Retrograde transvenous thoracic duct embolization for lymphatic leakage after retroperitoneal tumor and lymph node resection: a case report and literature review.

BACKGROUND: Postoperative lymphatic leakage is a complication of ineffective conservative treatment for retroperitoneal mass. Herein, we report a case of lymphatic leakage that arose after retroperitoneal tumor resection and that was treated with retrograde transvenous thoracic duct embolization. CASE PRESENTATION: A 28-year-old man with persistent abdominal pain was diagnosed with a large retroperitoneal metastatic tumor measuring 10 cm and a subdiaphragmatic lymph node originating from a testicular tumor. After high orchidectomy and neoadjuvant chemotherapy, the subdiaphragmatic lymph node and retroperitoneal tumor were resected together with the abdominal aorta; the latter was reconstructed using a prosthetic graft. Postoperatively, the patient developed chylothorax. No improvement was observed after conservative treatment that included fasting and somatostatin therapy. The leakage site could not be identified using antegrade lymphangiography of the bilateral inguinal lymph nodes, but was detected using retrograde transvenous lymphangiography. The leakage site was successfully embolized. CONCLUSION: This case report describes successful treatment with retrograde transvenous thoracic duct embolization for chylothorax following resection of a retroperitoneal tumor and lymph node. This approach is a less invasive and more effective mode of treatment for chylothorax and should be considered before surgical thoracic duct ligation when the leakage point cannot be identified using the antegrade approach.

Safety and clinical contribution of computed tomography-guided biopsy for cervical spine lesion.

INTRODUCTION: The purpose is to clarify the safety and clinical contribution of computed tomography (CT)-guided percutaneous needle-biopsy for patients with cervical spine lesion. MATERIAL AND METHODS: Between June 2015 and August 2022, CT-guided percutaneous needle biopsies were performed for 15 cervical spine lesions of 15 patients (8 male, 7 female; 2-81 years old). The technical success, clinical contribution, and safety were evaluated. Technical success was defined as the completion of the biopsy procedure. Clinical contribution was defined as any contribution to the therapeutic strategy. Safety was assessed by the Common Terminology Criteria for Adverse Events, version 5.0. RESULTS: The technical success rate was 100%. In all 15 patients, nontarget organs (e.g., major vessels, spinal cord) could be avoided. The post-biopsy histological diagnoses were myeloma (n = 2), metastatic adenocarcinoma (n = 2), chordoma (n = 2), Langerhans cell histiocytosis (n = 3), and one case each of malignant lymphoma, schwannoma, pyogenic spondylitis, non-pyogenic spondylitis, degenerative change, and non-pathological fracture. All of these diagnoses contributed to the therapeutic strategy decisions. One case of grade 2 pain was observed, but no complications with grade 3 or more were observed during or after the biopsies. CONCLUSION: CT-guided percutaneous needle biopsies for cervical spine lesions were safe and clinically beneficial.

Multiparametric assessment of microvascular invasion in hepatocellular carcinoma using gadoxetic acid-enhanced MRI.

PURPOSE: To elucidate how precisely microvascular invasion (MVI) in hepatocellular carcinoma (HCC) can be predicted using multiparametric assessment of gadoxetic acid-enhanced MRI. METHODS: In this retrospective single-center study, patients who underwent liver resection or transplantation of HCC were evaluated. Data obtained in patients who underwent liver resection were used as the training set. Nine kinds of MR findings for predicting MVI were compared between HCCs with and without MVI by univariate analysis, followed by multiple logistic regression analysis. Using significant findings, a predictive formula for diagnosing MVI was obtained. The diagnostic performance of the formula was investigated in patients who underwent liver resection (validation set 1) and in patients who underwent liver transplantation (validation set 2) using a receiver operating characteristic curve analysis. The area under the curves (AUCs) of these three groups were compared. RESULTS: A total of 345 patients with 356 HCCs were selected for analysis. Tumor diameter (D) (P = 0.021), tumor washout (TW) (P < 0.01), and peritumoral hypointensity in the hepatobiliary phase (PHH) (P < 0.01) were significantly associated with MVI after multivariate analysis. The AUCs for predicting MVI of the predictive formula were as follows: training set, 0.88 (95% confidence interval (CI) 0.82,0.93); validation set 1, 0.81 (95% CI 0.73,0.87); validation set 2, 0.67 (95% CI 0.51,0.80). The AUCs were not significantly different among three groups (training set vs validation set 1; P = 0.15, training set vs validation set 2; P = 0.09, validation set 1 vs validation set 2; P = 0.29, respectively). CONCLUSION: Our multiparametric assessment of gadoxetic acid-enhanced MRI performed quite precisely and with good reproducibility for predicting MVI.

