Prediction of Efficacy for Atezolizumab/Bevacizumab in Unresectable Hepatocellular Carcinoma with Hepatobiliary-Phase Gadolinium Ethoxybenzyl-Diethylenetriaminepentaacetic Acid MRI.

BACKGROUND: This study aimed to examine whether the coefficient of variation (CV) in the hepatobiliary-phase (HBP) of Gd-EOB-DTPA-MRI could be an independent predictive factor for tumor progression. METHODS: Patients who underwent Gd-EOB-DTPA-MRI before Atezolizumab/bevacizumab therapy at six affiliated institutions between 2018 and 2022 were included. CV for each patient was calculated as the mean value for up to five tumors larger than 10 mm, and CV of the whole tumor was calculated using LIFEx software. The tumor response was evaluated within 6-10 weeks. The primary endpoint was to investigate the predictive factors, including CV, related to tumor progression using logistic regression analysis. The secondary endpoints were tumor response rate and progression-free survival (PFS) based on CV. RESULTS: Of the 46 enrolled patients, 13 (28.3%) underwent early progressive disease. Multivariate analysis revealed that a high CV (≥0.22) was an independent predictive factor for tumor progression (p = 0.043). Patients with a high CV had significantly frequent PD than those with a low CV (43.5 vs. 13.0%, p = 0.047). Patients with a high CV tended to have shorter PFS than those with a low CV (3.5 vs. 6.7 months, p = 0.071). CONCLUSION: Quantitative analysis using CV in the HBP of Gd-EOB-DTPA-MRI may be useful for predicting tumor progression for atezolizumab/bevacizumab therapy.

Brugada syndrome in Japan and Europe: a genome-wide association study reveals shared genetic architecture and new risk loci.

BACKGROUND AND AIMS: Brugada syndrome (BrS) is an inherited arrhythmia with a higher disease prevalence and more lethal arrhythmic events in Asians than in Europeans. Genome-wide association studies (GWAS) have revealed its polygenic architecture mainly in European populations. The aim of this study was to identify novel BrS-associated loci and to compare allelic effects across ancestries. METHODS: A GWAS was conducted in Japanese participants, involving 940 cases and 1634 controls, followed by a cross-ancestry meta-analysis of Japanese and European GWAS (total of 3760 cases and 11 635 controls). The novel loci were characterized by fine-mapping, gene expression, and splicing quantitative trait associations in the human heart. RESULTS: The Japanese-specific GWAS identified one novel locus near ZSCAN20 (P = 1.0 × 10-8), and the cross-ancestry meta-analysis identified 17 association signals, including six novel loci. The effect directions of the 17 lead variants were consistent (94.1%; P for sign test = 2.7 × 10-4), and their allelic effects were highly correlated across ancestries (Pearson's R = .91; P = 2.9 × 10-7). The genetic risk score derived from the BrS GWAS of European ancestry was significantly associated with the risk of BrS in the Japanese population [odds ratio 2.12 (95% confidence interval 1.94-2.31); P = 1.2 × 10-61], suggesting a shared genetic architecture across ancestries. Functional characterization revealed that a lead variant in CAMK2D promotes alternative splicing, resulting in an isoform switch of calmodulin kinase II-δ, favouring a pro-inflammatory/pro-death pathway. CONCLUSIONS: This study demonstrates novel susceptibility loci implicating potentially novel pathogenesis underlying BrS. Despite differences in clinical expressivity and epidemiology, the polygenic architecture of BrS was substantially shared across ancestries.

A rapid simultaneous antigen detection of Haemophilus influenzae and Streptococcus pneumoniae for predicting the prognosis of acute otitis media.

