Safety of Apixaban Monotherapy for Non-Valvular Atrial Fibrillation-Related Acute Stroke with Intra-/Extracranial Artery Stenosis.

INTRODUCTION: We investigated whether apixaban is safe for the prevention of further adverse events in non-valvular atrial fibrillation (NVAF) patients with intra-/extracranial artery stenosis (Stenosis group) compared with acute large vessel occlusion without intra-/extracranial artery stenosis (No stenosis group). We also examined whether combination therapy using apixaban and antiplatelet is safe. METHODS: ALVO (Apixaban on clinical outcome of patients with Large Vessel Occlusion [LVO] or stenosis) was a historical and prospective multicenter registry at 38 centers in Japan. Patients with NVAF and acute LVO or stenosis who received apixaban within 14 days after onset were included. We conducted the post hoc analysis using the ALVO dataset. We compared patients with stenosis versus those without stenosis in terms of the primary outcome, which was defined as a composite of all-cause death, major bleeding events, and ischemic events 365 days after onset. RESULTS: Of the 662 patients, 54 (8.2%) patients were classified into the Stenosis group, and 104 patients of the total (16%) reached the primary outcome. The cumulative incidence of primary outcome was not significantly different between the No stenosis and the Stenosis groups (hazard ratio [HR] 1.2, 95% confidence interval [CI]: 0.64-2.4; p = 0.52). Even after adjustment for predictive clinical variates, no significant difference in the primary endpoint between the No stenosis and the Stenosis groups was shown (adjusted HR 1.2, 95% CI: 0.59-2.5; p = 0.60). Fifty patients (7.6%) used an antiplatelet with apixaban. Among the Stenosis group patients, the cumulative incidence of the primary outcome was significantly higher among patients treated with an antiplatelet and apixaban (HR 3.5, 95% CI: 1.0-12; p = 0.048). CONCLUSION: Apixaban monotherapy appears safe for the prevention of further adverse events in the Stenosis group patients similar to the No stenosis group patients. Concomitant use of an antiplatelet might not be favorable in patients with stenosis.

Endoscopic resection of local recurrences of diminutive polyps by cold forceps polypectomy.

OBJECTIVES: Cold forceps polypectomy (CFP) is an effective treatment for diminutive colorectal polyps. However, polyps occasionally recur, and there is no consensus on their long-term clinical management. Therefore, we investigated the short- and long-term clinical outcomes of re-CFP for recurrent diminutive colorectal polyps. MATERIALS AND METHODS: This was a follow-up of a multicenter, prospective study investigating the clinical outcomes of diminutive colorectal polyps excised by CFP with narrowband imaging-enhanced endoscopy and jumbo forceps. We evaluated short-term outcomes of re-CFP and patients at 1-year follow-up post re-CFP for recurrent colorectal polyps to determine long-term recurrence rates. Additionally, complete resection rates, clinicopathological features, number of forceps bites, and rate of short-term adverse events managed by re-CFP were evaluated. RESULTS: At 1-year follow-up, local recurrence was identified in 18 patients from the original study. The mean size of local recurrent polyps was 1.5 ± 0.6 mm, and all recurrent lesions were < 3 mm. Re-CFP could successfully excise locally recurrent polyps in all cases. All recurrent lesions were low-grade adenomas; no adverse events were reported. Additionally, 16 of 18 patients were evaluated endoscopically at 2-year follow-up; no recurrence was observed. CONCLUSIONS: Recurrent lesions following initial CFP were small and pathologically benign, and re-CFP was an effective treatment.

Selection of surgical approach for cerebellar hemangioblastomas based on venous drainage patterns.

