Accelerated Two-Point Dixon MR Angiography Improves Diagnostic Performance for Cervical Artery Diseases.

BACKGROUND: Nonenhanced MR angiography (MRA) studies are often used to manage acute and chronic large cervical artery disease, but lengthy scan times limit their clinical usefulness. PURPOSE: To develop an accelerated cervical MRA and test its diagnostic performance. STUDY TYPE: Prospective. POPULATION: Patients with cervical artery disease (n = 32, 17 males). FIELD STRENGTH/SEQUENCE: 3.0 T; accelerated two-point Dixon three-dimensional Cartesian spoiled gradient-echo (FLEXA) and conventional time-of-flight MRA (cMRA) sequences. ASSESSMENT: All patients underwent FLEXA (1'28″) and cMRA (6'47″) acquisitions. Quantitative evaluation (artery-to-background signal ratio and a blur metric) and qualitative evaluation using diagnostic performance measured by the sensitivity, specificity, and positive/negative predictive values (PPV/NPV), and vessel and plaque visualization scores from three board-certified radiologists' (with 10, 11, and 12 years of experience) independent readings using maximum intensity projection (MIP) for luminal diseases and axial images for plaque. The reference standards were contrast-enhanced angiography and fat-saturated T1-weighted images, respectively. STATISTICAL TESTS: All measures were compared between FLEXA and cMRA using the paired t, Wilcoxon signed-rank, McNemar's, or chi-squared test, as appropriate. Interreader agreement was assessed using Cohen's κ. P < 0.05 was considered statistically significant. RESULTS: The artery-to-background signal ratio was significantly higher for FLEXA (FLEXA: 7.20 ± 1.63 [fat]; 4.26 ± 0.52 [muscle]; cMRA: 2.57 ± 0.49 [fat]), while image blurring was significantly less (FLEXA: 0.24 ± 0.016; cMRA: 0.30 ± 0.029). In luminal disease detection, sensitivity (FLEXA: 0.97/0.91/0.91; cMRA:0.71/0.69/0.63), specificity (FLEXA: 0.98/0.93/0.98; cMRA:0.93/0.85/0.92), PPV (FLEXA: 0.92/0.86/0.86; cMRA: 0.64/0.5/0.58), and NPV (FLEXA: 0.99/0.98/0.98; cMRA: 0.92/0.91/0.9) were significantly higher for FLEXA. interreader agreement was substantial to almost perfect for FLEXA (κ = 0.82/0.86/0.78) and moderate to substantial for cMRA (κ = 0.67/0.56/0.57). MIP visualization scores were significantly higher for FLEXA, with substantial to almost perfect interreader agreement (FLEXA: κ = 0.83/0.86/0.82; cMRA: κ = 0.89/0.79/0.79). In plaque detection, sensitivity (FLEXA: 0.9/0.9/0.7; cMRA: 0.3/0.6/0.2) and specificity (FLEXA: 1/0.87/1; cMRA: 0.93/0.63/0.97) were significantly higher for FLEXA in two of three readers. The interreader plaque detection agreement was fair to substantial (FLEXA: κ = 0.63/0.69/0.48; cMRA: κ = 0.21/0.45/0.20). Side-by-side plaque and vessel wall visualization was superior for FLEXA in all readers, with moderate to substantial interreader agreement (plaque: κ = 0.73/0.73/0.77; vessel wall: κ = 0.57/0.40/0.39). DATA CONCLUSION: FLEXA enhanced visualization of the cervical arterial system and improved diagnostic performance for luminal abnormalities and plaques in patients with cervical artery diseases. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 2.

IDH-Mutant Astrocytoma With Chromosome 19q13 Deletion Manifesting as an Oligodendroglioma-Like Morphology.