BACKGROUND: Rapid identification of causative bacteria in treatment of acute otitis media (AOM) is of paramount importance for appropriate antibiotic use. MATERIALS AND METHODS: This prospective observational study was conducted in 15 hospitals and clinics in Japan between 2018 and 2020. A new rapid antigen test kit (AOS-116), which simultaneously detects antigens for Streptococcus pneumoniae (Sp) and Haemophilus influenzae (Hi), was applied for middle ear fluids (MEFs) and nasopharyngeal secretions (NPSs) in patients with moderate to severe AOM. We investigated relationship between the results of rapid test, severity at initial visit, and clinical course. RESULTS: Regarding performance accuracy based on culture results, AOS-116 showed 1) high (>80%) sensitivity, specificity, and negative predictive value (NPV) in MEFs for both antigens, 2) high sensitivity, specificity, and positive predictive value (PPV) in NPSs for Hi antigen, and 3) high specificity, and PPV in NPSs for Sp antigen. Regarding predictive value of nasopharyngeal culture and antigen detection for causative middle ear pathogens, similar results were observed between AOS-116 and culture, which was characterized with high sensitivity and NPV for both pathogens. MEFs/NPSs positive for Hi antigen were significantly associated with eardrum findings, and severity. MEFs/NPSs positive for pneumococcal antigen were significantly associated with severity of otalgia, fever, and otorrhea. Among patients with prior antimicrobial treatment, improvement tended to be slower in cases positive for Hi than in cases negative. CONCLUSION: The rapid antigen detection test is useful as a decision-making tool for prescribing antimicrobial agents and may play an important role in promoting appropriate antimicrobial use.

Effects of Short-Term Lenvatinib Administration Prior to Transarterial Chemoembolization for Hepatocellular Carcinoma.

AIM: Transarterial chemoembolization (TACE) combined with lenvatinib, employing a 4-day lenvatinib administration followed by TACE without an interval (short-term LEN-TACE), was performed for hepatocellular carcinoma (HCC). The aim was to assess tumor hemodynamics following the 4-day lenvatinib and to evaluate the treatment outcomes after the short-term LEN-TACE. METHODS: 25 unresectable HCC patients received this combined therapy. Lenvatinib (4-12 mg) was administrated for 4 days prior to TACE. Perfusion CT scans were obtained before and after the lenvatinib administration. Either cTACE (76%) or DEB-TACE (24%) were performed. RESULTS: intra-tumor blood flow significantly decreased after the 4-day lenvatinib (p < 0.05). The TACE procedure was successful with no severe adverse events in all patients. The overall complete response (CR) rate was 75% (cTACE 84%, DEB-TACE 40%). The lipiodol-washout ratio between 1 week and 4 months after cTACE correlated with the arterial flow reduction ratio by lenvatinib prior to TACE (r = -0.55). The 12-month progression-free survival (PFS) rate was 75.0%. CONCLUSIONS: The short-term LEN-TACE is feasible and safe, demonstrating promising outcomes with a high CR ratio, contributing to lipiodol retention in the tumor after cTACE, and extended PFS. To confirm the advantages of this treatment protocol, a prospective clinical trial is mandatory.

Jaw claudication and branch perfusion reduction as rare complications of fenestrated thoracic endovascular aortic repair.

We report a rare case of jaw claudication following fenestrated thoracic endovascular aortic repair for a saccular aortic arch aneurysm. The brachiocephalic artery (BCA) was preserved with fenestration and intentionally half covered. Although discharged without any complications 2 weeks after the procedure, the patient subsequently experienced right mandibular fatigue at mealtime and hypotension in the right upper extremity. Angiography revealed a flap-like structure in the BCA orifice, with a 100-mm Hg pressure gradient between the aorta and BCA. Intravascular ultrasound revealed a stenosed BCA with a cord-like structure, which was considered a graft protrusion. Bare metal stenting was performed, which promptly resolved the symptoms.

Pictorial Review of Pleural Disease: Multimodality Imaging and Differential Diagnosis.

