Catheter-related bloodstream infection by Microbacterium paraoxydans in a pediatric patient with B-cell precursor acute lymphocytic leukemia: A case report and review of literature on Microbacterium bacteremia.

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.

Intracellular Dynamics and Fate of a Humanized Anti-Interleukin-6 Receptor Monoclonal Antibody, Tocilizumab.

Tocilizumab (TCZ), a humanized anti-interleukin-6 (IL-6) receptor (IL-6R) monoclonal antibody, abrogates signal transducer protein gp130-mediated IL-6 signaling by competitively inhibiting the binding of IL-6 to the receptor, and shows clinical efficacy in autoimmune and inflammatory diseases. Despite accumulating evidence for therapeutic efficacy, the behavior and fate of TCZ at the cellular level remain largely unknown. To address this, we evaluated the endocytosis and intracellular trafficking of IL-6R in HeLa cells. The results of our study provide evidence that IL-6R is constitutively internalized from the cell surface by ligand or TCZ binding and the expression of gp130 in an independent manner and is targeted via endosomes without being significantly directed to the recycling pathway to, and degraded in, lysosomes. Furthermore, the cytoplasmic tail of IL-6R is required for constitutive endocytosis of the receptor, which is mediated by the clathrin and AP-2 complex. We further demonstrate that FcRn, whose function is to regulate the serum persistence of IgG, is confined primarily to early/recycling endosomes and rapidly transits between these compartments and late endosomes/lysosomes without being degraded. Importantly, the expression of FcRn induces the segregation of TCZ from IL-6R, resulting in extensive colocalization of TCZ and FcRn in IL-6R-depleted endosomal compartments. Collectively, our results suggest that FcRn can accelerate the retrieval of the internalized TCZ, not only from endosomes but also from lysosomes. Our findings provide new insight into the mechanism by which the antibody internalized into cells is rescued from lysosomal degradation and into how its serum levels are maintained.

High preoperative levels of serum glypican-3 containing N-terminal subunit are associated with poor prognosis in patients with hepatocellular carcinoma after partial hepatectomy.

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.

Hybrid thoracic endovascular aortic repair of ascending aortic pseudoaneurysm.

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.

Platelet function during cardiopulmonary bypass using multiple electrode aggregometry: comparison of centrifugal and roller pumps.

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 ß-thromboglobin (ß-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 ß-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.

Comprehensive and temporal analysis of secreted proteins in the medium from IL-6 exposed human hepatocyte.

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.

Successful lung lobectomy for a lung cancer following thoracic endovascular aortic repair for a thoracic aortic aneurysm: report of a case.

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.

Pericoronary pseudotumor caused by helicobacter cinaedi.

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.

[Left atrium thrombus after mitral valve replacement presented with syncope; report of a case].

Left atrial free ball thrombus (LABT) after mitral valve replacement (MVR) is very rare, and sudden death may occur by thrombus impaction to the mitral valve orifice. A 81-year-old woman who underwent MVR and tricuspid annuloplasty ten years ago presented with syncope. She was admitted to a hospital, and echocardiography revealed a LABT. When she took sitting position, she fainted. The free ball thrombus possibly impacted mitral valve orifice. She was transferred to our hospital and an emergent operation was performed. There was a LABT of 4 cm in diameter, which was removed. Postoperative course was uneventful. There are 12case reports which described LABT after MVR, and anticoagulant therapy was insufficient in most of those cases. Strict anticoagulant therapy is important to prevent left atrial thrombus after MVR.

Clinical results and pump analysis of the Gyro pump for long-term extracorporeal life support.

Rescuing patients in severe cardiac failure with extracorporeal support remains challenging. The Gyro pump is a centrifugal blood pump and was now used for cardiopulmonary bypass, although it was originally developed for long-term cardiac assist. Little is known about clinical experiences using this pump. Here, we report on the clinical results of long-term extracorporeal life support for over 4 days using the Gyro pump with Excelung, a hollow fiber oxygenator coated with silicone and heparin. Seven patients underwent extracorporeal life support with 15 pump and oxygenator combinations. Gyro and Excelung were used for venoarterial extracorporeal support in six patients and for right ventricular support in one patient. Patient characteristics, pump driving conditions, and blood chemistry were obtained retrospectively. All pumps were subsequently disassembled and examined macroscopically, with 6 of 15 pumps also examined by scanning electron microscopy (SEM). The patient mortality rate was 57.1%. Mean duration of support was 10.5 ± 7.2 days per pump and oxygenator combination. Lactate dehydrogenase and aspartate aminotransferase were generally maintained below 1000 and 100 IU/L, respectively, after the first 4 days of pump driving. Thrombi were found in two pumps, one used without anticoagulation and the other driven at a very slow rotational speed. SEM revealed no wear in the male bearings and very low wear and deformation (0.02 ± 0.03 mm) in the female bearings. The combination of Gyro and Excelung may be applicable for long-term biventricular and right ventricular support, although proper anticoagulation should be administrated to avoid thrombus formation inside the pump.

