Endovascular treatment of postoperative hemorrhage after pancreatectomy: a retrospective study.

BACKGROUND: Ruptured aneurysm is a serious complication of distal pancreatectomy (DP) or pancreatoduodenectomy (PD) that can be life-threatening if not treated promptly. This study aimed to examine the efficacy of a Viabahn stent graft for stopping bleeding after pancreatectomy. METHODS: Between April 2016 and June 2022, we performed 245 pancreatectomies in our institution. Six patients experienced postoperative bleeding and underwent endovascular treatment. RESULTS: All six cases of bleeding occurred post-PD (3.7%). The bleeding was from gastroduodenal artery (GDA) pseudoaneurysms in three patients, and Viabahn stent grafts were inserted. All three patients did not show liver function abnormalities or hepatic blood flow disorders. One patient with a Viabahn stent graft experienced rebleeding, which required further management to obtain hemostasis. Of the six cases in which there was hemorrhage, one case of bleeding from the native hepatic artery could not be managed. CONCLUSIONS: Using the Viabahn stent graft is an effective treatment option for postoperative bleeding from GDA pseudoaneurysms following PD. In most cases, using this device resulted in successful hemostasis, without observed abnormalities in hepatic function or blood flow.

Metformin suppresses epithelial sodium channel hyperactivation and its associated phenotypes in a mouse model of obstructive lung diseases.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death in the world, and has no radical treatment. Inhibition of amiloride-sensitive epithelial sodium ion channel (ENaC) has now been considered as a potential therapeutic target against COPD. One possible modulator of ENaC is AMP-activated protein kinase (AMPK), a key molecule that controls a wide variety of cellular signals; however, little is known about whether metformin, a clinically available AMPK activator, has a protective role against ENaC-associated chronic pulmonary phenotypes, such as emphysema and pulmonary dysfunction. We first used ENaC-overexpressing human bronchial epithelial cells (ß/γENaC-16HBE14o-) and identified that Metformin significantly reduced ENaC activity. Consistently, in vivo treatment of ENaC-overexpressing COPD mouse model (C57BL/6-ßENaC-Tg mice) showed improvement of emphysema and pulmonary dysfunction, without any detrimental effect on non-pulmonary parameters (blood glucose level etc.). Bronchoalveolar lavage fluid (BALF) and lung tissue analyses revealed significant suppression in the infiltration of neutrophils as well as the expression of inflammatory markers (KC), neutrophil gelatinase (MMP9) and macrophage elastase (MMP12) in metformin-treated C57BL/6-ßENaC-Tg mice. Overall, the present study demonstrates that metformin directly inhibits ENaC activity in vitro and provides the first evidence of therapeutical benefit of Metformin for COPD with higher ENaC activity.

A Splice Switch in SIGIRR Causes a Defect of IL-37-Dependent Anti-Inflammatory Activity in Cystic Fibrosis Airway Epithelial Cells.

Cystic fibrosis (CF) is a hereditary disease typically characterized by infection-associated chronic lung inflammation. The persistent activation of toll-like receptor (TLR) signals is considered one of the mechanisms for the CF hyperinflammatory phenotype; however, how negative regulatory signals of TLRs associate with CF inflammation is still elusive. Here, we showed that the cell surface expression of a single immunoglobulin interleukin-1 receptor (IL-1R)-related molecule (SIGIRR), a membrane protein essential for suppressing TLRs- and IL-1R-dependent signals, was remarkably decreased in CF airway epithelial cells compared to non-CF cells. Notably, CF airway epithelial cells specifically and highly expressed a unique, alternative splice isoform of the SIGIRR that lacks exon 8 (Δ8-SIGIRR), which results in the production of a C-terminal truncated form of the SIGIRR. Δ8-SIGIRR was expressed intracellularly, and its over-expression abolished the cell surface expression and function of the full-length SIGIRR (WT-SIGIRR), indicating its dominant-negative effect leading to the deficiency of anti-inflammatory activity in CF cells. Consistently, IL-37, a ligand for the SIGIRR, failed to suppress viral dsRNA analogue poly(I:C)-dependent JNK activation and IL-8 production, confirming the reduction in the functional WT-SIGIRR expression in the CF cells. Together, our studies reveal that SIGIRR-dependent anti-inflammatory activity is defective in CF airway epithelial cells due to the unique splicing switch of the SIGIRR gene and provides the first evidence of IL-37-SIGIRR signaling as a target of CF airway inflammation.

