Abstract: Pirarubicin (tetrahydropyranyl adriamycin: THP) is a doxorubicin (DOX) derivative with lower cardiotoxicity than DOX. However, there is little information on clinical outcome and toxicity in patients treated with an R-TCOP regimen including this drug (rituximab, THP, cyclophosphamide, vincristine, and prednisolone). We retrospectively analyzed the efficacy and safety of R-TCOP compared to TCOP in patients with diffuse large B-cell lymphoma (DLBCL) (n = 91) or follicular lymphoma (FL) (n = 25). In cases of DLBCL, the median follow-up times for surviving patients were 864 days in the TCOP group (n = 41) and 430 days in the R-TCOP group (n = 50). Patients treated with R-TCOP showed a significantly better response to treatment than those treated with TCOP (P < 0.01) and a significantly longer three-year overall survival (OS) (70% for R-TCOP vs. 50% for TCOP,P = 0.02). Factors influencing the improved OS with R-TCOP treatment were age < 60 years, clinical stage IV disease, International Prognostic Index HI-risk and H-risk, serum lactate dehydrogenase > normal, performance status ≥ 2, B symptoms, extranodal sites ≥ 2, and bone marrow involvement. In a Cox proportional hazard model, the addition of rituximab was associated with good OS. In cases of FL, the response to treatment, OS, and progression-free survival did not differ significantly between the two regimens. Adverse events including cardiac toxicities did not differ significantly between R-TCOP and TCOP treatment, and there were no deaths associated with adverse events. OS was significantly improved among IPI HI-risk or H-risk cases and in advanced-stage patients with DLBCL who received R-TCOP compared to those receiving TCOP. The incidence of adverse events did not differ between the two regimens.

View full abstract

Although CD56⁺ T cells comprise less than 5% of human peripheral blood mononuclear cells (PBMCs), we observed that the percentage of CD56⁺ T cells was increased in activated T-cell populations used for adoptive immunotherapy. We hypothesized that this cell subpopulation might be an important cytotoxic effector in immunotherapy. PBMCs were obtained from both cancer patients and healthy donors. CD8⁺ single-positive T cells were separated with magnetic beads, and stimulated with immobilized anti-CD3 monoclonal antibody and IL-2. FACS analysis showed that the CD56 antigen was expressed more strongly on CD8 cells than on CD4 cells. The CD8⁺ CD56⁺ T cells have a tendency for more cytotoxic effects than the CD8⁺ CD56^- T cells. SEM analysis showed that the CD56⁺ T cells adhered to one another, to form a cluster. Thus, T cell self-adhesion was increased by the expression of the adhesion molecule CD56. The cytotoxic CD8⁺ CD56⁺ T cells derived from CD8⁺ T cells in the peripheral blood are activated T cells that are distinct from natural killer T (NKT) cells.

View full abstract

After lung lobectomy, the residual thoracic cavity is filled by expansion of the remaining lobes and by mediastinal shifting. The mediastinal shift contributes to a change in the anatomical position of the heart. This change may affect electrocardiographic (ECG) findings but the relationship has not been examined. In this study, ECG intervals, including RR, P, PR, S-Tp, QRS, and QTc intervals, were analyzed before and after 86 lung lobectomies, consisting of 27 right upper (RU), 10 right middle (RM), 12 right lower (RL), 25 left upper (LU), and 12 left lower (LL) lobectomies. Persistent postoperative arrhythmia was observed in 10 patients (12%), all with atrial fibrillation. After RU lobectomies, the RR, PR, and S-Tp intervals became shorter. After RM lobectomies, the RR and QTc intervals became shorter and the P and PR intervals were prolonged. RL, LU, and LL lobectomies did not appreciably affect the ECG intervals. The post/pre-operative ratio of the P and PR intervals were greater following RM lobectomy than following RU or RL lobectomy. The post/pre-operative ratio of the QTc interval was smaller after RM lobectomy than after RL lobectomy. Lung lobectomy affected ECG intervals and the pattern of change varied depending on the lobe resected. Resection of the RM lobe, the lobe that is anatomically next to the right atrium, prolonged the PR interval and the change in pattern was different from RU or RL lobectomies. The change in the anatomical position of the heart following lung lobectomy may contribute to the changes in ECG intervals.

