The clinical impact of macrophage polarity after Kasai portoenterostomy in biliary atresia.

Introduction: Biliary atresia (BA) is a cholestatic hepatopathy caused by fibrosing destruction of intrahepatic and extrahepatic bile ducts, and its etiology has not been clearly revealed. In BA, liver fibrosis progression is often observed even after Kasai portoenterostomy (KPE), and more than half of cases require liver transplantation in their lifetime in Japan. Macrophages play an important role in liver fibrosis progression and are classically divided into proinflammatory (M1) and fibrotic macrophages (M2), whose phenotypic transformation is called "macrophage polarity." The polarity has been reported to reflect the tissue microenvironment. In this study, we examined the relationship between macrophage polarity and the post-KPE clinical course. Materials and methods: Thirty BA patients who underwent KPE in our institution from 2000 to 2020 were recruited. Multiple immunostainings for CD68, CD163, CK19, and α-SMA were carried out on liver biopsy specimens obtained at KPE. ROC curves were calculated based on each clinical event, and the correlation with the clinical data was analyzed. Results and discussion: The M2 ratio, defined as the proportion of M2 macrophages (CD163-positive cells), was correlated inversely with the occurrence of postoperative cholangitis (AUC: 0.7602). The patients were classified into M2 high (n = 19) and non-high (n = 11) groups based on an M2 ratio value obtained from the Youden index ( = 0.918). As a result, pathological evaluations (Metavir score, αSMA area fraction, and CK19 area fraction) were not significantly different between these groups. In mild liver fibrosis cases (Metavir score = 0-2), the M2 non-high group had a significantly lower native liver survival rate than the high group (p = 0.02). Moreover, 4 out of 8 cases in the M2 non-high group underwent early liver transplantation within 2 years after KPE. Conclusions: Non-M2 macrophages, including M1 macrophages, may be correlated with postoperative cholangitis, and the M2 non-high group in mild liver fibrosis cases had a significantly lower native liver survival rate than the high group, requiring early liver transplantation in this study. Preventing advanced liver fibrosis is a key factor in improving native liver survival for BA patients, and liver macrophages may play important roles in liver homeostasis and the promotion of inflammation and fibrosis.

Development of an individual display optimization system based on deep convolutional neural network transition learning for somatostatin receptor scintigraphy.

Somatostatin receptor scintigraphy (SRS) is an essential examination for the diagnosis of neuroendocrine tumors (NETs). This study developed a method to individually optimize the display of whole-body SRS images using a deep convolutional neural network (DCNN) reconstructed by transfer learning of a DCNN constructed using Gallium-67 (67Ga) images. The initial DCNN was constructed using U-Net to optimize the display of 67Ga images (493 cases/986 images), and a DCNN with transposed weight coefficients was reconstructed for the optimization of whole-body SRS images (133 cases/266 images). A DCNN was constructed for each observer using reference display conditions estimated in advance. Furthermore, to eliminate information loss in the original image, a grayscale linear process is performed based on the DCNN output image to obtain the final linearly corrected DCNN (LcDCNN) image. To verify the usefulness of the proposed method, an observer study using a paired-comparison method was conducted on the original, reference, and LcDCNN images of 15 cases with 30 images. The paired comparison method showed that in most cases (29/30), the LcDCNN images were significantly superior to the original images in terms of display conditions. When comparing the LcDCNN and reference images, the number of LcDCNN and reference images that were superior to each other in the display condition was 17 and 13, respectively, and in both cases, 6 of these images showed statistically significant differences. The optimized SRS images obtained using the proposed method, while reflecting the observer's preference, were superior to the conventional manually adjusted images.

Breath-hold High-resolution T1-weighted Gradient Echo Liver MR Imaging with Compressed Sensing Obtained during the Gadoxetic Acid-enhanced Hepatobiliary Phase: Image Quality and Lesion Visibility Compared with a Standard T1-weighted Sequence.