The pleura is a thin, smooth, soft-tissue structure that lines the pleural cavity and separates the lungs from the chest wall, consisting of the visceral and parietal pleurae and physiologic pleural fluid. There is a broad spectrum of normal variations and abnormalities in the pleura, including pneumothorax, pleural effusion, and pleural thickening. Pneumothorax is associated with pulmonary diseases and is caused by iatrogenic or traumatic factors. Chest radiography and US help detect pneumothorax with various signs, and CT can also help assess the causes. Pleural effusion occurs in a wide spectrum of diseases, such as heart failure, cirrhosis, asbestos-related diseases, infections, chylothorax, and malignancies. Chest US allows detection of a small pleural effusion and evaluation of echogenicity or septa in pleural effusion. Pleural thickening may manifest as unilateral or bilateral and as focal, multifocal, or diffuse. Various diseases can demonstrate pleural thickening, such as asbestos-related diseases, neoplasms, and systemic diseases. CT, MRI, and fluorodeoxyglucose (FDG) PET/CT can help differentiate between benign and malignant lesions. Knowledge of these features can aid radiologists in suggesting diagnoses and recommending further examinations with other imaging modalities. The authors provide a comprehensive review of the clinical and multimodality imaging findings of pleural diseases and their differential diagnoses. ©RSNA, 2024 Test Your Knowledge questions for this article are available in the supplemental material.

Successful management of splenic artery dissection after sigmoid colon perforation in vascular Ehlers-Danlos syndrome.

BACKGROUND: Ehlers-Danlos syndrome (EDS) is a genetic disorder that causes fragility of the systemic connective tissues. Of the 13 subtypes, vascular EDS (vEDS) is associated with abnormalities in collagen production, resulting in arterial rupture and intestinal perforation. Herein, we report the case of a man with confirmed vEDS who survived a ruptured dissected splenic artery aneurysm triggered by perforation of the sigmoid colon. CASE PRESENTATION: A 48-year-old man presented to our hospital with sudden severe lower abdominal pain. The patient was genetically diagnosed with vEDS at the age of 43 years. Abdominal computed tomography (CT) showed fluid and free air surrounding the sigmoid colon. These findings suggested sigmoid colon perforation, and emergency surgery was needed. Hartmann's procedure was performed. The resected specimen showed a 2-cm-sized depression around the perforation. Histopathological findings showed an abscess and exudate in the serosa of the perforation and thinning of the intrinsic muscular layer in the depressed area. The patient was doing well postoperatively; however, on the ninth postoperative day, sudden upper abdominal pain developed. CT revealed an intra-abdominal hemorrhage due to rupture of a dissecting splenic artery aneurysm. The aneurysm was not observed on preoperative CT and was distant from the surgical site. Urgent transcatheter arterial embolization was performed. Although embolization of the splenic artery was attempted during the procedure, the arterial dissection spread to the common hepatic artery. Moreover, the proper hepatic and gastroduodenal arteries were poorly visualized, probably due to vasospasm. Although complications associated with extensive embolization were a concern, embolization of the splenic and common hepatic arteries was necessary to save the patient's life. After embolization, angiography showed that the left hepatic blood flow was maintained from the inferior phrenic artery, and the right hepatic inflow was maintained from the superior mesenteric artery via the peribiliary vascular plexus in the hilar area. The patient recovered well and was discharged on the 19th postoperative day. CONCLUSIONS: vEDS can cause arterial rupture after intestinal surgery. Therefore, careful post-operative management is necessary. Moreover, cooperation with interventional radiologists is important for prompt treatment of vascular complications.

Anthracycline-based hepatic arterial infusion chemotherapy achieved 17 months of disease regression in a patient with breast cancer liver metastases resistant to multiple systemic chemotherapies.

Hepatic arterial infusion chemotherapy (HAIC) for liver metastases (LMs) from breast cancer is not a standard of care, but its effectiveness in patients with extensive LMs who cannot tolerate systemic therapy has been reported. Herein, we report a case of breast cancer LMs that were controlled by anthracycline-based HAIC. A 46-year-old woman with estrogen receptor-positive, human epidermal growth factor receptor 2-negative metastatic breast cancer who had multiple LMs and bone metastases underwent seven lines of systemic therapy (paclitaxel/bevacizumab for 38 months; letrozole, nivolumab/fulvestrant, eribulin, gemcitabine/vinorelbine, high-dose toremifene/abemaciclib, and capecitabine for 21 months in total). However, owing to its adverse effects and the continued progression of the LMs, systemic therapy was switched to HAIC (40 mg/body epirubicin on day 1, 4 mg/body mitomycin C on days 1 and 15, and 500 mg/body 5-fluorouracil on days 1, 8, and 15; 28-day courses). In response to HAIC, the LMs remarkably regressed and were controlled for 17 months without severe adverse effects. HAIC was stopped when multiple brain metastases arose, and the patient died 2 months later. This case suggests that HAIC is a reasonable option for patients with extensive LMs, even in the late stage of treatment. HAIC recipients should be carefully selected through multidisciplinary discussions as the survival benefits of HAIC over systemic treatment remain unclear. Our findings identify a potential window for the use of traditional chemotherapeutic agents such as anthracyclines. Novel strategies to improve drug delivery are warranted in the future.

