Clinical Outcomes and Validation of Ursodeoxycholic Acid Response Scores in Patients with Korean Primary Biliary Cholangitis: A Multicenter Cohort Study

Background/Aims@#The ursodeoxycholic acid (UDCA) response score (URS) was developed to identify poor responders to UDCA before treatment, in order to offer timely and proactive intervention. However, validation of the URS in Asian population is warranted. @*Methods@#A total of 173 Asian patients diagnosed with primary biliary cholangitis (PBC) between 2007 and 2016 at seven academic institutions in Korea who started UDCA treatment were analyzed to validate the performance of URS. UDCA response was defined as an alkaline phosphatase level less than 1.67 times the upper limit of normal after 1-year of UDCA treatment. In addition, prognostic performance of URS for liver-related events, defined as newly developed hepatic decompensation or hepatocellular carcinoma was evaluated. @*Results@#After 1 year of UDCA treatment, 133 patients (76.9%) achieved UDCA response. UDCAresponse rate was 98.7% for those with URS ≥1.41 (n=76) and 58.8% for those with URS <1.41(n=97). The area under the receiver operating characteristic curve of URS in predicting UDCAresponse was 0.84 (95% confidence interval, 0.78 to 0.88). During a median follow-up of 6.5years, liver-related events developed in 18 patients (10.4%). Among 117 patients with PBC stage I-III by histological evaluation, the 5-year liver-related event-free survival rate differed accordingto the URS; 100% for URS ≥1.41 and 86.5% for URS <1.41 (p=0.005). @*Conclusions@#URS demonstrated good performance in predicting a UDCA treatment response in Asian PBC patients. In addition, the risk of liver-related events differed according to the URS for the PBC stage. Thus, URS can be used to predict the response and clinical outcome in patients with PBC.

Efficacy of a Synbiotic Containing Lactobacillus paracasei DKGF1and Opuntia humifusa in Elderly Patients with Irritable Bowel Syndrome: A Randomized, Double-Blind, Placebo-Controlled Trial

Background/Aims@#There is increasing evidence that supplementation with pre- and probiotics appears to have positive effects on irritable bowel syndrome (IBS). The aim of this study was to determine the effects of a new synbiotic formulation on gastrointestinal symptoms in elderly patients with IBS. @*Methods@#Sixty-seven IBS patients aged ≥60 years were randomly assigned to either a placebogroup (n=34) or a synbiotic group (n=33). During a 4-week intervention, subjects used a placebo or a synbiotic containing Lactobacillus paracasei DKGF1 and extracts of Opuntia humifusa once a day. Patients were evaluated with the subject global assessment, visual analog scale, and Bristol stool chart. The primary outcome was the overall responder rate and the secondary outcome was the responder rates for abdominal symptom reduction at week 4. @*Results@#Overall, responder rates were significantly higher in the synbiotic group (51.5%) than in the placebo group (23.5%) (p=0.017). Abdominal pain (58.8% vs 81.8%) and psychological wellbeing (26.4% vs 60.6%) were noticeably improved in the synbiotic group (p=0.038 and p=0.004, respectively). However, there were no significant differences in gas and bloating symptoms (p=0.88 and p=0.88, respectively). In patients with constipation-dominant and diarrhea-dominant IBS (n=16), the synbiotic significantly improved abdominal pain and defecation symptoms (responder rates for the placebo vs the synbiotic: 22.2% vs 85.7%, p=0.04). There were no adverse events in either group. @*Conclusions@#The results indicate that this new synbiotic supplement can potentially relieve abdominal symptoms in elderly IBS patients.