Snuff box radial access in transcatheter arterial embolization for unruptured renal angiomyolipoma.

OBJECTIVE: We report the first three cases in which the feasibility and safety of the left snuff box radial access in transcatheter arterial embolization (TAE) for unruptured renal angiomyolipoma (AML) were evaluated. MATERIAL AND METHODS: Three patients with unruptured renal AMLs underwent TAE via the left snuff box radial artery. We retrospectively evaluated the characteristics of the AMLs, technical success rate, clinical success rate, and complications. Technical success and clinical success were defined as successful insertions of microballoon catheters selectively via the left distal radial artery into all intended arteries in a treatment session and shrinkage of tumor size as evaluated by CT or MRI after the procedure, respectively. RESULTS: The median size of the renal AMLs was 49 mm. TAE was successfully performed in all cases and all feeding arteries were successfully selected with a microballoon catheter through the left snuff box radial artery. The median amount of the mixture of ethanol and Lipiodol was 1.8 mL. Tumor shrinkage was confirmed in all with a median follow-up period of 6 months. The clinical success rate was 100%. No major complications occurred. CONCLUSION: The left snuff box access in TAE for an unruptured renal AML is safe and feasible.

Intratracheal GLP-1 receptor agonist treatment up-regulates mucin via p38 and exacerbates emphysematous phenotype in mucus hypersecretory obstructive lung diseases.

Glucagon-like peptide-1 (GLP-1) is a gastrointestinal hormone that stimulates glucose-mediated insulin production by pancreatic beta cells. It is also associated with protective effects in multiple tissues. GLP-1 receptor is highly expressed in pulmonary tissue, hinting possible pulmonary delivery of GLP-1 drugs. However, little is known about the role of GLP-1 signaling in the lung, especially in mucus hypersecretory obstructive lung diseases. Here, we showed that treatment with exendin-4, a clinically available GLP-1 receptor agonist, up-regulates mucin expression in normal airway epithelial cells and in the lung of normal mice, indicating mucus stimulatory effect of GLP-1 under physiological condition. Exendin-4 also increased mucin expression in in vitro cellular and in vivo murine models of obstructive lung diseases via the activation of p38 MAP kinase. Notably, mucin induction in vivo exacerbated key pulmonary abnormalities including emphysematous phenotypes, implying that GLP-1 signaling in the lung is detrimental under pulmonary obstructive condition. Another GLP-1 receptor agonist liraglutide had similar induction of mucin. Together, our studies not only demonstrate novel physiological and pathological roles of GLP-1 in the lung but may also caution against the clinical use of inhaled GLP-1 receptor agonists in the patients with obstructive lung diseases.

Azithromycin Inhibits Constitutive Airway Epithelial Sodium Channel Activation in Vitro and Modulates Downstream Pathogenesis in Vivo.

Epithelial sodium channel (ENaC) is an amiloride-sensitive sodium ion channel that is expressed in epithelial tissues. ENaC overexpression and/or hyperactivation in airway epithelial cells cause sodium over-absorption and dysregulated ciliary movement for mucus clearance; however, the agents that suppress constitutive airway ENaC activation are yet to be clinically available. Here, we focused on macrolides, which are widely used antibiotics that have many potential immunomodulatory effects. We examined whether macrolides could modulate constitutive ENaC activity and downstream events that typify cystic fibrosis (CF) and chronic obstructive pulmonary diseases (COPD) in in vitro and in vivo models of ENaC overexpression. Treatment of ENaC-overexpressing human bronchial epithelial cells (ß/γENaC-16HBE14o- cells) with three macrolides (erythromycin, clarithromycin, azithromycin) confirmed dose-dependent suppression of ENaC function. For in vivo studies, mice harboring airway specific ßENaC overexpression (C57BL/6J-ßENaC-transgenic mice) were treated orally with azithromycin, a well-established antimicrobial agent that has been widely prescribed. Azithromycin treatment modulated pulmonary mechanics, emphysematous phenotype and pulmonary dysfunction. Notably, a lower dose (3 mg kg-1) of azithromycin significantly increased forced expiratory volume in 0.1 s (FEV0.1), an inverse indicator of bronchoconstriction. Although not statistically significant, improvement of pulmonary obstructive parameters such as emphysema and lung dysfunction (FEV0.1%) was observed. Our results demonstrate that macrolides directly attenuate constitutive ENaC function in vitro and may be promising for the treatment of obstructive lung diseases with defective mucociliary clearance, possibly by targeting ENaC hyperactivation.

