Transcatheter Arterial Embolization for Bleeding Caused by Endoscopic Ultrasound-Guided Fine-Needle Aspiration: A Case Series.

Introduction Bleeding is the most frequent complication of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). In a few cases of massive bleeding caused by EUS-FNA, transcatheter arterial embolization (TAE) has been used to obtain hemostasis. We present a case series of patients who underwent TAE for bleeding due to EUS-FNA. Methods This case series included six patients (five men and one woman) who underwent TAE for bleeding caused by EUS-FNA between January 2018 and December 2022 at the four institutions involved in this study. The median age at TAE was 72.5 years (range, 67-83 years). The target sites for EUS-FNA were the pancreatic tail (n = 3), pancreatic head (n = 2), and hepatic hilar lymph nodes (n = 1). The angiographic findings, embolization procedures, technical and clinical success rates, and TAE complications were retrospectively assessed. Results Angiography revealed contrast-media extravasation or pseudoaneurysms in five patients. In all patients, TAE using a microcatheter was performed via the transfemoral approach. N-butyl cyanoacrylate, coils, and gelatin sponges were used for embolization. The technical and clinical success rates of TAE were 100%. One complication, a duodenal ulcer, developed in one patient and was managed conservatively. Conclusion TAE is an effective and safe treatment for EUS-FNA-induced bleeding.

Myelination- and migration-associated genes are downregulated after phagocytosis in cultured oligodendrocyte precursor cells.

In the central nervous system, microglia are responsible for removing infectious agents, damaged/dead cells, and amyloid plaques by phagocytosis. Other cell types, such as astrocytes, are also recently recognized to show phagocytotic activity under some conditions. Oligodendrocyte precursor cells (OPCs), which belong to the same glial cell family as microglia and astrocytes, may have similar functions. However, it remains largely unknown whether OPCs exhibit phagocytic activity against foreign materials like microglia. To answer this question, we examined the phagocytosis activity of OPCs using primary rat OPC cultures. Since innate phagocytosis activity could trigger cell death pathways, we also investigated whether participating in phagocytosis activity may lead to OPC cell death. Our data shows that cultured OPCs phagocytosed myelin-debris-rich lysates prepared from rat corpus callosum, without progressing to cell death. In contrast to OPCs, mature oligodendrocytes did not show phagocytotic activity against the bait. OPCs also exhibited phagocytosis towards lysates of rat brain cortex and cell membrane debris from cultured astrocytes, but the percentage of OPCs that phagocytosed beta-amyloid was much lower than the myelin debris. We then conducted RNA-seq experiments to examine the transcriptome profile of OPC cultures and found that myelination- and migration-associated genes were downregulated 24 h after phagocytosis. On the other hand, there were a few upregulated genes in OPCs 24 h after phagocytosis. These data confirm that OPCs play a role in debris removal and suggest that OPCs may remain in a quiescent state after phagocytosis.

Artificial Pneumothorax Using the Liver-Directed Approach and Seldinger's Technique: Technical Feasibility and Safety.

Purpose This study aimed to evaluate the technical feasibility and safety of artificial pneumothorax induction for percutaneous procedures using the liver-directed approach and Seldinger's technique. Materials and methods The data of 25 consecutive patients who underwent percutaneous procedures after inducing artificial pneumothorax were reviewed retrospectively. The liver surface was punctured with an 18-gauge indwelling needle via the intercostal space in the inferior thoracic cavity under ultrasound guidance, avoiding the lung parenchyma and leaving the catheter in place. After a deep inhalation pulled the catheter tip into the pleural cavity, a hydrophilic guidewire was inserted through the catheter. Finally, a small-diameter catheter was inserted into the pleural cavity over the guidewire to induce artificial pneumothorax. Procedure time (the time from local anesthesia to completion of the procedure), technical success (successful induction of artificial pneumothorax), clinical success (successful completion of the percutaneous procedure), and complications (categorized according to the Clavien-Dindo classification) were evaluated in this study. Results The artificial pneumothorax induction was successful in all cases. Clinical success was achieved in 23 of 25 procedures (92%). No severe complications were observed. Conclusion The liver-directed approach and Seldinger's technique for inducing artificial pneumothorax was safe and feasible for avoiding lung injury.

