Subcortical hemorrhage caused by cerebral amyloid angiopathy compared with hypertensive hemorrhage.

OBJECTIVES: Most published reports on lobular hemorrhage in cerebral amyloid angiopathy (CAA) include patients diagnosed only by imaging studies. This study analyzed patients with subcortical hemorrhage histologically diagnosed as CAA or non-CAA (hypertensive). METHODS: This is a retrospective study analyzing data from 100 craniotomy cases. Tissue of hematoma cavity wall was collected for histological investigation in hematoma removal by surgery in patients with subcortical hemorrhage. Statistical analyses of blood pressure, hematoma location and volume, outcome, and mortality was performed in CAA and non-CAA groups. RESULTS: There were 47 CAA and 53 non-CAA cases, and average age was significantly older in the CAA group (p < 0.01). Blood pressure was significantly lower (p < 0.01) but hematoma volume was significantly greater (p < 0.05) in the CAA group. Rebleeding occurred in two CAA cases and one non-CAA case, but no re-operations were required. Average score of modified Rankin Scale, which is used to measure the degree of disability in patients who have had a stroke, at three months after surgery was not significantly different between the two groups (CAA: 3.94 ± 1.28, non-CAA: 3.58 ± 1.50). There were seven deaths in the CAA and six in the non-CAA group, and intraventricular hemorrhage highly complicated in the death cases in both groups. In the CAA group, average age of the fatal cases was significantly older than that of the surviving cases (p < 0.05) and six cases demonstrated dementia before onset of hemorrhage. CONCLUSIONS: Surgical removal of a subcortical hemorrhage caused by CAA is not contraindicated. However, age > 80 years, complication with intraventricular hemorrhage, hematoma volume ≥ 50 ml, and dementia before onset of hemorrhage contribute to high mortality, and craniotomy should be carefully considered for such patients. A limitation of this study is that comparison between CAA and non-CAA groups was performed in the patients with only surgically indicated ICH, and does not evaluate entire ICH cases with CAA. However, this study appropriately compared pathologically diagnosed CAA and non-CAA in patients with moderate to severe lobular ICH with surgical indications.

Fulminant infectious endocarditis caused by Staphylococcus aureus with pseudoaneurysms in the superior mesenteric, hepatic, and popliteal arteries: a case report.

Staphylococcus aureus infectious endocarditis has a high mortality, major causes of death being cardiac failure, systemic embolism, and sepsis. Pseudoaneurysms, a rare complication of this infection, are not invariably fatal with appropriate treatment. A previously healthy 32-year-old man was found to have multiple cerebral infarctions, and infectious endocarditis with mitral valve vegetation was diagnosed by echocardiography. Because methicillin-resistant Staphylococcus aureus (MRSA) was identified from blood cultures, vancomycin was administered. Massive intracerebral hemorrhage in the left temporo-occipital lobe occurred in the patient on the 3rd day after admission, and the hematoma was completely removed surgically. Another hemorrhage was identified in the right occipital region on the 7th hospital day, which led the patient deep coma. Blood cultures on the 10th day were negative for MRSA; however, imaging studies revealed pseudoaneurysms in the superior mesenteric, hepatic, and left popliteal arteries 3 weeks after admission. No surgical indication was applied to these pseudoaneurysms because the patient remained comatose. On the 78th day after admission, the patient's blood pressure suddenly dropped and he died. Autopsy demonstrated massive bleeding in the abdominal cavity caused by rupture of the superior mesenteric artery pseudoaneurysm. Our patient's clinical course was fulminant, his endocarditis being complicated by cerebral infarctions, intracranial hemorrhages, and multiple pseudoaneurysms within 3 weeks of admission. In retrospect, he may have survived if emergency resection of the mitral valve vegetation had been performed on the first or second day of admission; however, the in-hospital mortality rate after such surgery is high.

Peroral Cholangioscopy-Guided Targeted Biopsy versus Conventional Endoscopic Transpapillary Forceps Biopsy for Biliary Stricture with Suspected Bile Duct Cancer.