The effects of interleukin-6 signal blockade on immune system, reproductive and skeletal development in juvenile mice.

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.

Alteration of Y-box binding protein-1 expression modifies the response to endocrine therapy in estrogen receptor-positive breast cancer.

Y-box binding protein-1 (YB-1) plays an important role in tumor progression and drug resistance. This study examined whether YB-1 is involved in the alteration of response to endocrine therapy in estrogen receptor (ER)-positive breast cancer cells. MCF7 cells that stably expressed YB-1 (MCF7-YB-1) and vector control cells (MCF7-vector) were established. These cells were used to analyze the expression of the factors related to ER and growth factor receptor signaling pathways and responses to antiestrogens (tamoxifen and fulvestrant) and estrogen responsive element (ERE) activity. The effect of knocking down endogenous YB-1 expression was tested in wild-type MCF7 cells. In addition, the expression of YB-1 and the factors related to ER and growth factor receptor signaling pathways were evaluated in clinical breast cancers treated with preoperative chemotherapy. The expression of HER2, AIB1, p-Erk, and c-Myc was increased in MCF7-YB-1 cells. In contrast, knocking down of YB-1 decreased the expression of these factors but increased the expression of ERα in wild-type MCF7 cells. Furthermore, sensitivity to antiestrogens was decreased in the MCF7-YB-1 in comparison to that in MCF7-vector cells. The introduction of YB-1 into MCF7 cells inhibited apoptosis and cell cycle arrest at G1 phase induced by antiestrogens. In MCF7-YB-1 cells, the expression levels of p-Erk and c-Myc were continuously upregulated when cells were treated with either tamoxifen or fulvestrant. The ERE activity was reduced in MCF7-YB-1 cells in comparison to MCF7-vector cells, and the ERE activity in MCF7-YB-1 cells was inhibited by fulvestrant at a lower concentration than that which inhibited the ERE activity in MCF7-vector cells. In ER-positive clinical breast cancers treated with preoperative chemotherapy, significantly more number of specimens that showed increased or positive YB-1 expression after chemotherapy was positive for HER2 expression. These data suggest that alteration of YB-1 may modify the crosstalk between the ER pathway and HER2 pathway in ER-positive breast cancer cells, and consequently, may alter the response to endocrine therapy in ER-positive breast cancer cells.

Alteration of intracellular secretory acute phase response proteins expressed in human hepatocyte induced by exposure with interleukin-6.

Interleukin-6 (IL-6) is a principal proinflammatory cytokine inducing the acute phase response in various tissues, including liver. Here, we adopt the FD-LC-MS/MS method, consisting of fluorogenic derivatization (FD), separation by liquid chromatography (LC), and identification of proteins by LC-tandem mass spectrometry (MS/MS), to reveal how exposure to IL-6 alters temporally the intracellular secretory acute phase response (sAPR) proteins expressed in human hepatocytes as compared to non-exposure. Nine altered sAPR proteins were identified in cultures in response to IL-6. Seven of them (serum amyloid A protein, haptoglobin, fibrinogen α chain, fibrinogen ß chain, fibrinogen γ chain, α(1)-acid glycoprotein and α(1)-antitrypsin) were significantly increased and two (ß(2)-glycoprotein 1 and transferrin) were significantly decreased in response to IL-6. In addition, the transmission speed of transferrin might be much faster than the other sAPR proteins. These results suggest a different molecular mechanism for protein synthesis and the secretory pathway among the sAPR proteins. In this study, we observed the simultaneously and temporally altered expression of sAPR proteins which had been induced by exposure to IL-6 in human hepatocytes, in contrast to previous reports, in all of which the proteins were tested from the time they were secreted into the medium from the cells.

The effects of interleukin-6 signal blockade on fertility, embryo-fetal development, and immunization in vivo.

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.

Combination of T cell-redirecting bispecific antibody ERY974 and chemotherapy reciprocally enhances efficacy against non-inflamed tumours.

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.

Painless acute aortic dissection. - Diagnostic, prognostic and clinical implications.-.

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 < 0.001), syncope (25% vs. 1%, P < 0.001) and a focal neurologic deficit (19% vs. 2%, P = 0.006) as presenting symptoms. Imaging study findings were not significantly different. Cerebral ischemia (50% vs. 1%, P < 0.001) and cardiac tamponade (38% vs. 13%, P = 0.01) were more frequent complications in the painless group. In-hospital mortality was not significantly different (19% vs. 15%). However, the painless group had a more unfavorable functional outcome on overall performance category (P < 0.001). CONCLUSIONS: Painless AAD may be more frequent than previously reported. Painless AAD patients often present with a disturbance of consciousness or a neurologic deficit, and have a higher morbidity than painful AAD patients.

CSLEX (Sialyl Lewis X) is a useful tumor marker for monitoring of breast cancer patients.