Acute Liver Injury and Bilateral Pulmonary Artery Thrombosis due to Hypereosinophilic Syndrome: A Case Report.

A 46-year-old Japanese man was referred to our hospital because of a marked increase in his eosinophil count (22,870/µL) and elevated liver enzyme levels. Computed tomography (CT) showed thrombi measuring approximately 8 cm in both femoral veins. A liver biopsy revealed eosinophilic infiltration, hepatocyte necrosis, fibrosis, and multiple thrombi. We suspected acute liver injury and deep vein thrombosis associated with hypereosinophilic syndrome and initiated steroids and heparin treatment. Four days after starting treatment, the patient experienced sudden chest pain and cardiopulmonary arrest. CT revealed bilateral pulmonary artery thrombosis, and despite administration of a tissue plasminogen activator, the patient died.

Effect of lipiodol marking before CT-guided cryoablation on the outcome of sporadic renal cell carcinoma.

PURPOSE: This retrospective study evaluates the impact of preoperative lipiodol marking on the outcomes of computed tomography (CT)-guided cryoablation for histologically diagnosed sporadic renal cell carcinoma (RCC). METHODS: This study analyzed the data of 173 patients who underwent CT-guided cryoablation for histologically proven sporadic RCC at a single institution between April 2014 and December 2020. The local control rate (LCR), recurrence-free survival rate (RFSR), overall survival rate (OSR), changes in renal function, and complications in patients with (n = 85) and without (n = 88) preoperative lipiodol marking were compared. RESULTS: The 5-year LCR and 5-year RFSR were significantly higher in patients with lipiodol marking (97.51% and 93.84%, respectively) than in those without (72.38% and 68.10%, respectively) (P value <0.01, log-rank test). There were no significant differences between the two groups regarding the 5-year OSR (97.50% vs. 86.82%) or the deterioration in chronic kidney disease stage (12.70% vs. 16.43%). Grade ≥3 complications occurred in patients with lipiodol marking (n = 2, retroperitoneal hematoma and cerebral infarction in 1 patient each) and without (n = 5; urinary fistula in 2, colonic perforation in 2, urinary infection in 1). CONCLUSION: Lipiodol marking before CT-guided cryoablation for sporadic RCC is a feasible approach to improving local control and RFS while mitigating the decline in renal function. Additionally, it may help reduce complications.

Impact of portal-phase signal intensity of dynamic gadoxetic acid-enhanced magnetic resonance imaging in hepatocellular carcinoma.