Cerebellar hemangioblastomas remain surgically challenging because of the narrow, deep surgical corridors and tumor hypervascularity. Various surgical approaches are used according to the location, but optimal approaches have not been established. We propose a system of surgical approaches based on the venous drainage systems to facilitate surgical planning and achieve acceptable neurological outcomes. Cerebellar hemangioblastomas were divided into five types based on the main drainage systems: suboccipital hemangioblastomas draining to the transverse sinus (TS) or torcula, tentorial hemangioblastomas draining to the tentorial sinus or straight sinus, petrosal hemangioblastomas draining to the superior petrosal sinus (SPS), quadrigeminal hemangioblastomas draining to the galenic system, and tonsillar hemangioblastomas draining to the TS or torcula in conjunction with jugular bulb or SPS. Microsurgical approaches and patient outcome were retrospectively reviewed according to this classification. This study included 17 patients who underwent 21 operations for resection of 19 cerebellar hemangioblastomas, classified into 9 suboccipital, 4 tentorial, 2 petrosal, 2 quadrigeminal, and 2 tonsillar. Standard suboccipital craniotomies were utilized for suboccipital hemangioblastomas, the occipital transtentorial approach (OTA), and supracerebellar infratentorial approach for tentorial hemangioblastomas, the retrosigmoid approach for petrosal hemangioblastomas, OTA for quadrigeminal hemangioblastomas, and midline suboccipital approach for tonsillar hemangioblastomas. Gross total resection was achieved in all patients except one. Two patients with large hemangioblastomas (tonsillar and quadrigeminal) required second-stage operation which finally achieved gross total removal. No single approach had a significantly higher incidence of postoperative neurological deficits. Selection of the optimum surgical approach for cerebellar hemangioblastomas was successful based on the main drainage systems. Understanding of tumor growth and extension with respect to the venous drainage system is critical to select the appropriate surgical approach.

Short-term experience with aspiration embolectomy using a ACE68 reperfusion catheter to treat embolic superior mesenteric artery occlusion.

We report the short-term results with aspiration embolectomy using an ACE68 reperfusion catheter to treat patients with acute embolic superior mesenteric artery (SMA) occlusion. Our study included 4 consecutive male patients ranging in age from 72 to 86 years (mean age 79 years). In all patients, the main trunk of the SMA was occluded. The technical success rate was 100% for all procedures. There were no major procedure-related complications. One patient underwent laparotomy with intestinal resection after successful recanalization. No patient reported clinical symptoms of abdominal ischemia at follow-up. Our short-term experience shows that percutaneous aspiration embolectomy using an ACE68 reperfusion catheter is an effective treatment for acute mesenteric ischemia.

[A Case of Anterior Cranial Fossa Dural Arteriovenous Fistula Involving Uncontrolled Seizures Diagnosed Based on Characteristic Findings on Arterial Spin-labeling Imaging].

We report a case of anterior cranial fossa dural arteriovenous fistula(ACF-DAVF)in a patient whose diagnosis was made according to characteristic findings on arterial spin labeling(ASL)MRI. CASE:A 68-year-old man was admitted to our hospital because of intractable epilepsy. Based on the initial MRI findings, an initial diagnosis of limbic encephalitis was made. Steroids and anticonvulsant drugs were administered;however, the seizures could not be controlled. A second MRI with ASL revealed abnormal vessel signals in the base segments of the left frontal and temporal lobes toward the basal vein of Rosenthal. Digital subtraction angiography(DSA)revealed an arteriovenous shunt in the left anterior cranial fossa, which drained toward the medial side of the left temporal lobe. A diagnosis of ACF-DAVF with status epilepticus was made, and the main drainer was cauterized. After the surgical procedure, the epilepsy was controlled with antiepileptic drugs, and postoperative MRI revealed obliteration of ACF-DAVF, disappearance of the high-intensity area on FLAIR sequences, and disappearance of the high-intensity signal area on ASL.

[A Case of Transorbital Penetrating Cavernous Sinus Injury by a Bamboo Stick Treated by Craniotomy in the Hybrid Operating Room].

Herein, we report a rare case of penetrating transorbital cavernous sinus injury caused by a bamboo stick, treated by craniotomy in a hybrid operating room. A 63-year-old gardener presented at our hospital with right upper orbital injury after falling on a bamboo basket. Neurological examination revealed right II, III, IV, and VI cranial nerve palsies. CT and MRI revealed a right transorbital penetrating injury by a small sharp wooden foreign body, extending from the orbit to the cavernous sinus via the superior orbital fissure. Preoperative digital subtraction angiography revealed partial occlusion of the right cavernous sinus by the foreign body and no internal carotid artery(ICA)injury. There was a nine-day waiting period after the injury because the patient was on dual antiplatelet therapy for ischemic heart disease. Subsequently, the bamboo stick was completely removed through the right fronto-temporo-orbito-zygomatic approach in a hybrid operating room. To treat the potential massive hemorrhage, a five-French balloon catheter was inserted in the right ICA at its origin via the right transfemoral approach before the craniotomy. The bamboo stick was completely removed with minor hemorrhage in the cavernous sinus; this was controlled using hemostatic materials. The postoperative course was uneventful. The patient was discharged with blindness and total ophthalmoplegia in the right eye but he was able to return to his prior job. This is the first report of such a treatment of a transorbital penetrating injury in a hybrid operating room.