Partial deletions in chromosomes 1p and 19q are found in a subset of astrocytic tumors; however, it remains unclear how these alterations affect their histological features and prognosis. Herein, we present 3 cases of isocitrate dehydrogenase (IDH)-mutant astrocytoma with chromosome 19q13 deletion. In the first case, the primary tumor harbored an IDH1 mutation with chromosome 1p/19q partial deletions, which covered 19q13 and exhibited a durable initial response to radiotherapy and temozolomide (TMZ) treatment. However, the tumor lost the chromosome 1p/19q partial deletions at recurrence and became resistant to TMZ. Histologically, an oligodendroglioma-like feature was found in the primary tumor but not in the recurrent tumor. Capicua transcriptional repressor (CIC), located on 19q13, was less expressed in the primary tumor but was highly expressed in the recurrent tumor. Similar histological findings were observed in 2 other astrocytic tumors with IDH1 or IDH2 mutations. These tumors also had chromosome 19q13 deletion, including the CIC gene, weakly expressed CIC, and oligodendroglioma-like morphology. These tumors recurred at 6 and 32 months, respectively. These findings suggest that IDH-mutant astrocytoma with chromosome 19q13 partial deletion, including the CIC gene, may induce an oligodendroglioma-like phenotype, but the clinical prognosis may not be similar to that of genetically defined oligodendroglioma.

Recent Advances in Liquid Biopsy Based on Circulating Tumor DNA.

Many types of cells secrete DNA, RNA, and proteins through microvesicles, such as exosomes and apoptotic bodies, for the purpose of extracellular communication [...].

Involvement of Nectin-Afadin in the Adherens Junctions of the Corneal Endothelium.

PURPOSE: The cell-cell adhesion molecules, cadherins and nectins, are involved in the formation of adherens junctions. However, involvement of nectins in the corneal endothelium has not yet been established. This study investigated the involvement of nectins in adherens junctions of the corneal endothelium. METHODS: Nectin and cadherin expression in the corneal endothelium was evaluated by real-time polymerase chain reaction. Colocalization and direct binding of nectin-1 and N-cadherin to anchoring proteins (afadin and ß-catenin, respectively) were determined by immunostaining and immunoprecipitation. The effect of afadin and N-cadherin knockdown on apical junctions was evaluated by immunostaining. RESULTS: Real-time polymerase chain reaction confirmed nectin-1, nectin-2, nectin-3, nectin-4, and afadin expression in the corneal endothelium. Immunofluorescence staining showed colocalization of nectin and afadin at the basal side of the tight junction (where adherens junctions typically locate) and immunoprecipitation confirmed direct binding of nectin to afadin. N-cadherin, P-cadherin, VE-cadherin, and OB-cadherin messenger RNAs were expressed in the corneal endothelium. N-cadherin and ß-catenin colocalized at the cell-cell border, where they directly bound and formed a cell-cell adhesion complex. N-cadherin knockdown disrupted the normal expression pattern of zonula occludens protein-1 and afadin, but afadin knockdown had no effect on the expression pattern of zonula occludens protein-1 and N-cadherin. CONCLUSIONS: We believe this to be the first report of conservation of the nectin-afadin system in the corneal endothelium and its involvement in the formation of adherens junctions. N-cadherin, as a member of the cadherin family, is also essential for the formation and maintenance of cell-cell adhesion mediated by nectins and tight junctions in the corneal endothelium.

Activation of the Rho/Rho Kinase Signaling Pathway Is Involved in Cell Death of Corneal Endothelium.

Purpose: Rho kinase (ROCK) pathways control fundamental cell functions, making ROCK an important therapeutic target in several pathophysiologic conditions. The purpose of this study was to investigate whether inhibition of ROCK can suppress apoptosis of the corneal endothelium and to determine the role of ROCK signaling in regulating apoptosis. Methods: The effects of inhibitors of ROCK or myosin light chain (MLC) were evaluated in cultured monkey corneal endothelial cells (MCECs) irradiated with ultraviolet (UV) (100 J/m2) to induce apoptosis. Annexin V and TUNEL staining and Western blot for apoptosis-related proteins and focal adhesion complexes were then performed. RhoA activation was further evaluated by pull-down assays. ROCK inhibitor and caspase inhibitor effects on apoptosis were also evaluated in MCECs treated with ethylene glycol tetraacetic acid (EGTA) to induce MLC phosphorylation. Results: ROCK or MLC inhibition suppressed the caspase-3 cleavage and Annexin V and TUNEL expression typically seen during UV-mediated apoptosis of MCECs. The apoptotic stimulus activated RhoA and then induced phosphorylation of MLC via ROCK activation. EGTA-mediated phosphorylation of MLC was sufficient to induce the loss of cell contact with the substrate and subsequent apoptosis. Western blot showed that ROCK inhibition upregulated the expression of the focal adhesion complex in adhered cells, following UV stress. Conclusions: Apoptotic stimuli activated Rho/ROCK/MLC phosphorylation in the corneal endothelium, and subsequent actomyosin contraction induced apoptosis by loss of cell adhesion. ROCK inhibition suppressed MLC phosphorylation and subsequent cell death, and it counteracted the loss of cell adhesion by activating the focal adhesion complex.

