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As a bridge between videos and natural languages, video-text matching has been a hot multimedia research topic in recent years. Such cross-modal retrieval is usually achieved by learning a common embedding space where videos and text captions are directly comparable. It is still challenging because existing visual representations cannot exploit semantic correlations within videos well, resulting in a mismatch with semantic concepts that are contained in the corresponding text descriptions. In this article, we propose a new Guided Graph Attention Learning (GGAL) model to enhance video embedding learning by capturing important region-level semantic concepts within the spatiotemporal space. Our model builds connections between object regions and performs hierarchical graph reasoning on both frame-level and whole video–level region graphs. During this process, global context is used to guide attention learning on this hierarchical graph topology so that the learned overall video embedding can focus on essential semantic concepts and can be better aligned with text captions. Experiments on commonly used benchmarks validate that GGAL outperforms many recent video-text retrieval methods with a clear margin. As multimedia data in dynamic environments becomes critically important, we also validate GGAL learned video-text representations that can be generalized well to unseen out-of-domain data via cross-dataset evaluations. To further investigate the interpretability of our model, we visualize attention weights learned by GGAL models. We find that GGAL successfully focuses on key semantic concepts in the video and has complementary attention on the context parts based on different ways of building region graphs.

PDF file - 2177KB, Scatter Plots of Gene Re-expression with Decitabine or Trichostatin-A in Eight Non-Small Cell Lung Cancer Cell Lines.

PDF file - 287KB, DNA Methylation of CDO1, HOXA9, and TAC1 is Highly Sensitive for Stage I NSCLC in the Cancer Genome Atlas.

PDF file - 399KB, Kaplan-Meier Survival Curves for Non-Small Cell Lung Cancer for p16 methylation in combination with APC, RASSF1, or CDH13.

Purpose: Non–small cell lung cancer (NSCLC) is the leading cause of cancer mortality in the world. Novel diagnostic biomarkers may augment both existing NSCLC screening methods as well as molecular diagnostic tests of surgical specimens to more accurately stratify and stage candidates for adjuvant chemotherapy. Hypermethylation of CpG islands is a common and important alteration in the transition from normal tissue to cancer.Experimental Design: Following previously validated methods for the discovery of cancer-specific hypermethylation changes, we treated eight NSCLC cell lines with the hypomethylating agent deoxyazacitidine or trichostatin A. We validated the findings using a large publicly available database and two independent cohorts of primary samples.Results: We identified >300 candidate genes. Using The Cancer Genome Atlas (TCGA) and extensive filtering to refine our candidate genes for the greatest ability to distinguish tumor from normal, we define a three-gene panel, CDO1, HOXA9, and TAC1, which we subsequently validate in two independent cohorts of primary NSCLC samples. This three-gene panel is 100% specific, showing no methylation in 75 TCGA normal and seven primary normal samples and is 83% to 99% sensitive for NSCLC depending on the cohort.Conclusion: This degree of sensitivity and specificity may be of high value to diagnose the earliest stages of NSCLC. Addition of this three-gene panel to other previously validated methylation biomarkers holds great promise in both early diagnosis and molecular staging of NSCLC. Clin Cancer Res; 20(7); 1856–64. ©2014 AACR.

PDF file - 100KB, DNA Methylation of CDO1, HOXA9, and TAC1 is Highly Sensitive for Stage I NSCLC in the Cancer Genome Atlas.

XLSX file - 25KB, List of Infinium 450K Methylation Probes from Figure 1.

PDF file - 108KB

Supplementary Table 1 from Hypermethylation of ASC/TMS1 Is a Sputum Marker for Late-Stage Lung Cancer

Supplementary Figure 3 from Hyaluronan Deficiency in Tumor Stroma Impairs Macrophage Trafficking and Tumor Neovascularization

Supplementary Figure 1 from Hyaluronan Deficiency in Tumor Stroma Impairs Macrophage Trafficking and Tumor Neovascularization