BACKGROUND: The recent improvement of peroral cholangioscopy (POCS) maneuverability has enabled the precise, targeted biopsy of bile duct lesions under direct cholangioscopic vision. However, as only small-cup biopsy forceps can pass through the scope channel, the resulting small sample size may limit the pathological diagnosis of biopsy specimens. This study compared the diagnostic abilities of POCS-guided biopsy and conventional fluoroscopy-guided biopsy for bile duct cancer. METHOD: This multicenter, retrospective cohort study included patients exhibiting bile duct stricture with suspected cholangiocarcinoma in whom POCS-guided and fluoroscopy-guided biopsies were performed in the same session. The primary endpoint was the diagnostic sensitivity for malignancy. The size and quality of the biopsy specimens were also compared. RESULT: A total of 59 patients were enrolled. The sensitivity of POCS-guided biopsy was similar to that of fluoroscopy-guided biopsy (54.0% and 64.0%, respectively). However, when the modalities were combined, the sensitivity increased to 80.0%. The mean specimen size from POCS-guided biopsy was significantly smaller than that from fluoroscopy-guided biopsy. The specimen quality using fluoroscopy-guided biopsy was also better than that using POCS-guided biopsy. CONCLUSIONS: The diagnostic sensitivity of POCS-guided biopsy is still insufficient, mainly because of the limited specimen quantity and quality. Therefore, conventional fluoroscopy-guided biopsy would be helpful to improve diagnostic sensitivity.

Periosteal Myxoid Leiomyosarcoma Histologically Mimicking Extraskeletal Myxoid Chondrosarcoma: Report of a Case with Histopathological and Cytopathological Comparison with Extraskeletal Myxoid Chondrosarcoma.

Myxoid leiomyosarcoma (MLS) is a rare variant of leiomyosarcoma, with most cases occurring in the uterus. A case of MLS arising in the periosteal region of the tibia, mimicking extraskeletal myxoid chondrosarcoma (EMC), is described. The evaluation included histological and cytological comparison with EMC. The patient was a 77-year-old man with a palpable mass at the anterior aspect of the right lower leg. After diagnosis by cytopathology and biopsy examination, a wide resection was performed. The resulting cytological smears were composed primarily of spindle-shaped tumor cells in a myxoid and hemorrhagic background. Histologically, the tumor showed abundant myxoid matrix and tumor cells proliferating in a cord-like to reticular pattern, exhibiting a lace-like arrangement that mimicked EMC. Although immunohistochemical findings suggested leiomyosarcoma, a diagnosis of EMC eventually was excluded by the lack of a split signal when assessed for a rearrangement of NR4A3 by chromogenic in situ hybridization. Despite histological similarity to EMC, characteristic cytological findings of EMC such as epithelioid structures with a cord-like pattern and chondroblast-like lacunar structures were not observed in the smears of this patient's MLS. We propose that cytopathological examination of bone and soft tissue lesions is useful as a diagnostic tool in similar cases. A total diagnostic workup, including clinical, radiographic, cytopathological, histopathological, and molecular findings, is needed to ensure an accurate final diagnosis and to reduce diagnostic error.

Cerebellar high-grade glioma with H3 K27M mutation: illustrative case.

BACKGROUND: Diffuse midline glioma H3 K27M-mutant is a distinct subtype of glial tumors newly introduced in the revised fourth edition of the World Health Organization Classification of Tumours of the Central Nervous System. They are aggressive pediatric tumors with a poor prognosis but have also been reported in adults. OBSERVATIONS: The authors present the case of a man in his 60s who presented with rotatory vertigo, taste disorder, and right facial paralysis. Magnetic resonance imaging showed a tumor expanding from the cerebellum to the pons, which was histologically identified as glioblastoma, grade IV, IDH wild type. After tumor resection, the patient received chemoradiotherapy but showed only a partial response. His condition gradually worsened, and he died of progressive disease 12 months postoperation, after which an autopsy was performed. Tumor cells with a high nuclear-to-cytoplasm ratio were immunohistochemically analyzed and found to test positive for H3 K27M and negative for H3 K27me3. Furthermore, mutational analysis revealed HIST1H3B K27M mutation, and the tumor was finally identified as a high-grade glioma H3 K27M-mutant. The tumor invaded widely along the cerebral ventricle and disseminated to the spinal cord. LESSONS: When a glioblastoma shows localization or dissemination patterns different from those of typical glioblastoma, an H3 K27M-mutant glioma should be suspected.

Long-term effects of pleural defect repair using sheet materials in a canine model.

OBJECTIVE: A sheet material is widely used to repair pleural defects due to its excellent pressure resistance. We examined the long-term effects of sheet materials using an animal pleural defect model. METHODS: Beagles were used for this study. The 5-mm circular pleural defects were created at 2 sites on each of the anterior, medial, and posterior lobe and repaired using a 2 cm square sheet material. The frequency of adhesion of those sheets to the thoracic walls and histological changes was examined after 6 months. In this study, three types of sheet materials were examined: polyglycolic acid, nano-polyglycolic acid, and oxidized regenerated cellulose where each sheet was tested with or without coating with fibrin glue, for a total of 6 groups. Each group contained an equal number of defect sites and evaluation of 12 defect sites was conducted. RESULTS: Adhesion was observed in 16 of 72 sites (22%). Presence or absence of adhesion was not affected by the repair method or by the type of sheet material used. However, the use of fibrin glue significantly reduced the occurrence of adhesion (p = 0.023). At the defected sites, the posterior lobe showed significantly less adhesion (p = 0.019). Histologically, the sheet materials caused a thickening of the pleural wall 6-10 times thicker than the normal pleural wall. CONCLUSION: No statistically significant differences regarding the presence or absence of adhesion to the thoracic wall were found among the sheet materials. The use of fibrin glue significantly reduced the adhesion to the thoracic wall.

