Prognostic Value of Erythroblastic Leukemia Viral Oncogene Homolog 2 and Neuregulin 4 in Hepatocellular Carcinoma.

Although the roles of erythroblastic leukemia viral oncogene homolog 2 (ERBB2), neuregulin 4 (NRG4), and mitogen-inducible gene 6 (MIG6) in epidermal growth factor receptor signaling in hepatocellular carcinoma (HCC) and other malignancies have been previously investigated, the prognostic value of their serum levels in HCC remains undetermined. In the present study, correlations between serum levels and tumor characteristics, overall survival, and tumor recurrence were analyzed. Furthermore, the prognostic potential of the serum levels of these biomarkers was evaluated relative to that of alpha-fetoprotein. Both ERBB2 and NRG4 correlated with the Barcelona Clinic Liver Cancer stage, ERBB2 correlated with the tumor-maximal diameter, and NRG4 correlated with a tumor number. Cox proportional hazards regression analysis revealed that ERBB2 (hazard ratio [HR], 2.719; p = 0.007) was an independent prognostic factor for overall survival. Furthermore, ERBB2 (HR, 2.338; p = 0.002) and NRG4 (HR, 431.763; p = 0.001) were independent prognostic factors for tumor recurrence. The products of ERBB2 and NRG4 had a better area under the curve than alpha-fetoprotein for predicting 6-month, 1-year, 3-year, and 5-year mortality. Therefore, these factors could be used to evaluate prognosis and monitor treatment response in patients with HCC.

Effect of Diminutive Adenoma with High-Grade Dysplasia on Surveillance Colonoscopy Interval.

BACKGROUND: Colonoscopy surveillance guidelines set the surveillance schedule based on polyp characteristics. Polyps with high-grade dysplasia (HGD) require 3 years of follow-up regardless of size. However, it is unclear whether patients with diminutive polyps (≤5 mm) with HGD have a higher risk. We evaluated the effect of diminutive adenoma with HGD on adenoma occurrence. METHODS: From January 2015 to December 2017, patients who underwent index and surveillance colonoscopy were retrospectively screened. The patients were grouped into no adenoma group, low-risk (patients with ≤2 low-grade dysplasia [LGD]), diminutive HGD, and high-risk (HGD >5 mm, ≥3 adenomas) groups according to the index colonoscopy results. Each group was analyzed using logistic analysis. RESULTS: The mean follow-up period was 22.47 months. Altogether, 610 (50.45%) patients had LGD and 152 (12.5%) had HGD. Among them, 61 (5.0%) patients had a diminutive polyp with HGD. Analysis of the risks of developing advanced adenoma in the surveillance colonoscopy showed that compared to the no adenoma group, the diminutive HGD group did not show a significant risk (odds ratio [OR] = 1.503 [0.449-5.027], p = 0.509), while the high-risk group showed a significant risk (OR = 2.044 [1.015-4.114], p = 0.045). CONCLUSIONS: Diminutive adenoma with HGD increased the risk of adenoma on surveillance colonoscopy, and in the case of advanced adenoma, the risk was increased, but it was not statistically significant.

Risk factors for the histologic discrepancy of gastric adenomatous lesions and long-term outcome.

ABSTRACT: Although endoscopic forceps biopsies (EFB) have a significant role in diagnosing gastric adenoma, there are still discrepancies between EFBs and finalized pathology results.Therefore, the objective of this study was to find the risk factors that cause this discrepancy and to analyze the effects of this discrepancy on the long-term outcome.In this study patients that had received endoscopic resection due to low-grade gastric adenoma diagnosis from EFB between January of 2011 and January of 2018 at the Chungnam National University Hospital were retrospectively analyzed. According to whether there was histological discrepancy the cumulative incidence of the metachronous lesions were analyzed.A total of 745 lesions diagnosed as low-grade gastric adenoma at EFB were enrolled, and the final pathology results were confirmed to be non-neoplastic (n = 19), low-grade adenoma (n = 614), High-grade adenoma (n = 63), and carcinoma (n = 49), and with the exception of non-neoplastic lesion, the results confirmed 84.6% (n = 614) for the concordant group and 15.4% (n = 112) for the discordant. The results of the multivariate analysis confirmed that depressed lesion (odds ratio [OR]: 2.056; 95% confidence interval [CI]: 1.130-3.451; P = .011), erythema (OR: 2.546; 95% CI: 1.604-4.030; P = .004), and a size >1.5 cm (OR: 1.903; 95% CI: 1.102-3.172; P = .018) were risk factors for discrepancy. The results also confirmed that for the average observation period of (SD) 39.12 (12.31) months, the cumulative incidence of metachronous neoplasm had a higher significance (P = 0.001) in the discordant group when compared to that of the concordant group.The factors related to the histologic discrepancy of low-grade gastric adenoma were depressed lesion, erythema and size >1.5 cm. In the groups with histological discrepancy, the cumulative incidence of the metachronous neoplasm was significantly higher and therefore closer observation of such patients after performing endoscopic resection is necessary.