Detection of Shunting Into Pulmonary Artery on Multidetector Row Computed Tomography Arteriography Before Bronchial Arterial Embolization: A Preliminary Study.

OBJECTIVE: The aim of this study was to investigate the diagnostic performance of detecting systemic arterial pulmonary circulation shunts on multidetector row computed tomography arteriography (MDCTA). METHODS: Thirty-five consecutive bronchial artery embolization sessions with preprocedural MDCTA were performed for 32 patients and 35 sessions. The MDCTA studies with computed tomography value of pulmonary trunk visually lower than that of ascending aorta were defined as "diagnostic MDCTA." Angiographic studies and "diagnostic MDCTA" were evaluated, respectively, for shunting into pulmonary artery. Based on the results of angiographic studies, diagnostic performance of "diagnostic MDCTA" was evaluated. RESULTS: The rate of diagnostic MDCTA was 63% (23 of 35). On "diagnostic MDCTA," sensitivity, specificity, and positive and negative predictive values for detecting shunts were 83% 100%, 100%, 94%, respectively. CONCLUSIONS: Systemic arterial pulmonary circulation shunts were detected on "diagnostic MDCTA" with high sensitivity and specificity.

Pulmonary perfusion by chest digital dynamic radiography: Comparison between breath-holding and deep-breathing acquisition.

PURPOSE: Pulmonary perfusion is an important factor for gas exchange. Chest digital dynamic radiography (DDR) by the deep-breathing protocol can evaluate pulmonary perfusion in healthy subjects. However, respiratory artifacts may affect DDR in patients with respiratory diseases. We examined the feasibility of a breath-holding protocol and compared it with the deep-breathing protocol to reduce respiratory artifacts. MATERIALS AND METHODS: A total of 42 consecutive patients with respiratory diseases (32 males; age, 68.6 ± 12.3 yr), including 21 patients with chronic obstructive pulmonary disease, underwent chest DDR through the breath-holding protocol and the deep-breathing protocol. Imaging success rate and exposure to radiation were compared. The correlation rate of temporal changes in each pixel value between the lung fields and left cardiac ventricles was analyzed. RESULTS: Imaging success rate was higher with the breath-holding protocol vs the deep-breathing protocol (97% vs 69%, respectively; P < 0.0001). The entrance surface dose was lower with the breath-holding protocol (1.09 ± 0.20 vs 1.81 ± 0.08 mGy, respectively; P < 0.0001). The correlation rate was higher with the breath-holding protocol (right lung field, 41.7 ± 9.3%; left lung field, 44.2 ± 8.9% vs right lung field, 33.4 ± 6.6%; left lung field, 36.0 ± 7.1%, respectively; both lung fields, P < 0.0001). In the lower lung fields, the correlation rate was markedly different (right, 15.3% difference; left, 14.1% difference; both lung fields, P < 0.0001). CONCLUSION: The breath-holding protocol resulted in high imaging success rate among patients with respiratory diseases, yielding vivid images of pulmonary perfusion.

Integrative expression analysis identifies a novel interplay between CFTR and linc-SUMF1-2 that involves CF-associated gene dysregulation.

Cystic fibrosis transmembrane regulator (CFTR) is a cyclic AMP-dependent Cl- channel, and its dysfunction, due to CFTR gene mutations, causes the lethal inherited disorder cystic fibrosis (CF). To date, widespread dysregulation of certain coding genes in CF airway epithelial cells is well studied and considered as the driver of pulmonary abnormality. However, the involvement of non-coding genes, novel classes of functional RNAs with little or no protein-coding capacity, in the regulation of CF-associated gene dysregulation is poorly understood. Here, we utilized integrative analyses of human transcriptome array (HTA) and characterized 99 coding and 91 non-coding RNAs that are dysregulated in CFTR-defective CF bronchial epithelial cell line CFBE41o-. Among these genes, the expression level of linc-SUMF1-2, an intergenic non-coding RNA (lincRNA) whose function is unknown, was inversely correlated with that of WT-CFTR and consistently higher in primary human CF airway epithelial cells (DHBE-CF). Further integrative analyses under linc-SUMF1-knockdown condition determined MXRA5, SEMA5A, CXCL10, AK022877, CTGF, MYC, AREG and LAMB3 as both CFTR- and linc-SUMF1-2-dependent dysregulated gene sets in CF airway epithelial cells. Overall, our analyses reveal linc-SUMF1-2 as a dysregulated non-coding gene in CF as well as CFTR-linc-SUMF1-2 axis as a novel regulatory pathway involved in CF-associated gene dysregulation.

