Prospective Randomized Controlled Trial Comparing Anesthetic Management With Remimazolam Besylate and Flumazenil Versus Propofol During Awake Craniotomy Following an Asleep-awake-asleep Method.

BACKGROUND: Awake craniotomy is performed to resect brain tumors in eloquent brain areas to maximize tumor reduction and minimize neurological damage. Evidence suggests that intraoperative anesthetic management of awake craniotomy with remimazolam is safe. We compared the time to arousal and efficacy of anesthetic management with remimazolam and propofol during awake craniotomy. METHODS: In a single-institution randomized, prospective study, patients who underwent elective awake craniotomy were randomized to receive remimazolam and reversal with flumazenil (group R) or propofol (group P). The primary end point was time to awaken. Secondary end points were time to loss of consciousness during induction of anesthesia, the frequency of intraoperative complications (pain, hypertension, seizures, nausea, vomiting, and delayed arousal), and postoperative nausea and vomiting. Intraoperative task performance was assessed using a numerical rating scale (NRS) score. RESULTS: Fifty-eight patients were recruited, of which 52 (26 in each group) were available for the efficacy analysis. Patients in group R had faster mean (±SD) arousal times than those in the P group (890.8±239.8 vs. 1075.4±317.5 s; P=0.013)and higher and more reliable intraoperative task performance (NRS score 8.81±1.50 vs. 7.69±2.36; P=0.043). There were no significant intraoperative complications. CONCLUSIONS: Compared with propofol, remimazolam was associated with more rapid loss of consciousness and, after administration of flumazenil, with faster arousal times and improved intraoperative task performance.

Diagnostic yield of flexible bronchoscopy for immunocompromised patients with lung infiltrates: A single-center, retrospective study.

BACKGROUND: Pulmonary complications are associated with mortality in immunocompromised patients. The usefulness of bronchoscopy has been reported. However, clinical factors and procedures that influence diagnostic yield are still not established. MATERIALS AND METHODS: We retrospectively analyzed 115 bronchoscopies performed on 108 immunocompromised patients, defined as those who take corticosteroids and/or immunosuppressants. We evaluated clinical factors, sampling procedures, final diagnosis, and severe complications of bronchoscopy. RESULTS: The clinical diagnosis was obtained in 51 patients (44%). Of those, 33 cases were diagnosed as infectious diseases and 18 as non-infectious diseases. Nine out of 115 cases (7.8%) initiated new immunosuppressive treatment for an underlying disorder based on the negative microbiological results obtained with bronchoscopy. Collagen vascular disease was the most common underlying disorders (62 patients, 54%). Bronchoscopy was useful regardless of whether the patient was immunosuppressed to treat collagen vascular disease (P = 0.47). Performing transbronchial biopsy correlated with better diagnostic yield of bronchoscopy (54.7% vs 35.5%, P = 0.049). Other clinical factors, such as radiological findings, respiratory failure or antibiotic use at the time of bronchoscopy did not significantly influence diagnostic yield. Respiratory failure requiring intubation after bronchoscopy occurred only in one case (0.9%). CONCLUSIONS: Our study implied the transbronchial biopsy may be a useful procedure for reaching a diagnosis in immunocompromised patients with pulmonary infiltrates. In addition, our data suggest the usefulness of bronchoscopy for immunocompromised patients due to the treatment of collagen vascular disease as well as other underlying disorders.

NECTIN2 is a prognostic biomarker and potential therapeutic target in lung adenocarcinoma.