PURPOSE: To evaluate the feasibility of breath-hold (BH) high-resolution (HR) T1-weighted gradient echo hepatobiliary phase (HBP) imaging using compressed sensing (CS) in gadoxetic acid-enhanced liver MRI in comparison with standard HBP imaging using parallel imaging (PI). METHODS: The study included 122 patients with liver tumors with hypointensity in the HBP who underwent both HR HBP imaging with CS and standard HBP imaging with PI. Two radiologists evaluated the liver edge sharpness, hepatic vessel conspicuity, bile duct conspicuity, image noise, and overall image quality, as well as the lesion conspicuity on HR and standard HBP imaging and the contrast-enhanced (CE) MR cholangiography (MRC) image quality reconstructed from HBP images. As a quantitative analysis, the SNR of the liver and the liver to lesion signal intensity ratio (LLSIR) were also determined. RESULTS: The liver edge sharpness, hepatic vessel conspicuity, bile duct conspicuity, and overall image quality as well as the lesion conspicuity and the LLSIR on HR HBP imaging with CS were significantly higher than those on standard HBP imaging (all of P < 0.001). The image quality of CE-MRC reconstructed from HR HBP imaging with CS was also significantly higher than that from standard HBP imaging (P < 0.001). Conversely, the SNR of liver in standard HBP was significantly higher than that in HR HBP with CS (P < 0.001). CONCLUSION: BH HR HBP imaging with CS provided an improved overall image quality, lesion conspicuity, and CE-MRC visualization when compared with standard HBP imaging without extending the acquisition time.

Longitudinal changes in renal volumes evaluated by automated three-dimensional volumetric computed tomography of the whole kidney: The association with the renal function and disease progression.

PURPOSE: To clarify the changes in the total renal volume over time with changes of the renal function using automated 3D volumetric CT of the whole kidney and to evaluate the usefulness of the total renal volume CT measurement in predicting chronic kidney disease (CKD) grade progression. METHODS: A total of 961 patients who underwent abdominal CT at least twice (an interval of more than 4 years) were included. The automated 3D volumetric CT measurement of the whole kidney was performed at the initial and latest CT examination. Patients with CKD grade G2 at the time of the initial CT were divided into two groups: a progression group (CKD grade progressed to G3-G5) and a non-progression group. Changes in the renal volume over time were compared between the two groups. RESULTS: The volume of both kidneys measured on initial CT was positively correlated with eGFR (ρ = 0.490, p < 0.001). There was a significant difference in the initial volume of both kidneys among CKD grades (p < 0.001, G1:318.7 ± 60.5 ml, G2:275.5 ± 53.5 ml, G3:233.7 ± 46.9 ml, G4:183.2 ± 22.5 ml, G5:157.7 ± 77.4 ml). When comparing the progression and non-progression groups, the initial volume of both kidneys was significantly smaller in the progression group, compared with the non-progression group (252.0 ± 50.6 ml vs. 278.9 ± 53.7 ml). In addition, the annual reduction volume in both the right and left kidneys was significantly greater in the progression group than in the non-progression group (p < 0.001). CONCLUSION: The automated 3D volumetric CT measurement of the whole kidney has the potential to monitor changes in renal volume over time with changes of the renal function.

Non-neoplastic Liver Lesions after Biliary Stenting: Gadoxetic Acid-enhanced MRI Findings and Clinical association.

BACKGROUND: Non-neoplastic liver lesions show low signal intensity in the hepatobiliary phase (HBP) of gadoxetic acid-enhanced magnetic resonance imaging (EOB-MRI) after biliary stenting and require differentiation from liver metastases. OBJECTIVE: The study aimed to evaluate the imaging findings and clinical association of non-neoplastic liver lesions showing hypointensity in the HBP of EOB-MRI after biliary stenting, and assess their differentiation from liver metastases. METHODS: This study included 30 patients who underwent EOB-MRI after biliary stenting for pancreaticobiliary malignancies. Among these, 7 patients had pathologically diagnosed non-neoplastic liver lesions, which appeared hypointense in the HBP, and were categorized into the non-neoplastic group. The remaining 23 patients without non-neoplastic liver lesions were included in the control group. Additionally, 29 patients with liver metastasis were included in the liver metastasis group. Clinical associations and imaging features were compared between the groups. RESULTS: A history of cholangitis and two or more biliary interventional procedures were significantly more frequently observed in the non-neoplastic group (p=0.002 and p=0.01, respectively) than in the control groups. Regarding the imaging findings, the liver-to-lesion signal intensity ratio in the HBP in the liver metastasis group was significantly higher than that in the non-neoplastic group (2.13 vs. 1.53, p=0.002). Additionally, liver metastases were visualized significantly more clearly on diffusion-weighted images (p=0.033) and HBP images (p<0.001) in comparison to non-neoplastic lesions. CONCLUSION: Non-neoplastic liver lesions due to biliary inflammation may be observed in the HBP of EOB-MRI in patients after biliary stenting. These lesions may be associated with a history of cholangitis and repeated biliary intervention procedure, and need to be differentiated from liver metastases.