View full abstract

It is believed that the rate of restenosis increases as chronic kidney disease (CKD) progresses. Although in random study of Sirolimus-eluting stent (SES) the rates of restenosis in patients on dialysis and those on non-dialysis have been compared, no comparison has been made among stages of CKD. We therefore compared the clinical results of percutaneous coronary intervention (PCI), using SES among stages of CKD. Of 1116 consecutive cases since the first PCI was performed using SES, 462 cases in which follow-up coronary angiography was performed in the remote phase were included in this study. These cases were classified into 6 groups, from stage 1 to stage 5 by degree of progression of CKD as well as dialysis, and clinical results were compared. Of the 462 cases in which follow-up coronary angiography in the remote phase was performed, 59.1% (273) of the cases were CKD stage 1, 14.9% (69) stage 2, 11.5% (53) stage 3, 2.2% (10) stage 4, 0% (0) stage 5, and 12.3% (57) were dialysis cases. In stage 1, the rate of restenosis was 8.1%, target lesion revascularization (TLR) 5.1% and target vessel revascularization (TVR) 6.6%; in stage 2, the rate of restenosis was 10.1%, TLR 8.7% and TVR 11.6%; in stage 3, the rate of restenosis was 7.5%, TLR 5.9% and TVR 11.6%; and in stage 4, the rate of restenosis, TLR and TVR were each 0%. In the dialysis group, the rate of restenosis was 31.6% (p < 0.0001), TLR 29.8% (p < 0.0001) and TVR 33.3% (p < 0.0001). When CKD stage 1 and the other stages were compared, no significant differences were observed in rate of restenosis, TLR and TVR except in the dialysis group. In the latter group, rate of restenosis, TLR and TVR were each significantly increased compared with CKD stage 1. The frequencies of restenosis, TLR and TVR in the remote phase of PCI using SES did not differ among stages of CKD.

View full abstract

It is believed that hepatocellular damage in human chronic cholestatic liver diseases is caused by the accumulation of hydrophobic bile acids, such as glycochenodeoxycholic acid (GCDCA). Previous reports have shown that GCDCA-induced apoptosis is promoted by both mitochondria-mediated and endoplasmic reticulum (ER) stress-associated pathways in HepG2 cells and that these two pathways are linked by the action of caspase-8 on BAP31. However, the interdependence of multiple pathways remains poorly understood and the role of caspases is unclear. Thus, in the present study, we investigated the interactions among the executioner caspases in GCDCA-induced apoptotic HepG2 cells. Cells were treated for 1-24 h with GCDCA (300μM), in the presence or absence of inhibitors of caspase-9, -4 or -3 (each at 30μM). Pretreatment of cells with the caspase-9 inhibitor significantly suppressed GCDCA-induced apoptosis; however, pretreatment of cells with the caspase-4 inhibitor had no effect. Furthermore, pretreatment of cells with the caspase-9 inhibitor significantly reduced GCDCA-induced increases in caspase-3 and -4 activity, as well as the mRNA expression of BiP, a molecular chaperone located in the ER. In contrast, pretreatment of cells with the caspase-4 inhibitor had no effect. These results suggest that, in GCDCA-treated HepG2 cells, caspase-4 acts downstream of both the proapoptotic Bcl-2 protein Bax and caspase-9. Because the major mechanism underlying GCDCA-induced apoptosis involves a mitochondria-mediated pathway, it is unlikely that caspase-4 has a major role in the initiation and promotion of GCDCA-induced apoptosis.

View full abstract

Atypical pleomorphic adenoma (PA) is a premalignant condition of PA, although its immunoreactivity for HER2/neu, which is a marker for carcinoma (Ca) ex PA, is still unclear. We investigated the pathology and HER2/neu immunoreactivity of atypical PA, and compared the results with Ca ex PA and benign PA cases. The mean age of atypical PA was statistically lower and the size tended to be smaller than Ca ex PA. Pathologically, hypercellularity was observed in 10 cases of atypical PA, and 8 cases showed capsule violation. Immunohistochemically, the HER2/neu positive ratio in hypercellular foci of atypical PA was 40%, significantly higher than the ratio in benign PA, and significantly lower than that in Ca ex PA. However, the ratio in capsule violation foci of atypical PA was 0%, as in benign PA. Thus, hypercellularity was considered to indicate greater potential for malignant transformation than capsular violation. Further studies are needed to determine whether atypical PA with HER2/neu expression undergoes malignant transformation more frequently than HER2/neu-negative atypical PA.

View full abstract

To assess the risk factors for severe infections developing as a complication of transbronchial biopsy in lung cancer patients. From April 2001 to March 2007, 1091 patients underwent bronchoscopy at our institution. We reviewed the records of 5 of these patients diagnosed with lung cancer and who developed lung abscess or cavitary infection after transbronchial biopsy necessitating surgical resection. The 5 patients (4 men, 1 woman; mean age at diagnosis, 62.4 years; range, 42-78 years) were all smokers and were immunocompetent. One patient suffered from diabetes mellitus. Of the 5 patients, chest CT revealed a cavitary lesion in 2 patients, central low attenuation in 2 patients, and a small nodule in 1 patient. The longest tumor diameter ranged from 20-60mm (mean, 42mm). Sputum cultures taken prior to bronchoscopy showed no significant bacterial growth in 4 of the patients, with 1 patient showing Streptococcus pneumoniae. Three cases showed elevated serum C-reactive protein. Histologically, the diagnosis was squamous cell carcinoma in 3 patients and adenocarcinoma in 2 patients. The risk factors for the development of a lung abscess after transbronchial biopsy include large mass lesions with central necrosis or cavitary lesions.

