Using ACGME milestones as a formative assessment for the internal medicine clerkship: a consecutive two-year outcome and follow-up after graduation.

BACKGROUND: This study evaluated the utility of using Accreditation Council for Graduate Medical Education (ACGME) Milestones as a formative assessment tool for the fifth- and sixth-grade medical students' performance in their internal medicine (IM) clerkship and the same students' performance in their post-graduate year (PGY) IM training. METHODS: Retrospective data were collected from 65 medical students completing the two-year IM clerkship in the academic years 2019 and 2020 and 26 of the above students completing their PGY-1 training at the same university hospital in the academic year 2021. Data included the assessment results of 7 of the ACGME IM Milestones, information on admitted patients assigned to the students, and surveys of the students' satisfaction. RESULTS: The analysis included 390 assessment results during the IM clerkship and 78 assessment results during the PGY-1 training. Clinical teachers commonly rated level 3 to medical students in the IM clerkship, with PC-2 subcompetency receiving the lowest rating among seven subcompetencies. The levels of most subcompetencies showed stationary in the two-year IM clerkship. Significant improvement was observed in all subcompetencies during the PGY-1 training. The medical students in the second-year IM clerkship expressed higher satisfaction with implementing Milestones than in their first-year IM clerkship and perceived Milestones assessments' usefulness as learning feedback. CONCLUSIONS: Using ACGME Milestones as a formative assessment tool in the IM clerkship yielded promising outcomes. Longitudinal follow-up of subcompetencies facilitated tracking students' development and providing constructive feedback.

Acute pancreatitis complicated with peripancreatic pseudoaneurysm and subsequent intra-abdominal hematoma.

Acute pancreatitis is a common disease, but peripancreatic pseudoaneurysm is rare. Bleeding from peripancreatic pseudoaneurysm without connection to GI tract may delay treatment and cause mortality. Being aware of this rare complication after acute pancreatitis is important.

Precise application of topical tranexamic acid to enhance endoscopic hemostasis for peptic ulcer bleeding: a randomized controlled study (with video).

BACKGROUND AND AIMS: Peptic ulcer recurrent bleeding occurs in 20% to 30% of patients after standard endoscopic hemostasis, particularly within 4 days after the procedure. The application of additional tranexamic acid (TXA) to the ulcer may enhance hemostasis. This study investigated the effectiveness of TXA powder application on bleeding ulcers during endoscopic hemostasis. METHODS: This study enrolled patients who had peptic ulcer bleeding between March 2022 and February 2023. After undergoing standard endoscopic therapy, the patients were randomly assigned to either the TXA group or the standard group. In the TXA group, an additional 1.25 g of TXA powder was sprayed endoscopically on the ulcer. Both groups then received 3 days of high-dose (8 mg/h) continuous infusion proton pump inhibitor therapy. Second-look endoscopy was conducted on days 3 to 4. The primary end point of early treatment failure was defined as ulcer recurrent bleeding within 4 days or major stigmata of recent hemorrhage on the second-look endoscopy. RESULTS: Sixty patients (30 in each group) with peptic ulcer bleeding and balanced baseline characteristics were randomly assigned to a treatment group. The early treatment failure rate was lower in the TXA group (6.7%) than in the standard group (30%) (P = .042). The freedom from treatment failure periods for 4 and 28 days was significantly longer in the TXA group than in the standard group (P = .023). No adverse events from TXA were recorded. CONCLUSIONS: The precise delivery of topical TXA alongside standard endoscopic hemostasis reduced the early treatment failure rate in patients with bleeding peptic ulcers. (Clinical trial registration number: NCT05248321.).

Hepatic arterial infusion chemotherapy and immune checkpoint inhibitors, alone or in combination, in advanced hepatocellular carcinoma with macrovascular invasion: a single-centre experience in Taiwan.

