Bo-Kyeong Kang

Infusion of Human Bone Marrow-Derived Mesenchymal Stem Cells Alleviates Autoimmune Nephritis in a Lupus Model by Suppressing Follicular Helper T-Cell Development

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by the production of autoantibodies to components of the cell nucleus. These autoantibodies are predominantly produced with the help of follicular/helper T (Tfh) cells and form immune complexes that trigger widespread inflammatory damage, including nephritis. In recent studies, mesenchymal stem cells (MSCs) elicited diverse, even opposing, effects in experimental and clinical SLE. Here we investigated the effect of human bone marrow-derived MSCs (hBM-MSCs) in a murine model of SLE, the F1 hybrid between New Zealand Black and New Zealand White strains (NZB/W). We found that infusion of female NZB/W mice with hBM-MSCs attenuated glomerulonephritis; it also decreased levels of autoantibodies and the incidence of proteinuria and improved survival. These effects coincided with a decrease in Tfh cells and downstream components. Infiltration of long-lived plasma cells into the inflamed kidney was also reduced in the hBM-MSC-treated mice. Importantly, hBM-MSCs directly suppressed the in vitro differentiation of naive CD4+ T cells toward Tfh cells in a contact-dependent manner. These results suggest that MSCs attenuate lupus nephritis by suppressing the development of Tfh cells and the subsequent activation of humoral immune components. They thus reveal a novel mechanism by which MSCs regulate humoral autoimmune diseases such as SLE.

Shear Wave Elastography for Assessment of Steatohepatitis and Hepatic Fibrosis in Rat Models of Non-Alcoholic Fatty Liver Disease.

The purpose of this study was to evaluate shear wave elastography (SWE) as a method for determining the severity of non-alcoholic fatty liver disease (NAFLD) and the stage of hepatic fibrosis, as well as the major determinants of liver elasticity among the various histologic and biomolecular changes associated with NAFLD. Rat NAFLD models with various degrees of NAFLD severity were created and imaged using SWE. The explanted livers were subjected to histopathologic evaluation and RNA expression analysis. Among the histologic and biomolecular findings, the fibrosis stage and the collagen RNA level were significant independent factors associated with liver elasticity (p < 0.001). Liver elasticity was effective in detecting non-alcoholic steatohepatitis (NASH) and in determining fibrosis stage, and the corresponding areas under the receiver operating characteristic curves were 0.963 and 0.927-0.997, respectively. In conclusion, SWE is a potential non-invasive method for the detection of NASH and staging of hepatic fibrosis in patients with NAFLD.

Cholecystectomy Causes Ultrasound Evidence of Increased Hepatic Steatosis

BackgroundCholecystectomy might contribute to the development of hepatic steatosis through metabolic changes. The biologic alteration of the enterohepatic circulation of bile acids and the alteration of the metabolic activity of bile acid that follows cholecystectomy may contribute to hepatic steatosis. This prospective study was conducted to clarify the possibility of steatosis development after cholecystectomy.MethodsFrom October 2013 to July 2014, 82 consecutive patients with a presumptive diagnosis of gallbladder disease were cholecystectomized. Liver parenchymal steatosis was measured using ultrasound and the hepatic steatosis index.ResultsIn all 82 patients, the hepatic steatosis index was found to be significantly correlated with the US fatty liver grade (Spearman’s correlation r2xa0=xa00.331, Pxa0<xa00.001). A total of 62 patients were followed up for 3xa0months. Comparison with the initial grade showed that 12 (18.5xa0%) patients had worsened from normal to mild (nxa0=xa010), from mild to moderate (nxa0=xa01), and from mild to severe (nxa0=xa01). The other patients stayed at their initial grade except one patient who improved (from moderated to mild). Analysis of laboratory findings showed that white blood cell count, aspartate transaminase, alanine transaminase level, and total bilirubin level were decreased. However, serum albumin and high-density lipoprotein cholesterol levels significantly increased.ConclusionsHepatic steatosis significantly developed 3xa0months after cholecystectomy. Therefore, cholecystectomy might be considered a risk factor for hepatic steatosis, but the relationship should be confirmed with long-term follow-up from a large group of patients.