DNA hypermethylated gene promoter sequences are extremely promising cancer markers. Their use for risk assessment, early diagnosis, or prognosis depends on the timing of this gene change during tumor progression. We studied this for the proapoptotic gene ASC/TMS1 in lung cancer and used the findings to develop a sputum marker. ASC/TMS1 protein levels are reduced in all lung cancer types (30 of 40; 75%) but not in 10 preinvasive lesions. Hypermethylation of ASC/TMS1 is also associated with invasive cancers (41 of 152 or 27.0% of all lung cancer types) with variation in incidence between histopathologic types including 32.1% (26 of 81) of adenocarcinomas, 13.2% (7 of 53) of squamous cell carcinomas, 38.5% (5 of 13) of large-cell carcinomas, and 60% (3 of 5) of small-cell lung cancers. The hypermethylation is particularly correlated with late tumor stages being present in only 14% of stage I but 60% of later-stage tumors. The incidence of ASC/TMS1 hypermethylation in sputum DNA fully mimics the tissue findings being present in only 2% (2 of 85) of high-risk, cancer-free smokers, 15% (3 of 18) of patients with stage I non–small-cell lung cancer (NSCLC), but 41% of patients with stage III NSCLC (18 of 44), including 56% (10 of 18) of those with adenocarcinoma. Importantly, sputum is positive for this marker in 24% (10 of 42) of very high risk, clinically cancer-free individuals previously resected for stage I NSCLC. Thus, hypermethylation of ASC/TMS1 is a marker for late-stage lung cancer and, in sputum, could predict prognosis in patients resected for early-stage disease. (Cancer Res 2006; 66(12): 6210-8)

Supplementary Figure 2 from Hyaluronan Deficiency in Tumor Stroma Impairs Macrophage Trafficking and Tumor Neovascularization

Supplementary Methods, Figure Legends 1-3 from Hyaluronan Deficiency in Tumor Stroma Impairs Macrophage Trafficking and Tumor Neovascularization

Microbacterium species are coryneform gram-positive rods that are widely distributed in the environment and have been recently recognized as rare pathogens in humans. However, information about the epidemiologic and clinical characteristics of Microbacterium species is scarce. We herein reported an 11-year-old girl with acute leukemia who was found to have catheter-related bloodstream infection in her neutropenic phase. Gram-positive bacilli repeatedly grew on the blood cultures and were later confirmed by 16S rRNA analysis as Microbacterium paraoxydans. A literature review found available clinical courses in 21 cases (7 pediatric cases) of Microbacterium spp. bacteremia. Our case and those in literature suggested that Microbacterium spp. bacteremia often occurs in patients with indwelling central venous catheters; the literature review further suggested that removal of central venous catheters is required in most cases and that 16S rRNA sequence was useful in identifying in detail the species of Microbacterium.

Identifying a strategy with strong efficacy against non-inflamed tumours is vital in cancer immune therapy. ERY974 is a humanized IgG4 bispecific T cell-redirecting antibody that recognizes glypican-3 and CD3. Here we examine the combination effect of ERY974 and chemotherapy (paclitaxel, cisplatin, and capecitabine) in the treatment of non-inflamed tumours in a xenograft model. ERY974 monotherapy shows a minor antitumour effect on non-inflamed NCI-H446 xenografted tumours, as infiltration of ERY974-redirected T cells is limited to the tumour-stromal boundary. However, combination therapy improves efficacy by promoting T cell infiltration into the tumour centre, and increasing ERY974 distribution in the tumour. ERY974 increases capecitabine-induced cytotoxicity by promoting capecitabine conversion to its active form by inducing thymidine phosphorylase expression in non-inflamed MKN45 tumour through ERY974-induced IFNγ and TNFα in T cells. We show that ERY974 with chemotherapy synergistically and reciprocally increases antitumour efficacy, eradicating non-inflamed tumours.

Background SA237 is a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody in which the constant and variable regions have been engineered for a longer plasma half-life. According to literature, blocking of IL-6 related functions could have an influence on pregnancy sustainment, development of the immune system, and brain growth. Methods SA237 effects on dams, embryo-fetal development, parturition and postnatal development were investigated in an enhanced pre- and postnatal development study, in which SA237 was subcutaneously administered to pregnant cynomolgus monkeys at dose levels of 2 or 50 mg/kg once weekly from gestation day 20 until parturition. Infant development, including immune function and learning ability tests, was comprehensively assessed at multiple examinations until approximately 10 months after birth. Results SA237 plasma concentrations were almost equivalent between dams and their infants and dropped throughout the postnatal period, pharmacologically relevant exposure was maintained for 147 days after birth at 50 mg/kg. Because the binding of SA237 to IL-6R inhibited IL-6R-mediated clearance of IL-6, serum IL-6 increased in dams and infants. However, there were no SA237-related adverse effects on dams, embryos, fetuses, or infants. SA237 pharmacological effects contributed to the suppression of plasma cell differentiation and antibody production by inhibiting IL-6 signaling, and T cell-dependent antibody reaction was minimally suppressed in infants, but physiological immunoglobulin class switching and general antibody production against a T cell-dependent antigen were maintained. Conclusion The exposure to SA237 did not adversely affect dams, embryo-fetal development, parturition, and postnatal development, including immune function and neuronal development. Birth Defects Research 109:843-856, 2017. © 2017 Wiley Periodicals, Inc.