Multimodality Imaging of Primary Hepatic Lymphoma: A Case Report and a Literature Review.

Primary hepatic lymphoma (PHL) is a rare form of non-Hodgkin lymphoma primarily affecting the liver. We present a case of an 84-year-old man diagnosed with PHL, incidentally detected during abdominal ultrasonography. The ultrasonography showed a hypoechoic nodule. When examined by CEUS, the nodule showed hyperenhancement in the arterial phase and hypoenhancement in the portal and late phases. Conversely, CECT demonstrated hypoenhancement through all the phases. The patient declined a tumor biopsy and opted for follow-up care. Ten months later, the lobular mass had increased from 15 mm to 65 mm, presenting as hypoechogenic and demonstrating the "vessel-penetrating sign" on color Doppler imaging. CEUS revealed reticulated enhancement, indicating intratumoral vessels. The mass displayed hypoattenuation on plain CT, hypointensity in T1-weighted images, and hyperintensity in T2-weighted images and exhibited significant restriction in diffusion-weighted images. Both CECT and contrast-enhanced MRI exhibited hypoenhancement. The patient underwent a partial hepatic segmentectomy, and the mass was pathologically diagnosed as a diffuse large B-cell lymphoma. Subsequent postoperative radiological examinations revealed no other lesions, confirming the diagnosis of PHL. Our report highlights specific ultrasonographic signs of PHL observed from an early stage and presents a review of the relevant literature.

Seroprevalence kinetics of SARS-CoV-2 antibodies in pediatric patients visiting a hospital during COVID-19 pandemic in Japan.

Children infected with SARS-CoV-2 are often asymptomatic or have mild symptoms. The studies on the seroprevalence kinetics of SARS-CoV-2 antibodies in children are limited. We conducted a cross-sectional survey of the positive rate of the SARS-CoV-2 IgG in pediatric patients without suspected COVID-19 infection between January 2007 and March 2022. We defined the serum samples from the pre-pandemic and pandemic groups (1st-6th waves). Totally, 2557 samples were collected and no samples from the pre-pandemic group or the 1st-4th waves were positive for IgG. There were 4/661 and 16/373 positives at the 5th and 6th waves, respectively. At the 5th wave, the prevalence of IgG was 1.3% in children aged 1-4 years. At the 6th wave, in children <1 year of age, the prevalence was 4.0%, and 2.4%, 5.3%, 5.2% and 10% in age groups 1-4, 5-9, 10-14 and 15-18 years, respectively. In conclusions, the pre-pandemic samples were negative, and the IgG positivity increased during the later period of the pandemic.

Palliative Radiofrequency Ablation Therapy for Intractable Cancer-Related Pain Due to Malignant Psoas Syndrome: Case Report.

Uncontrollable cancer pain is a highly feared and debilitating symptom. The effectiveness of radiofrequency ablation (RFA) for osseous metastases with intractable cancer-related pain refractory to pharmacological therapy has been reported previously. This case report is the first to demonstrate the use of RFA to achieve pain relief in a patient suffering severe pain caused by para-aortic lymph node metastasis. A 55-year-old male complained of intractable pain in the left groin and perineum due to malignant psoas syndrome caused by metastatic para-aortic lymph nodes. The pain was refractory to medications including opioids and nerve blocks. Considering the dermatome indicating referred pain and the imaging findings, RFA of the area of invasion was performed at the L3 level. The severe pain was relieved within 24 hours without any complications. Opioids were tapered at each postoperative outpatient visit. We discuss the use of RFA for control of intractable cancer-related pain refractory to medication, including opioids.