Computed tomography versus lower endoscopy as initial diagnostic method for evaluating patients with hematochezia at emergency room.

For acute lower gastrointestinal bleeding (LGIB), lower gastrointestinal endoscopy is the preferred initial diagnostic test. However, it is difficult to perform urgently. Computed tomography (CT) is a convenient alternative.This study aimed to determine the diagnostic performance of CT compared to lower endoscopy as an initial test for evaluating acute LGIB.The medical records of 382 patients who visited our emergency department with hematochezia between January 2012 and January 2017 were retrospectively analyzed. Of them, 112 underwent CT, 65 underwent colonoscopy, and 205 underwent sigmoidoscopy as an initial test. For each method, sensitivity, specificity, positive predictive value, and negative predictive value were calculated upon active bleeding site detection and LGIB etiology diagnosis.The sensitivity, specificity, positive predictive value, and negative predictive value of CT for active bleeding site detection were 85.7%, 100%, 100%, and 96.9%, respectively, while those for identifying the etiology of LGIB were 87.4%, 40.0%, 83.5, and 47.6%, respectively.CT was not inferior to lower endoscopy for active bleeding site detection. Early localization and the exclusion of active bleeding were possible with CT. Etiology was diagnosed with high sensitivity and PPV by CT. Thus, CT can be an alternative initial diagnostic tool for evaluating acute LGIB.

TEAD2 as a novel prognostic factor for hepatocellular carcinoma.

TEA Domain Transcription Factors (TEADs) are important in development and serve essential roles in tumorigenesis; however, the role of TEAD2 expression in hepatocellular carcinoma (HCC) has not been widely examined. The present study was conducted to investigate the expression status of TEAD2 in HCC and to evaluate whether the expression of TEAD2 is associated with the prognosis of patients with HCC. mRNA expression data was retrieved for Hippo pathway genes of 50 normal control and 377 HCC samples from The Cancer Genome Atlas data portal. Gene set enrichment, GeneNeighbors, ClassNeighbors and survival analyses were then performed based on the gene expression levels. The mRNA expression of TEAD2 and VGLL4 was significantly higher in HCC compared with the normal control samples, and the mRNA expression of TEAD2 was higher in advanced stages than in early stages. Specifically, survival analysis revealed that higher mRNA expression of TEAD2 was significantly associated with a less favorable overall survival rate (P=0.0067) and there was a trend towards significance between higher mRNA expression of VGLL4 and poor overall survival rate (P=0.051). According to the gene set enrichment analysis, patients with higher mRNA expression of TEAD2 and VGLL4 had strongly enhanced epithelial­mesenchymal transition and angiogenesis, which are associated with tumor progression. In conclusion, increased mRNA expression of TEAD2 is associated with a poor prognosis in patients with HCC. TEAD2 may serve as a prognostic factor for HCC and a novel therapeutic target.

Subepithelial Spread of Early Gastric Signet Ring Cell Carcinoma: How Far They Can Reach?