Glypican-3 (GPC3) is a glycosylphosphatidylinositol-anchored cell surface glycoprotein overexpressed in hepatocellular carcinoma (HCC) cells and may serve as a potential molecular target for therapeutic intervention. This study evaluated the prognostic significance of serum GPC3 in HCC patients receiving curative surgery. A novel sandwich enzyme-linked immunosorbent assay for the quantitative and sensitive determination of serum GPC3 N-terminal subunit antigen (sGPC3N) was developed and used to measure sGPC3N levels in 25 healthy volunteers and 115 HCC patients who underwent curative partial hepatectomy. The relationships between sGPC3N and clinicopathologic features were analyzed and the prognostic impact on overall survival (OS) or disease-free survival (DFS) was also investigated. Mean and median levels of sGPC3N in healthy controls were 110.12 and 115.95 pg mL(-1) , respectively, with 185.52 pg mL(-1) (mean + 2 SD) being set as the upper limit of the normal range. In HCC patients, sGPC3N levels were significantly increased (mean/median, 405.16/236.19 pg mL(-1) ) compared to healthy controls (p < 0.0001), and 60% of HCC cases (69/115) showed sGPC3N levels that were higher than the upper normal limit. High sGPC3N levels were significantly associated with serum AFP level, high Child-Pugh score and positive HCV. Kaplan-Meier analysis indicated that elevated pre-operative sGPC3N was associated with shorter OS and DFS after hepatectomy (p ≤ 0.01). Multivariate analysis revealed elevated sGPC3N as an independent poor prognostic marker for OS (p < 0.05) and DFS (p < 0.01). The pre-operative sGPC3N level serves as an independent prognostic biomarker in HCC patients.

SA237 is a humanized anti-interleukin-6 receptor (IL-6R) monoclonal antibody in which the constant and variable regions have been engineered for a longer plasma half-life. According to literature, blocking of IL-6 related functions could have an influence on pregnancy sustainment, development of the immune system, and brain growth.SA237 effects on dams, embryo-fetal development, parturition and postnatal development were investigated in an enhanced pre- and postnatal development study, in which SA237 was subcutaneously administered to pregnant cynomolgus monkeys at dose levels of 2 or 50 mg/kg once weekly from gestation day 20 until parturition. Infant development, including immune function and learning ability tests, was comprehensively assessed at multiple examinations until approximately 10 months after birth.SA237 plasma concentrations were almost equivalent between dams and their infants and dropped throughout the postnatal period, pharmacologically relevant exposure was maintained for 147 days after birth at 50 mg/kg. Because the binding of SA237 to IL-6R inhibited IL-6R-mediated clearance of IL-6, serum IL-6 increased in dams and infants. However, there were no SA237-related adverse effects on dams, embryos, fetuses, or infants. SA237 pharmacological effects contributed to the suppression of plasma cell differentiation and antibody production by inhibiting IL-6 signaling, and T cell-dependent antibody reaction was minimally suppressed in infants, but physiological immunoglobulin class switching and general antibody production against a T cell-dependent antigen were maintained.The exposure to SA237 did not adversely affect dams, embryo-fetal development, parturition, and postnatal development, including immune function and neuronal development. Birth Defects Research 109:843-856, 2017. © 2017 Wiley Periodicals, Inc.

We have previously identified intracellular secretory acute phase response (sAPR) proteins in human hepatocytes following interleukin-6 (IL-6) induction by fluorogenic derivatization (FD)–liquid chromatography (LC)–tandem mass spectrometry (MS/MS). In this report, we utilized this method, which uses 7-chloro-N-[2-(dimethylamino)ethyl]-2,1,3-benzoxadiazole-4-sulfonamide (DAABD-Cl) as the FD reagent, to comprehensively and time-dependently analyze secreted proteins in the medium, including sAPR proteins. Since DAABD-Cl selectively reacts with thiol moieties of cysteinyl residues, direct derivatization, high-resolution LC separation and identification of the secreted proteins in the culture medium were successfully achieved without a pretreatment step. As a result, 14 sAPR proteins were identified simultaneously during a 72 h induction by IL-6. The secretion levels of 11 proteins increased, whereas the secretion levels of three important transport proteins decreased (albumin, retinol-binding protein 4 and transthyretin). In addition, the secretion level of a haptoglobin was found to increase significantly between 0 and 6 h by 1.88-fold compared with the control sample. The secretion levels of four cytoplasmic proteins increased: LDH, a known marker for cell damage, and GSTA1, FABP1 and ADH1B, which are marker proteins for hepatocellular damage. The secretion levels of the other two newly identified cytoplasmic proteins, profilin-1 and SOD2, were also found to increase, suggesting that these two proteins represent novel markers for cell damage. These results suggest that the FD-LC-MS/MS proteomics method can be used to analyze comprehensively and time-dependently the secreted proteins and thereby can offer information that aids our understanding of the dynamics of protein secretion affected by the exposure of cytokines such as IL-6. Copyright © 2013 John Wiley & Sons, Ltd.