Necessity of Prophylactic Anticoagulation Therapy Following Inferior Vena Cava Stent Placement in Patients with Cancer.

Purpose: Although percutaneous stent placement for malignant inferior vena cava syndrome is a highly feasible and effective treatment option, there is no clear evidence for the necessity of prophylactic anticoagulation therapy after inferior vena cava stent placement. This study retrospectively evaluated the necessity of prophylactic anticoagulation following inferior vena cava stent placement in patients with malignant inferior vena cava syndrome. Methods: The data of 54 patients (28 men and 26 women; median age 61.2 years) with malignant inferior vena cava syndrome who received inferior vena cava stent placement between 2011 and 2021 were retrospectively reviewed. Prophylactic anticoagulation was administered to 15 of 54 patients (27.8%) following stent placement. Symptom recurrence rates at 1 and 2 months after stent placement were compared between patients with and without prophylactic anticoagulation using Gray relational analysis. The timeline of symptom recurrence, survival time, and adverse events were also evaluated. Results: At 1 and 2 months, symptom recurrence rates were 48.6% and 71.4%, respectively, in patients with prophylactic anticoagulation and 28.3% and 37.0%, respectively, in patients without prophylactic anticoagulation. The overall median follow-up duration was 27 days and that of the patients with and without prophylactic anticoagulation was 37 and 25 days, respectively. The median survival times of patients with and without anticoagulation therapy were 69 and 30 days, respectively (p = 0.236). No procedure-related complications occurred. Conclusions: There was no significant difference in the symptom recurrence rates after inferior vena cava stent placement with or without prophylactic anticoagulation in this study.

Role of A-Kinase Anchoring Protein 12 in the Central Nervous System.

A-kinase anchoring protein (AKAP) 12 is a scaffolding protein that anchors various signaling proteins to the plasma membrane. These signaling proteins include protein kinase A, protein kinase C, protein phosphatase 2B, Src-family kinases, cyclins, and calmodulin, which regulate their respective signaling pathways. AKAP12 expression is observed in the neurons, astrocytes, endothelial cells, pericytes, and oligodendrocytes of the central nervous system (CNS). Its physiological roles include promoting the development of the blood-brain barrier, maintaining white-matter homeostasis, and even regulating complex cognitive functions such as long-term memory formation. Under pathological conditions, dysregulation of AKAP12 expression levels may be involved in the pathology of neurological diseases such as ischemic brain injury and Alzheimer's disease. This minireview aimed to summarize the current literature on the role of AKAP12 in the CNS.

Percutaneous Image-Guided Transesophageal Long Intestinal Tube Placement for Palliative Decompression in Advanced Cancer Patients with Unresectable Malignant Small Bowel Obstruction.

PURPOSE: To assess the safety and efficacy of long intestinal tube placement following percutaneous image-guided esophagostomy for palliative decompression of incurable malignant small bowel obstruction. MATERIALS AND METHODS: Between January 2013 and June 2022, a single-institution retrospective study was conducted to examine patients undergoing percutaneous transesophageal intestinal intubation for an occluded intestinal segment. Patients' baseline characteristics, procedural details, and clinical courses were reviewed. Severe complications were defined as those with ≥ 4 grade according to the CIRSE classification. RESULTS: This study included 73 patients (mean age, 57.7 years) who underwent 75 procedures. All bowel obstructions were caused by peritoneal carcinomatosis or similar disease, which precluded transgastric access in almost 50% of the patients due to massive cancerous ascites (n = 28), diffuse gastric involvement (n = 5), or omental dissemination in front of the stomach (n = 3). Technical success (appropriate tube positioning) was achieved in 98.7% (74/75) of procedures. The cumulative 1-month overall survival and sustained clinical success (adequate bowel decompression) rates were estimated at 86.8% and 88%, respectively, using Kaplan-Meier analysis. At the median survival of 70 days, the disease progression required other gastrointestinal interventions, including additional tube insertion, repositioning, or venting enterostomy in 16 patients (21.9%). The severe complication rate was 4% (3/75); one patient aspirated to death due to tube clogging and two encountered fatal perforation of isolated intestinal loops developing far beyond the tip of the indwelling tube. CONCLUSION: Percutaneous image-guided transesophageal intestinal intubation achieves feasible bowel decompression as palliative care in advanced cancer patients. LEVEL OF EVIDENCE: Level 4, Case Series.