Local recurrence of diminutive colorectal polyps after cold forceps polypectomy with jumbo forceps followed by magnified narrow-band imaging: a multicenter prospective study.

BACKGROUND: Cold polypectomy has been increasingly used to remove diminutive colorectal polyps. We evaluated the local recurrence rate of diminutive polyps at the 1-year follow-up after cold forceps polypectomy (CFP). METHODS: In a prospective, multicenter, observational cohort study, patients with diminutive colorectal polyps ( ≤ 5 mm) were treated by CFP using jumbo forceps followed by magnified narrow-band imaging (NBI). Patients were assessed for local recurrence at 1-year follow-up. Risk factors associated with local recurrence were analyzed using logistic regression analysis. RESULTS: Overall, 955 lesions were resected in 471 patients who completed the 1-year follow-up. The endoscopic complete resection rate was 99.4 %. Immediate and delayed bleeding occurred in 0.8 % and 0.2 % of cases, respectively, with no perforations observed. Local recurrence occurred in 2.1 % of cases at the 1-year follow-up. Univariable analyses indicated that polyps > 3 mm (P < 0.01) and immediate bleeding (P = 0.04) were significantly associated with local recurrence. A trend was observed for patients ≥ 65 years (P = 0.06) and fractional resection (P = 0.09). Multivariable analyses confirmed that lesions > 3 mm were significantly associated with local recurrence (odds ratio 3.4, P = 0.02). CONCLUSIONS: CFP with jumbo forceps followed by NBI-magnified observation had a low local recurrence rate and is an acceptable therapeutic option for diminutive colorectal polyps. Although we recommend limiting the use of CFP with jumbo forceps to polyps ≤ 3 mm in size, future comparative studies are needed to make recommendations on cold polypectomy using either forceps or snares as the preferred approach for diminutive polyp resection.

Treatment patterns and outcomes of unresectable pancreatic cancer patients in real-life practice: a region-wide analysis.

BACKGROUND: FOLFIRINOX (FFX) and gemcitabine (GEM) plus nab-paclitaxel (GnP) have recently been available for treating pancreatic ductal adenocarcinoma (PDAC). We investigated trends in characteristics, treatment and outcomes of unselected patients with unresectable PDAC in real-life practice in Japan. METHODS: We retrospectively reviewed the medical records of 1085 patients diagnosed as having unresectable or recurrent PDAC in multiple centers in the Hokuriku area between January 2009 and July 2015. RESULTS: The incidence of pathologically proven PDAC had increased from 18.7% in 2009 to 56.2% in 2015. Oncological therapy was administered to 779 patients (71.8%): chemotherapy (n = 675), chemo-radiotherapy (n = 92) or radiotherapy (n = 12); the remaining patients were treated with best supportive care. Of 100 patients diagnosed in 2009, 62.0% received GEM as first-line chemotherapy; whereas 30.7% of the 75 patients diagnosed in 2015 received FFX, 25.3% GnP, 22.7% GEM and 17.3% S-1. The objective response rates of patients treated with FFX, GnP and GEM were 14.9%, 35.0% and 5.5%, respectively and the OS 10.3, 9.9 and 7.5 months after FFX, GnP and GEM, respectively. Grade 3 or greater any hematological toxicity occurred in 70.2%, 70.0% and 18.8% of the patients treated with FFX, GnP and GEM, respectively. The reasons for treatment discontinuation were adverse events in 9.8%, 26.7% and 24.1% of the patients treated with FFX, GnP and GEM, respectively. CONCLUSION: Chemotherapeutic protocols changed dramatically between 2009 and 2015. Continuous collection and analysis for our cohort with longer follow-up provides useful information about treatment selection and prediction of outcome.

Prediction of Blood-Brain Barrier Disruption and Intracerebral Hemorrhagic Infarction Using Arterial Spin-Labeling Magnetic Resonance Imaging.