Background Age is still considered a risk factor in the repair of acute type A aortic dissection. Instead of total arch replacement, we performed hemiarch or partial arch replacement with intimal tear exclusion to reduce death in elderly patients and evaluated early-term and midterm outcomes. Methods From January 2004 to April 2012, 59 patients older than 70 years (mean age, 77.0 ± 4.3 years) underwent emergency operations for acute type A aortic dissection at our institution. We performed hemiarch, partial arch, or total arch replacement, according to the location of the primary entry tear. The characteristics, surgical procedures, and early-term and midterm outcomes of these patients were reviewed. Results We performed hemiarch replacement in 47 patients, partial arch replacement in 4, and total arch replacement in 8. The primary entry site was excluded in 56 of 59 patients (94.9%). In-hospital mortality was 6.8%, and neurologic impairment occurred in 25.4%. We obtained midterm outcomes for 55 of 59 patients, with a mean follow-up period of 43.9 ± 23.7 months. Fourteen patients died, two of these of aortic-related causes. One patient required repeat aortic operation for rupture of a pseudoaneurysm. Follow-up computed tomography imaging was done in 28 of 55 patients during the 12 months after the operation. No significant difference was noted in the increase in maximal aortic diameter between patients with and without residual dissection. Conclusions In-hospital mortality was 6.8%; relatively low compared with previous reports. Hemiarch and partial arch replacement with entry tear exclusion may reduce deaths associated with acute type A aortic dissection repair in elderly patients, without increasing the risk of reoperation and aortic-related death.

Blood trauma may be lower with centrifugal pumps (CPs) than with roller pumps (RPs) during cardiopulmonary bypass (CPB), because, unlike RPs, CPs do not compress the tubing, and shear stress is considered lower in CPs than in RPs. However, relative platelet function remains unclear. Using multiple electrode aggregometry (MEA), we compared platelet function with CP and RP. Ten swine underwent CPB for 3 h, with five weaned off using CP and five using RP. Platelet function was measured using MEA, as were hemoglobin concentration and platelet count, before sternotomy, after heparin infusion, 30 min and 3 h after starting CPB, after protamine infusion, and 60 min after stopping CPB. Platelet activation was initiated with adenosine diphosphate (ADP), arachidonic acid (AA), and thrombin receptor-activating protein 6 (TRAP). Fibrinogen, platelet factor 4 (PF4), and β-thromboglobin (β-TG) concentrations were measured before sternotomy and 60 min after stopping CPB. In the CP group and using ADP, aggregation was significantly reduced 30 min (P = 0.019) and 3 h (P = 0.027) after starting CPB, recovering to baseline 60 min after CPB was stopped. In the RP group, aggregation was significantly decreased 30 min (P = 0.007) and 3 h (P = 0.003) after starting CPB and after protamine administration (P = 0.028). With AA, aggregation significantly decreased 30 min after starting CPB in both the CP (P = 0.012) and RP (P = 0.016) groups, slightly increasing 3 h after starting CPB and after protamine infusion, and recovering to baseline 60 min after CPB cessation. With TRAP, aggregation in the CP and RP groups decreased 30 min after starting the pump, although changes were not significant; aggregation gradually recovered after 3 h and returned to baseline 60 min after the pumps were stopped. There were no significant differences at all sampling points of MEA. In both groups, fibrinogen, PF4, and β-TG concentrations were similar 60 min after pump cessation and before sternotomy. Platelet function, evaluated with MEA, was lowest 30 min after CPB was started but did not decrease over time in either group. As assessed by MEA, platelet function using CP and RP did not differ significantly. Platelet dysfunction was caused mainly by initial contact with foreign materials and may not be dependent on type of pump.

We herein report a case of an intrathoracic low-grade fibromyxoid sarcoma arising from the chest wall and associated with massive pleural effusion. A 70-year-old man presented with a persistent cough. A chest computed tomography scan revealed a large mass in the right pleural cavity with massive pleural effusion. No malignant cells were recognized in the pleural effusion by thoracentesis. A malignant soft tissue tumor was suspected, and surgery was performed. The tumor arose from the posterior chest wall and was resected with the connected chest wall. The definitive diagnosis was a low grade fibromyxoid sarcoma. Because the posterior margin of the chest wall was microscopically tumor positive, postoperative irradiation was performed. The patient has now been followed up for 30 months with no evidence of recurrence.