INTRODUCTION: NECTINs are transmembrane proteins mediating cell-to-cell adhesion. NECTINs interact with integrins or other membrane receptors to trigger multiple cellular functions. Aberrant NECTIN expression is associated with cancer progression and poor outcomes. While NECTIN2 is overexpressed in various cancer types, its role in lung cancer is not well understood. MATERIAL AND METHODS: We investigated the function of NECTIN2 in lung adenocarcinoma (LUAD) using the Cancer Genome Atlas (TCGA) dataset and clinical samples of 105 LUAD patients who had undergone surgical resection. Cell proliferation, apoptosis, migration and invasion were investigated using human lung adenocarcinoma cell lines. RESULTS: We found that high NECTIN2 expression correlated with reduced overall survival in LUAD in TCGA database. In clinical samples, high NECTIN2 expression was associated with lower recurrence-free survival in all patients (P < 0.001) and in stage I patients (P = 0.001). Functional analyses demonstrated that NECTIN2 knockout promoted cell apoptosis and diminished cell proliferation and migration capacity. NECTIN2 overexpression did not significantly affect cellular functions. DISCUSSION: Our results suggest that NECTIN2 plays a significant role in cell apoptosis and cancer cell migration, leading to increased postoperative recurrence. Furthermore, NECTIN2 serves as a prognostic indicator and a potential therapeutic target in LUAD. CONCLUSIONS: High NECTIN2 expression in LUAD was found to be associated with postoperative recurrence, and was observed to play an important role in cell apoptosis and migration.

Improvement of limit of detection in primer extension-based multiplexed mutation assay using capillary electrophoresis.

One of the challenges in liquid biopsy for early cancer detection is ascribed to the fact that mutation DNA often represents an extremely small ratio of less than 1% compared to wild-type genes in blood. However, in conventional fragment analysis with capillary electrophoresis (CE), the detectable allele frequency could be about 5%. In this work, we developed an original reagent-based fragment analysis with single base extension (SBE) reactions for cancer-associated mutation assay using a commercially available CE device, and investigated on a possibility of improvement of limit of detection (LOD) for genetic mutation. First, after adjustment of reagent conditions for the SBE reactions, the linear relationship between gene template concentration and fluorescence intensity was obtained from 1 to 100 fmol of target genes. Next, from the results of an experiment to detect mutation EGFR L858R at abundance ratios of mutant type to wild type (100-fmol template) of 0, 1, 5, and 10%, it was shown that the target gene can be detected with LOD of 0.33%. This high sensitivity was realized in part by separating fluorescently labeled substrates into an individual tube for an each-colored SBE reaction. Moreover, mutations EGFR L858R and KRAS G12V were simultaneously detected at sensitivities equivalent to LODs of 0.57 and 0.47%, respectively. These results indicate that < 1% of mutations in multiplex gene mutations can be simultaneously detected, and that possibility suggests that the developed method can be used in clinical practice for detecting cancers.

Cancer of unknown primary histologically, genetically and spatially diagnosed as left ovary­derived cancer: A case report.

Cancer of unknown primary (CUP) is a heterogeneous syndrome of metastatic cancer in which the primary site cannot be determined even after a standard and comprehensive search. The present report describes a case in which the spatial distribution of the lymph node metastases contributed to the identification of the primary site. While the standard workup did not identify the primary tumor, genomic profiling analysis was useful in therapeutic management. A 68-year-old woman presented with a cancerous pleural effusion (adenocarcinoma). The primary site could not be identified, and the pleural effusion resolved spontaneously. After 11 months, the patient had elevated Krebs von den Lungen-6 and cancer antigen 125 levels, and multiple enlarged lymph nodes. Pathological diagnosis based on a biopsy sample of the para-aortic lymph nodes indicated that the tumor was a high-grade serous carcinoma of possible gynecological organ origin. The patient underwent surgery, including hysterectomy, bisalpingo-oophorectomy and lymph node dissection. Although there were no primary sites in the gynecological organs, marked lymphovascular invasion was found around the left ovary, suggesting a left ovary-derived tumor. Genetic testing revealed a high loss of heterozygosity score and high tumor mutational burden (TMB). The patient received paclitaxel and carboplatin therapy followed by a poly ADP-ribose polymerase inhibitor as regimens for ovarian cancer and achieved complete remission. The unique course of the disappearance of the effusion and the absence of tumor in the adnexa might be associated with the high immunogenicity of the tumor characterized by the high TMB. This case may provide insights into the pathogenesis of CUP.