Pulmonary Apical Opacities on Thin-Section Computed Tomography: Relationship to Primary Spontaneous Pneumothorax in Young Male Patients and Corresponding Histopathologic Findings.

OBJECTIVE: The purpose of this study was to test the hypothesis that apical opacities on computed tomography (CT) are related to occurrence of primary spontaneous pneumothorax (PSP) in young male patients. METHODS: We compared the frequency of apical opacities on thin-section CT between 70 male patients with PSP (PSP group) and 74 male patients without a history of PSP (non-PSP group). We also evaluated histopathologic findings of 39 specimens from 37 surgical cases in the PSP group. RESULTS: Apical opacities were significantly more frequent in the PSP group than in the non-PSP group (right side, P = 0.01; left side, P = 0.005). Histopathologically, subpleural band-like alveolar collapse was seen in 35 specimens (89.7%), which was always accompanied by fibroelastosis and fibroblastic foci. CONCLUSIONS: Apical opacities on CT were significantly associated with PSP in young male patients. These apical opacities histopathologically correspond to fibrotic pleural thickening with subpleural alveolar collapse.

Both cancerous miR-21 and stromal miR-21 in urothelial carcinoma are related to tumour progression.

AIMS: Urothelial carcinoma (UC) is a globally common cancer. miR-21 appears to be important in the tumorigenesis of almost all types of human cancer. However, its precise localization and significance in UC have yet to be clarified. The aim of this study was to examine miR-21 expression in UC and reveal its clinicopathological importance. METHODS AND RESULTS: Tissue arrays of 232 UCs were examined for miR-21 by the use of in-situ hybridization. One hundred and forty-eight transurethral resection specimens and 84 surgically resected specimens were used. After miR-21 positivity had been evaluated separately in tumour cells and the tumour stroma, it was compared with clinicopathological factors and overall survival. miR-21 was strongly expressed in tumour cells in 9% of cases and in the tumour stroma in 6% of cases. Stromal miR-21 positivity was lower than that of cancerous miR-21. Both miR-21s were correlated with each other and related to tumour stage, locus, and histological grade. In addition, strong positivity of miR-21 in cancer and the stroma was significantly related to poorer prognosis among surgically resected cases. In a Cox proportional hazard model, cancerous miR-21 was the only independent prognostic factor except for tumour stage. CONCLUSIONS: miR-21 in both cancer and stromal cells is closely related to tumour progression in UC. miR-21 may be a prognostic marker for cancer progression.

Design and synthesis of environmentally sensitive fluorescent 2-naphthylethynylated 2'-deoxyadenosines: Detection of target DNA via changes in fluorescence intensity and wavelength.

Various C2-naphthylethynylated 2'-deoxyadenosines were synthesized as environmentally sensitive fluorescent (ESF) nucleosides and their photophysical properties were examined. Among the ESF nucleosides synthesized, four exhibited strong solvatochromicity, two of which were incorporated into oligodeoxynucleotides (ODNs). These ODN probes were able to detect target DNA through distinct changes in fluorescence intensity and wavelength and acted as effective reporter probes.

Loss of ARID1A, ARID1B, and ARID2 Expression During Progression of Gastric Cancer.

BACKGROUND/AIM: Gastric cancer is a common cancer worldwide. Chromatin remodeling complexes have emerged as tumor suppressors and include AT-rich interaction domain-containing proteins (ARIDs) 1A, 1B, and 2. We examined their expression and clarified their roles in gastric carcinogenesis. MATERIALS AND METHODS: The expression of ARIDs was studied by immunohistochemistry in 469 gastric carcinoma and 47 adenoma samples and was analyzed according to clinicopathological factors. RESULTS: Low expression rates of ARID1A, 1B, and 2 in gastric carcinoma were 20%, 10%, and 15% respectively. ARIDs are correlated to each other. Low expression of ARID1A was related to advanced tumor and vessel infiltration. Loss of ARID1B and ARID2 was also related to tumor progression, but their relationship was weaker than that of ARID1A. CONCLUSION: ARID1A is the strongest tumor suppressor in gastric carcinogenesis among ARIDs. Their aberration might be caused by shared mechanisms such as mutation and methylation.