A 67-year-old man was referred to our hospital for an ascending aortic aneurysm, thoracoabdominal aortic aneurysm and aortic regurgitation. Graft repair of the thoracic aortic arch and aortic valve replacement was given priority and completed, however he developed descending aortic rupture before the second scheduled surgery, and endovascular stent grafting was performed. He subsequently developed tracheobronchial obstruction and esophageal perforation. The patient underwent urgent esophagectomy and enterostomy with continuity later reestablished. However, he died of sepsis 5 months after surgery. Despite the less invasive nature of endovascular treatment, esophageal perforation can nevertheless occur and postoperative vigilance is well warranted.

We herein report a case of infective endocarditis associated with mitral valve prolapse (MVP) in a 34-year-old man with Klinefelter syndrome. The patient was admitted with a fever and headache that had persisted for three weeks. Repeated blood cultures showed growth of Streptococcus oralis. Echocardiography demonstrated severe mitral regurgitation with a large vegetation attached to the prolapsed anterior leaflet. Surgical plasty of the mitral valve was performed because the vegetation measured over 10 mm in diameter and there was a risk of recurrence of embolic complications. This case demonstrates the link between MVP and Klinefelter syndrome and highlights the importance of performing cardiovascular screening and preventing endocarditis., Article, INTERNAL MEDICINE. 53(9):969-972 (2014)

Purpose Prosthetic graft infection is a fatal complication after thoracic aorta replacement, and it is sometimes difficult to perform a prompt re-operation when the patient carries the infectious source of the graft. We evaluated the early and mid-term outcomes of aortic graft infection after thoracic aorta replacement, focusing on the timing of the surgery. Methods This study included eight consecutive patients with thoracic graft infection from 1997 to 2011 among 513 patients of graft replacement during this period. We performed re-graft replacement in six patients. Of these six patients, emergency surgery was performed in two and scheduled surgery was performed in two. An unscheduled emergency surgery was required in two patients during the medical treatment of the infection source. Solo medical treatment was performed in two patients. Results In-hospital mortality occurred in two of the eight patients (25%). Re-graft infection was not observed in the six patients who underwent re-graft replacement or the one patient who underwent medical treatment during the 1.5- to 14-year observation period. Conclusions Prompt re-replacement of the infected graft should be performed even when an orthotopic infection source led to the graft infection. Medical treatment might be applicable when neither an abscess nor pseudoaneurysm is observed.

Objective Despite recent advances in video-assisted thoracoscopic lobectomy, some technical limitations still remain. Our current study purpose was to determine if the vessel sealing system (VSS) has utility in this procedure. Method 112 patients who underwent an anatomic pulmonary lobectomy at our institute were evaluated retrospectively. The burst pressure of pulmonary vessels, which was divided into VSS (VSS group; n = 44) or manual ligature (ligature group; n = 53) groups, was measured experimentally in transected lungs. Perioperative clinical data was also retrospectively evaluated in patients treated with (VSS group) or without using VSS (n-VSS group). Results Burst pressures achieved adequate strength in both the VSS (600.0 ± 436.8 mmHg) and ligature (1057.4 ± 462.3 mmHg) groups. Compared with the n-VSS group, the VSS group patients showed lower intraoperative blood loss (115.4 ± 181.1 vs. 183.3 ± 159.1 ml), lower chest fluids by 3rd post-operative day (POD) (533.8 ± 264.8 vs. 705.3 ± 339.3 ml) and a shorter period of chest tube duration (4.1 ± 1.2 vs. 5.4 ± 2.4 days). No serious complications or perioperative (30 days) deaths occurred in either group. Conclusion The VSS device has the advantage in pulmonary lobectomy procedures, especially those involving video-assisted thoracic surgery (VATS).

Primary cardiac tumors are uncommon, and papillary fibroelastoma is considered relatively rare compared to myxoma and lipoma in the primary cardiac tumors. We experienced three cases of fibroelastoma. The patients' age was 28-75 years, and one patient was female. Two patients were presented with cerebral infarction and cardiac ischemia although, the other patient had no symptoms. Echocardiography revealed a hyperechoic mass in the left atrium, ventricle and on the aortic valve and helpful for differential diagnosis from myxoma. Surgical excision of the tumor was successfully performed in all patients and post-operative course was uncomplicated.

Annual report by The Japanese Association for Thoracic Surgery: Committee for Scientific Affair Munetaka Masuda, Hiroyuki Kuwano and Meinoshin Okumura have contributed equally.