BACKGROUND AND PURPOSE: Arterial spin-labeling magnetic resonance imaging is sensitive for detecting hyperemic lesions (HLs) in patients with acute ischemic stroke. We evaluated whether HLs could predict blood-brain barrier (BBB) disruption and hemorrhagic transformation (HT) in acute ischemic stroke patients. METHODS: In a retrospective study, arterial spin-labeling was performed within 6 hours of symptom onset before revascularization treatment in 25 patients with anterior circulation large vessel occlusion on baseline magnetic resonance angiography. All patients underwent angiographic procedures intended for endovascular therapy and a noncontrast computed tomography scan immediately after treatment. BBB disruption was defined as a hyperdense lesion present on the posttreatment computed tomography scan. A subacute magnetic resonance imaging or computed tomography scan was performed during the subacute phase to assess HTs. The relationship between HLs and BBB disruption and HT was examined using the Alberta Stroke Program Early Computed Tomography Score locations in the symptomatic hemispheres. RESULTS: A HL was defined as a region where CBFrelative≥1.4 (CBFrelative=CBFHL/CBFcontralateral). HLs, BBB disruption, and HT were found in 9, 15, and 15 patients, respectively. Compared with the patients without HLs, the patients with HLs had a higher incidence of both BBB disruption (100% versus 37.5%; P=0.003) and HT (100% versus 37.5%; P=0.003). Based on the Alberta Stroke Program Early Computed Tomography Score locations, 21 regions of interests displayed HLs. Compared with the regions of interests without HLs, the regions of interests with HLs had a higher incidence of both BBB disruption (42.8% versus 3.9%; P<0.001) and HT (85.7% versus 7.8%; P<0.001). CONCLUSIONS: HLs detected on pretreatment arterial spin-labeling maps may enable the prediction and localization of subsequent BBB disruption and HT.

A case of cytomegalovirus infection with splenic infarction and an esophageal ulcer in an immunocompetent adult.

BACKGROUND: Recently, morbidities due to primary cytomegalovirus (CMV) infection have increased in young Japanese adults because of decreased anti-CMV antibodies in them. CMV infections are typically resolved naturally in immunocompetent individuals, and complications rarely occur. Here we present the case of an immunocompetent adult with CMV infection complicated by splenic infarctions and an esophageal ulcer. CASE REPORT: A 37-year-old male complaining of a prolonged fever and liver injury was admitted to hospital for a closed examination. The patient had general malaise and mild appetite loss but no abdominal pain. Symptoms of infectious mononucleosis, including liver injury, appearance of atypical lymphocytes in the blood, and hepatosplenomegaly, were observed. A primary CMV infection was confirmed by CMV-IgM positive and CMV-IgG negative serological tests. Enhanced abdominal computed tomography confirmed hepatitis and splenic infarction, and an upper gastrointestinal endoscopy revealed an esophageal ulcer. The patient exhibited no predisposing risk factors for thrombosis, and he was diagnosed with splenic infarctions associated with CMV infection. Because the patient was immunocompetent, he underwent symptomatic therapy without antiviral or anticoagulant therapies. The treatment improved his overall condition. Including the present case, only 11 cases of CMV infections with splenic infarction in immunocompetent individuals have been reported. Contrary to what is observed in immunocompromised hosts, upper gastrointestinal lesions with CMV infection are rare in immunocompetent individuals. The esophageal lesion observed in our patient was a typical punched-out ulcer. The immunohistochemical staining of the tissue biopsies revealed that the ulcer was associated with CMV. CONCLUSION: Although splenic infarctions and esophageal ulcers are rare, they should be considered as potential complications accompanying CMV infection in immunocompetent individuals. The administration of symptomatic therapy should be considered even when the patient is immunocompetent.

A rapidly growing, large, mature retroperitoneal teratoma in an adult male patient.

A 40-year-old man complaining of abdominal distention was referred to our hospital. Computed tomography of the abdomen demonstrated a very large abdominal mass with fat and calcification. The size of the mass rapidly increased from 30cm to 40cm over two weeks. The tumor was removed and diagnosed by pathological examination to be a retroperitoneal mature cystic teratoma that contained a 40-cm long, mature intestinal tract-like cyst, together with bone marrow and fat. The rapid growth of the tumor may have been caused by an increased secretion in the cyst.

Efficacy of a diagnostic and therapeutic algorithm for Clostridium difficile infection.