Background: The presence of vascular invasion is associated with poor survival in advanced hepatocellular carcinoma (HCC). We compared the effectiveness of hepatic arterial infusion chemotherapy (HAIC) and immune checkpoint inhibitors (ICIs), alone or in combination, in patients with advanced HCC. Methods: We retrospectively reviewed medical records of adult patients with unresectable HCC and macrovascular invasion (MVI) who were treated with HAIC or ICIs alone or in combination at a single centre in Taiwan. Overall tumour response, vascular thrombi response, overall survival (OS) and progression-free survival (PFS) in 130 patients were analysed. Results: The treatment group showed no significant effect on the overall tumour response [objective response rate (ORR), 22.86% for HAIC, 26.09% for ICI, 50.00% for HAIC+ICI; P=0.111], but showed a significant effect on vessel response (objective response rate of tumour thrombi (ORRT), 38.57% for HAIC, 45.65% for ICI, 78.57% for HAIC+ICI; P=0.023). Post-hoc comparisons followed by Bonferroni correction revealed that vessel ORRT was significantly different between the HAIC+ICI and HAIC groups (P=0.014). A significant effect of treatment group on portal vein tumour thrombus (PVTT) was also detected (ORRT, 40.00% for HAIC, 50.00% for ICI, 90.00% for HAIC; P=0.013), with significant difference between the HAIC+ICI and HAIC groups (P=0.005). Patients treated with HAIC, ICI, and HAIC+ICI respectively had 12-month OS rates of 44.9%, 31.4%, and 67.5% (P=0.127) and 12-month PFS rates of 21.2%, 24.6%, and 33.2% (P=0.091). In multivariate analysis of PFS, HAIC+ICI was associated with reduced risk of progression or death compared with HAIC alone (adjusted hazard ratio: 0.46; 95% confidence interval: 0.23-0.94; P=0.032). Conclusions: HAIC combined with ICIs had a superior response of PVTT compared to HAIC alone, and was associated with reduced risk of progression or death. Future studies are needed to address the survival benefit of the combination therapy in advanced HCC with MVI.

Real-World Effectiveness of Sorafenib versus Lenvatinib Combined with PD-1 Inhibitors in Unresectable Hepatocellular Carcinoma.

Immune checkpoint inhibitors (ICIs) combined with multitarget tyrosine kinase inhibitors (MTKIs) exert a synergistic effect and are effective in unresectable hepatocellular carcinoma (uHCC). However, precise data regarding the real-world clinical applications of these combination therapies in uHCC are lacking. This study compared the treatment efficacy of sorafenib versus lenvatinib in combination with programmed cell death protein-1 (PD-1) inhibitors in patients with uHCC in a clinical setting. Among 208 patients with uHCC treated with PD-1 inhibitors, 88 were administered with ICIs in combination with sorafenib or lenvatinib. The treatment response and survival outcomes were evaluated. Predictors of survival were assessed by multivariate analysis. A total of 49 patients were treated with PD-1 inhibitors combined with sorafenib, and 39 patients were treated with PD-1 inhibitors combined with lenvatinib. The lenvatinib group exhibited a stronger objective response rate (ORR) (20.51% vs. 16.33%) and had a higher disease control rate (41.03% vs. 28.57%) than did the sorafenib group. The median overall survival was longer in the lenvatinib group than the sorafenib group (13.1 vs. 7.8 months; hazard ratio = 0.39, p = 0.017). The incidence of treatment-related adverse events was similar. PD-1 inhibitors combined with lenvatinib can be a feasible treatment strategy for HCC patients receiving MTKI-based combination therapy. PD-1 inhibitors combined with lenvatinib resulted in more favorable survival outcomes without increased toxic effects compared with PD-1 inhibitors with sorafenib. Additional larger-scale and prospective studies should be conducted to verify the study results.

Real-World Comparative Effectiveness of Nivolumab versus Pembrolizumab in Patients with Unresectable Hepatocellular Carcinoma.