Percutaneous Trans-jejunum Pancreatojejunostomy Reconstruction for Intractable Pancreatic Fistula after Pancreatoduodenectomy.

We present an interventional radiology technique for percutaneous trans-jejunal pancreatojejunostomy reconstruction for intractable pancreatic fistula. A 70-year-old man with pancreatic cancer who had undergone pancreatoduodenectomy underwent percutaneous drainage for leakage from the anastomosis of the pancreatic duct to the jejunum. The leakage continued and the hole at the anastomosis site in the jejunum closed completely after 5 months. We performed percutaneous jejunostomy; the previously placed drainage catheter was then replaced with a balloon catheter, which was punctured by a 19-gauge needle from inside the jejunum through the percutaneous jejunostomy tube. The seeking catheter was inserted into the pancreatic duct. Finally, a side-holed 6-Fr straight catheter was successfully placed in the pancreatic duct through the percutaneous jejunostomy route.

A Case of Jejunal Artery Aneurysm Successfully Treated with Endovascular Embolization.

Jejunal artery aneurysms are extremely rare; only 58 cases have been reported up to 2022. The high rupture rate necessitates a curative treatment. Only four cases of true jejunal artery aneurysms treated with endovascular embolization were reported. We report a case of a 75-year-old man with a true jejunal artery aneurysm who was successfully treated with endovascular embolization. The aneurysm was located in the third jejunal branch. The proximal and distal distance to the superior mesenteric artery and the first bifurcation of the third jejunal branch, respectively, were too short to perform isolation. First, we performed packing in the aneurysm, followed by secondary parent artery embolization. Finally, we achieved total occlusion of the aneurysm and its parent artery with preserved distal intestinal blood flow.

Risk stratification of atrial fibrillation and stroke using single nucleotide polymorphism and circulating biomarkers.

BACKGROUND: Atrial fibrillation (AF) is the most common sustained arrhythmia, and it causes a high rate of complications such as stroke. It is known that AF begins as paroxysmal form and gradually progresses to persistent form, and sometimes it is difficult to identify paroxysmal AF (PAF) before having stroke. The aim of this study is to evaluate the risk of PAF and stroke using genetic analysis and circulating biomarkers. MATERIALS AND METHODS: A total of 600 adult subjects were enrolled (300 from PAF and control groups). Peripheral blood was drawn to identify the genetic variation and biomarkers. Ten single nucleotide polymorphisms (SNPs) were analyzed, and circulating cell-free DNA (cfDNA) was measured from plasma. Four microRNAs (miR-99a-5p, miR-192-5p, miR-214-3p, and miR-342-5p) were quantified in serum using quantitative RT-PCR. RESULTS: Genotyping identified 4 single nucleotide polymorphisms (SNPs) that were significantly associated with AF (rs6817105, rs3807989, rs10824026, and rs2106261), and the genetic risk score using 4 SNPs showed the area under the curve (AUC) of 0.631. Circulating miRNAs and cfDNA did not show significant differences between PAF and control groups. The concentration of cfDNA was significantly higher in patients with a history of stroke, and the AUC was 0.950 to estimate the association with stroke. CONCLUSION: The risk of AF could be assessed by genetic risk score. Furthermore, the risk of stroke might be evaluated by plasma cfDNA level.

The possibility of mutations of RAS signaling genes and/or TP53 in combination as a negative prognostic impact on pathological stage I non-small cell lung cancer.