Impact on the image quality of modified reduced field-of-view diffusion-weighted magnetic resonance imaging of pancreatic adenocarcinoma using spatially tailored two-dimensional radiofrequency pulses with a tilted excitation plane: A comparison with conventional field-of-view imaging.

PURPOSE: Modified reduced FOV diffusion-weighted imaging (DWI) using spatially-tailored 2D RF pulses with tilted excitation plane (tilted r-DWI) has been developed. The purpose of this study was to evaluate the impact on image quality and quantitative apparent diffusion coefficient (ADC) values of tilted r-DWI for pancreatic ductal adenocarcinomas (PDAC) in comparison to conventional full-FOV DWI (f-DWI). METHODS: This retrospective study included 21 patients (mean 70.7, range 50-85 years old) with pathologically confirmed PDAC. All MR images were obtained using 3 T systems. Two radiologists evaluated presence of blurring or ghost artifacts, susceptibility artifacts, and aliasing artifacts; anatomic visualization of the pancreas; interslice signal homogeneity; overall image quality; and conspicuity of the PDAC. For quantitative analysis, contrast-to-noise ratio (CNR), signal-to-noise ratio (SNR), signal-intensity ratio (SIR) and ADC values were measured using regions of interest. RESULTS: All image quality scores except aliasing artifacts in tilted r-DWI were significantly higher than those in f-DWI (p < 0.01). The CNR and SIR of PDAC were significantly higher in tilted r-DWI than in f-DWI (6.7 ± 4.4 vs. 4.7 ± 3.9, 2.02 ± 0.72 vs. 1.72 ± 0.60, p < 0.01). Conversely, the SNR of PDAC in tilted r-DWI was significantly lower than that in f-DWI (56.0 ± 33.1 vs. 113.6 ± 67.3, p < 0.01). No significant difference was observed between mean ADC values of the PDAC calculated from tilted r-DWI (tilted r-ADC) and those from f-DWI (f-ADC) (1225 ± 250 vs. 1294 ± 302, p = 0.11). CONCLUSION: The r-DWI using 2D RF techniques with a tilted excitation plane was shown to significantly improve the image quality and CNR and reduce image artifacts compared to f-DWI techniques in MRI evaluations of PDAC without significantly affecting ADC values.

Dual-Source Contrast-Enhanced Multiphasic CT of the Liver Using Low Voltage (70 kVp): Feasibility of a Reduced Radiation Dose and a 50% of Contrast Dose.

This study investigated the feasibility of both a reduced radiation dose and a 50% of contrast dose in multiphasic CT of the liver with a 70 kVp protocol compared with a standard-tube-voltage protocol derived from dual-energy (DE) CT (blended DE protocol) with a full-dose contrast-agents in the same patient group. This study included 46 patients who underwent multiphasic contrast-enhanced dynamic CT of the liver with both a 70 kVp and a blended DE protocols. For quantitative analysis, median CT values for the liver, aorta, and portal vein, as well as signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR), were measured and calculated. In addition, as a qualitative analysis, the contrast effect and overall image quality of the abdominal organs were evaluated on a five-point scale. CNR and SNR of the hepatic parenchyma were not significantly different between the 70kV protocol and the Blended DE protocol in all phases. The 70 kVp protocol showed significantly better image quality compared with the blended DE protocol in the arterial phase (p = 0.035) and the equilibrium layer phase (p = 0.016). A 70 kVp CT protocol in combination with a reduced radiation dose and half-dose iodine load is feasible for multiphasic dynamic CT of the liver by maintaining the contrast enhancement effects and image quality in comparison with the blended DE CT protocol.

Impact of fat on the apparent T1 value of the liver: assessment by water-only derived T1 mapping.