PURPOSE: Immune checkpoint inhibitors are effective therapies for advanced hepatocellular carcinoma (HCC); however, comparisons of the clinical efficacy and safety profile for these drugs are still scarce. Thus, the aims of this study were to investigate the differences in efficacy and safety between nivolumab and pembrolizumab in unresectable HCC patients in a real-world setting. PATIENTS AND METHODS: A total of 115 patients who received treatment with nivolumab (n = 73) or pembrolizumab (n = 42) in combination with or without tyrosine kinase inhibitors was enrolled. Therapeutic response, survival outcomes, and safety profiles were compared among these groups. Multivariate analysis of survival response was performed using Cox proportional hazards regression. RESULTS: Patients treated with pembrolizumab demonstrated a significantly higher objective response rate than those with nivolumab (38.1% vs. 15.1%; odds ratio 4.18, p = 0.005) regardless of the combination strategies. In addition, pembrolizumab performed a better overall survival (OS) than nivolumab, (34.9 vs. 9.5 months; hazard ratio (HR) = 0.39, p = 0.004). In subgroup analysis, pembrolizumab exhibited favorable OS than nivolumab for monotherapy (HR = 0.16, p = 0.001) or combination therapy (HR = 0.33, p = 0.006) as second-line or later-line (HR = 0.19, p = 0.001) therapy and those with (HR = 0.31, p = 0.006) or without (HR = 0.15, p = 0.004) well-compensated liver disease. The incidence of adverse events was comparable for both treatments. CONCLUSION: Both pembrolizumab and nivolumab had significant effects for HCC therapy, and pembrolizumab had a significant survival benefit as compared with nivolumab.

Longitudinal assessment of milestone development among internal medicine residents in Taiwan.

BACKGROUND/PURPOSE: The Accreditation Council for Graduate Medical Education (ACGME) milestones have been implemented in residency training worldwide. We investigated the development of individual competency in first-year residents (R1) and second-year postgraduate students (PGY2) who received internal medicine training in Taiwan. METHODS: A multicenter observational cohort study was conducted to evaluate the competency-based milestone evaluation designed by the Taiwan Society of Internal Medicine in 2019. The evaluation was based on the ACGME-accredited milestone ratings. Periodic evaluation of milestone achievements of R1 and PGY2, who entered the internal medicine residency training at six medical centers, was performed. Each resident was evaluated every 3 months. RESULTS: Among the 98 R1 enrolled in 2019, substantial improvement in sub-competencies, including skill in performing procedures (Patient Care 4), clinical knowledge (Medical Knowledge 1), knowledge of diagnostic testing and procedures (Medical Knowledge 2), and identify impact the cost of health care and practices cost-effective care (Systems Based Practice 3) during the two years of training. Among the 107 R1 and 46 PGY2 enrolled in 2020, no significant difference in baseline milestone ratings was observed. However, the milestone assessments of R1 in 2020 showed improvement in nearly all sub-competencies compared with the stationary status of PGY2 in 2020. CONCLUSION: We demonstrate the application of ACGME-based accredited milestone ratings to target the educational goals of internal medicine residency training in Taiwan. Differences in milestone ratings between different PGY training systems exist. The long-term impact of performance among different PGY training systems requires further investigation.

Comparison of Different Endoscopic Methods Used for Managing Choledocholithiasis in Patients with End-Stage Renal Disease Undergoing Hemodialysis.

BACKGROUND AND AIM: Endoscopic sphincterotomy (EST), endoscopic papillary balloon dilation (EPBD), and endoscopic sphincterotomy plus balloon dilation (ESBD) are all techniques used to manage choledocholithiasis. We aim to analyze the efficacy and safety of these techniques for treating choledocholithiasis in patients undergoing hemodialysis (HD). METHODS: We performed a retrospective study of 80 patients with end-stage renal disease (ESRD) on HD who underwent endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis management between August 1st, 2012, and December 31st, 2020, at a medical center in southern Taiwan. These patients were divided into three groups: EST (n = 21), EPBD (n = 28), and ESBD (n = 31). Post-ERCP complications, including pancreatitis, bleeding, cholangitis, and perforation, were reviewed for analysis. RESULTS: There were no significant among-group differences in the rate of complete stone clearance and hospitalization day after ERCP. Patients in the EST group had a higher post-ERCP complication rate than was the case in the other groups (p = 0.016). ESBD significantly reduced post-ERCP bleeding, compared with that occurring with EST (OR 0.07; 95% CI, 0.01-0.72, p = 0.026). There were no significant among-group differences in the rates of pancreatitis and cholangitis. There were no ERCP-related perforations or deaths in this study. CONCLUSIONS: EST, EPBD, and ESBD are efficient methods for treating choledocholithiasis in ESRD patients. ESBD was found to lead to a lower risk of bleeding than EST, and the rate of pancreatitis or cholangitis was comparable for EST and EPBD. Our results suggest that ESBD is the best choice of treatment of choledocholithiasis in patients with ESRD undergoing HD.