PURPOSE: To evaluate the prognostic impact of dynamic gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) in patients with hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the data of 206 patients with HCC who underwent preoperative Gd-EOB-DTPA-enhanced MRI and hepatectomy and quantitatively evaluated the signal intensity ratio of the tumor to the surrounding liver tissue in the portal phase (SIRPP). We verified the survival rates and assessed the prognostic factors associated with overall survival (OS) and recurrence-free survival (RFS) using SIRPP. RESULTS: Multivariate analysis revealed that the independent predictive factors for poorly-differentiated HCC were α-fetoprotein > 20 ng/mL (hazard ratio [HR]: 3.1909, 95% confidence interval [CI]: 1.3464-7.5622, p = .0084) and SIRPP ≤ 0.85 (HR: 3.7155, 95% CI: 1.521-9.076, p = .004). The 5-year OS and RFS rates in the high and low SIRPP groups were 83.2 and 52.1%, respectively (p < .0001) and 49.7 and 18.5%, respectively (p = .0003). Multivariate analysis revealed that SIRPP ≤ 0.68 was an independent prognostic factor related to OS (HR: 4.4537, 95% CI: 1.6581-11.9626, p = .003). CONCLUSION: The SIRPP of preoperative Gd-EOB-DTPA-enhanced MRI might predict the histological differentiation and prognosis of HCC.

Clinical association between intraoperative indocyanine green fluorescence imaging pattern, preoperative Gd-EOB-DTPA-enhanced magnetic resonance imaging findings, and histological differentiation in hepatocellular carcinoma.

AIM: We aimed to evaluate the association between the intraoperative indocyanine green (ICG) fluorescence imaging (FI) pattern, preoperative magnetic resonance imaging (MRI) findings using gadolinium ethoxybenzyl diethylenetriaminepentaacetic acid (Gd-EOB-DTPA), preoperative diffusion-weighted imaging (DWI) of MRI, and histological differentiation of hepatocellular carcinoma (HCC). METHODS: We retrospectively reviewed the data for 80 tumors of 64 patients. Intraoperative ICG FI patterns were classified into cancerous or rim-positive type. We evaluated the signal intensity ratio of the tumor and the surrounding liver tissue in the portal phase (SIRPP) and intensity in the hepatobiliary phase (HBP) of Gd-EOB-DTPA-enhanced MRI, the apparent diffusion coefficient (ADC) in the DWI of MRI, and clinicopathologic factors. RESULTS: In the rim-positive group, the rate of poorly differentiated HCC and hypointensity type in HBP were significantly higher, and SIRPP and ADC were significantly lower than the rim-negative group. In the cancerous group, the rate of well or moderately differentiated HCC and hyperintensity type in HBP, SIRPP, and ADC were significantly higher than the noncancerous group. Multivariate analysis identified low SIRPP, low ADC, and hypointensity type in HBP as the significant predictive factors for rim-positive HCC and high SIRPP, high ADC, and hyperintensity type in HBP as the significant predictive factors for cancerous HCC. The positive rate of programmed cell death 1-ligand 1 and vessels that encapsulate tumor clusters status of the rim-positive HCC and HCC with low SIRPP were significantly higher than the control group. CONCLUSIONS: The intraoperative ICG FI pattern of HCC closely correlated with histological differentiation, preoperative SIRPP and intensity type in the Gd-EOB-DTPA MRI, and preoperative ADC in the DWI of MRI.

Extracellular volume fraction determined by dual-layer spectral detector CT: Possible role in predicting the efficacy of preoperative neoadjuvant chemotherapy in pancreatic ductal adenocarcinoma.

PURPOSE: To clarify the relationship between extracellular volume (ECV) measured by dual-energy CT (DECT) and efficacy of preoperative neoadjuvant chemotherapy (NAC) in patients with pancreatic ductal adenocarcinoma (PDAC), as compared with single-energy CT (SECT). METHODS: We enrolled 67 patients with PDAC who underwent dynamic contrast-enhanced CT with a dual-energy CT system prior to NAC. Attenuation values were measured on unenhanced and the equilibrium-phase 120-kVp equivalent CT images for PDAC and the aorta. ΔHU-tumor, ΔHU-tumor/ΔHU-aorta, and SECT-ECV were calculated. Iodine densities of the tumor and aorta were measured in the equilibrium phase, and DECT-ECV of the tumor was calculated. Response to NAC was evaluated and the correlation between imaging parameters and response to NAC was statistically assessed. RESULTS: Tumor DECT-ECVs were significantly lower in the response group (n = 7) than in the non-response group (n = 60), with most significant difference (p = 0.0104). DECT-ECV showed highest diagnostic value with an Az value of 0.798. When using the optimal cut off value of DECT-ECV (<26.0 %), sensitivity, specificity, accuracy, positive predictive value, and negative value for predicting response group were 71.4 %, 85.0 %, 83.6 %, 35.7 % and 96.2 %, respectively. CONCLUSION: PDAC with lower DECT-ECV can potentially show better response to NAC. DECT-ECV might be a useful biomarker for predicting response to NAC in patients with PDAC.