OBJECTIVES: To determine the impact of fat on the apparent T1 value of the liver using water-only derived T1 mapping. METHODS: 3-T MRI included 2D Look-Locker T1 mapping and proton density fat fraction (PDFF) mapping. T1 values of the liver were compared among T1 maps obtained by in-phase (IP), opposed-phase (OP), and Dixon water sequences using paired t-test. The correlation between T1 values of the liver on each T1 map and PDFF was assessed using Spearman correlation coefficient. The absolute differences between T1 value of the liver on Dixon water images and that on IP or OP images were also correlated with PDFF. RESULTS: One hundred sixty-two patients (median age, 70 [range, 24-91] years, 90 men) were retrospectively evaluated. The T1 values of the liver on each T1 map were significantly different (p < 0.001). The T1 value of the liver on IP images was significantly negatively correlated with PDFF (r = - 0.438), while the T1 value of the liver on OP images was slightly positively correlated with PDFF (r = 0.164). The T1 value of the liver on Dixon water images was slightly negatively correlated with PDFF (r = - 0.171). The absolute differences between T1 value of the liver on Dixon water images and that on IP or OP images were significantly correlated with PDFF (r = 0.606, 0.722; p < 0.001). CONCLUSION: Fat correction for the apparent T1 value by water-only derived T1 maps will be helpful for accurately evaluating the T1 value of the liver. CLINICAL RELEVANCE STATEMENT: Fat-corrected T1 mapping of the liver with the water component only obtained from the 2D Dixon Look-Locker sequence could be useful for accurately evaluating the T1 value of the liver without the impact of fat in daily clinical practice. KEY POINTS: • The T1 values of the liver on the conventional T1 maps are significantly affected by the presence of fat. • The apparent T1 value of the liver on water-only derived T1 maps would be slightly impacted by the presence of fat. • Fat correction for the apparent T1 values is necessary for the accurate assessment of the T1 values of the liver.

Evaluation of diffusion-weighted magnetic resonance imaging of the rectal cancers: comparison between modified reduced field-of-view single-shot echo-planar imaging with tilted two-dimensional radiofrequency excitation pulses and conventional full field-of-view readout-segmented echo-planar imaging.

PURPOSE: To evaluate the image quality qualitatively and quantitatively, as well as apparent diffusion coefficient (ADC) values of modified reduced field-of-view diffusion-weighted magnetic resonance imaging (MRI) using spatially tailored two-dimensional radiofrequency pulses with tilted excitation plane (tilted r-DWI) based on single-shot echo planar imaging (SS-EPI) compared with full-size field-of-view DWI (f-DWI) using readout segmented (RS)-EPI in patients with rectal cancer. MATERIALS AND METHODS: Twenty-two patients who underwent an MRI for further evaluation of rectal cancer were included in this retrospective study. All MR images were analyzed to compare image quality, lesion conspicuity, and artifacts between f-DWI with RS-EPI and tilted r-DWI with SS-EPI. Signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR), and ADC values were also compared. The Wilcoxon signed-rank test or paired t test was performed to compare the qualitative and quantitative assessments. RESULTS: All image quality scores, except aliasing artifacts, were significantly higher (p < 0.01 for all) in tilted r-DWI than f-DWI with RS-EPI. CNR in tilted r-DWI was significantly higher than in f-DWI with RS-EPI (p < 0.01), while SNR was not significantly different. Regarding the ADC values, no significant difference was observed between tilted r-DWI and f-DWI with RS-EPI (p = 0.27). CONCLUSION: Tilted r-DWI provides a better image quality with fewer artifacts and higher rectal lesion conspicuity than f-DWI with RS-EPI, indicating the feasibility of this MR sequence in evaluating rectal cancer in clinical practice.

Development of anti-GD2 Antibody-producing Mesenchymal Stem Cells as Cellular Immunotherapy.

