Safety evaluation of combination treatment of drug-eluting bead transarterial chemoembolization and immune checkpoint inhibitors for hepatocellular carcinoma: An increased risk of liver abscess with treatment interval less than one month.

PURPOSE: To analyze the safety of combination treatment comprising drug-eluting bead transarterial chemoembolization (DEB-TACE) and immune checkpoint inhibitors (ICIs) in hepatocellular carcinoma (HCC). METHOD: In total, 208 HCC patients receiving DEB-TACE were enrolled for this retrospective single-institution study. Among them, 50 patients who received ICIs at an interval less than one month from DEB-TACE were categorized into the DEB-ICI group; the remaining 158 patients were categorized into the DEB group. Albumin-bilirubin (ALBI) score before and at three months after DEB-TACE were recorded to evaluate liver function changes. Adverse events within three months after DEB-TACE were considered TACE-related and were compared between the two groups. RESULTS: The DEB-ICI group had significantly higher incidence of liver abscess than the DEB group (14.0 % versus 5.1 %, p-value = 0.0337). No significant difference in the other TACE-related adverse events and change of ALBI score between the groups. Univariate logistic regression confirmed that combination with ICIs was an independent risk factor for liver abscess after DEB-TACE (odds ratio = 3.0523, 95 % confidence interval: 1.0474-8.8947, p-value = 0.0409); other parameters including subjective angiographic chemoembolization endpoint scale and combined targeted therapy were nonsignificant risk factors in this study population. In the DEB-ICI group, patients who received ICIs before DEB-TACE exhibited a trend toward liver abscess formation compared with those who received DEB-TACE before ICIs (23.8 % versus 6.9 %, p-value = 0.0922). CONCLUSIONS: Combination treatment involving DEB-TACE and ICIs at an interval less than one month increased the risk of liver abscess after DEB-TACE. Greater caution is therefore warranted for HCC patients who receive ICIs and DEB-TACE with this short interval.

Beneficial Effect of Combining Radiotherapy and Transarterial Chemoembolization on Patient Survival in Hepatocellular Carcinomas and Macrovascular Invasion Treated with Sorafenib.

BACKGROUND: Approximately 10-40% of hepatocellular carcinoma (HCC) patients have definite vascular invasion at the time of diagnosis. Without curative treatment options, these patients have an abysmal prognosis with a median survival of only a few months following systemic therapy. However, supportive evidence of combining multiple locoregional treatments with systemic therapy is limited. This study compared the outcomes of sorafenib alone versus multimodality therapy with sorafenib, radiotherapy (RT), and transarterial chemoembolization (TACE) in advanced HCC patients with macrovascular invasion (MaVI). METHODS: The process took place over a nine-year period between March 2009 and October 2017, wherein 78 HCC patients with MaVI who underwent either sorafenib therapy alone (n = 49) or combined sorafenib/RT/TACE (n = 29) therapy were chosen for the retrospective study. We compared the overall survival (OS) between the two groups using the Cox regression hazard model and adjusted imbalances using propensity score matching (PSM). RESULTS: At the last follow-up, 76 patients had died, with a median follow-up time of 4.8 months for all patients and 31 months for those who were alive. Patients treated with sorafenib/RT/TACE had superior OS compared to those treated with sorafenib alone, showing a median survival of 9.3 vs. 2.7 months and a one-year survival of 37.1% vs. 6.1% (p < 0.001). In the multivariable analysis, new diagnosis or recurrence of HCC and treatment modalities (sorafenib alone vs. sorafenib/RT/TACE) were independent prognostic factors for OS. Compared to patients treated with sorafenib alone, significantly better OS was further verified using PSM (p < 0.001) in patients who received multiple therapeutic modalities. CONCLUSION: Multimodality therapy with sorafenib/RT/TACE increased OS threefold versus sorafenib therapy alone in HCC patients with MaVI. This study offers promising benefits of combined locoregional and systemic therapy for advanced HCC in current patient management and prospective clinical trials.

Association of Hepatitis B and C Virus with the Risk of Coronary Artery Disease and Cerebrovascular Disease in Patients with Hepatocellular Carcinoma.