Computational Analysis of the SARS-CoV-2 RBD-ACE2-Binding Process Based on MD and the 3D-RISM Theory.

The binding process of angiotensin-converting enzyme 2 (ACE2) to the receptor-binding domain (RBD) of the severe acute respiratory syndrome-like coronavirus 2 spike protein was investigated using molecular dynamics simulation and the three-dimensional reference interaction-site model theory. The results suggested that the protein-binding process consists of a protein-protein approaching step, followed by a local structural rearrangement step. In the approaching step, the interprotein interaction energy decreased as the proteins approached each other, whereas the solvation free energy increased. As the proteins approached, the glycan of ACE2 first established a hydrogen bond with the RBD. Thereafter, the number of interprotein hydrogen bonds increased rapidly. The solvation free energy increased because of the desolvation of the protein as it approached its partner. The spatial distribution function of the solvent revealed the presence of hydrogen bonds bridged by water molecules on the RBD-ACE2 interface. Finally, principal component analysis revealed that ACE2 showed a pronounced conformational change, whereas there was no significant change in RBD.

Kinetics of Polymer Crystallization with Aggregating Small Crystallites.

The isothermal crystallization near the glass transition temperature from the melt state of poly(trimethylene terephthalate) has been studied by wide-angle x-ray diffraction (WAXD), small-angle x-ray scattering (SAXS), and optical microscopy. The SAXS and WAXD results show the crystallization mechanism in which the crystalline nodules cover the entire sample with the formation of aggregation regions. The analysis of the SAXS results using Kolmogorov-Johnson-Mehl-Avrami theory indicates that the formation kinetics of the aggregation regions is of three-dimensional homogeneous nucleation type. The analysis of the SAXS profiles using Sekimoto's theory provides the growth velocity and the nucleation rate of the aggregation region. The temperature dependence of the growth velocity of the aggregation region is a natural extrapolation of that of spherulite to the high supercooling region. The temperature dependence of the nucleation rate of the aggregation region is also represented by the parameters of the spherulitic growth rate. The result of the growth velocities of the aggregation region and the spherulite suggests the existence of precursors at the front of the crystal growth.

Differentiating Liver Hemangioma from Metastatic Tumor Using T2-enhanced Spin-echo Imaging with a Time-reversed Gradient-echo Sequence in the Hepatobiliary Phase of Gadoxetic Acid-enhanced MR Imaging.