Clinical outcomes of image-guided percutaneous drainage of pericardial effusion in cancer patients: A single-center retrospective analysis.

AIM: Catheter removal, survival, and recurrence rates after percutaneous pericardial effusion drainage in cancer patients are not fully understood. We evaluated the clinical outcomes of image-guided percutaneous pericardial effusion drainage in cancer patients. METHODS: From January 2014 to September 2017, 113 percutaneous drainages for symptomatic pericardial effusion were performed in 100 cancer patients (median 60 years; range, 7-84 years) using ultrasound or angio-computed tomography. An 8-Fr drainage catheter was placed using the Seldinger technique via the subxiphoid (n = 73), apical (n = 23), or left parasternal (n = 17) routes. Success rates, complications, and postprocedural clinical outcomes of drainages were retrospectively assessed. RESULTS: The technical and clinical success rates were 100% and 99%, respectively, without major complications. The median duration of catheterization and evacuated pericardial effusion volume were 6 days (range, 1-72 days) and 970 ml (range, 140-7635 ml), respectively. Catheters were removed after the first drainage in 86 cases (86%). Symptomatic pericardial effusion recurred in nine patients after catheter removal, in whom redrainages were performed 13 times with a median duration to redrainage time of 48 days (range, 13-529 days). During the follow-up period (median 106 days [range, 1-1396 days]), 61 patients died. The median survival was 140 days (95% confidence interval [CI], 95-276 days), and the median catheter-free survival was 111 days (95% CI, 60-152 days). CONCLUSIONS: Image-guided percutaneous pericardial effusion drainage for cancer patients is safe and helps alleviate symptoms. Additionally, catheter removal is possible in most patients, allowing a catheter-free period for patients.

Case Report: Surgical Treatment of Type IV Spinal Dermoid Sinus in a Shiba Inu.

A 2-year-old spayed female Shiba Inu was presented with progressive non-ambulatory bilateral paraparesis, back pain, and urinary incontinence. CT and MRI revealed multiple vertebral malformations and type IV dermoid sinus. Hemilaminectomy was performed in T1-T5 to remove the dermoid sinus and granulomatous lesion that infiltrated into the spinal cord parenchyma. Histopathological examination of the excised tissue revealed type IV dermoid sinus with granulomatous meningomyelitis. After surgery, back pain was resolved, and the dog recovered ambulation and voluntary urination at the time of follow-up 4 months after surgery.

Percutaneous Radiologic Gastrostomy in Patients After Partial Gastrectomy: A Retrospective Study to Assess the Technical Feasibility of Postsurgical Remnant Stomach Access.

PURPOSE: To evaluate the technical feasibility of percutaneous radiologic gastrostomy in patients after partial gastrectomy. MATERIALS AND METHODS: This retrospective study included 15 consecutive gastrectomized patients with attempted percutaneous radiologic gastrostomy at our institution between April 2014 and March 2021. When the stomach was sufficiently insufflated to distend below the left anterior subcostal margin, percutaneous radiologic gastrostomy with gastropexy was conventionally performed by the Seldinger technique. When the stomach was still highly positioned and/or overlaid by the other organs, some adjunctive maneuvers, such as hydro-displacement, intragastric balloon support, or cephalad oblique puncture or left intercostal puncture, were employed as modified gastrostomy. Ultrasonography or x-ray or computed tomography fluoroscopy was used for imaging guidance during the gastric puncture. Adequate tube placement was defined as technical success. Technical details, clinical outcomes, and complications were reviewed. RESULTS: One patient underwent percutaneous radiologic jejunostomy instead of gastrostomy because safe gastric access could not be ensured. Seven patients underwent conventional gastrostomy; the other seven underwent modified gastrostomy with no gastropexy. The technical success rate was 100% (7/7) in the conventional group and 85.7% (6/7) in the modified group. The stomach was punctured under x-ray or computed tomography fluoroscopy for conventional gastrostomy. In contrast, the combination of various modalities was used for modified gastrostomy except for one failed case with unintentional transhepatic access. During a median follow-up of 108 days, no major complications occurred. CONCLUSION: The adequate combination of multimodal imaging guidance and technical modifications could secure radiological creation of gastrostomy for the postsurgical stomach. LEVEL OF EVIDENCE: Level 4, Case Series.

