Hemobilia: another complication associated with anti-thrombotic therapy

It is generally accepted that anti-thrombotic therapy increases the risk of gastrointestinal bleeding, and concurrent therapy with a proton-pump inhibitor is the standard treatment for patients receiving aspirin. Therefore, much attention has been paid to the prevention of gastrointestinal bleeding in such patients; however, it should be noted that patients on anti-thrombotic therapy always carry a risk of hemorrhage from any organ, including the gastrointestinal tract. Here, we present a case with formation of a common bile duct stone caused by hemobilia associated with anti-thrombotic therapy. This case suggests that we need to be aware of the possibility of intrabiliary hemorrhage as well as gastrointestinal bleeding in patients receiving anti-thrombotic therapy. Patients with such complications show a variety of symptoms including liver abscess, cholangitis, pancreatitis, and duodenal bleeding.     

Loss of astrocyte polarization in the tg-ArcSwe mouse model of Alzheimer's disease

Aquaporin-4 (AQP4) is the predominant water channel in brain and is selectively expressed in astrocytes. Astrocytic endfoot membranes exhibit tenfold higher densities of AQP4 than non-endfoot membranes, making AQP4 an excellent marker of astrocyte polarization. Loss of astrocyte polarization is known to compromise astrocytic function and to be associated with impaired water and K+ homeostasis. Here we investigate by a combination of light and electron microscopic immunocytochemistry whether amyloid deposition is associated with a loss of astrocyte polarization, using AQP4 as a marker. We used the tg-ArcSwe mouse model of Alzheimer's disease, as this model displays perivascular plaques as well as plaques confined to the neuropil. 3D reconstructions were done to establish the spatial relation between plaques and astrocytic endfeet, the latter known to contain the perivascular pool of AQP4. Changes in AQP4 expression emerge just after the appearance of the first plaques. Typically, there is a loss of AQP4 from endfoot membranes at sites of perivascular amyloid deposits, combined with an upregulation of AQP4 in the neuropil surrounding plaques. By electron microscopy it could be verified that the upregulation reflects an increased concentration of AQP4 in those delicate astrocytic processes that abound in synaptic regions. Thus, astrocytes exhibit a redistribution of AQP4 from endfoot membranes to non-endfoot membrane domains. The present data suggest that the development of amyloid deposits is associated with a loss of astrocyte polarization. The possible perturbation of water and K+ homeostasis could contribute to cognitive decline and seizure propensity in patients with Alzheimer's disease.     

Diagnosis of undifferentiated type early gastric cancers by magnification endoscopy with narrow-band imaging

Background and Aims: The diagnostic use of magnification endoscopy with narrow‐band imaging (ME‐NBI) to assess histopathologically undifferentiated‐type early gastric cancers (UD‐type EGCs) is not well elucidated. The purpose of this study was to examine the comparative relationship between ME‐NBI images and histopathological findings in UD‐type EGCs. Methods: We analyzed 78 consecutive cases of UD‐type EGCs ≤ 20 mm in diameter that underwent ME‐NBI ≤ 2 weeks prior to resection. The ME‐NBI images were compared with histopathological findings following either endoscopic submucosal dissection (ESD) or surgery. Applying the comparative results, we prospectively evaluated the success of identifying the lateral extent of UD‐type EGCs resected by ESD in additional consecutive cases. Results: Lesions with preserved but irregular surface microstructures (S‐type based on ME‐NBI) showed mucosal atrophy and corresponded histologically to the non‐whole‐layer type of intramucosal cancer (24/24, 100%). Lesions with an irregular microvasculature type (V‐type, for example, corkscrew pattern) or mixed type upon ME‐NBI corresponded histopathologically to the non‐whole‐layer type of intramucosal cancer (15/54, 27.8%), the whole‐layer type of intramucosal cancer (27/54, 50.0%) or submucosal (sm) invasion cancer (12/54, 22.2%). Applying these comparative results, we used ME‐NBI to successfully predict the lateral extent of cancer, which corresponded to the histopathological lateral extent in all 18 additional consecutive UD‐type EGCs resected by ESD. Conclusions: ME‐NBI images of UD‐type EGCs were very closely related to the histopathological findings. Thus, ME‐NBI can be useful in the pretreatment assessment of the histopathological patterns of cancer development and the lateral extent of such lesions.     