Synthesis and photophysical properties of pyrene-labeled 3-deaza-2'-deoxyadenosines comprising a non-π-conjugated linker: fluorescence quenching-based oligodeoxynucleotide probes for thymine identification.

Pyrene-labeled 3-deaza-2'-deoxyadenosine comprising a non-π-conjugated linker (py3z)A (1) was synthesized and its photophysical properties were investigated. Oligodeoxynucleotide (ODN) probes containing (py3z)A (1) exhibited remarkable fluorescence quenching only when the opposite base of the complementary strand was the perfectly matched thymine. Such fluorescence quenching-based ODN probes exhibited excellent on-off switching properties, making them useful tools for single nucleotide polymorphism (SNP) genotyping and for the identification of target genes and structural studies of nucleic acids.

Preserved or enhanced OATP1B3 expression in hepatocellular adenoma subtypes with nuclear accumulation of ß-catenin.

AIM: Recent studies have indicated that hepatocellular adenoma (HCA) is a heterogenous group of benign tumors with various genetic and clinicopathological characteristics. We delineated the clinicopathological characteristics of HCA subtypes and evaluated the expression of transporter protein OATP1B3 in HCA. METHODS: HCA in 34 Japanese patients were investigated immunohistochemically and classified into four subtypes (HNF1α-inactivated type, H-HCA; ß-catenin-activated type, b-HCA; inflammatory type, I-HCA; unclassified type, u-HCA). Immunostaining of OATP1B3 protein in HCA tissue sections was performed to determine the association between OATP1B3 expression and HCA subtypes. RESULTS: HCA was categorized into the following four subtypes and two combined subtypes: 10 H-HCA (29%), 10 I-HCA (29%), seven b-HCA (21%), two b-HCA/H-HCA (6%), two b-HCA/I-HCA (6%) and three u-HCA (9%). The male-to-female ratio was 18:16. Oral contraceptive use was rare but seven HCA were found in patients with glycogen storage disease, congenital absence of the portal vein and idiopathic portal hypertension. OATP1B3 expression was decreased in 24 HCA but was preserved or increased in 10 HCA. All nine HCA with nuclear staining for ß-catenin showed preserved or enhanced OATP1B3 expression, indicating a significant association between nuclear ß-catenin accumulation and OATP1B3 expression in HCA. CONCLUSION: HCA subtype classification was validated in 91% of our Japanese subjects although their clinical backgrounds including rare contraceptive use were different from European subjects. A close association between preserved or enhanced OATP1B3 expression and b-HCA subtype indicated important modalities for clinical decisions in the treatment and follow up of patients with HCA.

Stromal miR-21 is more important than miR-21 of tumour cells for the progression of gastric cancer.

BACKGROUND: Gastric cancer (GC) is a common cancer globally. miRNA-21 (miR-21) appears to be important in the tumourigenesis of almost all types of human cancer. However its precise localization in GC has yet to be clarified. We thus examined miR-21 localization in GC and revealed its clinicopathological importance. METHODS: Tissue arrays of 469 GCs from 454 patients were examined for miR-21 using in situ hybridization (ISH). The positivity was evaluated separately in tumour cells and stromal cells. Conventional sections of 10 GCs were also stained. Eight cases were examined by quantitative RT-PCR (qRT-PCR). RESULTS: miR-21 was highly expressed in tumour cells of 44% of cases and in cancer stroma of 51% of cases. miR-21 of tumour cells was not related to clinicopathological factors, whereas stromal miR-21 was related to many factors including tumour stage, size, and nodal metastasis. Stromal miR-21 gradually increased during tumour progression. ISH of whole sections showed stronger stromal positivity in invasive areas with desmoplastic reaction. Cancer stroma also showed higher miR-21 expression than tumour and non-tumourous tissue in the qRT-PCR study. CONCLUSION: Stromal miR-21 is closely related to tumour progression in GC. Stromal miR-21 of tumours might be a target of treatment.

Predicting protein-protein relationships from literature using latent topics.

This paper investigates applying statistical topic models to extract and predict relationships between biological entities, especially protein mentions. A statistical topic model, Latent Dirichlet Allocation (LDA) is promising; however, it has not been investigated for such a task. In this paper, we apply the state-of-the-art Collapsed Variational Bayesian Inference and Gibbs Sampling inference to estimating the LDA model. We also apply probabilistic Latent Semantic Analysis (pLSA) as a baseline for comparison, and compare them from the viewpoints of log-likelihood, classification accuracy and retrieval effectiveness. We demonstrate through experiments that the Collapsed Variational LDA gives better results than the others, especially in terms of classification accuracy and retrieval effectiveness in the task of the protein-protein relationship prediction.