy

To predict the efficacy of the M-VAC neoadjuvant chemotherapy for invasive bladder cancers, we previously established the method to calculate the prediction score on the basis of expression profiles of 14 predictive genes. This scoring system had clearly distinguished the responder group from the non-responder group. To further validate the clinical significance of the system, we applied it to 22 additional cases of bladder cancer patients and found that the scoring system correctly predicted clinical response for 19 of the 22 test cases. The group of patients with positive predictive scores had significantly longer survival than that with negative scores. When we compared our results with a previous report describing the prognosis of the patients with cystectomy alone, the results imply that patients with positive scores are likely to benefit from M-VAC neoadjuvant chemotherapy, but that the chemotherapy would shorten the lives of patients with negative scores. We are confident that our prediction system to M-VAC therapy should provide opportunities for achieving better prognosis and improving the quality of life of patients. Taken together, our data suggest that the goal of 'personalized medicine', prescribing the appropriate treatment regimen for each patient, may be achievable by selecting specific sets of genes for their predictive values according to the approach shown here.