Validity of diagnoses of respiratory diseases recorded in a Japanese administrative database.

BACKGROUND: Validating the information recorded in administrative databases is essential. However, no study has comprehensively validated the accuracy of Japanese Diagnosis Procedure Combination (DPC) data on various respiratory diseases. Therefore, this study aimed to evaluate the validity of diagnoses of respiratory diseases in the DPC database. METHODS: We conducted chart reviews of 400 patients hospitalized in the departments of respiratory medicine in two acute-care hospitals in Tokyo, between April 1, 2019 and March 31, 2021, and used them as reference standards. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of DPC data on 25 respiratory diseases were determined. RESULTS: Sensitivity ranged from 22.2% (aspiration pneumonia) to 100% (chronic eosinophilic pneumonia and malignant pleural mesothelioma) and was <50% for eight diseases, while specificity was >90% for all diseases. PPV ranged from 40.0% (aspiration pneumonia) to 100% (coronavirus disease 2019, bronchiectasis, chronic eosinophilic pneumonia, pulmonary hypertension, squamous cell carcinoma, small cell carcinoma, lung cancer of other histological types, and malignant pleural mesothelioma) and was >80% for 16 diseases. Except for chronic obstructive pulmonary disease (82.9%) and interstitial pneumonia (other than idiopathic pulmonary fibrosis) (85.4%), NPV was >90% for all diseases. These validity indices were similar in both hospitals. CONCLUSIONS: The validity of diagnoses of respiratory diseases in the DPC database was high in general, thereby providing an important basis for future studies.

Integrin alpha 2 is associated with tumor progression and postoperative recurrence in non-small cell lung cancer.

BACKGROUND: Integrins are transmembrane proteins that mediate cell adhesion to extracellular matrix. Whereas expression of integrin alpha 2 is associated with motility, invasiveness and cellular differentiation in various tumors, the role of integrin alpha 2 in lung cancer has not been studied in detail. The aim of this study was to determine whether and how aberrant integrin alpha 2 expression in non-small cell lung cancer leads to different outcomes. METHODS: We measured expression of integrin alpha 2 by quantitative polymerase chain reaction in 100 samples collected from non-small cell lung cancer patients who had undergone surgical resection. We assigned patients to high and low expression groups and analyzed survival. Cellular morphology, adhesion, proliferation, migration and invasion were examined in human lung cancer cell lines. RESULTS: Among 100 cases, 41 were female, with a median age of 71 years. High expression of integrin alpha 2 in non-small cell lung cancer was associated with lower recurrence-free survival (P = 0.004). Overexpression of integrin alpha 2 in cell lines had no effect on cell proliferation or invasion but resulted in increased cell size (1416 µm2 versus 470 µm2 in H522 cells, P < 0.001; 1822 µm2 versus 1029 µm2 in H661 cells, P = 0.02), adhesion (P < 0.001 in H522 and H661 cells) and migration (gap area filled was 71% versus 36% in H522 cells, P < 0.001; 57% versus 26% in H661 cells, P = 0.001). These changes were suppressed by E7820, an inhibitor of integrin alpha 2. CONCLUSIONS: Integrin alpha 2 may play a significant role in lung cancer adhesion and migration, and may lead to a higher risk of recurrence.

Composite Clonal Analysis Reveals Transition of NSCLC Subtypes Through Accumulation of Gene Mutations: A Case Report.

We analyzed an EGFR-mutated lung cancer with a pathologic diagnosis of combined large cell neuroendocrine carcinoma with mixed adenocarcinoma subtypes. Targeted next-generation sequencing of each component suggested that mutations in RB1, TP53, and SMAD4 and apparent loss of heterozygosity of TP53 and SMAD4 accompanied the transition of different adenocarcinoma subtypes. Additional gene mutations including PTEN, MST1R, and PIK3CA were noted during transdifferentiation from acinar adenocarcinoma to large cell neuroendocrine carcinoma. Combined DNA and RNA analysis using Todai OncoPanel revealed that transdifferentiation to different pathologic subtypes occurred in a single tumor through the accumulation of gene mutations.