View full abstract

Abstract: It is well known that many stressors affect the circulatory system, including the heart and blood vessels, through neuronal and humoral mechanisms. However, the effect of stressors on blood fluidity –one of the most important factors in the circulatory system– is unclear. According to Poiseuille's law, reduced blood fluidity increases blood vessel resistance and enhances blood coagulation. Reduced blood fluidity also increases blood pressure and the risk of thrombosis. Therefore, this study examined the effects of electrical shock (ES) stress on blood fluidity in male Wistar rats using a microchannel array flow analyzer, which mimics capillary vessels. We found that blood fluidity was reduced following ES stress. In blood treated with the anticoagulants heparin and EDTA, the reduction in blood fluidity was greater in heparinized blood than in EDTA-treated blood. When the α-blocker phentolamine was used, blood fluidity was restored in heparin-treated but not EDTA-treated blood. Since heparin blocks blood coagulation, but EDTA blocks both blood coagulation and platelet agglutination, this result indicates that ES stress might reduce blood fluidity by affecting platelet agglutination. In addition, ES stress might reduce blood fluidity, at least partly, through the adrenergic system.

View full abstract

Esophageal epithelial lesions are important features with respect to the early diagnosis of esophageal cancer. Such lesions include inflammatory reactive lesions (inflammatory reactions, IR) and neoplastic lesions. However, while neoplastic lesions are also classified from low-grade intraepithelial neoplasia (LN) to high-grade intraepithelial neoplasia (HN), it is often difficult to differentiate esophageal epithelial lesions in a biopsy. Therefore, this study analyzed cases of endoscopic mucosal resection (EMR) and dissection by immunostaining for p53, MIB-1, glucose transporter-1 (GLUT-1), and cytokeratin (CK) in addition to cytohistological grading to establish lesions trends for classification. This study included 50 lesions of EMR performed at our hospital from 2004 to 2007, as well as 31 cases who underwent a pathological autopsy at our hospital during the period between 2006 and 2007. Tissue diagnoses by HE staining classified the specimens into five groups: normal, IR, LN, HN, and squamous cell cancer (SCC). This study undertook further comparison by immunostaining for p53, Ki-67 staining, GLUT-1 and CKs 17 and 14. All immunostaining revealed a significant difference between IR and LN grade of lesions. Specifically, GLUT-1 staining revealed a significant difference between LN and HN lesions, while CK17 staining differentiated significantly between HN and SCC. The findings indicated that pathological diagnoses of esophageal lesions should include GLUT-1, CK17, and CK14 immunostaining to differentiate LN and HN lesions.

View full abstract

This study compared steady-state free precession (SSFP) with Fast Low Angle Shot (FLASH) at 3.0 T cardiac Cine MRI with respect to contrast to noise ratio (CNR) and visual image quality assessment. All images were acquired on a 3.0-T Siemens MAGNETOM trio. Seven healthy volunteers (all males, mean age 32.5 ± 7.1 years) underwent magnetic resonance imaging using SSFP and FLASH sequence on the same day. For both SSFP and FLASH imaging, 8-mm thick short axis and long axis views were acquired with equal matrix size (192 × 192). CNR calculations were performed on the short axis images acquired at end systole time points. Three radiologists independently assessed image quality. SSFP images were superior to FLASH images with respect to CNR (SSFP: 7.14 ± 2.16, FLASH: 3.57 ± 1.83, P < 0.001). In image quality, SSFP images were superior to FLASH in both short and long axis views (P < 0.01). Although SSFP images contained dark blood artifacts in 3 cases, these images were improved by frequency offset. SSFP sequences provided higher quality images than FLASH sequences, and would be available for cardiac cine MRI at 3.0 T.

View full abstract

Atypical pleomorphic adenoma (APA) is a premalignant condition of pleomorphic adenoma (PA), and APA with hypercellularity (h-APA) is seldom positive for HER2/neu. Whether h-APA cells show higher mitotic activity and oncogenic mutations remains unclear. Thirteen cases of h-APA, 10 cases of carcinoma (Ca) -ex-PA, and 19 cases of PA were immunohistochemically examined for overexpression of the proliferation marker protein, Ki-67 and the tumor suppressor protein, p53. Ki-67 expression is higher in Ca-ex-PA than in other groups, and it is also higher in h-APA than in PA. p53 expression is also higher in Ca-ex-PA than in other groups, but there is no difference between h-APA and PA. We hypothesize the sequence of events during carcinogenesis of PA as follows: first there is an increase in proliferation in PA, which leads to h-APA, secondly, there is an amplification of the HER2/neu oncogene in h-APA and finally, p53 overexpression occurs in h-APA and leads to Ca-ex-PA. This hypothesis explains the increase in both patients' age and tumor size in each group, in the sequence from PA to Ca-ex-PA via h-APA.

View full abstract