Tumors of the heart and the great vessels are very rare disease, and there are many disorders such as tumors originated from the heart and great vessels, metastatic tumors, and tumor-like lesions which do not fit into the usual concept of tumor or neoplasm; thus, it is very difficult to classify these tumors. We proposed a new classification of cardiovascular tumors for clinical use based on the accumulated biological analyses and clinical data of the reported literatures and our own study as benign tumors, malignant tumors, ectopic hyperplasia/ectopic tumors/others, and tumors of great vessels, with reference to the series of Atlas of tumor pathology of the Armed Forces Institute of Pathology and the recent World Health Organization classification of cardiac tumors issued in 2004. More than 50 disorders have been reported as tumors originated from the cardiovascular system, and various metastatic tumors from nearby organs, distant lesions, and intravascular extension tumors to the heart were reported. Based on the new classification, we reviewed epidemiology and incidence of cardiovascular tumors. Metastatic tumors are more frequent than tumors originated from the heart and great vessels, and cardiac myxoma is the most frequent tumors in all cardiac tumors.

Interleukin-6 (IL-6) is involved in the pathogenesis of multiple disorders, including juvenile autoimmune diseases. IL-6 participates in a broad spectrum of physiological events, and the IL-6 receptor (IL-6R) is widely distributed across multiple organs. The interrelationship of development phases in juveniles together with organs involved in IL-6 signaling called for evaluations of anti-IL-6R antibody induced effects in a juvenile mouse model to assess the safety of such an approach in human juvenile arthritis. Here we show that naive mice in which IL-6 signals have been transiently blocked during the juvenile period develop normally. The fatal immunogenic reactions recorded earlier by repeated administration of the chosen rat anti-mouse IL-6R antibody, MR16-1, to mice were avoided successfully by application of a high loading dose followed by lower maintenance doses, with the support of modeling data. The high loading-dose regimen enabled us to conduct assessments without any major interference due to immunogenicity. Transient and complete inhibition of IL-6 signals from postnatal days 22 to 79 in mice exhibited no biologically important changes in sexual maturation or development of immune and skeletal systems. Although tendencies toward reductions of peripheral blood T-cell counts were observed, normal levels of antigen-specific IgG/IgM antibody productions indicating sufficient immunological functions were confirmed. Our results demonstrate that blockage of IL-6R by the neutralizing antibody does not affect juvenile development. This may be in part due to the generation or existence of compensatory pathways in the whole body system.

We here describe our experience with innovative uses of these devices.We reviewed treatment outcomes of 310 endovascular abdominal aortic repair (EVAR) and 83 thoracic endovascular aortic repair (TEVAR) cases performed between August 2007 and February 2012. We separately assessed results in elderly and high-risk patients who had a novel procedure. This group included 94 patients who underwent EVAR with IIA embolization, 10 patients who had EVAR and a renal artery chimney procedure for a short aortic neck, 20 patients who had two de-branching TEVAR or Chimney method for thoracic aortic aneurysms (TAA) and 3 patients who had debranching TEVAR for thoracic abdominal aortic aneurysms (TAAA).Of the 393 patients given stent grafts (SGs), 3 (0.8%) died in the hospital, including 1 patient with pneumonia who underwent EVAR and IIA embolization and 1 patient with a cerebral infarction who had TEVAR. Four patients (4.3%) who were treated with EVAR with internal iliac artery (IIA) embolization presented with residual buttock claudication 6 months postoperatively, and 3 patients (3.2%) had onset of ischemic enteritis; however, in all 7 patients, the condition resolved without additional intervention. In the 10 patients who had EVAR and a renal artery chimney method, the landing zone (LZ) was ≤10 mm, but neither endoleak nor renal artery occlusion was observed perioperatively or during midterm follow-up. Of the 20 patients who had a 2-debranching TEVAR, including 9 in whom the chimney method was used with the LZ in zone 0, 1 (5%) had a residual endoleak. In 3 patients with TAAA, we used SGs to cover 4 abdominal branches and bypassed the visceral artery; the outcomes were good, with all patients being ambulatory at hospital discharge.Among innovative SGs treatments, the debranching procedure and the chimney method using catheterization and the coil-embolization technique provided good outcomes, as used in addition to surgical procedures. Aortic aneurysm treatment will become increasingly noninvasive with the continuing development of more innovative ways to use the SGs currently available in Japan. (English Translation of Jpn J Vasc Surg 2012; 21: 165-173).