Factors Influencing Long-Term Blood Flow in Extracranial-to-Intracranial Bypass for Symptomatic Internal Carotid Artery Occlusive Disease: A Quantitative Study.

BACKGROUND: Maintaining the patency of extracranial-to-intracranial (EC-IC) bypass is critical for long-term stroke prevention. However, reports on the factors influencing long-term bypass patency and quantitative assessments of bypass patency are limited. OBJECTIVE: To quantitatively evaluate blood flow in EC-IC bypass using four-dimensional (4D) flow magnetic resonance imaging (MRI) and investigate factors influencing the long-term patency of EC-IC bypass. METHODS: Thirty-six adult Japanese patients who underwent EC-IC bypass for symptomatic internal carotid or middle cerebral artery occlusive disease were included. We examined the relationships between decreased superficial temporal artery (STA) blood flow volume and perioperative complications, long-term ischemic complications, patient background, and postoperative antithrombotic medications in patients for whom STA flow could be quantitatively assessed for at least 5 months using 4D flow MRI. RESULTS: The mean follow-up time was 54.7 ± 6.1 months. One patient presented with a stroke during the acute postoperative period that affected postoperative outcomes. No recurrent strokes were recorded during long-term follow-up. Two patients died of malignant disease. Seven cases of reduced flow occurred in the STA, which were correlated with single bypass (P = .0294) and nonuse of cilostazol (P = .0294). STA occlusion was observed in 1 patient during the follow-up period. Hypertension, age, smoking, dyslipidemia, and diabetes mellitus were not correlated with reduced blood flow in the STA. CONCLUSION: Double anastomoses and cilostazol resulted in long-term STA blood flow preservation. No recurrence of cerebral infarction was noted in either STA hypoperfusion or occlusion cases.

Utility of 4D Flow MRI in Thoracic Aortic Diseases: A Literature Review of Clinical Applications and Current Evidence.

Despite the recent technical developments, surgery on the thoracic aorta remains challenging and is associated with significant mortality and morbidity. Decisions about when and if to operate are based on a balance between surgical risk and the hazard of aortic rupture. These decisions are sometimes difficult in elective cases of thoracic aortic diseases, including aneurysms and dissections. Abnormal wall stress derived from flow alterations influences disease progression. Therefore, a better understanding of the complex hemodynamic environment inside the aortic lumen will facilitate patient-specific risk assessments of complications, which enable clinicians to provide timely prophylactic interventions. Time-resolved 3D phase-contrast (4D flow) MRI has many advantages for the in vivo assessment of flow dynamics. Recent developments in 4D flow imaging techniques has led to significant advances in our understanding of physiological flow dynamics in healthy subjects and patients with thoracic aortic diseases. In this clinically focused review of thoracic aortic diseases, we demonstrate the clinical advances acquired with 4D flow MRI from published studies. We provide a systematic overview of key evidences and considerations regarding normal thoracic aortas, thoracic aortic aneurysms, aortic dissections, and thoracic aortas with prosthetic graft replacement.

Dual-VENC 4D Flow MRI Can Detect Abnormal Blood Flow in the Left Atrium That Potentially Causes Thrombosis Formation after Left Upper Lobectomy.