BACKGROUND: CSLEX is a type II carbohydrate antigen that interacts with the CSLEX-1 monoclonal antibody. CSLEX in combination with carbohydrate antigen 15-3 may be more useful than Carcinoembryonic Antigen with carbohydrate antigen 15-3 as tumor markers for monitoring of breast cancer. METHODS: The serum levels of tumor markers, including CSLEX, were measured in 480 consecutive breast cancer patients with or without metastasis who visited the outpatient clinic of the Division of Breast and Endocrine Surgery, Shinshu University Hospital, between April 2007 and September 2007. RESULTS: Serum levels of each of the tumor markers correlated significantly with the status of metastasis (P < 0.01). Combinations of Carcinoembryonic Antigen and carbohydrate antigen 15-3, Carcinoembryonic Antigen and Nation Cancer Center-Stomach-439, Carcinoembryonic Antigen and CSLEX, carbohydrate antigen 15-3 and Nation Cancer Center-Stomach-439, and carbohydrate antigen 15-3 and CSLEX levels also correlated significantly with the status of metastasis (P < 0.01). The sensitivity, specificity, positive predictive value, negative predictive value and accuracy were almost the same for CSLEX and Nation Cancer Center-Stomach-439, which are both type II carbohydrate antigens. The cutoff indexes of serum CSLEX and Nation Cancer Center-Stomach-439 for detection of breast cancer metastasis were 38.8 ± 52.7-fold and 22.1 ± 27.8-fold, respectively (P = 0.16). CONCLUSIONS: These data suggest that the diagnostic values of CSLEX and Nation Cancer Center-Stomach-439 are similar in single or combined use. However, the cutoff index of serum CSLEX tended to be higher than that of Nation Cancer Center-Stomach-439, which may make CSLEX more useful for detection of breast cancer metastasis.

Full-thickness chest-wall resection followed by thorax reconstruction for recurrent malignant phyllodes tumor.

We present a case of a 39-year-old woman with a giant recurrent malignant phyllodes tumor accompanied with bleeding and infection. She underwent full-thickness chest-wall resection. Bony thorax reconstruction and stabilization was accomplished using a Composix mesh™, and soft tissue reconstruction was performed with a musculocutaneous flap of latissimus dorsi muscle. The patient had a good postoperative outcome, and the surgical treatment remarkably improved her quality of life. Because chemotherapy and radiation are not established for treating malignant phyllodes tumors, an aggressive surgical approach should be considered for patients with a locally advanced malignant phyllodes tumor.

[Cardiac tumor, constrictive pericarditis and pulmonary thromboembolism].

Cardiac tumors are rare, and 3-quarters of these tumors are benign and nearly half of the benign tumors are myxomas. Metastases to the heart are more common than primary cardiac tumors. Cardiac tumors present obstructive, constitutional and embolic signs and symptoms. Echocardiograms, chest computed tomography (CT) and magnetic resonance imaging (MRI) scan are very useful for diagnosis. Surgery is indicated in patients with benign tumor, and chemo/radio-therapy in patients with malignant tumors. Prognosis after surgery is good, instead poor prognosis for patients with malignancy. Constrictive pericarditis is mainly result of idiopathic, previous cardiac surgery and radiation in recent years. Diagnosis is made by echo cardiography and cardiac catheterization along with clinical presentation. Thickened pericardium is directly diagnosed by currently advanced transesophageal echocardiography, CT and MRI although normal thickness of the pericardium with constrictive pericarditis is observed in some patients. Pericardiectomy is the only treatment for permanent constriction. The incidence of pulmonary thromboembolism is currently increasing in Japan. Guidelines for the diagnosis, treatment and prevention of pulmonary thromboembolism and deep vein thrombosis (JCS 2009) is helpful for diagnosis and treatment decision. Anticoagulant is initial treatment for acute pulmonary thromboembolism, and intravenous thrombolysis is performed in hemodynamically unstable cases. Chronic thromboembolic pulmonary hypertention is treated by pulmonary endarterectomy whereas anticoagulant and vasodilator are used for peripheral type and mild cases.

[A retrospective study of high-dose toremifene treatment for patients with aromatase inhibitor refractory advanced or metastatic hormone receptor-positive breast cancer].

Aromatase inhibitors (AI) have largely replaced tamoxifen as the first-line of treatment for postmenopausal women with advanced or metastatic hormone-receptor-positive breast cancer. However, there is no established strategy for treating AI refractory cases. In this study, we investigated the efficacy of high-dose Toremifene therapy (HD-TOR). From January 2001 through April 2010, nineteen patients received 120 mg of TOR daily. The overall response rate was 36.8% (CR; 1, PR; 6), and the clinical benefit was 47.4%. The clinical benefit rate to each of the metastatic organs were: lung, 42.9%; bone, 13%; liver, 25%; and lymph node, 40%. A higher clinical benefit rate was observed in lung or lymph node metastases. The clinical benefit rate of HD-TOR as first to third-line therapy was 50%, which was more effective than that of fourth-line therapy. Our data suggests that HD-TOR may be one of the effective treatment strategies for patients with AI refractory advanced or metastatic hormone receptor-positive breast cancer.