BACKGROUND/AIM: Using the tyrosine hydroxylase (TH)-MYCN mouse neuroblastoma (NB) model, we have previously reported the accumulation of mouse mesenchymal stem cells (mMSCs) on tumors in vivo and the antitumor effect of mMSCs transfected with a small molecule (IFN-ß) expression gene. In this study, we have developed novel MSCs secreting anti-disialoganglioside GD2 antibody (anti-GD2-MSCs) and evaluated their antitumor effects in vitro. MATERIALS AND METHODS: We generated an anti-GD2 antibody construct (14.G2a-Fcx2-GFP) incorporating FLAG-tagged single-chain fragment variable against GD2 fused to a linker sequence, a fragment of the constant portion of human IgG1, and GFP protein. The construct was lentivirally transduced into mMSCs and the transduction efficiency was assessed by GFP expression. The secretion of FLAG-tagged anti-GD2 antibody was detected by Western blotting using anti-FLAG antibody. Antibody binding capacity was confirmed by flow cytometry. Antibody-dependent cellular cytotoxicity (ADCC) was evaluated using human NB cells and human natural killer (NK) cells to assess whether the antitumor activity was enhanced in the presence of the produced antibodies. RESULTS: The transduction efficiency of anti-GD2-MSCs was more than 90%. anti-GD2-MSCs secreted antibodies extracellularly and these antibodies had high affinity to GD2-expressing human NB cells. ADCC assays showed that the addition of antibodies secreted from anti-GD2-MSCs significantly increased the cytotoxic activity of NK cells against NB cells. CONCLUSION: Newly developed anti-GD2-MSCs produced functional antibodies that have affinity to the GD2 antigen on NB cells and can induce ADCC-mediated cytotoxicity. Anti-GD2-MSCs based cellular immunotherapy has the potential to be a novel therapeutic option for intractable NB.

Automated whole-volume measurement of CT fat fraction of the pancreas: correlation with Dixon MR imaging.

OBJECTIVES: This study aimed to assess the feasibility of pancreatic steatosis quantification by automated whole-volume measurement of the fat fraction of the pancreas on CT in comparison to MRI using proton-density fat fraction (PDFF) techniques. METHODS: Fifty-nine patients who underwent both CT and MRI were analyzed. Automated whole-volume measurement of pancreatic fat on unenhanced CT was performed by a histogram analysis with local thresholding. Three sets of CT fat volume fraction (FVF) (%) values with thresholds of -30 Hounsfield unit (HU), -20 HU and -10 HU were compared to MR-FVF (%) values measured on a PDFF map. RESULTS: The median -30 HU CT-FVF, -20 HU CT-FVF, -10 HU CT-FVF and MR-FVF values of the pancreas were 8.6% (interquartile range (IQR), 11.3), 10.5% (IQR, 13.2), 13.4% (IQR, 16.1) and 10.9% (IQR, 9.7), respectively. The -30 HU CT-FVF (%), -20 HU CT-FVF (%) and -10 HU CT-FVF (%) of the pancreas showed a significant positive correlation with the MR-FVF (%) of the pancreas (ρ = 0.898, p < 0.001, ρ = 0.905, p < 0.001, ρ = 0.909, p < 0.001, respectively). The -20 HU CT-FVF (%) displayed reasonable agreement with the MR-FVF (%) with a low absolute fixed bias (mean difference, 0.32%; limit of agreement from -10.1 to 10.7%). CONCLUSION: The automated whole-volume measurement of the CT fat fraction of the pancreas using the threshold CT attenuation value of -20 HU may be a feasible, non-invasive, and convenient technique for quantifying pancreatic steatosis. ADVANCES IN KNOWLEDGE: CT-FVF value of the pancreas had a positive correlation with the MR-FVF value. The -20 HU CT-FVF may be a convenient technique for quantifying pancreatic steatosis.

Lobar hepatic steatosis: Association with portal flow hemodynamics evaluated by multiphasic dynamic contrast-enhanced CT.

PURPOSE: This study aimed to evaluate the association of portal flow hemodynamics with lobar hepatic steatosis by means of dynamic contrast-enhanced (DCE) CT. METHODS: The study population consisted of 235 patients, 77 with lobar hepatic steatosis (right, n = 67; left, n = 10), 158 with diffuse hepatic steatosis with (n = 76) and without (n = 82) a focal fatty spared area. CT attenuation values (Hounsfield units: HU) of the liver with and without hepatic steatosis were measured in unenhanced and arterial-phase CT. The contrast enhancement (CE) values were calculated as the difference in HU values between unenhanced and arterial-phase CT. RESULTS: In 67 patients with lobar steatosis of the right lobe, the median CE values of the areas of right lobar steatosis were significantly lower than those of the non-fatty left lobe (13 [IQR 7-19] vs 23 [13-33] HU, P < 0.01), suggesting dominant SMV flow to the right lobe with lobar hepatic steatosis. Conversely, in 10 patients with lobar steatosis of the left lobe, the median CE values of the areas of left lobar steatosis were lower than those of the non-fatty right lobe (15.5 [11.75-21.5] vs 16 [14.5-22] HU); however, this difference was not statistically significant (P = 0.20). In 76 patients with a focal fatty spared area, there were significant differences in the median CE values between hepatic steatosis areas and focal fatty spared areas in the gallbladder fossa group (P = 0.01) and in the segment IV group (P < 0.01). CONCLUSION: Lobar hepatic steatosis may be associated with regional changes of the portal flow hemodynamics (i.e., predominant perfusion from the SMV flow to the lobes with steatosis).