Design and Fabrication of a Thin-Walled Free-Form Scaffold on the Basis of Medical Image Data and a 3D Printed Template: Its Potential Use in Bile Duct Regeneration

Three-dimensional (3D) printing, combined with medical imaging technologies, such as computed tomography and magnetic resonance imaging (MRI), has shown a great potential in patient-specific tissue regeneration. Here, we successfully fabricated an ultrathin tubular free-form structure with a wall thickness of several tens of micrometers that is capable of providing sufficient mechanical flexibility. Such a thin geometry cannot easily be achieved by 3D printing alone; therefore, it was realized through a serial combination of processes, including the 3D printing of a sacrificial template, the dip coating of the biomaterial, and the removal of the inner template. We demonstrated the feasibility of this novel tissue engineering construct by conducting bile duct surgery on rabbits. Moving from a rational design based on MRI data to a successful surgical procedure for reconstruction, we confirmed that the presented method of fabricating scaffolds has the potential for use in customized bile duct regeneration. In addition to the specific application presented here, the developed process and scaffold are expected to have universal applicability in other soft-tissue engineering fields, particularly those involving vascular, airway, and abdominal tubular tissues.

Comparison of conventional sonographic signs and magnetic resonance imaging proton density fat fraction for assessment of hepatic steatosis

This study correlated conventional ultrasonography (US) signs with the magnetic resonance imaging (MRI) proton density fat fraction (PDFF) to evaluate the diagnostic performance of US signs (alone or combined) to predict presence and degree of hepatic steatosis (HS). Overall, 182 subjects met the study inclusion criteria between February 2014 and October 2016. Four US signs were evaluated independently by two radiologists. MRI PDFF was defined as the average of 24 non-overlapping regions of interest (ROIs) within eight liver segments obtained by drawing three ROIs within each segment. The latter acted as the reference standard to evaluate diagnostic accuracy of the US signs and their combinations. Diagnostic performance of US for HS was assessed using receiver operating characteristic (ROC) curve analyses. There was a strongly positive correlation between some combinations of US signs and PDFF (σu2009=u20090.780, pu2009<u20090.001). The sensitivity, specificity, PPV, and NPV were 96.6%, 74.8%, 64.8%, and 97.9%, respectively, determined using abnormal hepatorenal echoes to detect grade 1 or higher HS (area under the ROC curveu2009=u20090.875). The sensitivity and NPV for detecting HS with US were good and US may be considered a suitable screening tool for exclusion of HS.

Estimating of hepatic fat amount using MRI proton density fat fraction in a real practice setting

Abstract The recently developed magnetic resonance imaging (MRI) proton density fat fraction (PDFF) allows measurement of the fat in all segments of hepatic tissue. However, it is time consuming and inconvenient to measure each segment repeatedly. Moreover, volume of each segment also should be adjusted with arithmetic mean of the selected segments when total amount of liver fat is estimated. Therefore, we try to develop a clinically-relevant and applicable method of estimating hepatic fat in PDFF image. A total of 164 adults were enrolled. We addressed the measurement frequency and segment selection to determine the optimal method of measuring intrahepatic fat. Total hepatic fat was estimated by the weighted mean of each segment reflecting their respective segmental volumes. We designed 2 models. In Model 1, we determined the segment order by which the mean was closest to the whole weighted mean. In Model 2, we determined the segment order by which the arithmetic mean of the selected segments was closest to the whole weighted mean. Fat fraction (FF) was most important risk factor of hepatic heterogeneity in multivariable analysis (&bgr;u200a=u200a0.534, Pu200a<u200a.001). In severe fatty liver (FFu200a>u200a22.1%), intrahepatic fat variability was 2.47% (1.16–6.26%). The arithmetic mean total intrahepatic FF was 12.66%. But the weighted mean that applied to each segmental volume was 12.90%. In Model 1, arithmetic mean of segments 4 and 5 was closest to the total estimated hepatic fat amount. However, when we added segment 8, the mean of segments 4, 5, and 8 was significantly different from the estimated total hepatic fat amount (Pu200a=u200a.0021). In Model 2, arithmetic mean of segments 4 and 5 was closest to the total estimated hepatic fat amount. There was a significant reduction in variability between segment 4 and segments 4 and 5 (Pu200a<u200a.0001). Averaging the mean hepatic FF of segments 4 and 5 was the most reasonable method for estimating total intrahepatic fat in practice.