INTRODUCTION: Although signet ring cell carcinoma (SRC) is a poorly differentiated cancer subtype, recent studies suggest that endoscopic resection can be applied in small, mucosal early gastric SRC. However, other studies report frequent positive lines at the lateral resection margin after endoscopic treatment. Subepithelial spread beneath normal mucosa can exist in SRC, and such lesions may be the cause of positive margins after endoscopic resection. Thus, we conducted a retrospective study in order to evaluate the significance of subepithelial spread in early gastric SRC. METHOD: Medical records of early gastric SRC patients who underwent surgery or endoscopic resection from January 2011 to December 2016 at a single tertiary hospital (Daejeon, South Korea) were reviewed to examine subepithelial spread and clinical datum. Two expert pathologists reviewed all pathologic specimens, and only patients showing a pure SRC component were included. RESULTS: Eighty-six patients were initially enrolled, and subepithelial spread existed in 62 patients (72.1%). The mean distance of subepithelial spread was 1,132.1 µm, and the maximal distance was 6,000 µm. Only discoloration was significantly associated with the presence of a subepithelial spread (p < 0.05, χ2 test, and logistic regression test). Distance of subepithelial spread did not correlate with total lesion size. CONCLUSION: Subepithelial spread of early gastric SRC occurs frequently and can reach up to 6 mm. Lesion discoloration may be associated with the presence of subepithelial spread. Our results suggest that careful decision of the margin is needed when performing endoscopic resection of early gastric SRC.

Feasibility of using two-dimensional axial computed tomography in pretreatment decision making for patients with early gastric cancer.

Computed tomography (CT) is widely used in the pretreatment period of early gastric cancer (EGC). Only few studies have reported low accuracy of CT imaging for T and N staging in patients with EGC. However, owing to the limited number of studies, the value of CT imaging for EGC staging is not well known. Thus, we conducted a retrospective cross-sectional study regarding the associations among submucosal invasion, lymph node metastasis, and CT findings.The medical records of patients with EGC who had surgery or endoscopic resection were reviewed in a single center from January 2011 to December 2016. We evaluated the histological type, invasion depth, and lymph node (LN) metastasis on the basis of two-dimensional CT findings.We enrolled 1544 patients. Submucosal (SM) invasion was related to tumor size, histological type, and wall thickening or enhancement on CT images. Deep SM invasion (>500 µm) was also related to tumor size, poorly differentiated type, and abnormal CT findings (wall thickening, enhancement, and central depression). Among the patients with LN reactive positivity (0.5-1 cm), those who were female and had a tumor invasion of >1000 µm showed a higher prevalence of LN metastasis. The false-negative LN group had a higher prevalence of large tumors (>3 cm), poor differentiation, and SM invasion than the true-negative group.Wall thickening, enhancement, and central depression on CT images might be related to SM invasion. Patients with any positive CT findings needs more attention when performing ESD.

Efficacy of Early Endoscopic Intervention for Restoring Normal Swallowing Function in Patients with Lateral Medullary Infarction.

Dysphagia is considered to be a significant barrier for recovery after lateral medullary infarction (LMI). However, there is still no gold standard treatment for dysphagia. The aim of this study was to explore an effect of an early treatment options for swallowing dysfunction after acute LMI. Medical records of acute LMI patients who had been admitted to the department of rehabilitation medicine from January 2014 to December 2017 were reviewed retrospectively. We compared the clinical efficacy of conventional dysphagia rehabilitation to early endoscopic intervention using either botulinum toxin injection into cricopharyngeal muscle or endoscopic balloon dilatation of the muscle. Outcomes, such as duration of parental feeding, albumin level at diet transition to enteral feeding, and complications, were analyzed. A total of 18 patients with LMI were included. While eight patients (8/9, 88.89%) in the endoscopic group were capable of orally ingesting their diet after intervention, the conversion from tube feeding to an oral diet was possible in only five patients (5/9, 55.56%) of the conventional group during hospitalization. However, the difference between the two groups was not significant (p-value ≤ 0.147, chi-square test). Only the final dietary level at the time of discharge was higher level in endoscopic group. The conversion interval from tube feeding to oral diet was also comparable between groups. There was no re-conversion from the oral diet to tube feeding in patients of either group during the median follow-up period of 20 months. Early endoscopic intervention may be a better option for dysphagia with LMI, compared to conventional dysphagia rehabilitation. However, a larger and prospective trial may be needed to confirm our observations.

Colonoscopic withdrawal time and adenoma detection in the right colon.