BACKGROUND: Hepatocellular carcinoma accounts for approximately 90% of primary liver cancers and hepatitis virus was believed to have the potential for altering the pathogenesis of arteriosclerosis. However, the influence of the hepatitis virus on coronary artery disease or cerebral vascular disease remains unclear. This study used the Taiwan National Health Insurance Research Database to clarify the virus-associated risk of coronary artery disease and cerebral vascular disease in patients with hepatocellular carcinoma (HCC). METHODS: A total of 188,039 HCC individuals, age 20 years or older, were enrolled from the Longitudinal Health Insurance Database between 2000 and 2017 for cohort analysis. A total of 109,348 with hepatitis B virus (HBV) infection, 37,506 with hepatitis C virus (HCV) infection, 34,110 without HBV or HCV, and 7075 with both HBV and HCV were recorded. Statistically, propensity score matched by sex, age, and index year at a ratio of 15:5:5:1 and a sensitivity test using multivariable Cox regression were used. RESULTS: The risk of coronary artery disease in the HCV-related HCC group was 1.516-fold (95% CI: 1.328-2.034, p < 0.001) higher than in the HBV-related HCC group, followed by the HBV/HCV-related HCC group and the non-B/C HCC group; the cerebral vascular disease risk in the HCV-related HCC group was 1.467-fold higher than in the HBV-related HCC group (95% CI: 1.335 to 1.786, p < 0.001), followed by the HBV/HCV-related HCC group and the non-B/C HCC group. CONCLUSION: Hepatitis C virus infection was found to have a higher risk of developing coronary artery disease or cerebral vascular disease in patients with hepatocellular carcinoma. For patients with hepatocellular carcinoma, our findings warrant the importance in preventing artherosclerotic disease in the setting of hepatitis C virus infection.

Drug-eluting beads loaded with irinotecan to treat synchronous liver-only metastases of colorectal cancer non-responsive to bevacizumab-based chemotherapy.

OBJECTIVE: To evaluate the efficacy of drug-eluting beads loaded with irinotecan (DEBIRI) in colorectal cancer (CRC) patients with synchronous liver-only metastases non-responsive to bevacizumab-based chemotherapy (BBC). METHODS: Fifty-eight patients were enrolled in this study. Treatment response to BBC and DEBIRI were determined by the morphological criteria and Choi's criteria, respectively. Progression-free survival (PFS) and overall survival (OS) were recorded. The correlation between pre-DEBIRI CT parameters and treatment response to DEBIRI was analyzed. RESULTS: CRC patients were divided into the BBC responsive group (R group) (n = 16) and the non-responsive group (n = 42), which was further divided into the NR group (23 patients who did not receive DEBIRI) and the NR+DEBIRI group (19 patients who received DEBIRI after failing BBC). Among the R, NR and NR+DEBIRI groups, the median PFS were 11, 12, and 4 months, respectively (p < 0.01); median OS were 36, 23, and 12 months, respectively (p = 0.01). In the NR+DEBIRI group, 33 metastatic lesions were treated with DEBIRI, of which 18 (54.5%) reached objective response. The receiver operating characteristic curve showed that the contrast enhancement ratio (CER) before DEBIRI could predict objective response (AUC = 0.737, p < 0.01). CONCLUSION: In CRC patients, DEBIRI can achieve acceptable objective response for liver metastases non-responsive to BBC. However, this locoregional control does not prolong survival. The pre-DEBIRI CER can predict OR in these patients. ADVANCES IN KNOWLEDGE: DEBIRI can act as an acceptable locoregional management in CRC patients with liver metastases non-responsive to BBC, and the pre-DEBIRI CER is a potential indicator of locoregional control.

The Clinical Dilemma of Esophagogastroduodenoscopy for Gastrointestinal Bleeding in Cardiovascular Disease Patients: A Nationwide-Based Retrospective Study.