PURPOSE: The purpose of the current study was to clarify the blood flow pattern in the left atrium (LA), potentially causing the formation of thrombosis after left upper lobectomy (LUL). The blood flow in the LA was evaluated and compared between LUL patients with and without thrombosis. For the evaluation, we applied highly accelerated 4D flow MRI with dual-velocity encoding (VENC) scheme, which was expected to be able to capture slow flow components in the LA accurately. METHODS: Eight volunteers and 18 patients subjected to LUL underwent dual-VENC 4D Flow MRI. Eight patients had a history of thrombosis. We measured the blood flow velocity and stasis ratio (proportion in the volume that did not exceed 10 cm/s in any cardiac phase) in the LA and left superior pulmonary vein (LSPV) stump. For visual assessment, the presence of each collision of the blood flow from pulmonary veins and vortex flow in the LA were evaluated. Each acquired value was compared between healthy participants and LUL patients, and in LUL patients with and without thrombosis. RESULTS: In LUL patients, blood flow velocity near the inflow part of the left superior pulmonary vein (Lt Upp) and mean velocity in the LA were lower, and stasis ratio in the LA was higher compared with healthy volunteers (Lt Upp 9.10 ± 3.09 vs.13.23 ± 14.19 cm/s, mean velocity in the LA 9.81 ± 2.49 vs. 11.40 ± 1.15 cm/s, and stasis ratio 25.28 ± 18.64 vs. 4.71 ± 3.03%, P = 0.008, 0.037, and < 0.001). There was no significant difference in any quantification values between LUL patients with and without thrombosis. For visual assessment, the thrombus formation was associated with no collision pattern (62.5% vs. 10%, P = 0.019) and not with vortex flow pattern (50% vs. 30%, P = 0.751). CONCLUSION: The net blood flow velocity was not associated with the thrombus formation. In contrast, a specific blood flow pattern, the absence of blood flow collision from pulmonary veins, correlates to the thrombus formation in the LA.

Multiple cerebral infarctions in ROS1-rearranged lung adenocarcinoma.

Rearrangements of specific tyrosine kinases are associated with an elevated risk of venous thrombosis in lung adenocarcinoma, although their effects on arterial thrombosis have not been fully elucidated. Here, we report two cases of ROS proto-oncogene 1 (ROS1)-rearranged lung adenocarcinoma with cerebral infarction during the peri-diagnostic period. Two cases took contrasting clinical courses: one patient could not receive targeted therapy because of a significant decline in performance status, whereas in the other patient, the performance status was maintained and targeted therapy drastically reduced the tumour size. Our cases suggest close monitoring could be considered in the selected cohort.

Cross-Comparison of 4-Dimensional Flow Magnetic Resonance Imaging and Intraoperative Middle Cerebral Artery Pressure Measurements Before and After Superficial Temporal Artery-Middle Cerebral Artery Bypass Surgery.

BACKGROUND: The hemodynamic changes after superficial temporal artery (STA) to middle cerebral artery (MCA) bypass surgery are unclear. OBJECTIVE: To clarify the hemodynamics by comparing flow parameters obtained by 4-dimensional (4D) flow magnetic resonance imaging (MRI) and intraoperative MCA pressure measurement. METHODS: We recruited 23 patients who underwent STA-MCA bypass surgery for internal carotid artery (ICA) or MCA stenosis. We monitored intraoperative MCA, STA, and radial artery (RA) pressure. All patients underwent 4D flow MRI preoperatively and 3 wk after surgery to quantify the blood flow volume (BFV) of the ipsilateral ICA (BFViICA), contralateral ICA (BFVcICA), basilar artery (BFVBA), ipsilateral STA (BFViSTA), and contralateral STA (BFVcSTA). The sum of intracranial BFV was defined as BFVtotal. We compared BFV parameters and intraoperative pressure. RESULTS: BFViSTA significantly increased after surgery (P < .001). BFViICA and BFVBA significantly decreased after surgery (BFViICAP = .005; BFVBAP = .02). No significant difference was observed between BFVcICA before and after surgery. As a result, BFVtotal postoperatively increased by 6.8%; however, no significant difference was observed. Flow direction at M1 changed from antegrade to unclear after surgery in 5 patients. Intraoperative MCA pressure and MCA/RA pressure ratio significantly increased after surgery (P < .001). We found a stronger positive correlation between MCA pressure increase ratio and BFVtotal increase ratio in patients with lower pre-MCA pressure (r = 0.907, P < .001). CONCLUSION: The visual and quantitative assessment of 4D flow MRI revealed that intracranial blood flow changes complementarily after STA-MCA bypass surgery. 4D flow MRI may detect the improvement of cerebral perfusion pressure.