In July 2012, metronidazole was approved for the treatment of Clostridium difficile infection (CDI). To clarify the selection criteria for the drug in terms of CDI severity, we established a diagnostic and therapeutic algorithm with reference to the SHEA-IDSA Clinical Practice Guidelines. We compared patients whose treatments were guided by the algorithm (29 cases, October 2012-September 2013) with patients treated prior to the development of the algorithm (37 cases, October 2011-September 2012). All cases treated with reference to the algorithm were diagnosed using enzyme immunoassay of C. difficile toxins A and B and glutamate dehydrogenase;an appropriate drug was prescribed in 93.1% of the cases. We found no significant between-group differences in the cure, recurrence, or complication rates. However, drug costs in cases wherein treatments were guided by the algorithm were markedly reduced. We have, thus, shown that algorithm-guided treatment is efficacious and cost-effective.

Clarithromycin Versus Metronidazole as First-line Helicobacter pylori Eradication: A Multicenter, Prospective, Randomized Controlled Study in Japan.

BACKGROUND: Helicobacter pylori eradication rates achieved with a first-line regimen of clarithromycin (CLR) combined with amoxicillin (AMX) and a proton pump inhibitor have recently fallen to ≤80% because of the increasing incidence of CLR resistance in Japan. This randomized multicenter trial aimed to compare the eradication success of 2 first-line triple therapy regimens: rabeprazole, amoxicillin, and clarithromycin (RAC) versus rabeprazole, amoxicillin, and metronidazole (RAM). METHODS: A total of 124 consecutive patients infected with H. pylori were randomized into one of two 7-day therapeutic regimens: RAC (n=60) or RAM (n=64). Eradication was confirmed by the C-urea breath test. Adverse effects were also assessed. RESULTS: Intention-to-treat and per protocol H. pylori eradication rates were 73.3%/77.2% in the RAC group and 90.6%/93.5% in the RAM group. The eradication rate of RAM therapy was significantly higher than that of RAC therapy. CLR, metronidazole, and AMX resistance was found in 36.2%, 2.1%, and 0% of patients, respectively. In addition, no relevant differences in adverse effects were observed. CONCLUSIONS: Metronidazole-based therapy (RAM) was superior to standard CLR-based therapy (RAC) for first-line H. pylori eradication. This reflects the progressive increase in CLR resistance observed in Japan.

Immunoglobulin G4-related periaortitis complicated by aortic rupture and aortoduodenal fistula after endovascular AAA repair.

PURPOSE: To report a rare and complicated case of immunoglobulin (Ig) G4-related periaortitis involving both the aortic wall and the retroperitoneum without aneurysmal formation. CASE REPORT: A 79-year-old man with IgG4-related periaortitis suffered aortic rupture despite a normal caliber aorta after 6 months of steroid therapy (20 mg/d). Endovascular repair with an aortic cuff sealed the rupture. Steroid therapy was halted 2 weeks later due to infection. Four months later, a biopsy during esophagogastroduodenoscopy to investigate gastrointestinal bleeding suggested a relapse of IgG4-RD in the duodenum. Subsequent aortoduodenal fistula formation proved fatal. Generally, IgG4-related periaortitis does not result in such complications due to the absence of aneurysm formation and a thick aortic wall. CONCLUSIONS: Our report highlights a rare case of IgG4-related periaortitis where complications resulted following steroid therapy and surgical intervention, emphasizing the difficulties in dealing with IgG4-related cardiovascular lesions.

Epidemiological Study of Metastatic Brain Tumors in Miyazaki Prefecture: A Regional 10-year Survey in Southern Japan.

Advances in cancer treatment have improved the survival of patients with cancer, with a concomitant increase in the proportion of patients with metastatic brain tumors (MBTs). In this study, we used cancer registries established in Japan after 2016 and available patient data by organ in order to conduct an accurate epidemiological study. To the best of our knowledge, this is the first study to report on the detailed epidemiological data on MBT at the prefectural level in Japan using the Miyazaki Brain Tumor Database and Miyazaki Cancer Registry. This study included 425 new cases of MBTs diagnosed in Miyazaki Prefecture from 2007 to 2016. As per our findings, the most frequent primary tumor in Miyazaki Prefecture was found to be in the lung (49.4%), followed by colon/rectum/anus (9.4%) and breast (8.5%). Among patients with MBTs, 59.1% were males, a number closely similar to that of Japan, as shown in the Japanese Brain Tumor Registry (55.5%). The median age at diagnosis was 68 and 63 years in Miyazaki Prefecture and Japan, respectively. Although more patients were symptomatic in Miyazaki Prefecture than in Japan (88.5% vs. 15.5%), fewer patients opted for surgery (33.6% vs. 61.9%), probably because of their advanced age at diagnosis. As per the findings of this study, the annual incidence rate of new MBTs (i.e., ratio of the number of new cancer registrations to that of new MBT patients in Miyazaki Prefecture) was at 0.41%. The number of tumor sites in MBTs was independent of the total number of cancers per organ. Considering the expansion of cancer registries worldwide, including those on brain tumors, further epidemiological analysis of MBTs is deemed warranted.