Proton Pump Inhibitor Use Increases Pyogenic Liver Abscess Risk: A Nationwide Cohort Study

Background/Aims@#Proton pump inhibitors (PPIs) increase gastric pH and alter the gut microbiome. An increased risk for infectious diseases has been reported in PPI users. However, little is known about the association of PPI use with pyogenic liver abscess (PLA) incidence risk. @*Methods@#We conducted a population-based cohort study using data from a nationwide representative sample of the Korean general population followed up for 10 years (January 1, 2003 to December 31, 2013). We identified PPI prescriptions and considered PPI as a timevarying variable. Proportional hazards regression model was used for incident PLA comparing PPI use versus non-use. Propensity score matching was also conducted. @*Results@#During the 4 209 229 person-years of follow-up, 58 595 participants had at least 1 PPI prescription and 541 patients developed liver abscess. The age-, sex-, residential area-, and income-adjusted hazard ratio for PLA incidence with PPI use was 4.19 (95% CI, 2.54-6.92). The association was observed in fully adjusted models (hazard ratio 3.88; 95% CI, 2.33-6.44). The positive association between PPI use and PLA was consistent in all subgroups analyzed and in propensity score matching group. @*Conclusion@#The present data indicate that PPI use is associated with an increased PLA risk. Therefore, it is necessary to prescribe PPIs with clear indication and to avoid improper use of PPIs.

Proton Pump Inhibitor Use Increases Pyogenic Liver Abscess Risk: A Nationwide Cohort Study

Background/Aims@#Proton pump inhibitors (PPIs) increase gastric pH and alter the gut microbiome. An increased risk for infectious diseases has been reported in PPI users. However, little is known about the association of PPI use with pyogenic liver abscess (PLA) incidence risk. @*Methods@#We conducted a population-based cohort study using data from a nationwide representative sample of the Korean general population followed up for 10 years (January 1, 2003 to December 31, 2013). We identified PPI prescriptions and considered PPI as a timevarying variable. Proportional hazards regression model was used for incident PLA comparing PPI use versus non-use. Propensity score matching was also conducted. @*Results@#During the 4 209 229 person-years of follow-up, 58 595 participants had at least 1 PPI prescription and 541 patients developed liver abscess. The age-, sex-, residential area-, and income-adjusted hazard ratio for PLA incidence with PPI use was 4.19 (95% CI, 2.54-6.92). The association was observed in fully adjusted models (hazard ratio 3.88; 95% CI, 2.33-6.44). The positive association between PPI use and PLA was consistent in all subgroups analyzed and in propensity score matching group. @*Conclusion@#The present data indicate that PPI use is associated with an increased PLA risk. Therefore, it is necessary to prescribe PPIs with clear indication and to avoid improper use of PPIs.

Comparison of outcome between liver resection, radiofrequency ablation, and transarterial therapy for multiple small hepatocellular carcinoma within the Milan criteria

Purpose@#Although surgical resection is usually considered for a single tumor, several reports have suggested that resection can be considered for multiple tumors. The objective of this study was to determine whether resection could provide better long-term outcome for patients with multiple hepatocellular carcinomas (HCCs) within Milan criteria. @*Methods@#A total of 276 patients with multiple HCCs within Milan criteria with liver function preserved who underwent resection, radiofrequency ablation (RFA), or transarterial chemoembolization (TACE) between 2009 and 2013 were analyzed. Propensity-score (PS) matching was conducted. @*Results@#Five-year overall survival (OS) and recurrence-free survival (RFS) were better in the resection group than that in the RFA or TACE group. Patients who underwent resection had more preserved liver function and different tumor characteristics compared to those received RFA or TACE. With similar baseline characteristics generated in the PS model, there was no difference in 5-year OS among 3 groups (79.5% vs. 72.3% or 62.0%, P = 0.232), but the 5-year RFS was better for patients who received resection than those who received RFA or TACE (51.9% vs. 22.0% or 0.0%, P < 0.001). Although the major complication rate was slightly higher than RFA or TACE, there was no significant difference between the 3 groups before and after PS matching. @*Conclusion@#Resection was associated with better RFS than RFA or TACE and showed comparable OS in multiple HCC patients within the Milan criteria, but at a cost of slightly increased risk of complication. Resection can be considered as a first-line option if selected appropriately.