Incomplete small bowel obstruction in a patient with ankylosing spondylitis.

Small bowel obstruction is a blockage in the small intestine, which is usually caused by adhesion scar tissue, hernia, medication, or malignancy. The symptoms of small bowel obstruction include nausea and vomiting of bile, abdominal distention and obstipation. We present a case of a 61-year-old man with ankylosing spondylitis and scoliosis, who suffered from incomplete small bowel obstruction due to unusual direction of duodenum and externally compressed by liver, gallbladder and pancreas. We gave conservative treatment and inserted a nasojejunal tube for enteral feeding, and the duodenum broke free from the grip of liver, gallbladder and pancreas to its normal anatomical direction. Besides common etiology of small bowel obstruction, unusual body shape and smaller abdominal cavity may cause obstruction due to external compression of neighbor organs. Conservative treatments include gastrointestinal decompression, correction of electrolytes abnormality and nutrition support, while surgical intervention is suggested for the patient without improvement on conservative management.

Real-world outcome of immune checkpoint inhibitors for advanced hepatocellular carcinoma with macrovascular tumor thrombosis.

Programmed cell death protein-1 (PD-1) inhibitors have shown promising results for treating advanced hepatocellular carcinoma (HCC). However, the clinical utility of such inhibitors in HCC patients with vascular tumor thrombosis remains unclear. This study investigated PD-1 inhibitor efficacy in advanced HCC with macrovascular invasion in a clinical setting. Among the 110 patients with unresectable HCC treated with PD-1 inhibitors, 34 patients with vascular metastases in the portal vein and inferior vena cava were retrospectively compared with 34 patients without tumor thrombi. The vascular response and its effect on survival were assessed. Predictors of survival were identified using multivariate analysis. Among patients achieving objective response, those with and without thrombi exhibited similar response to immunotherapy and comparable survival. Among the 34 patients with tumor thrombi, including 13 receiving PD-1 inhibitors alone and 21 receiving it in combination with tyrosine kinase inhibitors, the median overall survival was 8.9 months (95% confidence interval 3.2-12.6). The objective response rate of vascular metastasis was 52.9%, and vascular responders had a significantly longer survival than did non-responders (11.1 vs 3.9 months). Failure to obtain a vascular response correlated significantly with increased post-treatment Child-Pugh score or class. Multivariate analysis showed that vascular response was a significant positive factor for longer overall survival. Treatment-related grade 3/4 adverse events occurred in 3 (8.8%) of the patients with tumor thrombi. Immunotherapy with PD-1 inhibitors may be a feasible treatment option for HCC with tumor thrombi owing to the high response rate of tumor thrombi and favorable survival outcomes.

Safety and effectiveness of new embolization microspheres SCBRM for intermediate-stage hepatocellular carcinoma: A feasibility study.

Transarterial chemoembolization (TACE) is, currently, the recommended treatment for hepatocellular carcinoma (HCC). However, long-term chemoembolization triggers the inflammatory response and may lead to postembolization syndrome (PES). Although several types of degradable microspheres have been developed to reduce drug toxicity and PES incidence, the clinical outcomes remain unsatisfactory. Previously, we have developed a new type of spherical, calibrated, biodegradable, radiopaque microspheres (SCBRM) and demonstrated their safety and efficacy in a pig model. Thus, the goal of this feasibility study was to determine the clinical safety and efficacy of the new SCBRM in intermediate-stage HCC patients. In this study, 12 intermediate-stage HCC patients underwent TACE using SCBRM with a calibrated size of 100-250 µm. The disease control rates at 1 month and 3 months after TACE-SCBRM treatment were 100% and 75.0%, respectively. The objective response rates at 1 month and 3 months after treatment were 66.7% and 58.3%, respectively. Very few adverse events were observed with one patient developing nausea. One day after the treatment, alanine aminotransferase, alanine aminotransferase, and total bilirubin levels were slightly elevated in the patients, but all returned to baseline on day 7. The median and mean overall survival times were 33 months (interquartile range, 12.8-42.0) and 29.2 ± 14.3 months, respectively. The 1-year and 2-year survival rates were 91.7% and 58.3%, respectively. In conclusion, TACE with the new SCBRM microspheres is clinically safe and effective, and it represents a promising approach in the management of intermediate-stage HCC.