Rho kinase inhibitor enables cell-based therapy for corneal endothelial dysfunction.

The corneal endothelium maintains corneal transparency; consequently, its dysfunction causes severe vision loss. Tissue engineering-based therapy, as an alternative to conventional donor corneal transplantation, is anticipated to provide a less invasive and more effective therapeutic modality. We conducted a preclinical study for cell-based therapy in a primate model and demonstrated regeneration of the corneal endothelium following injection of cultured monkey corneal endothelial cells (MCECs) or human CECs (HCECs), in combination with a Rho kinase (ROCK) inhibitor, Y-27632, into the anterior chamber. We also evaluated the safety and efficacy of Good Manufacturing Practice (GMP)-grade HCECs, similar to those planned for use as transplant material for human patients in a clinical trial, and we showed that the corneal endothelium was regenerated without adverse effect. We also showed that CEC engraftment is impaired by limited substrate adhesion, which is due to actomyosin contraction induced by dissociation-induced activation of ROCK/MLC signaling. Inclusion of a ROCK inhibitor improves efficiency of engraftment of CECs and enables cell-based therapy for treating corneal endothelial dysfunction as a clinically relevant therapy.

[Study on cine view of relative enhancement ratio map in O2-enhanced MRI].

Magnetic resonance imaging (MRI) enables the evaluation of organ structure and function. Oxygen-enhanced MRI (O2-enhanced MRI) is a method for evaluating the pulmonary ventilation function using oxygen as a contrast agent. We created the Cine View of Relative Enhancement Ratio Map (Cine RER map) in O2-enhanced MRI to easily observe the contrast effect for clinical use. Relative enhancement ratio (RER) was determined as the pixel values of the Cine RER map. Moreover, six healthy volunteers underwent O2-enhanced MRI to determine the appropriate scale width of the Cine RER map. We calculated each RER and set 0 to 1.27 as the scale width of the Cine RER map based on the results. The Cine RER map made it possible to observe the contrast effect over time and thus is a convenient tool for evaluating the pulmonary ventilation function in O2-enhanced MRI.

Chest wall resection and reconstruction using titanium micromesh covered with Marlex mesh for metastatic follicular thyroid carcinoma: a case report.

INTRODUCTION: The distant metastases from differentiated thyroid carcinomas are often untreatable. In particular, bone metastasis is significantly related to poor prognosis since radioactive iodine therapy is generally less effective. Therefore, surgical resection is considered one of the treatments for patients with bone metastases. We report chest wall resection and reconstruction using titanium micromesh covered with polypropylene mesh (Marlex mesh) for metastatic rib bones as a result of follicular thyroid carcinoma. CASE PRESENTATION: A 51-year-old man was referred to our institution with a painful chest wall tumor. He presented with a 15 x 10 cm bony swelling on the left chest wall and multiple small lung nodules from follicular thyroid carcinoma. Completion total thyroidectomy, chest wall resection and reconstruction using titanium micromesh covered with Marlex mesh were performed. There were no critical complications associated with surgical treatments and tumor pain disappeared during the postoperative period. Then, he received radioactive iodine therapy and the uptake of radioactive iodine was well observed in bilateral lung fields. CONCLUSION: Reconstruction using titanium micromesh covered with Marlex mesh is possible for repairing the wide chest wall resection required for thyroid carcinoma metastasis. This technique would help to enhance treatment efficacy in the combination therapy of radioactive iodine and surgery in patients with large thyroid carcinoma metastasis in the chest wall.