Preoperative use of pirfenidone and reduced risk of postoperative severe respiratory complications in patients with idiopathic pulmonary fibrosis: Propensity score-matched analysis using a nationwide database in Japan.

BACKGROUND AND OBJECTIVE: Patients with idiopathic pulmonary fibrosis (IPF) often develop postoperative severe respiratory complications such as acute exacerbation. Pirfenidone, an oral anti-fibrotic drug, may reduce the incidence of such complications. However, the preventive effect of pirfenidone on postoperative severe respiratory complications remains unclear. METHODS: We identified patients with IPF who underwent surgery with general anaesthesia from July 2010 to March 2018 using the Diagnosis Procedure Combination database. We compared the occurrence of postoperative severe respiratory complications (receiving mechanical ventilation under endotracheal intubation and/or intravenous infusion of a high-dose corticosteroid and in-hospital death within 30 days after surgery) between patients who did and did not receive preoperative treatment with pirfenidone. Pearson's chi-square test and logistic regression analysis fitted with a generalized estimating equation were conducted in 1:4 propensity score-matched patients. RESULTS: Among 631 patients identified, 19% were treated with pirfenidone before surgery. The 30-day mortality rate was 3.1% and 1.7% in the control patients (n = 510) and pirfenidone-treated patients (n = 121), respectively. In the propensity score-matched population, preoperative treatment with pirfenidone was significantly associated with a lower proportion of postoperative severe respiratory complications (OR: 0.24; 95% CI: 0.07-0.76; p = 0.015). CONCLUSION: In this Japanese nationwide cohort, preoperative treatment with pirfenidone was significantly associated with a lower risk of postoperative severe respiratory complications in patients with IPF. Preoperative pirfenidone may thus be useful in preventing postoperative severe respiratory complications in patients with IPF who are planning to undergo surgery with general anaesthesia.

Long-Term Outcomes of Bronchial Artery Embolization for Patients with Non-Mycobacterial Non-Fungal Infection Bronchiectasis.

BACKGROUND: There is no study on the predictive factors of recurrent haemoptysis after bronchial artery embolization (BAE) with the long-term outcomes in patients with bronchiectasis (BE). OBJECTIVES: To evaluate the long-term outcomes of BAE in BE patients without accompanying refractory active infection of mycobacteriosis and aspergillosis with analysis for the predictive factors of recurrent haemoptysis. METHODS: Data of 106 patients with BE who underwent BAE using coils between January 2011 and December 2018 were retrospectively reviewed. The cumulative haemoptysis control rate was estimated using Kaplan-Meier methods with log-rank tests to analyze differences in recurrence-free rate between groups based on technical success and failure, bacterial colonization status, number of BE lesions, and vessels embolized to bronchial arteries (BAs) or BAs + non-bronchial systemic arteries (NBSAs). RESULTS: Bacterial colonization was detected in approximately 60% of patients. Computed tomography showed bronchiectatic lesions with 2.9 ± 1.4 lobes. In the first series of BAE, embolization was performed in the BAs alone and BAs + NBSAs in 65.1 and 34.9% of patients, respectively, with 2.4 ± 1.4 embolized vessels in total. The median follow-up period was 1,000 (7-2,790) days. The cumulative haemoptysis control rates were 91.3, 84.2, 81.5, and 78.9% at 1, 2, 3, and 5 years, respectively. The haemoptysis control rates were higher in the technical success group than in the technical failure group (p = 0.029). CONCLUSIONS: High haemoptysis control rates for long-term periods were obtained by embolization for all visualized abnormal arteries, regardless of the colonization status, number of bronchiectatic lobes, and target vessels, irrespective of NBSAs.