Peroral endoscopic tumor resection (POET) with preserved mucosa technique for management of upper gastrointestinal tract subepithelial tumors.

BACKGROUND: Third space endoscopy technique facilitates therapeutic endoscopy in subepithelial space. This study aimed to investigate peroral endoscopic tumor resection (POET) with preserved mucosa technique for upper gastrointestinal tract subepithelial tumors (UGI-SETs) removal. METHODS: Between February 2011 and December 2019, consecutive patients with SETs of esophagus and stomach who underwent POET for enlarging size during follow-up, malignant endoscopic ultrasound features or by patient's request were enrolled. Demographic, endoscopic and pathological data were analyzed retrospectively. RESULTS: Totally 18 esophageal (mean ± SD age, 55.23 ± 4.15 year-old, 38.89% female) and 30 gastric (52.65 ± 2.43 year-old, 53.33% female) SETs in 47 patients (one with both esophageal and gastric lesions) were resected. The mean (± SD) endoscopic/pathological tumor size, procedure time, en-bloc/complete resection rate, and hospital stays of esophageal and gastric SET patients were 12.36 (± 7.89)/11.86 (± 5.67) and 12.57 (± 6.25)/12.35 (± 5.73) mm, 14.86 (± 6.15) and 38.21 (± 15.29) minutes, 88.89%/94.44% and 86.77%/93.30%, and 4.14 (± 0.21) and 4.17 (± 0.20) days, respectively. The overall complication rate was 18.75%, including 6 self-limited fever and 3 pneumoperitoneum relieved by needle puncture. There was no mortality or recurrence reported with mean follow-up period of 23.74 (± 4.12) months. CONCLUSIONS: POET is a safe and efficient third space endoscopic resection technique for removal of UGI-SETs less than 20 mm. Long term data are warranted to validate these results.

Novel upper gastrointestinal monitoring system to track upper gastrointestinal bleeding: A pilot study.

Background and study aims Early detection of upper gastrointestinal (UGI) rebleeding is not easy by observing clinical symptoms. We developed a novel UGI monitoring system and aimed to test its feasibility of continuous tracking of UGI bleeding. Patients and methods A prospective study was conducted on patients with moderate to high risk of rebleeding. The UGI monitoring system was installed to monitor their gastric contents. It would alarm if rebleeding was suspected and the physician could review the images to make a further decision. The patient's comfort level was also evaluated. Results Sixteen patients were enrolled. Rebleeding occurred in one patient and was detected by this system more than 5 hours earlier than with clinical symptoms. The interobserver reliability for reviewing the images to define the blood clearance in the stomach was excellent (intraclass correlation coefficient 0.79-0.96). The comfort level assessed by patients was 1.90 ±â€Š1.39 (on the scale of 0-5). Conclusions This pilot study demonstrated the potential of this UGI monitoring system for early detection of rebleeding.

Validation of genome-wide association study-identified single nucleotide polymorphisms in a case-control study of pancreatic cancer from Taiwan.