Lung cancer and a thoracic aortic aneurysm were detected simultaneously in a 79-year-old male patient with diabetes. The aneurysm was first treated by thoracic endovascular aortic repair. A right lower lobectomy was subsequently performed after the blood flow of the bronchial and intercostal arteries was confirmed by computed tomographic angiography. The bronchial stump was covered with an intercostal muscle flap. The patient's postoperative course was uneventful. Thoracic endovascular aortic repair is a useful and less invasive treatment for such cases, but a blood flow evaluation of the aortic branches should be done following this procedure before a lung resection is considered., Article, SURGERY TODAY. 44(5):940-943 (2014)

Possible effects of interleukin-6 (IL-6) on reproductive performance, embryonal development, parturition, and postnatal development have been suggested based on protein/mRNA expression level of IL-6 in related organs, but less is known about functions of IL-6 signals in these areas. Following two different approaches have been employed to investigate the role of IL-6 signals in fertility and pre-/postnatal development: administration of a rat anti-mouse IL-6 receptor antibody, MR16-1, to mice as a neutralizing antibody system, and B6.129S2-Il6(tm1Kopf)/J (IL-6 knockout [KO]) mice as a KO system. By intravenously dosing 50 mg/kg of MR16-1 every 3 days, animals in male and female fertility studies and dams in a pre-/postnatal development study exhibited plasma MR16-1 concentrations much higher than the effective plasma concentration, indicating that MR16-1 exposure was sufficient to completely block IL-6 signals. The concentration of MR16-1 in the plasma of fetuses exceeded that in the plasma of pregnant animals, and MR16-1 concentration in milk was about one-fourth of that in plasma. Both the transient IL-6 signal blockade by MR16-1, and the constitutive IL-6 signal inhibition using IL-6 KO mice in a combined fertility and pre-/postnatal development study, revealed no biologically important effects on fertility, early embryonic development to implantation, or pre-/postnatal development, including IgG/IgM production by keyhole limpet hemocyanin sensitization. These results indicate that IL-6 signals have no unique, noncompensable roles in reproduction and development in the whole body system, although contributions of IL-6 in the signaling network appear to exist, as suggested by previously published investigations.

Recent studies have shown the usefulness of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) in differentiating between World Health Organization (WHO) histological subgroups of thymic epithelial tumours. However, these reports may have included many advanced cases of these lesions (Masaoka stage III or IV) of high-risk subtypes. The objective of our present study was to assess the usefulness of FDG-PET for distinguishing the histological subtypes of early stage thymic epithelial tumours (Masaoka stage I or II).Twenty patients who had undergone an FDG-PET examination prior to treatment and had been diagnosed with an early stage thymic epithelial tumour between July 2005 and July 2011 were enrolled in the present study. All patients underwent a total thymectomy. This cohort was divided into two groups according to the WHO histological classification of their lesion, i.e. low-risk tumours (types A, AB or B1) in one group and high-risk tumours (types B2, B3 or thymic carcinoma) in the other. Focal FDG accumulation was evaluated by determining the maximum standardized uptake value (SUV-max).The patient cohort for this study included 13 men and 7 women ranging in age from 26 to 70 years (mean 55 years). The low-risk group included seven cases (type A, 0; type AB, 7; type B1, 0), and the high-risk group comprised 13 cases (type B2, 7; type B3, 3; thymic carcinoma, 3). The SUV-max values of the low-risk and high-risk tumours were 3.09 ± 0.51 and 6.19 ± 3.13, respectively, and this was a significant difference. For the differential diagnosis of low-risk and high-risk tumours, sensitivity and specificity were 92.3% and 83.3%, respectively, when an SUV-max of 3.5 was used as a cutoff.FDG-PET is a useful method for distinguishing histological types of early stage thymic epithelial tumours.

信州大学博士（医学）・学位論文・平成23年12月28日授与（乙第21139号）・髙橋耕平, Article, Annals of Vascular Diseases. 4(3):209-217 (2011)

Extraskeletal myxoid chondrosarcoma (EMC) is typically a slow-growing tumor with a prolonged clinical course. We describe a case of EMC that was complicated by intrathoracic rupture of the tumor and took an aggressive clinical course. A 64-year-old man with a precordial tumor suddenly began suffering from acute chest pain. Radiographic examination revealed a massive pleural effusion. Emergency surgery was performed but resulted in rupture of the pleural side of the tumor. The tumor was resected with the chest wall. The patient died 16 months after surgery owing to abdominal wall recurrence.

Background: Acute aortic dissection (AAD) classically presents as sudden, severe chest, back, or abdominal pain. However, there have been several documented cases presenting with atypical features. The clinical characteristics and outcomes of patients with painless AAD were investigated. Methods and Results: The study group comprised 98 patients (53 males, 45 females; 66±12 years) with AAD admitted to hospital from 2002 to 2007: 16 patients (17%) had no pain (Painless group) and 82 patients had pain (Painful group). In 81% of the Painless group and 70% of the Painful group there was a type A dissection. The Painless group more frequently had a persistent disturbance of consciousness (44% vs. 6%, P