Performing esophagogastroduodenoscopy (EGD) in recently occurring peri-coronary artery disease (CAD) accident settings is always a dilemma. This study used the Taiwan National Health Insurance Research Database to identify patients with CAD and gastrointestinal bleeding who had received EGD or not between 2000 and 2013.The final population included in this study was 15,147 individuals, with 3801 individuals having received EGD (study cohort group) and 11,346 individuals not having received EGD (comparison cohort group). We initially performed a sensitivity test for CAD recurrence-related factors using multivariable Cox regression during the tracking period. A relatively earlier EGD intervention within one week demonstrated a lower risk of CAD recurrence (adjusted HR = 0.712). Although there were no significant differences in the overall tracking period, the adjusted HR of CAD recurrence was still lower in patients in the EGD group. Furthermore, our findings revealed that there were no remarkably short intervals to CAD recurrence in the study group. The Kaplan-Meier survival curve demonstrated that individuals who underwent EGD were not associated with a significantly increased CAD recurrence rate compared with the control (Log-rank test, p = 0.255). CAD recurrence is always an issue in recent episodes of peri-CAD accident settings while receiving EGD. However, there is not a higher risk in comparison with the normal population in our study, and waiting periods may not be required.

Combination therapy of sorafenib and drug-eluting bead transarterial chemoembolization for advanced hepatocellular carcinoma with and without hepatic arteriovenous shunt.

BACKGROUND: To compare the efficacy and safety of combination therapy with sorafenib and drug-eluting bead transarterial chemoembolization (DEB-TACE) in advanced hepatocellular carcinoma (HCC) with or without hepatic arteriovenous shunt (HAVS). METHODS: This retrospective, single-center study enrolled 59 advanced HCC patients treated with combination therapy, of whom 33 (55.9%) patients had HAVS. Tumor response according to the mRECIST criteria was evaluated based on the CT images 1 month after TACE, and changes in the arterial enhancement ratio (AER) of tumors and portal vein tumor thrombosis were also documented. Time-to-progression (TTP), overall survival (OS), and prognostic factors were analyzed. Safety was evaluated with the incidence of TACE-related complications within 6 weeks after TACE. RESULTS: The tumor response between the two groups showed no significant difference in the objective response rate (69.2% in the group without HAVS vs 60.6% in the group with HAVS, p = 0.492) or disease control rate (92.3% vs 87.9%, p = 0.685). The two groups showed comparable TTP (4.23 vs 2.33 months, p = 0.235) and OS (12.77 vs 12.97 months, p = 0.910). A drop in the AER of tumors of more than 20% on post-TACE CT independently predicted better OS. With regard to safety, there was no significant difference between the two groups. CONCLUSION: For advanced HCC, combination therapy had equal efficacy and safety in patients with HAVS compared to those without HAVS, indicating that DEB-TACE is an optional and effective treatment in these patients.

SPAK Deficiency Attenuates Chemotherapy-Induced Intestinal Mucositis.

INTRODUCTION: Ste20-related protein proline/alanine-rich kinase (SPAK) affects cell proliferation, differentiation, and transformation, and sodium and chloride transport in the gut. However, its role in gut injury pathogenesis is unclear. OBJECTIVE: We determined the role of SPAK in chemotherapy-induced intestinal mucositis using in vivo and in vitro models. METHODS: Using SPAK-knockout (KO) mice, we evaluated the severity of intestinal mucositis induced by 5-fluorouracil (5-FU) by assessing body weight loss, histological changes in the intestinal mucosa, length of villi in the small intestine, pro-inflammatory cytokine levels, proliferative indices, and apoptotic indices. We also evaluated changes in gut permeability and tight junction-associated protein expression. Changes in cell permeability, proliferation, and apoptosis were assessed in SPAK siRNA-transfected 5FU-treated IEC-6 cells. RESULTS: 5-FU-treated SPAK-KO mice exhibited milder intestinal mucositis, reduced pro-inflammatory cytokine expression, increased villus length, good maintenance of proliferative indices of villus cells, decreased apoptotic index of enterocytes, reduced gut permeability, and restoration of tight junction protein expression (vs. 5-FU-treated wild-type mice). Under in vitro conditions, siRNA-mediated SPAK-knockdown in IEC-6 cells decreased cell permeability and maintained homeostasis following 5-FU treatment. CONCLUSION: SPAK deficiency attenuated chemotherapy-induced intestinal mucositis by modulating gut permeability and tight junction-associated protein expression and maintaining gut homeostasis in murine small intestinal tissues following gut injury. The expression of SPAK may influence the pathogenesis of chemotherapy-induced intestinal mucositis.