BACKGROUND: Due to differences in genetic background, it is unclear whether the genetic loci identified by the previous genome-wide association studies (GWAS) of pancreatic cancer also play significant roles in the development of pancreatic cancer among the Taiwanese population. METHODS: This study aimed to validate the 25 pancreatic cancer GWAS-identified single nucleotide polymorphisms (SNPs) in a case-control study (278 cases and 658 controls) of pancreatic cancer conducted in Taiwan. Statistical analyses were conducted to determine the associations between the GWAS-identified SNPs and pancreatic cancer risk. Gene-environment interaction analysis was conducted to evaluate the interactions between SNPs and environmental factors on pancreatic cancer risk. RESULTS: Among the 25 GWAS-identified SNPs, 7 (rs2816938 (~ 11 kb upstream of NR5A2), rs10094872 (~ 28 kb upstream of MYC), rs9581943 (200 bp upstream of PDX1) and 4 chromosome 13q22.1 SNPs: rs4885093, rs9573163, rs9543325, rs9573166) showed a statistically significant association with pancreatic cancer risk in the current study. Additional analyses showed two significant gene-environment interactions (between poor oral hygiene and NR5A2 rs2816938 and between obesity and PDX1 rs9581943) on the risk of pancreatic cancer. CONCLUSIONS: The current study confirmed the associations between 7 of the 25 GWAS-identified SNPs and pancreatic risk among the Taiwanese population. Furthermore, pancreatic cancer was jointly influenced by lifestyle and medical factors, genetic polymorphisms, and gene-environment interaction. Additional GWAS is needed to determine the genetic polymorphisms that are more relevant to the pancreatic cancer cases occurring in Taiwan.

Impact of Immune Checkpoint Inhibitors with or without a Combination of Tyrosine Kinase Inhibitors on Organ-Specific Efficacy and Macrovascular Invasion in Advanced Hepatocellular Carcinoma.

INTRODUCTION: The tumor microenvironments of different organs often differ and thus may affect the immunotherapy response. OBJECTIVE: This study elucidated that the efficacy of programmed cell death protein-1 (PD-1) inhibitors varies across different metastatic sites among individuals with advanced hepatocellular carcinoma (HCC). METHODS: We retrospectively analyzed treatment outcomes in advanced HCC patients receiving PD-1 inhibitors with or without a combination of tyrosine kinase inhibitors (TKIs). Both the overall response rate (ORR) and organ-specific response rate (OSRR) were assessed using Response Evaluation Criteria in Solid Tumors 1.1 criteria. A survival analysis and its predictors were determined using a multivariate analysis. RESULTS: We analyzed 42 advanced HCC patients (median age: 58.0 years; 78.6% males). Thirty (71.4%) patients were sorafenib-experienced and 27 (64.3%) were administered a combination of TKIs. The ORR was 14.3% and the disease control rate was 33.3%. The median overall survival (OS) and progression-free survival (PFS) were 12.0 and 2.9 months, respectively. The OSRRs were 14.7, 23.8, 28.6, and 50.0% for the liver, lungs, lymph nodes, and vascular response, respectively. The multivariate analysis indicated that the vascular response was significantly associated with PFS. ECOG performance status was a significant independent predictor of OS. CONCLUSIONS: PD-1 inhibitors improved OS and PFS in advanced HCC patients. Their efficacies varied among the metastatic locations regardless of the combination of TKIs; in particular, a higher response in vascular metastases was correlated with a longer PFS. PD-1 inhibitors may deliver a synergistic benefit in patients undergoing traditional therapy and progression in other organs in vascular responders.

Computed tomography classification of endoscopic retrograde cholangiopancreatography-related perforation.

Endoscopic retrograde cholangiopancreatography (ERCP)-related perforation leads to high morbidity and mortality. The Stapfer classification divides patients with different perforation locations and suggests management accordingly. The classification may be unknown if perforation is not detected during endoscopy. We classified patients with ERCP-related perforation (ERP) through computed tomography (CT) and observed the clinical outcomes with varyingly invasive management. Fifty-two cases of ERP between July 2009 and December 2017 were retrospectively reviewed. Of them, 41 who underwent CT for ERCP were included. According to their CT findings, we divided patients into air-alone (n = 16), air-fluid (n = 18), and fluid-alone (n = 7) groups. Perforation severity was graded using the Clavien-Dindo classification for surgical complications. Demographic data and clinical outcomes among different groups were analyzed. Fifteen patients (37%) had an unknown Stapfer classification. More than half of the patients in the air-fluid group had a Clavien-Dindo complication grade of >3. Four patients underwent surgical repair; all of them were from the air-fluid group. All patients in the air- and fluid-alone groups underwent medical treatment without need for subsequent salvage surgery. The air-fluid group had the longest mean hospital stay (25.1 ± 21.9 days) and the exclusive two mortality cases in this study. Patients with ERCP can be divided into groups with different outcomes according to the presence of air or fluid on CT images. Because patients with both air and fluid have the worst clinical outcome, they may require more aggressive treatment than patients with either air or fluid alone.