Arterial spin-labeled perfusion imaging to predict mismatch in acute ischemic stroke.

BACKGROUND AND PURPOSE: We assigned a threshold to arterial spin-labeling (ASL) perfusion-weighted images (PWI) from patients with acute ischemic stroke and compared them with dynamic susceptibility contrast perfusion images to examine whether mismatch can be determined. METHODS: Pseudocontinuous ASL was combined with dynamic susceptibility contrast PWI in 23 patients with acute ischemic stroke. Scans were obtained within 24 hours of symptom onset. PWI volumes were defined by ASL cerebral blood flow (<15, <20, and <25 mL/100 g per minute) and dynamic susceptibility contrast-mean transit time (MTT) thresholds (>10 s) that show a strong association with cerebral blood flow <20 mL/100 g per minute in Xenon CT studies. Agreement between the ASL-diffusion-weighted imaging and MTT-diffusion-weighted imaging mismatch and the correlation between penumbra salvage and infarct growth, defined as the difference between the baseline PWI and the baseline diffusion-weighted imaging lesion, respectively, and the final infarct volume were assessed. RESULTS: The lesion volumes defined by MTT>10 s and ASL<20 mL/100 g per minute showed an excellent correlation. There was 100% agreement on the mismatch status between MTT>10 s and ASL<20 mL/100 g per minute. The correlation between infarct growth and penumbra salvage volume was significantly better for PWI lesions defined by ASL<20 mL/100 g per minute and MTT>10 s. CONCLUSIONS: In acute ischemic stroke, PWI lesions based on ASL threshold of <20 mL/100 g per minute can provide a reliable estimate of mismatch in correspondence at MTT threshold of >10 s.

Spontaneous malignant transformation of trigeminal schwannoma: consideration of responsible gene alterations for tumorigenesis-a case report.

Malignant peripheral nerve sheath tumors (MPNSTs) arising from the trigeminal nerves are extremely rare (only 45 cases, including the present case, have been published) and have been reported to develop de novo from the peripheral nerve sheath and are not transformed from a schwannoma or neurofibroma. Here, we report a case of MPNSTs of the trigeminal nerve caused by the malignant transformation of a trigeminal schwannoma, with a particular focus on genetic considerations. After undergoing a near-total resection of a histologically typical benign schwannoma, the patient presented with regrowth of the tumor 10 years after the primary excision. Histopathologic and immunochemical examinations confirmed the recurrent tumor to be an MPNST. Comprehensive genomic analyses (FoundationOne panel-based gene assay) showed that only the recurrent MPNST sample, not the initial diagnosis of schwannoma, harbored genetic mutations, including NF1-p.R2637* and TP53-p.Y234H, candidate gene mutations associated with malignant transformation. Moreover, the results of reverse transcription polymerase chain reaction showed that the fusion of SH3PXD2A and HTRA1, which has been reported as one of the responsible genetic aberrations of schwannoma, was detected in the recurrent tumor. Taken together, we could illustrate the accumulation process of gene abnormalities for developing MPNSTs from normal cells via schwannomas.

Hepatocellular carcinoma and survival in patients with autoimmune hepatitis (Japanese National Hospital Organization-autoimmune hepatitis prospective study).