Generation of Functional Cardiomyocytes from Human Gastric Fibroblast-Derived Induced Pluripotent Stem Cells.

Coronary artery diseases are major problems of the world. Coronary artery disease patients frequently suffer from peptic ulcers when they receive aspirin treatment. For diagnostic and therapeutic purposes, the implementation of panendoscopy (PES) with biopsy is necessary. Some biopsy samples are wasted after the assay is completed. In the present study, we established a protocol for human gastric fibroblast isolation and induced pluripotent stem cell (iPSC) generation from gastric fibroblasts via PES with biopsy. We showed that these iPSCs can be differentiated into functional cardiomyocytes in vitro. To our knowledge, this is the first study to generate iPSCs from gastric fibroblasts in vitro.

Transcatheter Arterial Chemoembolization with Drug-Eluting Beads for the Treatment of Hepatocellular Carcinoma: Recommended Selection for Small-Caliber (<100 µm) Beads.

Drug-eluting beads transarterial chemoembolization (DEB-TACE) is an alternative to conventional lipiodol-based TACE (cTACE) to treat hepatocellular carcinoma (HCC). With the advancement in pharmacology, small-caliber DEB-TACE (<100 µm) has been introduced since 2016. For the treatment of hepatic neoplasms or HCC, there is a tendency to use smaller beads by DEB-TACE to achieve more extensive tumor necrosis and a significant reduction in liver toxicity in comparison with that caused by cTACE. However, the indications and potential complications of small-caliber DEB-TACE remain uncertain and have not been well established, due to lack of randomized phase III clinical trials. Instead of systematic or meta-analysis review, this narrative review article describes the suggested indications and contraindications of DEB-TACE with small DEBs, benefit of super-selective embolization of the feeding arteries and the recommended selection of small-caliber DEB. This review was approved by the institutional review board (File Number: 1-105-05-158).

CRNDE-h transcript/miR-136-5p axis regulates interleukin enhancer binding factor 2 expression to promote hepatocellular carcinoma cell proliferation.

AIMS: Hepatocellular carcinoma (HCC) is a primary malignancy of the hepatocyte. Interleukin enhancer binding factor 2 (ILF2) plays a role in the development of HCC. However, the regulatory mechanisms of ILF2 expression in HCC remain unclear. In this study, we aimed to identify ILF2-targeting microRNAs (miRNAs) and to explore how they affect ILF2 expression in HCC. MAIN METHODS: The tissue specimens were collected from 25 HCC patients. The underlying regulatory mechanism of ILF2 expression in HCC progression was determined using luciferase reporter assay, quantitative real-time PCR, Western blotting, and BrdU incorporation assay. KEY FINDINGS: Of predicted miRNA candidates (miR-122-5p, miR-425-5p, miR-136-5p, miR-7-5p, miR-421 and miR-543), a statistically significant inverse correlation by linear correlation analysis was observed between miR-136-5p and ILF2 mRNA expressions in patients with HCC (r = -0.627, P < 0.001). Further analysis demonstrated that ILF2 was directly regulated by miR-136-5p. In addition, we showed that long noncoding RNA colorectal neoplasia differentially expressed-h (lncRNA CRNDE-h) transcript expression was significantly up-regulated in HCC, and a miR-136-5p binding site was newly found in the lncRNA CRNDE-h transcript sequence using IntaRNA tool. In terms of mechanism, highly-expressed lncRNA CRNDE-h transcript can sponge miR-136-5p, thereby preventing it from interacting with target ILF2 mRNA while promoting the proliferation of HCC cells. SIGNIFICANCE: The lncRNA CRNDE-h/miR-136-5p/ILF2 axis plays a significant regulatory role in HCC progression, which may partly explain the pathogenic mechanisms of HCC and may provide promising potential targets for the diagnosis, treatment, and prognosis of HCC.

Safety Issues in Magnetic Resonance Imaging Scan with Retention of Olympus Long Clips in the Gastrointestinal Tract.