Auto-measure emphysematous parameters and pathophysiological gene expression profiles in experimental mouse models of acute and chronic obstructive pulmonary diseases.

Pulmonary emphysema, inflammation and senescence-like phenotype are pathophysiological characteristics of chronic obstructive pulmonary disease (COPD). Recently, a murine model of COPD has been established by inducing airway-specific overexpression of epithelial Na+ channel ß subunit (ßENaC-Tg mice). However, little is known about the histological and biochemical differences between ßENaC-Tg mice and an existing acute emphysematous mouse model (elastase-induced model). Here, we first utilized whole lung image-based quantification method for histological analysis to determine auto-measure parameters, including alveolar area, alveolar perimeter, (major axis + minor axis)/2 and Feret diameter. Even though the extent of emphysema was similar in both models, the coefficient of variation (CV) of all histological parameters was smaller in ßENaC-Tg mice, indicating that ßENaC-Tg mice show homogeneous emphysema as compared with elastase-induced acute model. Expression analysis of lung tissue RNAs further revealed that elastase-induced model exhibits transient changes of inflammation markers (Kc, Il-6, Lcn2) and senescence-related markers (Sirt1, p21) at emphysema-initiation stage (1 day), which does not last until emphysema-manifestation stage (3 weeks); while the up-regulation is stable at emphysema-manifestation stage in ßENaC-Tg mice (14-week old). Thus, these studies demonstrate that ßENaC-Tg mice exhibit diffuse-type emphysema with stable expression of inflammatory and senescence-like markers.

FOXO1 stimulates tip cell-enriched gene expression in endothelial cells.

Forkhead box O (FOXO) family proteins are expressed in various cells, and play crucial roles in cellular metabolism, apoptosis, and aging. FOXO1-null mice exhibit embryonic lethality due to impaired endothelial cell (EC) maturation and vascular remodeling. However, FOXO1-mediated genome-wide regulation in ECs remains unclear. Here, we demonstrate that VEGF dynamically regulates FOXO1 cytosol-nucleus translocation. FOXO1 re-localizes to the nucleus via PP2A phosphatase. RNA-seq combined with FOXO1 overexpression/knockdown in ECs demonstrated that FOXO1 governs the VEGF-responsive tip cell-enriched genes, and further inhibits DLL4-NOTCH signaling. Endogenous FOXO1 ChIP-seq revealed that FOXO1 binds to the EC-unique tip-enriched genes with co-enrichment of EC master regulators, and the condensed chromatin region as a pioneer factor. We identified new promoter/enhancer regions of the VEGF-responsive tip cell genes regulated by FOXO1: ESM1 and ANGPT2. This is the first study to identify cell type-specific FOXO1 functions, including VEGF-mediated tip cell definition in primary cultured ECs.

Retracted: Chest digital dynamic radiography to detect changes in human pulmonary perfusion in response to alveolar hypoxia.