Primary cardiac angiosarcoma of the right auricle with difficult-to-treat bilateral pleural effusion

A 70-year-old woman was admitted to our hospital with pleuritis and pericarditis. Cytological examination of pleural and pericardial effusion, and pleural biopsy specimens under thoracoscopy revealed no specific pathological findings. The pleural effusion was drained continuously; however, she died of circulatory insufficiency at day 45 from admission. At autopsy, a fragile hemorrhagic mass arising from the right auricle had invaded bilateral pleura and the pericardium directly without distant metastasis. Immunohistochemical staining showed that the tumor cells expressed endothelial markers such as CD31 and CD34 antibodies, and factor VIII-related protein. These findings supported the diagnosis of a poorly differentiated angiosarcoma.     

A case of T cell prolymphocytic leukemia involving blast transformation

We report a case of T cell prolymphocytic leukemia (T-PLL) involving blast transformation. At the initial diagnosis, most peripheral blood cells demonstrated proliferation of indolent T cell small cell variants, i.e., small to medium prolymphocytes with inconspicuous nucleoli and a normal karyotype. These cells were positive for surface CD4, CD5, and CD7, and cytoplasmic CD3, but negative for surface CD3 and CD8 and cytoplasmic terminal deoxynucleotidyl transferase (TdT). The T cell receptor (TCR) Cβ1 gene was rearranged in the cells. Large prolymphocytes with prominent nucleoli, irregular nuclei, and cytoplasmic vacuoles that exhibited chromosome 8 trisomy were observed about 1.5 years later. The CD4+CD8− single positive effector memory T cells transformed into surface CD4+CD8+ double positive precursor T cells. The clonal TCR gene rearrangement patterns of these cells were identical throughout the clinical course, suggesting clonal blast transformation. The CD4+CD8+ cells demonstrated increased chromosome 8 trisomy combined with complex chromosome abnormalities with t(14;14)(q11.2;q32) containing a 14q32 chromosome after transformation. T cell leukemia 1a (TCL1a) (14q32.1) may be implicated in this case. The TCL1a oncoprotein is expressed in approximately 70% of T-PLL cases. The disease gradually developed resistance to chemotherapy, and the patient died of the disease. It is known that indolent T-PLL can become aggressive. Therefore, similar transformations may occur in other aggressive T-PLL cases, particularly those involving trisomy 8 and TCL1a.     

Increases in thigh muscle volume and strength by walk training with leg blood flow reduction in older participants

We examined the effects of walk training combined with leg blood flow reduction (BFR) on muscle hypertrophy as well as on peak oxygen uptake (VO? peak) in older individuals. Both the BFR walk training (BFR-Walk, n = 10, age; 64 ± 1 years, body mass index [BMI]; 22.5 ± 0.9 kg/m2) and control walk training (CON-Walk, n = 8, age; 68 ± 1 years, BMI; 23.2 ± 1.0 kg/m2) groups performed 20 minutes of treadmill walking at an exercise intensity of 45% of heart rate reserve, 4 days per week, for 10 weeks. The BFR-Walk group wore pressure belts (160-200 mm Hg) on both legs during training. After the training, magnetic resonance imaging-measured thigh muscle cross-sectional area (3.1%, p < .01) and muscle volume (3.7%, p < .01) as well as maximal isometric (5.9%, p < .05) and isokinetic (up to 22%, p < .01) strength increased in the BFR-Walk group, but not in the CON-Walk group. Estimated VO? peak during a bicycle graded exercise test increased (p < .05) and correlated with oxygen pulse in both groups. In conclusion, BFR walk training improves both muscle volume and strength in older women.     

Prognostic significance of right ventricular dimension on acute decompensation in chronic left-sided heart failure

Right ventricular (RV) dysfunction has been discussed in relation to an adverse outcome in heart failure (HF). The aim of this study was to analyze the relationship between RV function with HF exacerbation and its subsequent long-term outcome in patients with chronic left-sided HF.We studied 122 consecutive patients who were admitted for dyspnea due to exacerbated left-sided HF with a left ventricular (LV) ejection fraction of less than 40%. Conventional echocardiography was performed in the study subjects on admission and at discharge. Cox proportional hazards analysis revealed that RV end-diastolic dimension (RVDd) (hazard ratio 1.131, P = 0.005, 95% confidence interval 1.039-1.231) and the serum level of creatinine on admission were independent predictors of subsequent cardiac-related death, but RVDd at discharge and other LV parameters were not. Thus, patients were divided into tertiles on the basis of RVDd on admission: < 32 mm (n = 37), 32-40 mm (n = 43), and ≥ 40 mm (n = 42). According to the increase in the RVDd category, the cardiac-related death-free rate significantly decreased. Among the 3 groups, the pulse pressure and serum total bilirubin levels that demonstrated low cardiac output syndrome (LOS) parameters had significant differences.RVDd on admission could be measured noninvasively and easily to predict a worse long-term prognosis of chronic left-sided HF on admission, and showed correlations with LOS parameters.