PURPOSE: To evaluate the utility of T2-enhanced spin-echo imaging using the time-reversed gradient echo sequence (T2FFE imaging) in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced MRI (Gd-EOB-MRI) for differentiating hemangiomas from metastatic tumors. METHODS: A total of 61 patients with 133 liver lesions, including 37 hemangiomas and 96 metastatic tumors, were scanned by Gd-EOB-MRI. Four data sets were independently analyzed by two readers: (1) 3D fat-suppressed T2-weighted imaging (FS-T2WI) alone; (2) the combination of 3D FS-T2WI and T2FFE imaging in the HBP of Gd-EOB-MRI; (3) the combination of 3D FS-T2WI, diffusion-weighted imaging (DWI) with the b-value of 1000 s/mm2 and the apparent diffusion coefficient (ADC); and (4) a dynamic study of Gd-EOB-MRI. After classifying the lesion sizes as ≤ 10 mm or > 10 mm, we conducted a receiver-operating characteristic analysis to compare diagnostic accuracies among the four data sets for differentiating hemangiomas from metastatic tumors. RESULTS: The areas under the curves (AUCs) of the four data sets of two readers were: (1) ≤ 10 mm (0.85 and 0.91) and > 10 mm (0.88 and 0.97), (2) ≤ 10 mm (0.94 and 0.94) and > 10 mm (0.96 and 0.95), (3) ≤ 10 mm (0.90 and 0.87) and > 10 mm (0.89 and 0.95), and (4) ≤ 10 mm (0.62 and 0.67) and > 10 mm (0.76 and 0.71), respectively. Data sets (2) and (3) showed no significant differences in AUCs, but both showed significantly higher AUCs compared to that of (4) regardless of the lesion size (P < 0.05). CONCLUSION: The combination of 3D FS-T2WI and T2FFE imaging in the HBP of Gd-EOB-MRI achieved an accuracy equivalent to that of the combination of 3D FS-T2WI, DWI, and ADC and might be helpful in differentiating hemangiomas from metastatic tumors.

Genetic Background of Mesalamine-induced Fever and Diarrhea in Japanese Patients with Inflammatory Bowel Disease.

BACKGROUND: Some patients with inflammatory bowel disease (IBD) who were under mesalamine treatment develop adverse reactions called "mesalamine allergy," which includes high fever and worsening diarrhea. Currently, there is no method to predict mesalamine allergy. Pharmacogenomic approaches may help identify these patients. Here we analyzed the genetic background of mesalamine intolerance in the first genome-wide association study of Japanese patients with IBD. METHODS: Two independent pharmacogenetic IBD cohorts were analyzed: the MENDEL (n = 1523; as a discovery set) and the Tohoku (n = 788; as a replication set) cohorts. Genome-wide association studies were performed in each population, followed by a meta-analysis. In addition, we constructed a polygenic risk score model and combined genetic and clinical factors to model mesalamine intolerance. RESULTS: In the combined cohort, mesalamine-induced fever and/or diarrhea was significantly more frequent in ulcerative colitis vs Crohn's disease. The genome-wide association studies and meta-analysis identified one significant association between rs144384547 (upstream of RGS17) and mesalamine-induced fever and diarrhea (P = 7.21e-09; odds ratio = 11.2). The estimated heritability of mesalamine allergy was 25.4%, suggesting a significant correlation with the genetic background. Furthermore, a polygenic risk score model was built to predict mesalamine allergy (P = 2.95e-2). The combined genetic/clinical prediction model yielded a higher area under the curve than did the polygenic risk score or clinical model alone (area under the curve, 0.89; sensitivity, 71.4%; specificity, 90.8%). CONCLUSIONS: Mesalamine allergy was more common in ulcerative colitis than in Crohn's disease. We identified a novel genetic association with and developed a combined clinical/genetic model for this adverse event.

Analysis of the Long-Term Prognosis in Japanese Patients with Ulcerative Colitis Treated with New Therapeutic Agents and the Correlation between Prognosis and Disease Susceptibility Loci.

BACKGROUND: New therapeutic agents, including biologics and small-molecule drugs, are widely used to treat ulcerative colitis (UC). This study evaluates long-term prognosis in Japanese patients treated with these agents and the association between prognosis and genetic susceptibility to UC. METHODS: We evaluated surgery-free rates using the Kaplan-Meier method in the total cohort and in patients treated with prednisolone and new therapeutic agents. Multivariate analysis was performed to identify clinical factors affecting surgical rates using Cox's proportional hazard model. The rate of use of new therapeutic agents was compared using the Kaplan-Meier method, and multivariate analysis was conducted to investigate the correlation between the single-nucleotide polymorphism (SNP) rs117506082 and long-term prognosis. RESULTS: Surgery-free survival decreased over time. There was no significant difference in this parameter between patients who were administered prednisolone and those who were administered new therapeutic agents. Poor response to prednisolone and treatment without topical 5-aminosalicylic acid were poor prognostic factors. Shorter time from diagnosis to initiation of treatment with new therapeutic agents was a risk factor for colectomy. The AA genotype of SNP rs117506082 was associated with a shorter time to surgery and increased use of new therapeutic agents. CONCLUSIONS: The use of new therapeutic agents might improve long-term prognosis in patients with more severe UC. Previously identified genetic risk factors were not significantly associated with a higher rate of colectomy.