INTRODUCTION: Hypoxic pulmonary vasoconstriction optimises oxygenation in the lung by matching the local-blood perfusion to local-ventilation ratio upon exposure to alveolar hypoxia. It plays an important role in various pulmonary diseases, but few imaging evaluations of this phenomenon in humans. This study aimed to determine whether chest digital dynamic radiography could detect hypoxic pulmonary vasoconstriction as changes in pulmonary blood flow in healthy individuals. METHODS: Five Asian men underwent chest digital dynamic radiography before and after 60 sec breath-holding at the maximal inspiratory level in upright and supine positions. Alveolar partial pressure of oxygen and atmospheric pressure were calculated using the blood gas test and digital dynamic radiography imaging, respectively. To evaluate the blood flow, the correlation rate of temporal change in each pixel value between the lung fields and left cardiac ventricles was analysed. RESULTS: Sixty seconds of breath-holding caused a mean reduction of 26.7 ± 6.4 mmHg in alveolar partial pressure of oxygen. The mean correlation rate of blood flow in the whole lung was significantly lower after than before breath-holding (before, upright 51.5%, supine 52.2%; after, upright 45.5%, supine 46.1%; both P < 0.05). The correlation rate significantly differed before and after breath-holding in the lower lung fields (upright, 11.8% difference; supine, 10.7% difference; both P < 0.05). The mean radiation exposure of each scan was 0.98 ± 0.09 mGy. No complications occurred. CONCLUSIONS: Chest digital dynamic radiography could detect the rapid decrease in pulmonary perfusion in response to alveolar hypoxia. It may suggest hypoxic pulmonary vasoconstriction in healthy individuals.

Endovascular Repair for Abdominal Aneurysm with Concomitant Aortoiliac Vein Fistula Diagnosed by Four-Dimensional Computed Tomography.

A 78-year-old man complaining of left leg swelling was diagnosed with an abdominal aortic aneurysm with an irregular margin. A four-dimensional computed tomography (CT) showed an aortoiliac vein fistula. An AFX stent graft was urgently implanted, and a Viabahn VBX was inserted into the left iliac vein. The aneurysmal sac was embolized. After the procedure, enhanced CT confirmed a patent stent graft without any endoleak or fistula. The patient was discharged ambulatory. An aortoiliac vein fistula is a differential diagnosis for leg edema, and a four-dimensional CT is beneficial in diagnosing the condition.

The usefulness of vertebral needle targeting simulation training system using ray-summation imaging: experimental study.

PURPOSE: Using the multi-detector computed tomography and related three-dimensional imaging technology, we developed a vertebral needle targeting simulation training system named spinal needling intervention practice using ray-summation imaging (SNIPURS). Herein, we assessed the utility of SNIPURS by evaluating changes in the learning curves of SNIPURS trainees. METHODS: Twenty-one examinees were enrolled: seven experienced operators (expert group), seven trainees with coaching (coaching group), and seven trainees without coaching (non-coaching group). They performed six tests of vertebral needle targeting simulation on the workstation-generated spinal ray-summation images of six patients with vertebral fractures. In each test, they determined the bilateral trans-pedicular puncture points and angles on two thoracic and two lumbar vertebrae on ray-summation imaging (i.e., 8 simulations per test). The coaching group received coaching by a trainer after Tests 1 and 4, while the others did not. Scores were given based on the trans-pedicular pathway (1 point) or not (0 point). Eight virtual needles were evaluated in each of Tests 1-6. RESULTS: Among the three groups, the expert group had the highest average scores on Tests 1-4 (expert: 3.86, 6.57, 7.43, and 7.57; coaching: 1.86, 6.14, 6, and 6.29; and non-coaching: 1.14, 4.14, 4.71, and 4.86). The coaching group's scores caught up with the expert groups' average scores on Tests 5 and 6, whereas those of the non-coaching group did not (expert and coaching: 7.86 and 8.00, non-coaching: 5.86 and 7.14). All examinees in the expert and coaching groups achieved a perfect score on the final Test 6, whereas three of the seven non-coaching trainees did not. CONCLUSION: SNIPURS might be suitable for vertebral needle targeting training. The coaching provided during SNIPURS training helped the trainees to acquire the spinal puncture techniques in PVP.

Dose length product and outcome of CT fluoroscopy-guided interventions using a new 320-detector row CT scanner with deep-learning reconstruction and new bow-tie filter.