Shorter colonoscopic withdrawal time (CWT) has been associated with lower adenoma detection rate (ADR), which can increase the risk of interval colorectal cancer (ICC) that commonly arises in the right colon (RC). Therefore, a better ADR in the RC could decrease the incidence of ICC. We analyzed the relationship between CWT and ADR in the RC and entire colon.We retrospectively reviewed the patients who had undergone screening colonoscopy at Chungnam National University Hospital between March 2015 and February 2016. We enrolled 5370 patients in whom colonoscopies were performed by 7 gastroenterologists. We categorized patients into 4 groups in the RC and 6 groups in the entire colon by CWT. Multivariable analysis was used for detection of adenoma in the RC and entire colon.In the RC, the odds ratio (OR) of CWT longer than 3 minutes was 3.70, compared to CWT of <2 minutes [3.06-4.85, 95% confidence interval (CI), P < .001]. In the entire colon, the OR of CWT between 9 to 10 minutes and longer than 10 minutes was 3.34 [2.61-4.27, 95% CI, P < .001] and 3.49 [2.80-4.33, 95% CI, P < .001] compared to CWT of <6 minutes.Based on our result, we suggest that the optimum CWT in the RC should exceed 3 minutes, and considering the "ceiling effect," the optimum CWT in the entire colon should exceed 9 minutes.

Serum procalcitonin levels can be used to differentiate between inflammatory and non-inflammatory diarrhea in acute infectious diarrhea.

In this study, we assess the possibility of using procalcitonin levels to differentiate between inflammatory diarrhea and non-inflammatory diarrhea in acute infectious diarrhea.We reviewed the records of 1176 patients who had symptoms of diarrhea, fever (≥37.8 °C), and abdominal pain between March 2011 and May 2015. After applying exclusion criteria, a sample of 514 patients was considered for study. The patient sample was divided into Group A and Group B for inflammatory diarrhea and non-inflammatory diarrhea, respectively. The assessment involved comparing the laboratory characteristics with the clinical characteristics of the groups.The characteristics of Group A, such as white blood cell (WBC), C-reactive protein (CRP), absolute neutrophil count (ANC), and procalcitonin levels, were relatively higher than those of Group B (P < .001 for Group A). A receiver operator characteristic (ROC) analysis revealed that the highest area-under-the-curve (AUC) value of procalcitonin (0.797; 95% confidence interval [CI] [0.760, 0.831]; P < .001), could be used to differentiate between the 2 groups. Procalcitonin exhibited a sensitivity and a specificity of 87.03% and 68.75%, respectively, at a 0.08 ng/mL cut-off level.Procalcitonin was a good candidate biomarker of inflammatory diarrhea than other inflammatory markers.

[Abdominal Pain Due to Hem-o-lok Clip Migration after Laparoscopic Cholecystectomy].

During laparoscopic cholecystectomy, a surgical clip is used to control the cystic duct and cystic artery. In the past, metallic clips were usually used, but over recent years, interest in the use of Hem-o-lok clips has increased. Surgical clip migration into the common bile duct (CBD) after laparoscopic cholecystectomy has rarely been reported and the majority of reported cases involved metallic clips. In this report, we describe the case of a 53-year-old woman who presented with abdominal pain caused by migration of a Hem-o-lok clip into the CBD. The patient had undergone laparoscopic cholecystectomy 10 months previously. Abdominal CT revealed an indistinct, minute, radiation-impermeable object in the distal CBD. The object was successfully removed by sphincterotomy via ERCP using a stone basket and was identified as a Hem-o-lok clip.

Gene expression of NOX family members and their clinical significance in hepatocellular carcinoma.

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase complex-derived reactive oxygen species (ROS) promote chronic liver inflammation and remodeling that can drive hepatocellular carcinoma development. The role of NOX expression in hepatocellular carcinoma (HCC) has been partially investigated; however, the clinical relevance of collective or individual NOX family member expression for HCC survival remains unclear. Here, we obtained NOX mRNA expression data for 377 HCC samples and 21 normal liver controls from the TCGA data portal and performed Kaplan-Meier survival, gene ontology functional enrichment, and gene set enrichment analyses. Although most NOX genes exhibited little change, some were significantly induced in HCC compared to that in normal controls. In addition, HCC survival analyses indicated better overall survival in patients with high NOX4 and DUOX1 expression, whereas patients with high NOX1/2/5 expression showed poor prognoses. Gene-neighbour and gene set enrichment analyses revealed that NOX1/2/5 were strongly correlated with genes associated with cancer cell survival and metastasis, whereas increased NOX4 and DUOX1 expression was associated with genes that inhibit tumour progression. On the basis of these data, NOX family gene expression analysis could be a predictor of survival and identify putative therapeutic targets in HCC.