Identification of Novel Oxindole Compounds That Suppress ER Stress-Induced Cell Death as Chemical Chaperones.

Endoplasmic reticulum (ER) stress and oxidative stress lead to protein misfolding, and the resulting accumulation of protein aggregates is often associated with the pathogenesis of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and prion disease. Small molecules preventing these pathogenic processes may be effective interventions for such neurodegenerative disorders. In this paper, we identify several novel oxindole compounds that can prevent ER stress- and oxidative stress-induced cell death. Among them, derivatives of the lead compound GIF-0726-r in which a hydrogen atom at the oxindole ring 5 position is substituted with a methyl (GIF-0852-r), bromine (GIF-0854-r), or nitro (GIF-0856-r) group potently suppressed global ER stress. Furthermore, GIF-0854-r and -0856-r prevented protein aggregate accumulation in vitro and in cultured hippocampal HT22 neuronal cells, indicating that these two compounds function effectively as chemical chaperones. In addition, GIF-0852-r, -0854-r, and -0856-r prevented glutamate-induced oxytosis and erastin-induced ferroptosis. Collectively, these results suggest that the novel oxindole compounds GIF-0854-r and -0856-r may be useful therapeutics against protein-misfolding diseases as well as valuable research tools for studying the molecular mechanisms of ER and oxidative stress.

Novel oxindole compounds inhibit the aggregation of amyloidogenic proteins associated with neurodegenerative diseases.

Amyloidogenic proteins form aggregates in cells, thereby leading to neurodegenerative disorders, including Alzheimer's and prion's disease, amyotrophic lateral sclerosis (ALS) in humans, and degenerative myelopathy (DM) and cognitive dysfunction in dogs. Hence, many small-molecule compounds have been screened to examine their inhibitory effects on amyloidogenic protein aggregation. However, no effective drug suitable for transition to clinical use has been found. Here we examined several novel oxindole compounds (GIF compounds) for their inhibitory effects on aggregate formation of the canine mutant superoxide dismutase 1 (cSOD1 E40K), a causative mutation resulting in DM, using Thioflavin-T fluorescence. Most GIF compounds inhibited the aggregation of cSOD1 E40K. Among the compounds, GIF-0854-r and GIF-0890-r were most effective. Their inhibitory effects were also observed in cSOD1 E40K-transfected cells. Additionally, GIF-0890-r effectively inhibited the aggregate formation of human SOD1 G93A, a causative mutation of ALS. GIF-0827-r and GIF-0856-r also effectively inhibited aggregate formation of human prion protein (hPrP). Subsequently, the correlation between their inhibitory effects on cSOD1 and hPrP aggregation was shown, indicating GIF compounds inhibited the aggregate formation of multiple amyloidogenic proteins. Conclusively, the novel oxindole compounds (GIF-0827-r, GIF-0854-r, GIF-0856-r, and GIF-0890-r) are proposed as useful therapeutic candidates for amyloidogenic neurodegenerative disorders.

Microendoscopic Dorsal Laminectomy for Multi-Level Cervical Intervertebral Disc Protrusions in Dogs.

The objective of this study was to evaluate the feasibility and clinical outcomes of microendoscopic dorsal laminectomy for multi-level cervical intervertebral disc protrusions in dogs. Eight client-owned dogs diagnosed with multi-level cervical intervertebral disc protrusions using computed tomography (CT) and magnetic resonance imaging (MRI) were included in this retrospective case series. Microendoscopic dorsal laminectomies (MEL) were performed with an integrated endoscopic system to the cranial and caudal vertebrae of the affected intervertebral joints. Pre- and post-operative neurological status, operation time, intra-operative complications, and postoperative complications were reviewed. Post-operative CT images were obtained to measure the dimensions of laminectomy and compared to those of planned laminectomy. Full endoscopic procedures were feasible in 7 dogs (87.5%) and the laminectomy dimensions were in agreement with pre-operative planning. In all dogs, major intra- and postoperative complications did not occur. Conversion to open surgery was required in one case. Short-term postoperative clinical deterioration was found in two dogs. Long-term clinical outcomes were good and comparable to those reported in previous studies of open dorsal laminectomies. MEL is a promising minimally invasive approach to multi-level cervical dorsal laminectomy for intervertebral disc protrusions. This technique may improve postoperative discomfort compared to the open approach. Further studies are needed to directly compare outcomes between these two approaches.