OBJECTIVES: To investigate the dose length product (DLP) and outcomes of CT fluoroscopy (CTF)-guided interventions using a novel 320-detector row CT scanner with deep-learning reconstruction (DLR) and a new bow-tie filter (i.e., Aquilion ONE Prism Edition) and compare with a 320-detector row CT system without DLR and the new bow-tie filter (i.e., Aquilion ONE Vision Edition) (Vision). METHODS: CTF-guided interventions performed using Prism and Vision were retrospectively investigated in terms of the technical success rates, clinical success rates of biopsies, complications, DLPs of total CT scans (total DLPs) from February 2019 to January 2021. The total CT scans included pre-interventional CT scans, CTF scans during the CTF-guided procedure, additional CT scans for additional treatment, CTF scans for additional treatment, and post-interventional CT scans. RESULTS: In this study, 87 and 85 CTF-guided interventions were performed using Vision (Vision group) and Prism (Prism group), respectively. There was no significant difference in the technical success rate (96.6% vs 98.8%, p = 0.621), clinical success rate of biopsies (92.9% vs 93.4%, p = 1.000), and minor (8.0% vs 7.1%, p = 0.807) and major (0% vs 3.5%, p = 0.119) complications between the Prism and Vision groups. The total DLPs for the Prism group were significantly lower than those for the Vision group regardless of the procedure (278 vs 548 mGy*cm, p < 0.001, in the biopsy and 246 vs 667 mGy*cm, p < 0.001, in the drainage and aspiration). CONCLUSIONS: CTF-guided interventions on Prism reduce the total DLP without performance degradation of the intervention. ADVANCES IN KNOWLEDGE: The total DLPs of biopsies and drainages/aspirations in the Prism group decreased by 49 and 63%, respectively.

CT-guided bone biopsy using electron density maps from dual-energy CT.

Computed tomography (CT) -guided bone biopsy is a diagnostic procedure performed on the musculoskeletal system with a high diagnostic yield and low complications. However, CT-guided bone biopsy has the disadvantage that it is difficult to confirm the presence of tumor cells during the biopsy procedure. Recently, the clinical benefits of dual-energy CT (DECT) over single-energy CT have been revealed. DECT can provide material decomposition images including calcium suppression images, and effective atomic number (Zeff) and electron density (ED) maps. ED maps have been reported to indicate cellularity. A 61-year-old woman with a history of breast cancer surgery was admitted to our hospital and underwent a CT-guided bone biopsy of the right ilium using ED maps. As a result, she was diagnosed with breast cancer metastases of intertrabecular bone. A comparison of ED maps with a pathological specimen revealed that high ED values occurred exclusively in the tumor area with high cellularity. This study indicates that ED maps produced using DECT may have potential utility in the accurate identification of metastases with high cellularity in bone lesions.

First experience of efficacy and radiation exposure in 320-detector row CT fluoroscopy-guided interventions.

OBJECTIVE: We investigated the efficacy and exposure to radiation in 320-detector row computed tomography fluoroscopy-guided (CTF-guided) interventions. METHODS: We analysed 231 320-detector row CTF-guided interventions (207 patients over 2 years and 6 months) in terms of technical success rates, clinical success rates, complications, scanner settings, overall radiation doses (dose-length product, mGy*cm), patient doses of peri-interventional CT series, and interventional CT (including CTF), as a retrospective cohort study. The relationships between patient radiation dose and interventional factors were assessed using multivariate analysis. RESULTS: Overall technical success rate was 98.7% (228/231). The technical success rates of biopsies, drainages, and aspirations were 98.7% (154/156), 98.5% (66/67), and 100% (8/8), respectively. The clinical success rate of biopsies was 93.5% (146/156). All three major complications occurred in chest biopsies. The median total radiation dose was 522.4 (393.4-819.8) mGy*cm. Of the total radiation dose, 87% was applied during the pre- and post-interventional CT series. Post-interventional CT accounted for 24.4% of the total radiation dose. Only 11.4% of the dose was applied by CTF-guided intervention. Multilinear regression demonstrated that male sex, body mass index, drainage, intervention time, and helical scan as post-interventional CT were significantly associated with higher dose. CONCLUSION: The 320-detector row CTF interventions achieved a high success rate. Dose reduction in post-interventional CT provides patient dose reduction without decreasing the technical success rates. ADVANCES IN KNOWLEDGE: This is the first study on the relationship between various interventional outcomes and patient exposure to radiation in 320-detector row CTF-guided interventions, suggesting a new perspective on dose reduction.

Differential mode of cholesterol inclusion with 2-hydroxypropyl-cyclodextrins increases safety margin in treatment of Niemann-Pick disease type C.