Insulin Resistance Associated Disorders Pivoting Long-Term Hepatitis B Surface Antigen Decline During Entecavir Therapy.

Insulin resistance associated disorders (IRAD), including prediabetes, type 2 diabetes mellitus (T2DM), and fatty liver are significant risk factors of liver-related death in chronic hepatitis B (CHB). However, their relationship remains unclear. We aimed to evaluate how IRAD influence the kinetics of serum hepatitis B surface antigen (HBsAg) in patients with CHB during long-term entecavir treatment. We enrolled 140 patients with CHB receiving at least 3 years of consecutive entecavir treatment in this retrospective study. A linear mixed effects model was adopted to examine the effects of variables and their interaction over time on the HBsAg trajectory. Furthermore, we acquired cytokine profiles and baseline fibrosis-4 index (FIB-4) scores for in-depth analysis. The median treatment time was 6.90 (4.47-9.01) years. Multivariate analysis revealed that older patients or those with prediabetes or T2DM had a significantly slower HBsAg decline over time (p = 0.0001 and p < 0.0001, respectively). Conversely, advanced fatty liver engendered a more rapid HBsAg decrease (p = 0.001). Patients with prediabetes or T2DM possessed higher IP-10 levels six years after entecavir therapy (p = 0.013). Compared to patients without prediabetes or T2DM, diabetic patients had more unfavorable features at the baseline, especially higher FIB-4 scores. Prediabetes or T2DM delays the clearance of HBsAg, but advanced hepatic fatty change counterbalances the effect. Additionally, IRAD could cause hepatic sequelae in CHB through immune-metabolic pathways.

Combined Transarterial Embolization/Chemoembolization-Based Locoregional Treatment with Sorafenib Prolongs the Survival in Patients with Advanced Hepatocellular Carcinoma and Preserved Liver Function: A Propensity Score Matching Study.

BACKGROUND: Sorafenib is the standard treatment for patients with Barcelona Clinic Liver Cancer (BCLC) stage C hepatocellular carcinoma (HCC). However, the treatment outcome is not satisfactory. We retrospectively analyzed whether adding transarterial embolization/chemoembolization (TA(C)E)-based locoregional therapy to sorafenib can further improve treatment efficacy. PATIENTS AND METHODS: We included 147 BCLC stage C HCC patients with Child-Turcotte-Pugh class A liver function and treated with sorafenib for analysis. Through propensity score matching, we divided patients into the combined treatment group (n = 63; patients received TA(C)E-based locoregional treatment and sorafenib) and the sorafenib monotherapy group (n = 63). We analyzed the effects of patients' clinical and tumor-related factors on their overall survival (OS) and time to tumor progression. RESULTS: The OS was better in the combined treatment group than in the sorafenib monotherapy group (419 vs. 223 days, p = 0.028). In the Cox regression model, combined treatment, a lower baseline α-fetoprotein (AFP) level < 400 ng/mL, tumors without main portal venous tumorous thrombosis, and age ≥60 years were identified as independent factors for OS. Subgroup analysis demonstrated that patients with a higher baseline AFP level > 400 ng/mL, age < 60 years, tumors with branched portal venous tumorous thrombosis only or without extrahepatic metastasis benefited the most from combined treatment. CONCLUSION: Combining TA(C)E-based locoregional treatment with sorafenib resulted in better OS in patients with BCLC stage C HCC compared with sorafenib alone. TA(C)E-based locoregional treatment can be an adjunctive treatment to sorafenib for patients with advanced HCC and a satisfactory liver functional reserve.

Clinical features and outcomes of gastric neuroendocrine tumors after endoscopic diagnosis and treatment: A Digestive Endoscopy Society of Tawian (DEST).