Intraperitoneal administration of synthetic microRNA-214 elicits tumor suppression in an intraperitoneal dissemination mouse model of canine hemangiosarcoma.

Canine hemangiosarcoma (HSA) has an extremely poor prognosis, making it necessary to develop new systemic treatment methods. MicroRNA-214 (miR-214) is one of many microRNAs (miRNA) that can induce apoptosis in HSA cell lines. Synthetic miR-214 (miR-214/5AE), which showed higher cytotoxicity and greater nuclease resistance than mature miR-214, has been developed for clinical application. In this study, we evaluated the effects of miR-214/5AE on stage 2 HSA in a mouse model. Mice intraperitoneally administered with miR-214/5AE (5AE group) had significantly fewer intraperitoneal dissemination tumor foci (median number: 72.5 vs. 237.5; p < 0.05) and a lower median foci weight (0.26 g vs. 0.61 g; p < 0.05). Mice in the 5AE group had increased expression of p53 and cleaved caspase-3, and a significantly lower proportion of Ki-67-positive cells, than those in the non-specific miR group. Notably, no significant side effects were observed. These results indicate that intraperitoneal administration of miR-214/5AE exhibits antitumor effects in an intraperitoneal dissemination mouse model of HSA by inducing apoptosis and suppressing cell proliferation. These results provide a basis for future studies on the antitumor effect of miR-214/5AE for HSA.

Molecular Mechanisms of Aggregation of Canine SOD1 E40K Amyloidogenic Mutant Protein.

Canine degenerative myelopathy (DM) is a human amyotrophic lateral sclerosis (ALS)-like neurodegenerative disease. It is a unique, naturally occurring animal model of human ALS. Canine DM is associated with the aggregation of canine superoxide dismutase 1 (cSOD1), which is similar to human ALS. Almost 100% of cases in dogs are familial, and the E40K mutation in cSOD1 is a major causative mutation of DM. Therefore, it is important to understand the molecular mechanisms underlying cSOD1(E40K) aggregation. To address this, we first analyzed the structural model of wild type cSOD1. Interactions were evident between amino acid E40 and K91. Therefore, the mutation at residue E40 causes loss of the interaction and may destabilize the native structure of cSOD1. Differential scanning fluorimetry revealed that the E40K mutant was less stable than the wild type. Moreover, stability could be recovered by the E40K and K91E double mutation. Acceleration of amyloid fibril formation in vitro and aggregate formation in cells of cSOD1(E40K) was also suppressed by the introduction of this double mutation in thioflavin T fluorescence assay results and in transfectant cells, respectively. These results clearly show the importance of the interaction between amino acid residues E40 and K91 in cSOD1 for the stability of the native structure and aggregation.

Case Report: Spinal Stabilization Surgery Using a Novel Custom-Made Titanium Fixation System for the Spinal Instability Caused by Vertebral Malformation in a Dog.

A 2-year-old Maltese was presented with wobbly gait of the pelvic limbs. Based on imaging examinations, a diagnosis of congenital malformation at T5-T8 and severe kyphosis causing spinal cord compression at T6-T7 was made. Dorsal laminectomy and stabilization of T6 and T7 vertebrae were performed. As the size of the vertebrae was small and they were severely deformed, novel custom-made titanium implants were used for spinal stabilization. Clinical signs were resolved 2 weeks after surgery. Although radiographic examination 373 days after surgery showed slight loosening of implants, post-operative course remained uneventful. This report describes the use of novel custom-made titanium implants for spinal fixation surgery in a dog.

Microendoscopic Mini-Hemilaminectomy and Discectomy in Acute Thoracolumbar Disc Extrusion Dogs: A Pilot Study.