NRXN1 as a novel potential target of antibody-drug conjugates for small cell lung cancer.

Small cell lung cancer (SCLC) is a high-grade malignancy, and treatment strategies have not changed for decades. In this study, we searched for novel targets for antibody-drug conjugate (ADC) therapy for SCLC. We identified transmembrane proteins overexpressed specifically in SCLC with little or no expression in normal tissues and decided to focus on the cell adhesion molecule neurexin-1 (NRXN1). The cell surface overexpression of NRXN1 was confirmed using flow cytometry in SCLC cell lines (SHP77 and NCI-H526). The combination of a primary anti-NRXN1 monoclonal antibody and a secondary ADC exhibited anti-tumor activity in SCLC cell lines. Moreover, the knockout of NRXN1 in SHP77 cells resulted in a loss of the anti-tumor activity of NRXN1-mediated ADC therapy. Thus, NRXN1 could be a novel target for ADC therapy for the treatment of SCLC that is worth further research.

Multiparametric flow analysis using four-dimensional flow magnetic resonance imaging can detect cerebral hemodynamic impairment in patients with internal carotid artery stenosis.

PURPOSE: MRI-based risk stratification should be established to identify patients with internal carotid artery stenosis (ICS) who require further PET or SPECT evaluation. This study assessed whether multiparametric flow analysis using time-resolved 3D phase-contrast (4D flow) MRI can detect cerebral hemodynamic impairment in patients with ICS. METHODS: This retrospective study analyzed 26 consecutive patients with unilateral ICS (21 men; mean age, 71 years) who underwent 4D flow MRI and acetazolamide-stress brain perfusion SPECT. Collateral flow via the Willis ring was visually evaluated. Temporal mean flow volume rate (Net), pulsatile flow volume (ΔV), and pulsatility index (PI) at the middle cerebral artery were measured. Cerebral vascular reserve (CVR) was calculated from the SPECT dataset. Patients were assigned to the misery perfusion group if the CVR was < 10% and to the nonmisery perfusion group if the CVR was ≥ 10%. Parameters showing a significant difference in both groups were statistically evaluated. RESULTS: Affected side ΔV, ratio of affected to contralateral side Net (rNet), and ratio of affected to contralateral side ΔV were significantly correlated to CVR (p = 0.030, p = 0.010, p = 0.015, respectively). Absence of retrograde flow at the posterior communicating artery was observed in the misery perfusion group (p = 0.020). Combined cut-off values of the affected side ΔV (0.18 ml) and rNet (0.64) showed a sensitivity and specificity of 100% and 77.8%, respectively. CONCLUSION: Multiparametric flow analysis using 4D flow MRI can detect misery perfusion by comprehensively assessing blood flow data, including blood flow volume, pulsation, and collateral flow.

Integrin α11 in non-small cell lung cancer is associated with tumor progression and postoperative recurrence.

Integrins are transmembrane proteins that mediate cell adhesion to the extracellular matrix. Integrin α11 (ITGA11) is not expressed in normal alveolar epithelial cells and is a known receptor for collagen. While integrin α11ß1 overexpression in the tumor stroma has been associated with tumor growth and metastatic potential of non-small cell lung cancer (NSCLC), little is known about the role of ITGA11 in tumor cells. Thus, we examined the RNA expression of ITGA11 by quantitative RT-PCR in 80 samples collected from NSCLC patients who had undergone surgical resection and analyzed the clinical outcomes. We found that high expression of ITGA11 was associated with lower recurrence-free survival in all NSCLC patients (P = 0.043) and in stage I NSCLC patients (P = 0.049). These results were consistent with in silico analyses of the Cancer Genome Atlas database. We also analyzed cell proliferation, migration and invasion capacity in lung cancer cell lines after overexpression of ITGA11. Overexpression of ITGA11 in lung cancer cell lines had little effect on cell proliferation but resulted in increased migration and invasion capacity. Our findings suggest that ITGA11 plays a significant role in cancer migration and invasion, leading to higher recurrence. ITGA11 expression may be a predictor of poor prognosis in patients with surgically resected NSCLC.