BACKGROUND/AIMS: Although the outcome of autoimmune hepatitis (AIH) is generally good, the natural course and likelihood of progression to cirrhosis or hepatocellular carcinoma (HCC) remain undefined, and may vary by region and population structure. Our aims were to evaluate risk factors that contribute to poor outcome and particularly development of HCC in a prospective multicentric cohort study of AIH. METHODS: The study group comprised 193 Japanese patients with AIH who were prospectively followed up at annual intervals between 1995 and 2008. The mean follow-up period was 8.0 ± 4.5 years. RESULTS: Twenty-one (10.9%) patients had cirrhosis at presentation and a further 15 (7.8%) developed cirrhosis during the follow-up period. Survival rates were 94.2% at 10 years and 89.3% at 15 years. HCC was diagnosed in seven of the 193 patients. The presence of cirrhosis at presentation was a risk factor for HCC according to a Cox proportional hazard model, and the HCC-free survival rate was significantly lower in those with cirrhosis compared to those without cirrhosis according to Kaplan-Meier analysis. CONCLUSIONS: Although the outcome of AIH is as good if not better among Japanese than for other populations, there was an increased risk of HCC in these patients. Cirrhosis at presentation was predictive of development of HCC in AIH in Japan.

T2-fluid-attenuated inversion recovery mismatch sign in lower grade gliomas: correlation with pathological and molecular findings.

After the new molecular-based classification was reported to be useful for predicting prognosis, the T2-fluid-attenuated inversion recovery (FLAIR) mismatch sign has gained interest as one of the promising methods for detecting lower grade gliomas (LGGs) with isocitrate dehydrogenase (IDH) mutations and chromosome 1p/19q non-codeletion (IDH mut-Noncodel) with high specificity. Although all institutions could use T2-FLAIR mismatch sign without any obstacles, this sign was not completely helpful because of its low sensitivity. In this study, we attempted to uncover the mechanism of T2-FLAIR mismatch sign for clarifying the cause of this sign's low sensitivity. Among 99 patients with LGGs, 22 were T2-FLAIR mismatch sign-positive (22%), and this sign as a marker of IDH mut-Noncodel showed a sensitivity of 55.6% and specificity of 96.8%. Via pathological analyses, we could provide evidence that not only microcystic changes but the enlarged intercellular space was associated with T2-FLAIR mismatch sign (p = 0.017). As per the molecular analyses, overexpression of mTOR-related genes (m-TOR, RICTOR) were detected as the molecular events correlated with T2-FLAIR mismatch sign (p = 0.020, 0.030. respectively). Taken together, we suggested that T2-FLAIR mismatch sign could pick up the IDH mut-Noncodel LGGs with enlarged intercellular space or that with overexpression of mTOR-related genes.

Reperfusion Therapy Brings Apixaban Administration Forward in Patients with Nonvalvular Arterial Fibrillation with Anterior Circulation Large Vessel Occlusion or Stenosis.

OBJECTIVE: The initiation of anticoagulant administration after large vessel occlusion (LVO) or stenosis with nonvalvular arterial fibrillation (NAVF) is controversial. We evaluate the timing of anticoagulation and its relationship with clinical factors. METHODS: We enrolled 595 anterior circulation LVO or stenosis with NAVF cases from 38 stroke centers. Laboratory data; activities of daily living; the Alberta Stroke Program Early CT Score (ASPECTS); the National Institutes of Health Stroke Scale (NIHSS) score; occluded artery; treatment methods; date of the initiation of apixaban administration and outcome were recorded. Multivariate analyses were performed after univariate analysis. RESULTS: The median start of apixaban administration after the stroke was 2 days (interquartile range, 1-5; range, 0-14). Multivariate analysis of variance showed that non-internal carotid artery occlusion (F value 4.60), reperfusion therapy (31.1), high ASPECTS (6.27) before anticoagulant intake, and absence of intracranial hemorrhage (12.9) were significantly correlated with early apixaban administration. Multiple logistic regression analysis for independent living at 90 days after the stroke showed significant factors: aging (odds, 0.94; 95% confidence interval [CI], 0.91-0.97); male (odds, 0.46; 95% CI, 0.26-0.79); prestroke independence (odds, 20.7; 95% CI, 6.48-93.9); number of white blood cells (odds, 0.99; 95% CI, 0.97-1.00); non-internal carotid artery occlusion; NIHSS score at 72 hours after the stroke (odds 0.92; 95% CI, 0.89-0.96); ASPECTS before apixaban intake (odds, 1.15; 95% CI, 1.00-1.31) and initiation of apixaban (odds, 0.91; 95% CI, 0.83-0.99). CONCLUSIONS: Early administration of apixaban is induced by nonsevere infarction, reperfusion therapy or none of intracranial hemorrhage and it correlates with an independent long-term outcome.