The objective of this study was to evaluate the clinical outcomes and complications of a microendoscopic laminectomy and discectomy (MED) for acute thoracolumbar intervertebral disc extrusions in dogs. Eleven client-owned dogs with acute thoracolumbar intervertebral disc extrusions were included in this retrospective case-series. Dogs were diagnosed with acute thoracolumbar intervertebral disc extrusions using computed tomography (CT) and magnetic resonance imaging (MRI). MED was performed with an integrated endoscopic system to the affected intervertebral disc. Surgery time, intra-operative complications, causes of conversion to microscopic surgery if necessary, post-operative complications, and neurological status on presentation at discharge, as well as any further evaluations in hospital, and long-term concerns via owner contact, were recorded. Post-operative CT images were obtained to compare the extent of laminectomy performed to the planned region of laminectomy. The fully endoscopic procedure was completed in eight dogs without major complications. Three cases were converted to an open surgery due to difficulty removing extruded disc material and controlling hemorrhage. The clinical outcome was good in all cases and equivalent to previously reported prognoses after open surgery. MED is an effective and safe alternative to conventional open procedures in dogs with acute thoracolumbar intervertebral disc extrusion.

Artepillin C, a major component of Brazilian green propolis, inhibits endoplasmic reticulum stress and protein aggregation.

Propolis, a compound produced by honeybees, has long been used in food and beverages to improve health and prevent diseases. We previously reported that the ethanol extracts of Brazilian green propolis and its constituents artepillin C, kaempferide, and kaempferol mitigate oxidative stress-induced cell death via oxytosis/ferroptosis. Here, we investigated the potential of Brazilian green propolis and its constituents to protect against endoplasmic reticulum stress in the mouse hippocampal cell line HT22. Ethanol extracts of Brazilian green propolis, artepillin C, and kaempferol attenuated tunicamycin-induced unfolded protein response and cell death. Interestingly, artepillin C inhibited both tunicamycin-induced protein aggregation in HT22 cells and the spontaneous protein aggregation of mutant canine superoxide dismutase 1 (E40K-SOD1-EGFP) in Neuro2a cells. These findings indicate that in addition to oxidative stress, the ethanol extracts of Brazilian green propolis help prevent endoplasmic reticulum stress-related neuronal cell death, which is proposedly involved in several neurodegenerative diseases. Moreover, artepillin C, a major constituent of Brazilian green propolis, may exhibit chemical chaperone-like properties.

Transgastric Feeding Tube Insertion into the Jejunum after Esophagectomy: Direct Puncture of the Gastric Conduit.

PURPOSE: To evaluate the safety and efficacy of percutaneous ultrasound (US)-guided direct puncture of a reconstructed gastric conduit after esophagectomy for performing a percutaneous radiologic gastrojejunostomy. MATERIALS AND METHODS: Between 2014 and 2020, 26 consecutive patients with esophageal cancer (mean age, 70 years ± 8.3) with a total of 27 attempts of percutaneous radiologic gastrojejunostomy for postsurgical enteral feeding at the National Cancer Center Hospital were included in this study. One patient required a repeat procedure because of persistent anorexia after the removal of the first tube. All patients except 1 had a gastric conduit reconstructed via a retrosternal route. All procedures were performed under local anesthesia with moderate sedation and analgesia. A gastric conduit was directly punctured with an 18-gauge needle under ultrasonographic guidance, followed by feeding tube insertion into the proximal jejunum. Technical details of the procedures, technical success (defined as adequate tube placement), procedure-related complications, and clinical outcomes were reviewed. RESULTS: The mean procedure time was 25 minutes ± 15, and technical success was obtained in every attempt. Minor complications included mild local pain (n = 7), unintentional tube removal (n = 2), local abdominal wall hematoma (n = 1), and superficial cellulitis (n = 1); no major complications were observed. During a mean follow-up period of 118.3 days ± 85.8, 13 patients resumed oral intake, and the feeding tube could be removed in 4 patients. No procedure-related deaths occurred. CONCLUSIONS: The US-guided direct puncture technique is feasible for percutaneous gastrojejunal tube insertion in postsurgical patients with esophageal cancer with gastric conduit reconstruction.