Current treatment strategies for postoperative intrahepatic bile duct stones in congenital biliary dilatation: a single center retrospective study.

BACKGROUND: Intrahepatic bile duct (IHBD) stones are one of the most common late complications of Roux-en-Y hepaticojejunostomy for congenital biliary dilatation (CBD). We report the current treatment strategies for IHBD stones and their outcomes in our institute. METHODS: Between 1983 and 2021, 117 patients with CBD were surgically treated in our institute. Our treatment strategies included oral ursodeoxycholic acid (UDCA), double-balloon endoscopic retrograde cholangiography (DB-ERC), percutaneous cholangio-drainage (PTCD), and open surgery. A retrospective study was conducted using medical charts. RESULTS: Postoperative IHBD stones were identified in 12 of 117 patients with CBD (10.2%). Five patients received UDCA, and small stones were successfully resolved in two cases. DB-ERC was performed eight times in five patients, but the endoscope could not reach the porta hepatis due to a long jejunal loop in two of five patients. One patient presented with severe acute pancreatitis induced by prolonged DB-ERC. PTCD was performed in three patients, two of whom finally underwent open surgery due to unsuccessful lithotomy. Open surgery was eventually performed in three patients. Lithotomy was performed in one patient; lithotomy with strictureplasty was performed in another patient. The other patient was diagnosed with intrahepatic cholelithiasis with adenocarcinoma. He underwent left lobectomy and died of carcinomatous peritonitis. CONCLUSIONS: Oral UDCA may be effective for small stones. Although DB-ERC should be considered as a first-line interventional therapy for lithotomy, it may not be feasible due to a long jejunal loop, and pancreatitis may occur. Long-term follow-up and early detection and treatment for IHBD stones may yield a good prognosis.

Pancreatic Steatosis Evaluated by Automated Volumetric CT Fat Fraction of the Pancreas: Association with Severity in COVID-19 Pneumonia.

This study investigated the relationship between the severity of pneumonia based on chest CT findings and that of pancreatic steatosis assessed using an automated volumetric measurement of the CT fat volume fraction (CT-FVF) of the pancreas, using unenhanced three-dimensional CT in polymerase chain reaction (PCR)-confirmed COVID-19 patients. The study population consisted of 128 patients with PCR-confirmed COVID-19 infection who underwent CT examinations. The CT-FVF of the pancreas was calculated using a histogram analysis for the isolation of fat-containing voxels in the pancreas. The CT-FVF (%) of the pancreas had a significantly positive correlation with the lung severity score on CT (ρ = 0.549, p < 0.01). CT-FVF (%) of the pancreas in the severe pneumonia group was significantly higher than that of the non-severe pneumonia group (21.7% vs. 7.8%, p < 0.01). The area under the curve of CT-FVF (%) of the pancreas in predicting the severity of pneumonia on CT was calculated to be 0.82, with a sensitivity of 88% and a specificity of 68% at a threshold for the severity score of 12.3. The automated volumetric measurement of the CT-FVF of the pancreas using unenhanced CT can help estimate disease severity in patients with COVID-19 pneumonia based on chest CT findings.

Development of minimally invasive cancer immunotherapy using anti-disialoganglioside GD2 antibody-producing mesenchymal stem cells for a neuroblastoma mouse model.