Congestion Area of the Right Lobe Graft in Living Donor Liver Transplantation: Quantitative Evaluation of Hemodynamics Using Computed Tomography Perfusion.

BACKGROUND: The hemodynamics of congestion areas in the right lobe graft after living donor liver transplantation (LDLT) remains unclear. The aim of this study was to elucidate the hemodynamics of congestion areas in the right lobe graft after LDLT using computed tomography (CT) perfusion imaging and the dual-input maximum slope method. METHODS: Sixteen recipients underwent CT perfusion of the liver and portal phase abdominal to pelvic CT 1week after LDLT using a right lobe graft. The attenuation of segments V and VIII on the portal venous phase abdominal to the pelvic CT scan was classified into 3 categories: hyperattenuation, iso-attenuation, and hypoattenuation. Mean arterial blood flow (AF, mL/min/100 mL tissue), portal blood flow (PF, mL/min/100 mL tissue), and perfusion index (%) [PI = AF/(AF + PF) × 100] were compared between the hyperattenuation group and iso-attenuation group. The independent t test was used for these statistical analyses. RESULTS: On the portal phase abdominal scan, 15 segments, 16 segments, and 1 segment showed hyperattenuation, iso-attenuation, and hypoattenuation, respectively. The mean AF and PI of the hyperattenuation group (44.4 ± 24.4, 30.2 ± 13.5) were significantly higher than those of the iso-attenuation group (28.0 ± 7.8, 19.9 ± 6.2) (P < .05, P < .05). CONCLUSIONS: The congested liver segments showed high AF and high PI on CT perfusion imaging. This method enables the feasible quantification of the hemodynamics and the description of focal hemodynamic change in the graft after LDLT.

Repertoire analysis of memory T-cell receptors in Japanese patients with inflammatory bowel disease.

BACKGROUND AND AIM: The T-cell receptor (TCR) repertoire was assessed in response to various antigens and was considered to be associated with the pathogenesis of inflammatory bowel disease (IBD). Thus, we performed TCR repertoire analysis to examine the pathology of IBD from changes in the TCR repertoire of memory T cells in the intestinal lamina propria mononuclear cells (LPMCs) and peripheral blood mononuclear cells (PBMCs) of patients with IBD. METHODS: LPMCs in the surgical specimens and PBMCs were isolated from 12 patients with IBD (5 patients with ulcerative colitis [UC] and 7 patients with Crohn's disease [CD]). PBMCs were collected from 10 healthy individuals as controls. Comprehensive TCR sequence analyses of adaptor-ligation polymerase chain reaction (PCR) products were performed using MiSeq. RESULTS: The diversity of TCR-α and TCR-ß in PBMCs was significantly lower in patients with IBD than that in controls (P = 0.00084 and 0.0013, respectively). Comparisons of TCR diversity in LPMCs and PBMCs between CD and UC showed that the diversity in LPMC was not affected by diseases, whereas that in PBMCs was significantly lower in CD than in UC (P = 0.045 and 0.049, respectively). Some TCR clones may have shown a specific increase or decrease in CD and UC, and many clones were common to both LPMCs and PBMCs in the same patients. CONCLUSION: The diversity of TCR clones in LPMCs and PBMCs in patients with IBD was significantly lower than that of PBMCs in controls. TCR diversity in PBMCs was particularly low in patients with CD.