A Hepatic Lymphoma Mimicking Multiple Liver Metastases or an Intrahepatic Cholangiocarcinoma / 대한내과학회지

A primary hepatic lymphoma (PHL) is a rare malignancy; misdiagnosis and mistreatment are very common. We report the case of a 56-year-old female who presented with a 2-week history of upper abdominal pain. She exhibited no risk factors for hepatocellular carcinoma (HCC) and her serum tumor marker levels were normal. A computed tomography scan and gadolinium-enhanced magnetic resonance imaging of the liver revealed multiple liver masses, suggestive of multiple liver and lung metastases or an intrahepatic cholangiocarcinoma with lung metastasis. A diagnosis of PHL (a diffuse large B cell lymphoma) was confirmed by biopsy followed by immunohistochemistry. This case emphasizes that a PHL must be considered in the differential diagnosis of space-occupying liver lesions in patients with no risk factors for HCC and normal levels of serum tumor markers. It is notable that neither B cell lymphoma symptoms nor an elevated lactate dehydrogenase level were apparent in this case. We thus report a case of PHL mimicking multiple liver metastases or an intrahepatic cholangiocarcinoma, and we review the literature.

Transaxillary Subpectoral Placement of Cardiac Implantable Electronic Devices in Young Female Patients

BACKGROUND: The current indications of cardiac implantable electronic devices (CIEDs) have expanded to include young patients with serious cardiac risk factors, but CIED placement has the disadvantage of involving unsightly scarring and bulging of the chest wall. A collaborative team of cardiologists and plastic surgeons developed a technique for the subpectoral placement of CIEDs in young female patients via a transaxillary approach. METHODS: From July 2012 to December 2015, subpectoral CIED placement via an axillary incision was performed in 10 young female patients, with a mean age of 25.9 years and mean body mass index of 20.1 kg/m². In the supine position, with the patient's shoulder abducted, an approximately 5-cm linear incision was made along one of the deepest axillary creases. The submuscular plane was identified at the lateral border of the pectoralis major, and the dissection continued over the clavipectoral fascia until the subpectoral pocket could securely receive a pulse generator. Slight upward dissection also exposed an entrance to the subclavian vein, allowing the cardiology team to gain access to the vein. One patient with dilated cardiomyopathy underwent augmentation mammoplasty and CIED insertion simultaneously. RESULTS: One case of late-onset device infection occurred. All patients were highly satisfied with the results and reported that they would recommend the procedure to others. CONCLUSIONS: With superior aesthetic outcomes compared to conventional methods, the subpectoral placement of CIEDs via a transaxillary approach is an effective, single-incision method to hide operative scarring and minimize bulging of the device, and is particularly beneficial for young female or lean patients.

Effects of Human Adipose-Derived Stem Cells on the Survival of Rabbit Ear Composite Grafts

BACKGROUND: Composite grafts are frequently used for facial reconstruction. However, the unpredictability of the results and difficulties with large defects are disadvantages. Adipose-derived stem cells (ADSCs) express several cytokines, and increase the survival of random flaps and fat grafts owing to their angiogenic potential. METHODS: This study investigated composite graft survival after ADSC injection. Circular chondrocutaneous composite tissues, 2 cm in diameter, from 15 New Zealand white rabbits were used. Thirty ears were randomly divided into 3 groups. In the experimental groups (1 and 2), ADSCs were subcutaneously injected 7 days and immediately before the operation, respectively. Similarly, phosphate-buffered saline was injected in the control group just before surgery in the same manner as in group 2. In all groups, chondrocutaneous composite tissue was elevated, rotated 90 degrees, and repaired in its original position. Skin flow was assessed using laser Doppler 1, 3, 6, 9, and 12 days after surgery. At 1 and 12 days after surgery, the viable area was assessed using digital photography; the rabbits were euthanized, and immunohistochemical staining for CD31 was performed to assess neovascularization. RESULTS: The survival of composite grafts increased significantly with the injection of ADSCs (P<0.05). ADSC injection significantly improved neovascularization based on anti-CD31 immunohistochemical analysis and vascular endothelial growth factor expression (P<0.05) in both group 1 and group 2 compared to the control group. No statistically significant differences in graft survival, anti-CD31 neovascularization, or microcirculation were found between groups 1 and 2. CONCLUSIONS: Treatment with ADSCs improved the composite graft survival, as confirmed by the survival area and histological evaluation. The differences according to the injection timing were not significant.