BACKGROUND: The recurrence rate of non-small cell lung cancer (NSCLC) is as high as 30%, even in the cancer with pathological stage I disease. Therefore, identifying factors predictive of high-risk pathological recurrence is important. However, few studies have examined the genetic status of these tumors and its relationship to prognosis. MATERIALS AND METHODS: A cohort of 328 cases of primary lung cancer that underwent complete resection at Tokyo Medical and Dental University (TMDU) was screened for 440 cancer-associated genes using panel testing. Further analyses included 92 cases of pathological stage I NSCLC who did not receive adjuvant chemotherapy. Ridge regression was performed to identify association studies mutational status and postoperative recurrence. These data were then validated using clinical and genetic data from 56 patients in The Cancer Genome Atlas (TCGA). RESULTS: Mutations in TP53, RAS signaling genes KRAS and HRAS, and EGFR were recurrently detected. Ridge regression analysis relevant to recurrence, as well as survival analysis, performed using data from the TMDU cohort revealed significantly shorter relapse-free survival (RFS) for patients with RAS signaling or TP53 gene mutations than for those without (log-rank test, p = 0.00090). This statistical trend was also suggested in the TCGA cohort (log-rank test, p = 0.10). CONCLUSION: Mutations in RAS signaling genes and/or TP53 could be useful for the prediction of shorter RFS of patients with stage I NSCLC.

Association of adverse childhood experiences and cortical neurite density alterations with posttraumatic stress disorder symptoms in autism spectrum disorder.

Background: Posttraumatic stress disorder (PTSD) can be a source of significant social and daily distress in autism spectrum disorder (ASD). Compared to typically developed (TD) individuals, people with ASD are at an increased risk of adverse childhood experiences (ACEs), which can result in abnormal neuronal development. However, whether or how ACEs influence abnormal neural development and PTSD symptoms in ASD has not been fully elucidated. Methods: Thirty-nine TD individuals and 41 individuals with ASD underwent T1-weighted magnetic resonance imaging and neurite orientation dispersion and density imaging (NODDI), with axonal and dendritic densities assessed in terms of the orientation dispersion index and neurite density index (NDI), respectively. Voxel-based analyses were performed to explore the brain regions associated with PTSD symptoms, and the relationships between the severity of ACEs and PTSD symptoms and NODDI parameters in the extracted brain regions were examined. Results: There was a significant positive association between PTSD symptom severity and NDI in the bilateral supplementary motor area; right superior frontal, left supramarginal, and right superior temporal gyrus; and right precuneus in the ASD group, but not in the TD group. ACE severity was significantly associated with NDI in the right superior frontal and left supramarginal gyrus and right precuneus in the ASD group. Moreover, NDI in the right precuneus mainly predicted the severity of PTSD symptoms in the ASD group, but not the TD group. Conclusion: These results suggest that ACE-associated higher neurite density is of clinical importance in the pathophysiology of PTSD symptoms in ASD.

A Case of Refractory Esophageal Varices Caused by an Inferior Mesenteric Arteriovenous Malformation with All Portal System Occlusion Successfully Treated via Transarterial Embolization.

Inferior mesenteric arteriovenous fistulas/malformations are rare, reported in only 40 cases as of 2021. Their main manifestations include portal hypertension and ischemic bowel disease. We report the case of a 50-year-old man with refractory esophageal varices caused by this condition that was successfully treated with transarterial embolization. Computed tomography revealed an inferior mesenteric arteriovenous malformation and ascending blood flow into the esophageal varices through a remarkably dilated marginal vein. All portal systems were occluded, possibly because of the myointimal hyperplasia of the inferior mesenteric vein. The patient recovered without hemorrhagic events after transarterial embolization and endoscopic injection sclerotherapy. This is the first report of an inferior mesenteric arteriovenous malformation resulting in refractory esophageal varices with all-portal system occlusion successfully treated with transarterial embolization.

Role of Percutaneous Deep Venous Arterialization for Patients with Chronic Limb-threatening Ischemia.

Efficacy of percutaneous deep venous arterialization (pDVA) has been reported for patients with no-option chronic limb-threatening ischemia (CLTI). In the countries where a manufactured device dedicated for pDVA has not been reimbursed, pDVA using the off-the-shelf technique has alternatively spread. The off-the-shelf techniques for arteriovenous fistula (AVF) creation reported are as follows: AV spear technique, venous arterialization simplified technique (VAST), and a use of penetration guidewire or a reentry device. Technical success rates of the procedures are similar to those using the dedicated device. pDVA could be a last resort for the patients with no-option CLTI, including those suffering from stump ulcer after major limb amputation or those with occluded surgical bypass.