Advantages of Laparoscopic Radiofrequency Ablation Over Percutaneous Radiofrequency Ablation in Hepatocellular Carcinoma.

BACKGROUND: Inoperable hepatocellular carcinoma (HCC) can be treated with laparoscopic radiofrequency ablation (LRFA), which is generally a more accurate and accessible procedure than percutaneous RFA (PRFA). However, few studies have compared survival outcomes between LRFA and PRFA in patients with HCC. AIMS: This study aimed to compare the efficacy of LRFA and PRFA for HCC treatment. METHODS: Patients who underwent PRFA or LRFA as an initial treatment modality between April 2005 and April 2016 were enrolled in this study. The overall and recurrence-free survival rates were examined for each patient. Additionally, propensity score matching was performed for both groups. RESULTS: The baseline characteristics of patients in the PRFA and LRFA groups showed several minor differences. Multivariate analysis showed that the RFA method was not a critical determinant of recurrence-free or overall survival (p = 0.069 and p = 0.406). Among patients who underwent RFA as the initial treatment modality, there was no significant effect between either RFA procedures on survival. After propensity score matching, univariate analysis showed a significant difference in overall survival between PRFA and LRFA (p = 0.031). Multivariate analysis showed that LRFA is a strong factor that contributed to an improved overall survival in HCC patients (hazard ratio 0.108, p = 0.040). Furthermore, our data showed that LRFA was able to limit multiple intrahepatic recurrences, as well as prevent marginal recurrence. CONCLUSIONS: LRFA appears to be superior to PRFA in terms of survival. LRFA may help reduce mortality in HCC patients.

Fimasartan-induced liver injury in a patient with no adverse reactions on other types of angiotensin II receptor blockers: A case report.

RATIONALE: Angiotensin II receptor blockers (ARBs) are widely used for patients with hypertension, and fimasartan is a recently approved ARBs. Fimasartan can cause headache, dizziness, itching, and coughing. There have been several reports of hepatotoxicity in ARBs. However, there have not yet been published reports of the hepatotoxicity of fimasartan. PATIENT CONCERNS: A 73-year-old man with hypertension experienced liver injury after fimasartan administration. He had a previous history of taking 3 types of ARBs each for more than 2 years before taking fimasartan, and there were no side effects on ARBs except for fimasartan. DIAGNOSES: Other factors that could cause liver injury were excluded in diagnostic tests, and fimasartan was suspected to be the causative agent. INTERVENTION: Fimasartan was immediately discontinued and the patient was managed with supportive care via hepatotonics. DIAGNOSES: Other factors that could cause liver injury were excluded in diagnostic tests, and fimasartan was suspected to be the causative agent. OUTCOME: The liver injury due to fimasartan was confirmed by histology and accidental redosing. LESSONS: We emphasize that liver function should be monitored during fimasartan administration because fimasartan may cause hepatotoxicity in patients who have no side effects with other types of ARBs. And fimasartan-induced liver injury may appear later than other ARBs.

Atypical onset of bicalutamide-induced liver injury.

Anti-androgen therapy is the leading treatment for advanced prostate cancer and is commonly used for neoadjuvant or adjuvant treatment. Bicalutamide is a non-steroidal anti-androgen, used during the initiation of androgen deprivation therapy along with a luteinizing hormone-releasing hormone agonist to reduce the symptoms of tumor-related flares in patients with advanced prostate cancer. As side effects, bicalutamide can cause fatigue, gynecomastia, and decreased libido through competitive androgen receptor blockade. Additionally, although not as common, drug-induced liver injury has also been reported. Herein, we report a case of hepatotoxicity secondary to bicalutamide use. Typically, bicalutamide-induced hepatotoxicity develops after a few days; however, in this case, hepatic injury occurred 5 mo after treatment initiation. Based on this rare case of delayed liver injury, we recommend careful monitoring of liver function throughout bicalutamide treatment for prostate cancer.