OBJECTIVE: Not all endoscopic clips are compatible with magnetic resonance imaging (MRI). The aim of this study is to investigate the safety of MRI-incompatible endoscopic clips in patients undergoing MRI scans. METHODS: We retrospectively reviewed the medical records of patients who had received endoscopic clip placement of Olympus Long Clip MRI-incompatible clips and then had undergone MRI scans within two weeks in our hospital between 2014 and 2019. RESULTS: A total of 44,292 patients had undergone an MRI examination at our hospital. Only 15 patients had MRI scans within two weeks after the endoscopic clip placement. Their median age was 65.5 years, and 12 of the 15 patients were men. At the time of the clip placement and MRI scan, four patients were taking anti-coagulation or anti-platelet agents. The indication for endoscopic clip placement of the 15 patients was mucosal/submucosal defect or hemorrhage and colonic perforation. Endoscopic clips were placed in the colon of 14 patients and in the stomach of only one patient for gastric hemorrhage. One patient experienced clip migration and three displayed artifacts in abdominal images. No patient complications of mortality, hemorrhage, or organ perforation occurred. CONCLUSION: No serious adverse event occurred during MRI scans of patients with MRI-incompatible clips in this study, suggesting that MRI-incompatible clips may be safe to use in MRI scans. However, this does not guarantee the safety of the Long Clip for MRI scans, as further tests are needed to verify that this clip is safe for use during MRI.

Impact of endoscopic sedation on gastric polyp detection: A one-center retrospective observational study.

Sedation esophagogastroduodenoscopy (EGD) has become more prevalent in many countries. However, owing to the limitation of health insurance payment for sedation EGD in Taiwan, non-sedation EGD still accounts for the majority of cases. This study was aimed to explore the differences between the sedation and non-sedation groups in terms of endoscopic findings, such as detection rate of gastric polyp of any size, number of detected gastric polyps, and location of the gastric polyps detected.We enrolled 10,940 patients who underwent EGD between January 1, 2016 and December 31, 2016 at the Tri-Service General Hospital; among the patients, 1900 received intravenous sedation (IVS) and 9040 did not. The data reviewed included demographics, parameters of the polyp (number, size, and location), and pathology.Compared with the non-sedation group, the sedation group had a higher overall polyp detection rate (P < .001); a greater number of detected polyps (Odds ratio 1.50, P = .007); and a higher detection rate of smaller polyps, such as fundic gland polyp, and hyperplastic polyp (P < .001). Among the pathological findings, gastric neuroendocrine tumor (NET) was detected using EGD in 2 cases and manifested as small polyps (<0.05 cm), and it showed significantly better detection rates in the sedation EGD group than in the non-sedation EGD group (P = .002).Sedation EGD could enhance a patients willingness and cooperation during EGD. Furthermore, sedation EGD increased the detection rates of small gastric polyps and was more likely to enable identification of unusual findings, such as gastric NET.

Time to peak enhancement of malignant hypervascular hepatic tumors versus that of the aorta evaluating by test bolus sequence of magnetic resonance imaging.

PURPOSE: To determine the relationship between time to peak enhancement (TPE) of malignant hypervascular hepatic tumors and that of the aorta. METHOD: Sixty patients with malignant hypervascular hepatic tumors (48 with hepatocellular carcinoma and 12 with metastatic neuroendocrine tumor) who received abdominal MRI with test bolus sequence between January 2015 and May 2019 were enrolled. The test bolus images were monitored every 3 s after the injection of 2 mL gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) and 10 mL saline flush, to evaluate the TPE of the tumors and aorta. We used linear regression with a least squares approach to show the relationship between TPE of the malignant hypervascular hepatic tumors and that of the aorta. RESULTS: TPE of malignant hypervascular hepatic tumors and abdominal aorta were 43.4 ±â€¯12.9 and 23.3 ±â€¯7.4 s, respectively (mean ±â€¯standard deviation). In univariate regression analysis, the TPE of malignant hypervascular hepatic tumors have a positively linear correlation with that of the aorta by the following equation: (TPE of malignant hypervascular hepatic tumor) = 1.4 X (TPE of the aorta) + 10.6 s (r = 0.65, p < 0.005). CONCLUSIONS: TPE of malignant hypervascular hepatic tumors can be predicted by a simple linear transformation from that of the aorta.