Higher visceral fat area/subcutaneous fat area ratio measured by computed tomography is associated with recurrence and poor survival in patients with mid and low rectal cancers

PurposeObesity is thought to influence postoperative complications and recurrence of mid and low rectal cancer (MLRC) because of intraoperative technical difficulties. However, few reports have described the relationship between obesity indices and the clinical outcomes of MLRC. This study aimed to investigate the association between visceral obesity on computed tomography (CT) and oncolofical outcomes after surgery for MLRC and identify the obesity index that most accurately reflects clinical outcomes.MethodsWe investigated 125 patients who underwent curative resection for MLRC between 2004 and 2010. Visceral fat area (VFA) was defined as the umbilicus-level intra-abdominal adipose tissue area measured by CT. Body mass index (BMI), total fat area, VFA, subcutaneous fat area (SFA) and VFA/SFA ratio (V/S ratio) were analysed.ResultsThe median follow-up time was 60.3xa0months (range, 38.2–122.6xa0months). Recurrence was detected in 28 (22.4%) patients. Among the various obesity indices, recurrence was significantly associated with V/S ratio only (1.02u2009±u20090.45 versus 0.86u2009±u20090.34; Pu2009=xa00.046). Stage, preoperative carcinoembryonic antigen level, V/S ratio, lymphatic invasion and perineural invasion were significantly associated with recurrence on univariate analysis, while only V/S ratio (Pu2009=xa00.019; 95% confidence interval, 1.22 to 9.09) was significantly associated with recurrence on multivariate analysis. Disease-free and overall survival of the obese group (V/S ratio >u20091.0) were shorter than those of the non-obese group.ConclusionsV/S ratio is the optimal obesity index for predicting stage I–III MLRC recurrence.

Feasibility of modified Dixon MRI techniques for hepatic fat quantification in hepatic disorders: validation with MRS and histology

OBJECTIVEnTo assess the feasibility of proton density fat fraction (PDFF) MRI for estimating hepatic fat fraction with magnetic resonance spectroscopy (MRS) and histology as references and to investigate intrahepatic fat distribution and variability.nnnMETHODSnBetween November 2014 and September 2015, 85 adults (48 males, 47 females) who underwent MRI-PDFF (n = 139), MRS-PDFF (n = 49) and liver biopsy (n = 29) were enrolled in this study. Data were compared using linear regression. MRI-PDFF and standard deviations (variability) and differences between maximum and minimum PDFF (PDFF range) for whole liver, the lobes, and segment levels were calculated for each subject.nnnRESULTSnWhole-liver MRI-PDFF showed good correlation with MRS-PDFF (r = 0.961) and histologic degree of hepatic steatosis (σ = 0.809). Hepatic fat fraction is different between lobes and segments. Mean PDFF and mean PDFF range of the right lobe were higher than for the left lobe, whereas variability in the right lobe was lower than in the left lobe.nnnCONCLUSIONnMRI-PDFF is an accurate non-invasive method for quantifying hepatic fat for various hepatic disorders, and may be preferable for measuring fat fraction in the right liver for more precise values in longitudinal monitoring, while avoiding FF measurement in the left liver. Advances in knowledge: MRI-PDFF provides a non-invasive and accurate quantification of hepatic steatosis in various hepatic disorders. It would be preferable to measure FF in the right liver than in the left liver.

Laparoscopic treatment of Castleman's disease in a patient with a history of malignant Brenner tumor.

Castlemans disease (CD) is a rare, atypical, lymphoproliferative disease of unknown etiology. The most common location for CD is the mediastinum (63%) [1]. A retroperitoneal location has been reported in 7% of patients, with only 2% of cases involving the pararenal region [2]. For this reason, CD located in the retroperitoneum is difficult to differentiate from other benign or malignant lesions. Here, we report a patient with CD located in the anterior lower pole of the right kidney who had been diagnosed with a malignant Brenner tumor after hysterectomy. A 56-year-oldwoman visited our hospital with a chief complaint of a growing abnormal retroperitoneal mass. She had undergone a total abdominal hysterectomy (TAH) and bilateral salpingooophorectomy (BSO) due to a malignant Brenner tumor at another university hospital 3 months previously. Baseline serum levels of CA-125 and CA 19-9 were normal (5.59 U/mL and 8.11 U/ mL, respectively). An abdominal computed tomography (ACT) scan revealed a 3.0-cm nodule in the anterior lower pole of the right kidney that had been visualized by ACT prior to the TAH and BSO. The mass had increased in size over the course of 3 months (Figure 1). No distant metastases or other abnormal findings were noted on ACT. We suspected that the mass was a metastatic lymph node and performed laparoscopic retroperitoneal removal. The patient was placed in the dorsolithotomy position, and four ports were used for the procedure (Figure 2). The first assistant gradually rotated the telescope 180 clockwise from the pelvic