Effects of Human Adipose-Derived Stem Cells on the Survival of Rabbit Ear Composite Grafts

BACKGROUND: Composite grafts are frequently used for facial reconstruction. However, the unpredictability of the results and difficulties with large defects are disadvantages. Adipose-derived stem cells (ADSCs) express several cytokines, and increase the survival of random flaps and fat grafts owing to their angiogenic potential. METHODS: This study investigated composite graft survival after ADSC injection. Circular chondrocutaneous composite tissues, 2 cm in diameter, from 15 New Zealand white rabbits were used. Thirty ears were randomly divided into 3 groups. In the experimental groups (1 and 2), ADSCs were subcutaneously injected 7 days and immediately before the operation, respectively. Similarly, phosphate-buffered saline was injected in the control group just before surgery in the same manner as in group 2. In all groups, chondrocutaneous composite tissue was elevated, rotated 90 degrees, and repaired in its original position. Skin flow was assessed using laser Doppler 1, 3, 6, 9, and 12 days after surgery. At 1 and 12 days after surgery, the viable area was assessed using digital photography; the rabbits were euthanized, and immunohistochemical staining for CD31 was performed to assess neovascularization. RESULTS: The survival of composite grafts increased significantly with the injection of ADSCs (P<0.05). ADSC injection significantly improved neovascularization based on anti-CD31 immunohistochemical analysis and vascular endothelial growth factor expression (P<0.05) in both group 1 and group 2 compared to the control group. No statistically significant differences in graft survival, anti-CD31 neovascularization, or microcirculation were found between groups 1 and 2. CONCLUSIONS: Treatment with ADSCs improved the composite graft survival, as confirmed by the survival area and histological evaluation. The differences according to the injection timing were not significant.

Age-Associated Changes in Parameters of Left Ventricular Diastolic Function Assessed by Pulsed Doppler Myocardial Imaging of Mitral Annulus in Healthy Korean Adults

BACKGROUND AND OBJECTIVES: Left ventricular (LV) diastolic function can be evaluated by obtaining parameters from Doppler analysis of the mitral inflow, which are known to change with increase in age. Pulsed Doppler myocardial imaging (DMI) analysis of mitral annular velocity has been proposed as a more accurate method for evaluation of LV diastolic function. This study sought to find out the age-associated changes in parameters of LV diastolic function acquired from pulsed DMI analysis of the mitral annulus in a large group of heathy Korean adults. MATERIALS AND METHODS: Two hundred and eighty-nine apparently healthy Korean subjects who visited the Center for Health Promotion for routine health checkup were studied. All went through pulsed DMI by echcardiography for acquisition of velocities in the septal, lateral, anterior, and inferior annuli of the mitral valve. Peak early diastolic velocity (Em), peak late diastolic velocity (Am), and their ratio (Em/Am) were obtained and their correlation with age was evaluated. Doppler flow analysis of mitral inflow was also performed. Peak early and late diastolic flow velocity (E and A), deceleration time (DT) and isovolumic relaxation time (IVRT) were assessed and their relationship with increase in age was also evaluated. RESULTS: Mean age of the subjects was 55.7+/-10.9. Em velocities of all portions of mitral annulus showed good correlation with age, showing continuous decline with increase in age (R=-0.60, -0.58, -0.59, -0.58 for septal, lateral, anterior and inferior annuli, respectively, p<0.01). Am velocities showed a significant but minimal increase with increase in age in all of the sampled positions. Em/Am ratio also showed a significant decline similar to the change in Em velocities. The A velocity and E/A ratio obtained from mitral inflow Doppler analysis showed a significant decline and DT and IVRT showed a significant increase with increase in age. CONCLUSION: Parameters of left ventricular diastolic function evaluated by pulsed DMI show significant changes that correlate well with increase in age. This supports the finding that left ventricular diastolic function continuously declines with increase in age.