BACKGROUND AND PURPOSE: Niemann-Pick disease type C (NPC) is a lysosomal storage disorder with disrupted intracellular cholesterol trafficking. A cyclic heptasaccharide, 2-hydroxypropyl-ß-cyclodextrin (HP-ß-CD), is a cholesterol solubilizer that is being developed to treat NPC, but its ototoxicity and pulmonary toxicity remain important issues. We have characterized 2-hydroxypropyl-γ-cyclodextrin (HP-γ-CD), a cyclic octasaccharide with a larger cavity than HP-ß-CD, as a candidate drug to treat NPC. However, the molecular target of HP-γ-CD with respect to NPC and its potential for clinical application are still unclear. EXPERIMENTAL APPROACH: We investigated the mode of interaction between HP-γ-CD and cholesterol by phase-solubility analysis, proton NMR spectroscopy and molecular dynamics simulations. We then evaluated the therapeutic effects of HP-γ-CD compared with HP-ß-CD using cellular and murine NPC models. Mouse auditory and pulmonary function tests were also conducted. KEY RESULTS: HP-γ-CD solely formed a 1:1 inclusion complex with cholesterol with an affinity similar to that of HP-ß-CD. In vitro, HP-γ-CD and HP-ß-CD amelioration of NPC-related manifestations was almost equivalent at lower concentrations. However, at higher concentrations, the cholesterol inclusion mode of HP-ß-CD shifted to the highly soluble 2:1 complex whereas that of HP-γ-CD maintained solely the 1:1 complex. The constant lower cholesterol solubilizing ability of HP-γ-CD conferred it with significantly reduced toxicity compared with HP-ß-CD, but equal efficacy in treating a mouse model of NPC. CONCLUSIONS AND IMPLICATIONS: HP-γ-CD can serve as a fine-tuned cholesterol solubilizer for the treatment of NPC with a wider safety margin than HP-ß-CD in terms of ototoxicity and pulmonary toxicity.

Bronchial artery embolization for haemothorax and haemoptysis caused by primary lung cancer.

Primary lung cancer (PLC) presents with various symptoms. However, there have been no reports of PLC causing haemothorax and haemoptysis simultaneously. We present an unusual case of massive haemothorax and haemoptysis caused by a PLC, in which haemostasis was secured with interventional radiology. A 58-year-old woman was hospitalized for a right secondary pneumothorax associated with emphysema. Chest computed tomography showed a mass shadow at the right lower lobe and on the right parietal pleura. Three days after air drainage, about 2000 mL of bloody pleural effusion accompanied by massive haemoptysis was observed. Haemoglobin concentration decreased to 4.9 g/dL and the patient was treated with selective embolization of the bronchial artery and the intercostal arteries. A diagnosis of PLC was made based on pleural fluid cytology. The patient was transferred to the palliative care hospital three months later without recurrence of haemothorax and haemoptysis.

Transcatheter arterial embolization for unruptured renal angiomyolipoma using a 1.8-Fr tip microballoon catheter with a mixture of ethanol and Lipiodol.

BACKGROUND: To evaluate the efficacy and safety of transcatheter arterial embolization for renal angiomyolipoma using a 1.8-French tip microballoon catheter and a mixture of ethanol and Lipiodol. METHODS: Seven consecutive patients with total of eight angiomyolipomas underwent this procedure between June 2014 and June 2017. A 1.8-French tip microballoon catheter was advanced to the feeding artery of the angiomyolipoma, and transcatheter arterial embolization was performed with a mixture of ethanol and Lipiodol under microballoon inflation. We retrospectively evaluated the characteristics of angiomyolipomas, technical success rate, clinical success rate, renal function, and adverse events. Technical success and clinical success were defined as complete embolization of all feeding arteries and reduction of tumor size, respectively. RESULTS: The median size of the angiomyolipomas was 46 mm (range, 40-64 mm). Transcatheter arterial embolization was successful in all eight angiomyolipomas. The median volume of the mixture of ethanol and Lipiodol was 6.0 ml (range, 2.0-14 ml). The median ratio of ethanol to Lipiodol was 71% (range, 71-75%). All eight angiomyolipomas shrank with a median shrinkage rate of 34% in diameter (range, 9-63%) and 77% in volume (range, 48-94%). The median follow-up period was 13 months (range, 9-54 months). Clinical success was achieved in all cases. Serum creatinine concentrations and the pre- and post-procedural estimated glomerular filtration rates did not change notably, and there were no major complications. CONCLUSION: Transcatheter arterial embolization for renal angiomyolipoma using a 1.8-French tip microballoon catheter with a mixture of ethanol and Lipiodol is effective and safe.