症例は11歳，男児．母親が左頸部腫瘤に気付き受診．初診時，左頸部に3cm大，弾性硬で可動性良好な腫瘤を触知した．甲状腺機能検査では，Tg 94.3ng/mlと軽度上昇していた．USでは，甲状腺左葉に3cm大，境界明瞭で内部に嚢胞変性を伴う低エコー腫瘤を認め，ドップラーで腫瘤内部に豊富な血流を認めた．CTでは腫瘤は造影早期に濃染され，後期に早くwash outされた．穿刺吸引細胞診では濾胞性腫瘍と腺腫様甲状腺腫の鑑別が困難と診断された．濾胞性腫瘍の可能性を考え，甲状腺左葉切除術および頸部リンパ節郭清を施行した．病理組織学的には核の腫大した細胞が濾胞構造をとって増殖し，明瞭な線維性被膜を有していたが一部に被膜外浸潤が認められ，微小浸潤型の濾胞癌と診断された．甲状腺濾胞癌は術前に確定診断を得ることが難しく，また小児例は非常に稀である．USで濾胞性腫瘍が疑われた場合には濾胞癌を念頭に置いて術式を選択することが重要と考えられる．

We report the successful thoracic endovascular aortic repair of an ascending aortic pseudoaneurysm. Because the risk of resternotomy after conventional surgery was very high, endovascular repair with extra-anatomic reconstruction of the supra-aortic vessels was performed using the femoral artery as the donor artery. Complete exclusion of the pseudoaneurysm was achieved, with no postoperative complications or neurologic sequelae.

Cardiac tumors and tumor-like lesions are uncommon; most are true neoplasms. We here report a case of a pericoronary tumor-like lesion surrounding the right coronary artery in a 39-year-old man who presented with fever and chest pain. Although clarithromycin was administered for 1 week, his fever persisted. Helicobacter cinaedi (H. cinaedi) was isolated from blood cultures and found to be sensitive to ceftriaxone. A computed tomography scan showed a tumor-like lesion with no (18)F-fl uorodeoxyglucose uptake surrounding the right coronary artery. After administration of ceftriaxone, the tumor-like lesion diminished in size according to meticulous computed tomography examinations. We therefore concluded that it was caused by H. cinaedi infection. The patient has been followed up closely for 1 year and remains asymptomatic.

An 81-year-old woman, who had undergone mitral valve replacement (MVR) with a porcine bioprosthesis after mitral valve repair, presented with hemolysis 4 years and 6 months after MVR. Transthoracic echocardiography (TTE) revealed trivial mitral regurgitation, which was diagnosed based on the observed perivalvular leakage. Hemolysis gradually increased, and she developed dyspnea and edema 2 years after the appearance of mitral regurgitation. We performed a reoperation. Intraoperative transesophageal echocardiography (TEE) after intubation showed no perivalvular leakage of the mitral prosthesis, but transvalvular leakage through a leaflet perforation was present. The leaflets of the bioprosthesis had slit-shaped perforations at their hinges. There was no sign of infection on the leaflet or annulus. We implanted a new bioprosthesis after removal of the deteriorated valve. The postoperative course was uneventful. Microscopic examination verified collagen degeneration, histiocyte infiltration, and hyalinization. It is important to perform TEE to rule out structural valve deterioration (SVD) even when regurgitation occurs soon after valve replacement.

Anti-HM1.24 monoclonal antibody (AHM) is a humanized anti-HM1.24 monoclonal antibody that binds to the HM1.24 antigen, a protein that is highly expressed in multiple myeloma cells. The pharmacokinetics of AHM was determined in experiments in which AHM was administered intravenously to cynomolgus monkeys. The area under the plasma concentration-time curve increased by more than the dose ratio between 2 and 20 mg/kg, and nonlinear pharmacokinetics was observed. The elimination half-life of AHM from the plasma was 7.56 h at 2 mg/kg and 28.6 h at 20 mg/kg, which was shorter than that observed for other therapeutic humanized monoclonal antibodies, such as trastuzumab and bevacizumab. Although antibodies to AHM were detected in all monkeys on or after 10 days of administration, there was a temporal disassociation between the rapid elimination of AHM and the appearance of anti-AHM antibodies. HM1.24 antigen-dependent internalization and intracellular metabolism of AHM were investigated in peripheral blood mononuclear, KPMM2, and U937 cells. In all cases, AHM was rapidly internalized from the cell surface; this internalization was significantly prevented by phenylarsine oxide in KPMM2 cells, an inhibitor of receptor-mediated endocytosis, and the internalized AHM was subsequently degraded within the cells. Furthermore, immunofluorescence microscopy revealed that the internalized AHM is delivered to and degraded in late endosomes/lysosomes. Taken together, our results suggest that the rapid elimination of AHM from plasma in monkey is due to HM1.24 antigen-dependent internalization followed by delivery to the lysosomes.