Time-Enhancement Curve of Four-Dimensional Computed Tomography Predicts Aneurysm Enlargement with Type-II Endoleak after Endovascular Aneurysm Repair.

OBJECTIVE: We investigated the hemodynamic features of Type-II endoleaks after endovascular aneurysm repair (EVAR) using four-dimensional (4D) computed tomography (CT) to identify patients with aneurysm enlargement. METHODS: During a 13-month period (January 2017-January 2018) at our institution, we performed 4D-CT examinations in 13 patients after EVAR because of suspected Type-II endoleaks. Three patients were excluded from the study because of other endoleaks or absence of detectable endoleaks. The ramaining 10 patients were divided into two groups: enlargement group (n = 4), in which the aneurysm volume increased, and stable group (n = 6), in which the aneurysm remained stable or shrank. A CT scanner and three-dimensional workstation were used. All images were obtained using a consistent protocol (22 phase scans using the test bolus tracking method). We analyzed the hemodynamics of the endoleak cavity (EC) relative to those of the aorta and evaluated the time-enhancement curves (TECs) using measurement protocols. The strengths of correlations between these factors in the two groups were analyzed statistically. RESULTS: TECs in the enlargement group showed a more gradual curve, and the upslope, the gradient of TEC in the ascending phase and the upslope index were significantly more gradual than those in the stable group (p = 0.0247, 0.0243). The EC washout and the EC washout index were also more gradual than in the stable group's (p = 0.019, 0.019). The enhancement duration was longer in the former than in the latter (80%, p = 0.0195; 70%, p = 0.0159; 60%, p = 0.0159). The CT number in the equilibrium phase was larger in the enlargement group than in the stable group (p = 0.019). CONCLUSION: The 4D-CT is useful for predicting aneurysm enlargement with Type-II endoleaks after EVAR.

An Integrated Genomic and Transcriptomic Analysis Reveals Candidates of Susceptibility Genes for Crohn's Disease in Japanese Populations.

Expression quantitative trait locus (eQTL) analyses have enabled us to predict the function of disease susceptibility SNPs. However, eQTL for the effector memory T cells (TEM) located in the lamina propria mononuclear cells (LPMCs), which play an important role in Crohn's disease (CD), are not yet available. Thus, we conducted RNA sequencing and eQTL analyses of TEM cells located in the LPMCs from IBD patients (n = 20). Genome-wide association study (GWAS) was performed using genotyping data of 713 Japanese CD patients and 2,063 controls. We compared the results of GWAS and eQTL of TEM, and also performed a transcriptome-wide association study using eQTL from Genotype Tissue Expression project. By eQTL analyses of TEM, correlations of possible candidates were confirmed in 22,632 pairs and 2,463 genes. Among these candidates, 19 SNPs which showed significant correlation with tenascin-XA (TNXA) expression were significantly associated with CD in GWAS. By TWAS, TNFSF15 (FDR = 1.35e-13) in whole blood, ERV3-1 (FDR = 2.18e-2) in lymphocytes, and ZNF713 (FDR = 3.04e-2) in the sigmoid colon was significantly associated with CD. By conducting integration analyses using GWAS and eQTL data, we confirmed multiple gene transcripts are involved in the development of CD.

Rare Genotype of His/His in NUDT15 Codon 139 and Thiopurine-associated Adverse Events in a Case of Ulcerative Colitis.

Thiopurine drugs are commonly used to treat immunologic diseases. However, the narrow therapeutic safety margin demands evidence-based precision medicine approaches. NUDT15 variants are associated with thiopurine-induced adverse events, particularly in Asians. We herein report a rare genotype of His/His in NUDT15 codon 139 in a case of ulcerative colitis and review the relevant literature. The patient experienced severe thiopurine-associated adverse events, including leukopenia and alopecia. There is no literature on the His/His genotype in NUDT15 codon 139, and our case suggests cautious use or the contraindication of thiopurines for patients with this genotype.