Oropharyngeal dysphagia increased the risk of pneumonia in patients undergoing nasogastric tube feeding.

BACKGROUND AND OBJECTIVES: Aspiration pneumonia is a major cause of death in patients on nasogastric tube (NGT) feeding. This study aimed to evaluate the oropharyngeal dysphagia and stratify risk of pneumonia in patients undergoing NGT feeding. METHODS AND STUDY DESIGN: The study included patients on NGT feeding who underwent UGI endoscopy at Tri-Service General Hospital, Taiwan. Endoscopy was performed to examine the pharyngolaryngeal region. The severity of oropharyngeal dysphagia was evaluated according to the visualized amount and location of pooling of secretions in the pharyngolaryngeal region; 60 patients showed absent or minimal amount of secretions (control group), 14 patients showed moderate-to-large amounts of secretions filling the pyriform sinus (pharyngeal group), and 27 patients showed secretions entering the laryngeal vestibule (laryngeal group). Demographic data and occurrence of pneumonia were analyzed. RESULTS: The incidence of pneumonia was highest in the pharyngeal group (4.2±3.6 episodes/person-years), followed by the laryngeal (2.6±2.2 episodes/ person-years) and control groups (1.7±3.8 episodes/person-years) (p=0.042). Multivariable regression showed significantly higher risk of pneumonia in the pharyngeal (adjusted odds ratio=2.7, 95% CI, 2.4-2.8, p<0.001) and laryngeal (adjusted odds ratio=2.0, 95% CI, 1.7-2.4, p<0.001) groups. The cumulative incidence rate of pneumonia was significantly higher in the laryngeal and pharyngeal groups than in the control group (log rank test, p<0.001). CONCLUSIONS: Endoscopic pharyngolaryngeal observation can evaluate the oropharyngeal dysphagia. Visual evidence of oropharyngeal dysphagia increase the risk of pneumonia in patients on NGT feeding.

Nonalcoholic Fatty Liver Disease Associated With Bladder Cancer.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is regarded as a feature of metabolic syndrome in the liver. Metabolic syndrome is associated with a higher risk of bladder cancer. However, the association between NAFLD and bladder cancer is unclear. We aimed to investigate the association between NAFLD and bladder cancer. MATERIALS AND METHODS: The records of all patients (n = 251) diagnosed with the bladder cancer in our hospital between 2009 and 2013 were reviewed. We also randomly collected the records of adults without cancer (n = 266) as the control group. Clinical characteristics, biochemical tests for liver and metabolic function and abdominal computed tomography were assessed. RESULTS: The incidence of NAFLD was 12.0% in the bladder cancer group and 4.9% in the control group. By multiple logistic regression analysis, NAFLD (P = 0.007; odds ratio [OR]: 2.61; 95% confidence interval [CI]: 1.30-5.22), male sex (P < 0.001; OR: 2.34; 95% CI: 1.61-3.41) and use of lipid lowering drugs (P = 0.001; OR: 0.43; 95% CI: 0.26-0.72) showed significant associations with bladder cancer. In bladder cancer patients, the median survival time was significantly longer in patients without NAFLD than in these with NAFLD (40 months versus 21.5 months, P = 0.022). CONCLUSIONS: NAFLD was positively associated with bladder cancer and was a poor prognostic factor of bladder cancer. Further studies are needed to confirm whether NAFLD is a factor for the development of bladder cancer.

Upregulation of amphiregulin by retinoic acid and Wnt signalling promotes liver cancer cell proliferation.