PURPOSE: Mouse IgG anti-disialoganglioside GD2 antibody-secreting mouse mesenchymal stem cells (anti-GD2-MSCs) were developed, and their anti-tumor effects were validated in an in vivo neuroblastoma mouse model. METHODS: Anti-GD2 antibody constructs were generated, incorporating FLAG-tagged single-chain fragment variables against GD2 fused to a linker sequence, and a fragment of a stationary portion was changed from human IgG to mouse IgG and GFP protein. The construct was lentivirally introduced into mouse MSCs. A syngeneic mouse model was established through the subcutaneous transplantation of a tumor tissue fragment from a TH-MYCN transgenic mouse, and the homing effects of anti-GD2-MSCs were validated by In vivo imaging system imaging. The syngeneic model was divided into three groups according to topical injection materials: anti-GD2-MSCs with IL-2, IL-2, and PBS. The tumors were removed, and natural killer (NK) cells were counted. RESULTS: Anti-GD2-MSCs showed homing effects in syngeneic models. The growth rate of subcutaneous tumors was significantly suppressed by anti-GD2-MSCs with IL-2 (p < 0.05). Subcutaneous tumor immunostaining showed an increased NK cell infiltration in the same group (p < 0.01). CONCLUSION: Anti-GD2-MSCs using mouse IgG showed a homing effect and significant tumor growth suppression in syngeneic models. Anti-GD2-MSC-based cellular immunotherapy could be a novel therapeutic strategy for intractable neuroblastoma.

The Evaluation of Transmural Healing by Low-dose Computed Tomography Enterography in Patients with Crohn's Disease.

Objective Transmural healing (TH) has been attracting attention as a new therapeutic target for Crohn's disease, but there are few clinical data on TH in Japan. We introduced low-dose computed tomography enterography (CTE) as a monitoring method for Crohn's disease and retrospectively investigated the accuracy of evaluating TH by CTE. Methods Among Crohn's disease patients who underwent low-dose CTE at our hospital from January 2009 to March 2021, 122 patients who underwent colonoscopy or balloon endoscopy within 2 weeks were included. Results of radiological and endoscopic examinations were reviewed independently by radiologists and gastrointestinal endoscopists, respectively. The concordance rate of the diagnosis between CTE and endoscopy was evaluated. Results Twenty-six patients (21.3%) achieved TH, and the kappa index was 0.743. On comparing the TH and non-TH groups, the Crohn's disease activity index (p=0.02), endoscopic healing rate (p<0.001), serum albumin (p=0.043), and serum C-reactive protein level (p=0.018) showed significant differences. Among the 122 patients, 69 (56.5%) showed concordance between the diagnosis of CTE and endoscopy, and 22 (18.0%) achieved both TH and endoscopic healing. Conclusion This study provides real-world data on Crohn's disease evaluated with low-dose CTE in Japan. The TH criterion used in this study has a high kappa coefficient and can be used reproducibly in many institutions.

IL13 and periostin in active fibrogenic areas of the extrahepatic bile ducts in biliary atresia patients.

BACKGROUND: The leading pathology of biliary atresia (BA) is inflammatory and fibrous obstruction of extrahepatic bile duct, but the pathogenesis remains unclear. IL13 is a cytokine associated with allergies and inflammatory fibrosis, and periostin induces fibrogenesis by stimulation with IL13. We analyzed the involvement of IL13 and periostin in inflammatory fibrosis in the extrahepatic bile duct of BA patients. MATERIALS AND METHODS: Surgically resected tissues from the hepatic hilar area of BA patients were immunostained with CD45, α-SMA, IL13 and periostin and statistically analyzed. Fibroblasts from the resected tissue were cultured with recombinant IL13, and periostin production was analyzed by quantitative polymerase chain reaction and Western blotting. RESULTS: IL13 was stained in 93% of large and micro bile ducts, and 92.1% matched with the CD45 location (p = 0.006) around the large bile ducts. Periostin staining correlated with the localization of IL13 and αSMA (p < 0.001) around the large bile ducts. Periostin mRNA and protein were upregulated by IL13 stimulation in cultured fibroblasts. CONCLUSION: IL13 was associated with induced periostin expression by fibroblasts, playing a vital role in the pathogenesis of fibrogenesis around the extrahepatic bile duct in BA.

Pancreatic liposarcoma: a case report.