Gastric neuroendocrine tumors (GNETs) are a heterogeneous group of neoplasm with varying biological characteristics. This study aimed to investigate the clinical features and outcomes of GNET patients after endoscopic diagnosis and treatment in a multicenter registry. Patients with GNETs confirmed histologically were recruited from 17 hospitals between January 2010 and April 2016 in Taiwan. Clinical, laboratory, radiological, endoscopic, pathological data, treatment strategies, follow-up periods, and survivals were collected retrospectively. Totally 187 (107 female, 80 male) patients were recruited. Mean ( ±â€Šstandard deviation [SD]) age and size of tumors were 63.2-year-old ( ±â€Š14.6) and 2.3-cm ( ±â€Š3.0). World Health Organization (WHO) grading were 93 (49.7%) G1, 26 (13.9%) G2, 40 (21.4%) G3, and 28 (15.0%) unknown. G3 patients were older (mean ±â€ŠSD, 71.6 ±â€Š12.4 vs. 60.9 ±â€Š14.3/56.7 ±â€Š15.4 years), larger (6.1 ±â€Š4.0 vs.1.2 ±â€Š1.3/2.4 ±â€Š2.5 cm), more distally located (35.0% vs. 7.6%/15.4%), lower proportion of superficial lesions (17.5% vs. 61.9%/53.8%) and higher rates of lymphovascular invasion (32.5% vs. 3.2%/7.7%) than G1/G2. There was no nodal or distant organ metastases despite different grading of lesions≦10 mm and those <20 mm limited to mucosa and submucosa layers. GNETs larger than 20 mm with G1, G2, and G3 had lymph node (LN) metastatic rates of 21.4%, 30.0%, and 59.3%, respectively. Survivals were different between grading for those >20 mm (log-rank test P = .02). Male gender (P = .01), deeper invasion (P = .0001), nodal (P < .0001), and distant organ metastases (P = .0001) were associated with worse outcome. In conclusion, treatment strategies for GNET should be decided by grading, size, invasiveness, and LN metastasis risk. Curative endoscopic resection is feasible for G1/2 lesions less than 20 mm and limited to mucosa/submucosa layers without lymphovascular invasion.

Clinical utility of hepatitis B surface antigen kinetics in treatment-naïve chronic hepatitis B patients during long-term entecavir therapy.

AIM: To investigate the utility of hepatitis B surface antigen (HBsAg) kinetics in chronic hepatitis B patients during long-term entecavir treatment. METHODS: This retrospective study included treatment-naïve chronic hepatitis B patients who received at least 2 years of consecutive entecavir treatment. Patients were followed up at three to six month intervals with liver biochemistry, hepatitis B virus DNA, and abdominal sonography. In hepatitis B e antigen (HBeAg)-positive patients, HBeAg levels were assessed every three to six month until results became negative. Serum HBsAg levels were determined at the baseline, one-year and five-year time points. Liver cirrhosis was diagnosed through liver biopsy, imaging examinations, or clinical findings of portal hypertension. Hepatocellular carcinoma was diagnosed by histological examination or dynamic image studies. RESULTS: A total of 211 patients were enrolled. The median treatment time was 5.24 (2.00-9.62) years. Multivariate analysis showed that lower baseline HBsAg levels were associated with an earlier virological response, earlier hepatitis B e antigen (HBeAg) seroconversion, and earlier biochemical response in HBeAg-positive patients (cut-off value: 4 log IU/mL) and an earlier virological response in HBeAg-negative non-cirrhotic patients (cut-off value: 2.4 log IU/mL). Although HBsAg levels decreased slowly during long-term entecavir treatment, higher HBsAg decrease rates were found in the first year for HBeAg-positive non-cirrhotic patients, and patients with higher baseline HBsAg levels. More favorable clinical outcomes were not observed by a rapid HBsAg decline per se, but depended on lower baseline HBsAg levels. CONCLUSION: Baseline HBsAg can be used to predict treatment responses. HBsAg levels and decrease rates should be considered together according to disease status while interpreting HBsAg changes.