Activated hepatic stellate cells promote hepatocellular carcinoma (HCC) progression. Hepatic stellate cells play a key role in retinoid metabolism, and activation of stellate cells increases retinoic acid (RA) in the liver. However, the role of RA in HCC proliferation remains unclear. We aimed to analyse the mechanism of RA in HCC proliferation. Thirty-eight patients who had undergone hepatic resection for HCCs were recruited. Paired non-tumour tissues, adjacent and distal to HCCs, were collected, and the RA levels in the tissues were analysed. The mechanisms of RA and HCC proliferation were assessed in liver cancer cell lines by protein and gene expression analyses. Early recurrence of HCC was significantly higher in patients with a higher RA concentration than in those with a lower RA concentration in tissues adjacent to HCCs (61.1% vs. 20%, p = .010). RA promoted HCC cell proliferation and activated the expression of Amphiregulin, a growth factor in hepatocarcinogenesis. The promoter of Amphiregulin contained the binding sites of the RA receptor, RXRα. Wnt signalling also activated the expression of Amphiregulin, and the RA and Wnt pathways acted synergistically to increase the expression of Amphiregulin. Furthermore, RXRα interacted with ß-catenin and then translocated to the nucleus to activate Amphiregulin. An increased RA concentration in the tissues adjacent to the tumour was associated with an early recurrence of HCC. RA activated the expression of Amphiregulin, and then promoted HCC proliferation, which might partly contribute to early recurrence of HCC after hepatic resection.

Evaluation of Oropharyngeal Dysphagia in Patients Who Underwent Percutaneous Endoscopic Gastrostomy: Stratification Risk of Pneumonia.

BACKGROUND: Aspiration pneumonia is the most common cause of death in patients who undergo percutaneous endoscopic gastrostomy (PEG). This study aims to evaluate the severity of oropharyngeal dysphagia and predict the risk of pneumonia in such patients, using upper gastrointestinal endoscopy. METHODS: Endoscope examined the pharyngolaryngeal region in patients who underwent PEG. The severity of oropharyngeal dysphagia was evaluated according to the amount and location of pooling of secretions in the pharyngolaryngeal region. Overall, 55 patients showed absent or minimal amount of secretions (control group), 10 patients showed moderate-to-large amounts of secretions filling the pyriform sinus (pharyngeal group), and 23 patients showed secretions entering the laryngeal vestibule (laryngeal group). Demographic data, swallowing level scale, and occurrence of pneumonia were recorded. RESULTS: The incidence of pneumonia was the highest in the pharyngeal group (70.0%), followed by that in the laryngeal (60.9%) and control groups (30.9%; P = 0.010). Multivariable regression showed that risk of pneumonia was significantly higher in the pharyngeal and laryngeal groups. Cumulative incidence rate of pneumonia was significantly higher in the laryngeal and pharyngeal groups than in the control group (log-rank test, P = 0.001). Mortality rate was significantly higher in patients with suboptimal protective cough reflex than in others (50.0% vs 5.9%, P = 0.034). CONCLUSION: Accumulation of abnormal amounts of secretions in the pyriform sinus or in the laryngeal vestibule increased the risk of the hospital admission following pneumonia in patients who underwent PEG. The mortality rate was higher in patients with suboptimal protective cough reflex.

Relationships Between Vitamin D Status and Cytokine: Results from Interferon-Based Therapy in Non-Cirrhotic, Treatment-Naïve Patients with Chronic Hepatitis C Infection.

BACKGROUND: Vitamin D contributes to bone health and extra-skeletal effects. The mechanisms underlying vitamin D metabolism have not been extensively evaluated. The relationships between vitamin D and inflammatory cytokines are debated. Our objective was to investigate whether supplemental interferons are associated with longitudinal change of vitamin D status in humans. METHODS: A total of 48 patients with 24 or 48 weeks of pegylated interferon-α plus ribavirin therapy were examined for serum 25-hydroxyvitamin D (25[OH]D) level before treatment, at the end of treatment, and 24 weeks after treatment. In addition, we analyzed publicly available RNA sequencing data from accession GSE42697 and GSE7123 in the Gene Expression Omnibus. FINDINGS: The overall sustained virologic response (SVR) rate was 62.5%. There was no statistically significant association between baseline 25(OH)D concentrations and liver fibrosis. In patients with SVR, serum 25(OH)D increased markedly at end-of-treatment and decreased markedly by the end of the 24-week follow-up period. In the non-SVR group, this treatment-dependent change was lost. In gene expression analysis, the vitamin D biosynthesis process was activated in subjects with SVR, but not in patients without SVR. Furthermore, vitamin D receptor (VDR) signaling in peripheral blood mononuclear cells (PBMCs) was triggered in marked responders but not in poor responders. CONCLUSION: In the aggregate, these data suggest that interferons have a regulatory influence on vitamin D status that can contribute to VDR signaling in PBMCs.