An 81-year-old woman who had undergone total thyroidectomy for papillary thyroid cancer 12 years earlier was found to have a tumor in the tail of the pancreas. Four years earlier, skin, lung, and mediastinal lymph node metastases had appeared. Computed tomography (CT) showed a mass 26 mm in diameter in the tail of the pancreas. Thereafter, the pancreatic tumor increased in size, while the lung metastases remained stable. Unenhanced CT at the time of first detection showed that the tumor was heterogeneous, with low-attenuation areas indicating fat components. As the tumor grew, the fat components became unclear. Laparoscopic distal pancreatectomy and splenectomy were performed. The tumor was diagnosed as dedifferentiated liposarcoma with a well-differentiated liposarcoma component at the tumor margin. The pancreas is an extremely rare site of primary liposarcoma. In the present case, a pancreatic liposarcoma appeared during follow-up of thyroid cancer, and the changes over time were able to be observed with CT.

Bile Flow Dynamics in Patients with Cholelithiasis: An Evaluation with Cine-Dynamic Magnetic Resonance Cholangiopancreatography Using a Spatially Selective Inversion-Recovery Pulse.

BACKGROUND: A variety of pathophysiological changes in the biliary system occur in patients with cholelithiasis, but the changes in the bile flow dynamics in those patients remain unclear. The purpose of this study was to elucidate the changes in the bile flow dynamics in patients with cholelithiasis using cine-dynamic magnetic resonance cholangiopancreatography (MRCP) with a spatially selective inversion-recovery (IR) pulse. METHODS: We retrospectively examined 25 patients with gallstones (gallstone group) and 69 patients without gallstones (non-gallstone group) who underwent abdominal MRI, including in- and opposed-phase T1-weighted images and cine-dynamic MRCP with a spatially selective IR pulse. The frequency and secretion grade of the antegrade and reverse flow of the bile on the cine dynamic MRCP images and the signal intensity ratio (SIR) of the gallbladder in the in- and opposed-phase T1-weighted images were evaluated. RESULTS: The frequency and mean secretion grade of the antegrade bile flow were significantly higher in the gallstone group than in the non-gallstone group (p = 0.011 and p = 0.003), while no significant differences in those values of the reverse bile flow were found between the two groups. The SIR of the gallbladder in the T1-weighted gradient-echo in-phase images was significantly lower in the gallstone group than in the non-gallstone group (p = 0.004). CONCLUSIONS: Cine-dynamic MRCP with a spatially selective IR pulse can noninvasively visualize changes in the bile flow dynamics of patients with gallstones.

The pancreatic exocrine function in patients with pancreatic endocrine insufficiency: the evaluation with cine-dynamic magnetic resonance cholangiopancreatography using a spatially selective inversion-recovery pulse and T1 mapping.

PURPOSE: To evaluate the association of the pancreatic exocrine function estimated by cine-dynamic magnetic resonance cholangiopancreatography (MRCP) using a spatially selective inversion-recovery (IR) pulse with the pancreatic endocrine function estimated by the T1 relaxation time of the pancreatic parenchyma and HbA1c values. MATERIALS AND METHODS: Forty-three patients with suspected hepatobiliary or pancreatic diseases were included. Patients were classified into three groups: HbA1c < 5.7% (normal group), 5.7% ≤ HbA1c < 6.5% (prediabetes group), and HbA1c ≥ 6.5% (diabetes group). The frequency of the secretory flow of the pancreatic juice was observed within the area of the IR pulse, and the moving distance (mean secretion grade) of the pancreatic juice inflow within the area of the IR pulse on cine-dynamic MRCP, and the T1 relaxation time of the pancreatic parenchyma on the T1 map images were assessed. The MR imaging measurements were compared using Spearman's rank correlation coefficient analysis and the Kruskal-Wallis and Mann-Whitney U tests. RESULTS: Both the mean secretion grade and frequency of the pancreatic secretory inflow had a significant negative correlation with the T1 relaxation time of the pancreatic parenchyma (r = - 0.335, p = 0.028 and r = - 0.305, p = 0.047, respectively) and HbA1c values (r = - 0.308, p = 0.044 and r = - 0.313, p = 0.041, respectively). Both the mean secretion grade and frequency of the pancreatic secretory inflow in the elevated HbA1c (prediabetes and diabetes) group were significantly lower than those in the normal group (p = 0.030 and p = 0.029, respectively). CONCLUSION: The pancreatic exocrine function estimated by cine-dynamic MRCP was significantly lower in patients with prediabetes and diabetes than in controls. Cine-dynamic MRCP with a spatially selective IR pulse may be useful for the early diagnosis of pancreatic exocrine insufficiency in patients with pancreatic endocrine insufficiency.