Genetic Analysis of Ulcerative Colitis in Japanese Individuals Using Population-specific SNP Array.

BACKGROUND: To clarify the genetic background of ulcerative colitis (UC) in the Japanese population, we conducted a genome-wide association study (GWAS) using a population-specific single nucleotide polymorphism (SNP) array. METHODS: We performed a GWAS and replication study including 1676 UC patients and 2381 healthy controls. The probability of colectomy was compared between genotypes of rs117506082, the top hit SNP at HLA loci, by the Kaplan-Meier method. We studied serum expression of miR-622, a newly identified candidate gene, from 32 UC patients and 8 healthy controls by quantitative reverse-transcription polymerase chain reaction. RESULTS: In the GWAS, only the HLA loci showed genome-wide significant associations with UC (rs117506082, P = 6.69E-28). Seven nominally significant regions included 2 known loci, IL23R (rs76418789, P = 6.29E-7) and IRF8 (rs16940202, P = 1.03E-6), and 5 novel loci: MIR622 (rs9560575, P = 8.23E-7), 14q31 (rs117618617, P = 1.53E-6), KAT6B (rs12260609, P = 1.81E-6), PAX3-CCDC140-SGPP2 (rs7589797, P = 2.87E-6), and KCNA2 (rs118020656, P = 4.01E-6). Combined analysis revealed that IL23R p.G149R (rs76418789, P = 9.03E-11; odds ratio [OR], 0.51) had genome-wide significant association with UC. Patients with GG genotype of rs117506082 had a significantly lower probability of total colectomy than those with the GA+AA genotype (P = 1.72E-2). Serum expression of miR-622 in patients with inactive UC tended to be higher than in healthy controls and patients with active UC (inactive UC vs healthy controls, P = 3.03E-02; inactive UC vs active UC, P = 6.44E-02). CONCLUSIONS: IL23R p.G149R is a susceptibility locus for UC in Japanese individuals. The GG genotype of rs117506082 at HLA loci may predict a better clinical course.

Safety and Efficacy of Embolization Using N-Butyl Cyanoacrylate via a Percutaneous Direct Approach for Endoleaks after Abdominal/Thoracic Endovascular Aortic Repair.

PURPOSE: To elucidate the safety and efficacy of embolization using N-butyl cyanoacrylate (NBCA) for endoleaks after abdominal/thoracic endovascular aortic repair (EVAR/TEVAR) via a direct percutaneous approach versus a transarterial approach. MATERIALS AND METHODS: The retrospective design of the study was approved by the institutional ethics committee, and the requirement for informed written consent was waived. Sixteen patients underwent embolization for endoleaks after EVAR/TEVAR, which was diagnosed as type II, from March 2010 to December 2013 at our institution. The number of embolization sessions was 21. A direct percutaneous approach was used in 10 sessions, and a transarterial approach was used in 11 sessions. There were 11 and 15 embolic sites for the two approaches, respectively. The procedure time, amount of contrast media used, therapeutic effect, and complications were evaluated. RESULTS: The mean procedure time (per embolic site) was 100 min (53-170) in the direct percutaneous approach, which was significantly shorter than the 191 min (76-275) in the transarterial approach. The mean amount of contrast media used during the procedure (per embolic site) was 12.8 ml (3-25) by the direct percutaneous approach, which was significantly lesser than the 71.8 ml (30-180) in the transarterial approach. Local control of the embolic site and interval increase in the size of aneurysm after embolization were not significantly different between the two approaches. In one case each, mesenteric hematoma and migration of the embolic agent occurred with a direct percutaneous approach, and a small arterial injury occurred with the transarterial approach; aneurysmal rupture/perianeurysmal hematoma and neurological dysfunction were not observed. CONCLUSION: A direct percutaneous approach is a feasible procedure for embolization of endoleaks after EVAR/TEVAR.