[Long survival of a case of unresected duodenal cancer treated by S-1 before and after duodenojejunostomy].

A 52-year-old woman visited our hospital with epigastralgia. Detailed examination revealed a duodenal cancer of the ascending limbs. Since she refused the resection, the administration of S-1 alone was commenced. After one course of this treatment, oral intake became impossible. Duodenography and endoscopy showed duodenal obstruction, and she underwent surgery. The tumor proved to be unresectable due to direct invasion of the inferior vena cava. Duodenojejunostomy was performed. After surgery, she was treated by S-1 and survived 2 years and 11 months, which resulted in 3 years and 2 months' long survival from her first visit. The intervals of the intake and home stay, after the operation, were 2 years and 8 months and 2 years and 5 months, respectively. The combination of S-1 administration and bypass operation provides a useful alternative for the treatment of unresectable duodenal cancer with stenosis.

[A case of recurrent gastrointestinal stromal tumor of the stomach with complete response to imatinib mesilate].

We report a patient who long had a complete response by chemotherapy with imatinib mesilate(IM)for locally recurrent gastrointestinal stromal tumor(GIST)of the stomach. On July 2000, a 58-year-old woman was pointed out to have anemia in the course of surveillance for malignant melanoma of skin. Endoscopic examination revealed continuous bleeding from a submucosal tumor with ulceration on the posterior wall of the stomach. After endoscopic homeostasis failed, emergency laparotomy was performed and a biopsy was also done. The diagnosis made was GIST from immunohistological findings of positive c-kit, positive CD34, negative HMB45, and negative S100. After diagnosis, total gastrectomy, distal pancreatectomy, and splenectomy were performed. On September 2003, a local recurrence was recognized, and then chemotherapy by 400 mg IM daily was started. After beginning with a dose of IM 400 mg daily, the reduction of the tumor was monitored. The IM dose then had to be reduced to 300 mg daily. Because of the adverse side effects of IM, systemic edema and body weight increased. After reduction of IM, the adverse reactions resolved promptly, and a complete response of the primary tumor has been maintained for 4 years 3 months.

[Quantitative assessment of wall motion in gated SPECT using the centerline method].

Evaluation of myocardial wall motion is an important assessment of heart function. Specific analysis programs in nuclear medicine, such as QGS (quantitative gated SPECT) analysis and p-FAST (perfusion-function assessment for myocardial SPECT), have been used to assess wall motion, but they have not evaluated it through a comparison of normal data. The centerline method, using left ventriculograms (LVG), evaluates regional wall motion quantitatively through a comparison of normal data and patient data, and abnormality of wall motion is expressed in units of standard deviation (SD) s from the mean motion in a reference population. However, angiography is an invasive inspection, wall motion analysis is usually in one direction, and the conventional centerline method is not a three-dimensional analysis. The purpose of this study was to apply the centerline method to nuclear medicine and examine the wall motion of subjects through a comparison of normal wall motion non-invasively and in a three-dimensional way. We arranged the analysis program using C language and inspected it using a dynamic cardiac phantom and computed tomography (CT) scanner. We made a polar map that indicated the mean and SD of normal wall motion. Our proposed method was able to assess the wall motion of subjects quantitatively through a comparison of normal wall motion in nuclear medicine.

Video-assisted thoracoscopic surgery for pulmonary arteriovenous malformations: report of five cases.

We experienced five cases of pulmonary arteriovenous malformations (PAVMs) that were successfully treated by video-assisted thoracoscopic surgery. Four malformations were treated by local wedge resection and one was treated by segmentectomy. Criteria for patient selection for surgery were peripheral and solitary lesions, with feeding arteries larger than 3 mm. Postoperative hospital stays were 1-7 days (median, 2 days). All patients showed unchanged or increased values of PaO(2) in arterial blood after operation. No major postoperative complication occurred in any patient, but a persistent air leak for 5 days occurred in the one patient who was treated by segmentectomy. No growth of accessory vessels or untreated malformations were seen in any patient throughout the follow-up period of 14-54 months. Thoracoscopic surgical resection for well-selected patients provides a high certainty of eliminating fistulae and was associated with lower morbidity, lower mortality, and shorter hospital stays.