Case of Barrett's adenocarcinoma with marked endoscopic morphological changes in Barrett's esophagus over a long follow‐up period of 15 years

The natural history of Barrett's esophagus (BE) is unclear. We herein describe a case of Barrett's adenocarcinoma (BAC) in which we could closely observe marked morphological changes in BE over a long follow‐up period of 15 years. A man in his seventies received routine esophagogastroduodenoscopy (EGD) and was diagnosed as having reflux esophagitis and short‐segment BE. The BE gradually became elongated, and BAC was detected 9 years following the initial EGD examination with continued administration of a proton pump inhibitor. We witnessed that BE elongated sporadically over time and mucosal breaks of reflux esophagitis were detectable several years before elongation. The patient underwent endoscopic submucosal dissection for BAC and has been monitored by EGD every year thereafter. These remarkable morphological changes may be representative of the natural history of BE and aid in deciding long‐term disease management.     

Distinct subsynaptic localization of type 1 metabotropic glutamate receptors at glutamatergic and GABAergic synapses in the rodent cerebellar cortex

Type 1 metabotropic glutamate (mGlu1) receptors play a pivotal role in different forms of synaptic plasticity in the cerebellar cortex, e.g. long‐term depression at glutamatergic synapses and rebound potentiation at GABAergic synapses. These various forms of plasticity might depend on the subsynaptic arrangement of the receptor in Purkinje cells that can be regulated by protein–protein interactions. This study investigated, by means of the freeze‐fracture replica immunogold labelling method, the subcellular localization of mGlu1 receptors in the rodent cerebellum and whether Homer proteins regulate their subsynaptic distribution. We observed a widespread extrasynaptic localization of mGlu1 receptors and confirmed their peri‐synaptic enrichment at glutamatergic synapses. Conversely, we detected mGlu1 receptors within the main body of GABAergic synapses onto Purkinje cell dendrites. Although Homer proteins are known to interact with the mGlu1 receptor C‐terminus, we could not detect Homer3, the most abundant Homer protein in the cerebellar cortex, at GABAergic synapses by pre‐embedding and post‐embedding immunoelectron microscopy. We then hypothesized a critical role for Homer proteins in the peri‐junctional localization of mGlu1 receptors at glutamatergic synapses. To disrupt Homer‐associated protein complexes, mice were tail‐vein injected with the membrane‐permeable dominant‐negative TAT‐Homer1a. Freeze‐fracture replica immunogold labelling analysis showed no significant alteration in the mGlu1 receptor distribution pattern at parallel fibre–Purkinje cell synapses, suggesting that other scaffolding proteins are involved in the peri‐synaptic confinement. The identification of interactors that regulate the subsynaptic localization of the mGlu1 receptor at neurochemically distinct synapses may offer new insight into its trafficking and intracellular signalling.     

Comprehensive risk evaluation for metachronous carcinogenesis after endoscopic submucosal dissection of superficial pharyngeal squamous cell carcinoma

Esophagus - Pharyngeal squamous cell carcinoma (PSCC) is associated with a high likelihood of metachronous carcinogenesis, which is known to have a poor prognosis. This study aimed to identify...     

Anticoagulation strategies and clinical outcomes after bleeding events during anticoagulation therapy for venous thromboembolism in the practice-based Japanese registry

Journal of Thrombosis and Thrombolysis - There is a paucity of data on anticoagulation strategies and clinical outcomes after bleeding events for venous thromboembolism (VTE). In a multicenter...     

Impact of no,distal, and proximal deep vein thrombosis on clinical outcomes in patients with acute pulmonary embolism: From the COMMAND VTE registry

BackgroundThe majority of acute pulmonary embolism (PE) is caused by thrombus developed from leg veins. However, impact of concomitant deep venous thrombosis (DVT) on clinical outcomes has not been fully evaluated in patients with acute PE.MethodsThe COMMAND VTE Registry is a multicenter registry enrolling consecutive 3027 patients with acute symptomatic venous thromboembolism (VTE) in Japan. The current study population consisted of 655 acute PE patients who underwent lower extremities ultrasound examination at diagnosis for the assessment of concomitant DVT status.ResultsThere were 424 patients with proximal DVT (64.7%), 162 patients with distal DVT (24.7%), and 69 patients with no DVT (10.5%). The cumulative 90-day incidence of all-cause death was higher in proximal DVT patients than in distal DVT and no DVT patients (7.9%, 2.5%, and 1.4%, p = 0.01). Regarding the causes of death, the cumulative 90-day incidence of PE-related death was low, and not significantly different across the 3 groups (1.4%, 0.6%, and 1.7%, p = 0.62). The most frequent cause of death was cancer in proximal and distal DVT patients. There were no significant differences in 90-day rates of recurrent VTE and major bleeding, regardless of the status of concomitant DVT (2.9%, 3.2%, and 2.2%, p = 0.79, and 1.5%, 4.4%, and 4.9%, p = 0.46, respectively).ConclusionsAcute PE with proximal DVT at diagnosis was associated with a higher risk for short-term mortality than in patients without DVT, while the risk for short-term mortality was not significantly different between distal DVT patients and patients without DVT.     

Impact of Chronic Kidney Disease on Aortic Disease-related Mortality: A Four-year Community-Based Cohort Study

Objective Despite advances in medicine, aortic diseases (ADs), such as aneurysm rupture and aortic dissection, remain fatal and carry extremely high mortality rates. Due to its low frequency, the risk of developing AD has not yet been fully elucidated. Chronic kidney disease (CKD) is an established risk factor for cardiovascular disease and mortality. The aim of the present study was to examine whether or not CKD is a risk for AD-related mortality in the general population. Methods We used a nationwide database of 554,442 subjects (40-75 years old) who participated in the annual “Specific Health Check and Guidance in Japan” checkup between 2008 and 2013. Results There were 131 aortic aneurysm and dissection deaths during the follow-up period of 2,123,512 person-years. A Kaplan-Meier analysis revealed that subjects with CKD had a higher rate of AD-related deaths than those without it. A multivariate Cox proportional hazard regression analysis demonstrated that CKD was an independent risk factor for AD-related death in the general population after adjusting for cardiovascular risk factors. The addition of CKD to cardiovascular risk factors significantly improved the C, net reclassification, and integrated discrimination indexes. Conclusion CKD is an additional risk for AD-related death, suggesting that CKD may be a target for the prevention and early identification of subjects at high risk for AD-related death in the general population.     

Metachronous carcinogenesis of superficial esophagus squamous cell carcinoma after endoscopic submucosal dissection: incidence and risk stratification during long-term observation

Esophagus - This study aimed to reveal long-term outcomes, such as incidence of metachronous esophageal and head and neck squamous cell carcinomas and overall survival rate, through long-term...