Exacerbation of chronic pulmonary aspergillosis was associated with a high rebleeding rate after bronchial artery embolization.

BACKGROUND: Hemoptysis is a common symptom associated with chronic pulmonary aspergillosis (CPA). While surgery is the primary choice to manage hemoptysis, it is often avoided because patients with CPA are more likely to have complications such as respiratory insufficiency and low pulmonary function. Bronchial artery embolization (BAE) may be considered one of the treatments of massive and persistent hemoptysis for such patients. METHODS: We retrospectively reviewed medical records of 41 patients, admitted to National Hospital Organization Tokyo National Hospital, Tokyo, Japan with hemoptysis arising from CPA between January 2011 to December 2016, who were considered inoperable and had undergone BAE. RESULTS: Out of the 41 cases analyzed in this study, 21 (51.2%) developed rebleeding after BAE within the mean follow-up duration of 24 months. The non-rebleeding rate of patients after BAE was 92.7% within a month and 65.8% within a year. Patients who developed rebleeding had significantly more non-bronchial systemic arteries responsible for the bleeding compared with patients who did not develop rebleeding (mean of 2.55 vs. 4.86, respectively, P = 0.011). Patients with stable or improved radiological findings demonstrated significantly lower rebleeding rates than those with radiological deterioration (P < 0.001). The non-rebleeding patients had significantly better survival than those with rebleeding (79.7% vs. 39.9% over 5 years, P = 0.046). CONCLUSIONS: Bronchial artery embolization was effective in controlling hemoptysis in patients with CPA, especially those who could not undergo surgical resection. However, disease control of CPA was important to prevent rebleeding over the long term and to improve survival after BAE.

Four-Dimensional Flow MRI Analysis of Cerebral Blood Flow Before and After High-Flow Extracranial-Intracranial Bypass Surgery With Internal Carotid Artery Ligation.

BACKGROUND: The hemodynamic changes that occur after high-flow (extracranial-intracranial) EC-IC bypass surgery with internal carotid artery (ICA) ligation are not well known. OBJECTIVE: To assess blood flow changes after high-flow EC-IC bypass with ICA ligation by time-resolved 3-dimensional phase-contrast (4D Flow) magnetic resonance imaging (MRI). METHODS: We enrolled 11 patients who underwent high-flow EC-IC bypass. 4D Flow MRI was performed before and after surgery to quantify the blood flow volume (BFV) of the ipsilateral ICA (BFViICA), bypass artery (BFVbypass), contralateral ICA (BFVcICA), and basilar artery (BFVBA). Subsequently, we calculated the total BFV (BFVtotal = BFViICA + BFVcICA + BFVBA [before surgery], BFVcICA + BFVBA + BFVbypass [after surgery]). The BFV changes after bypass was statistically analyzed. RESULTS: BFVbypass was slightly lower than BFViICA, but the difference was not statistically significant (3.84 ± 0.94 vs 4.42 ± 1.38 mL/s). The BFVcICA and BFVBA significantly increased after bypass surgery (BFVcICA 5.89 ± 1.44 vs 7.22 ± 1.37 mL/s [P = .0018], BFVBA 3.06 ± 0.41 vs 4.12 ± 0.38 mL/s [P < .001]). The BFVtotal significantly increased after surgery (13.37 ± 2.58 vs 15.18 ± 1.77 mL/s [P = .015]). There was no evidence of hyperperfusion syndrome in any cases. CONCLUSION: After high-flow EC-IC bypass with permanent ICA ligation, the bypass artery could partially compensate for the loss of BFV of the sacrificed ICA. The increased flow of the contralateral ICA and BA supply collateral blood flow. Clinically irrelevant hyperperfusion was observed.