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Abdominal tuberculosis (TB) is uncommon in Taiwan and frequently mimics malignancy or other infectious diseases due to nonspecific clinical manifestations, often leading to delayed diagnosis. We report a 72‐year‐old man who presented with fever, anorexia, weight loss, and epigastric discomfort. Esophagogastroduodenoscopy (EGD) revealed a subepithelial lesion (SEL) on the posterior wall of the upper gastric body. Contrast‐enhanced computed tomography (CE‐CT) demonstrated mass‐like lesions involving the liver and upper gastrointestinal tract with enlarged abdominal lymph nodes (LNs), raising concern for malignancy. Endoscopic ultrasound–guided fine‐needle biopsy (EUS‐FNB) was performed on the gastric wall, hepatic lesion, and enlarged LNs. Histopathology revealed necrotizing granulomatous inflammation in all specimens, and tuberculosis polymerase chain reaction (PCR) confirmed Mycobacterium tuberculosis infection. Anti‐tuberculosis therapy resulted in marked clinical improvement and significant radiologic regression. This case highlights a rare presentation of extrapulmonary tuberculosis (EPTB) involving multiple digestive organs and underscores the diagnostic value of endoscopic ultrasound–guided tissue acquisition (EUS‐TA). Key Clinical Message (KCM) Gastrointestinal tuberculosis can closely mimic malignancy, presenting as mass‐like lesions. Integrating clinical context with characteristic endoscopic ultrasound findings and endoscopic ultrasound–guided tissue acquisition, particularly fine‐needle biopsy, facilitates timely diagnosis, appropriate therapy, and favorable clinical outcomes.

This study investigated whether oncogenic and tumor-suppressive gene mutations are involved in the differential outcomes of patients with rectal carcinoma receiving neoadjuvant chemoradiotherapy (nCRT). Genomic DNA was obtained from formalin-fixed paraffin-embedded (FFPE) specimens of patients with rectal carcinoma who received a complete nCRT course. Gene mutation status was examined in specimens from patients before and after nCRT by using the AmpliSeq platform. Our data revealed that the nonsynonymous p53, APC, KRAS, CDKN2A, and EGFR mutations were observed in 93.1%, 65.5%, 48.6%, and 31% of the patients with rectal adenocarcinoma, respectively. BRAF, FBXW7, PTEN, and SMAD4 mutations were observed in 20.7% of patients with rectal carcinoma. The following 12 gene mutations were observed more frequently in the patients exhibiting a complete response than in those demonstrating a poor response before nCRT: ATM, BRAF, CDKN2A, EGFR, FLT3, GNA11, KDR, KIT, PIK3CA, PTEN, PTPN11, SMAD4, and TP53. In addition, APC, BRAF, FBXW7, KRAS, SMAD4, and TP53 mutations were retained after nCRT. Our results indicate a complex mutational profile in rectal carcinoma, suggesting the involvement of BRAF, SMAD4, and TP53 genetic variants in the outcomes of patients with nCRT.

Background The isocitrate dehydrogenase (IDH) gene family expresses key functional metabolic enzymes in the Krebs cycle and mediates the epigenetic reprogramming, which serves as an important biomarker of breast cancer. However, the expression levels of the IDH protein and their biological function in human breast cancer remain largely unknown. Methods In this study, the clinical impact of IDH1 expression on the progression and prognosis of breast cancer was evaluated using immunohistochemistry assay (IHC) of the corresponding tumor-adjacent normal, ductal carcinoma in situ (DCIS), and invasive ductal carcinoma (IDC) tissues from 309 patients with breast ductal carcinoma. The relationship between microRNA (miRNA) and IDH1 were examined by a bioinformatics approach, western blot and reporter assay. The biological functions of IDH1 were examined in breast cancer cells with IDH1 knockdown, including proliferation, migration and invasion. Results The present findings revealed that the mRNA and protein expression levels of IDH1 were both significantly lower in breast cancer tissues than in adjacent normal tissues. A low expression level of IDH1 in breast cancer significantly correlated with advanced stage ( p = 0.012), lymph node metastasis ( p = 0.018), and poor disease-specific survival (DSS) (adjusted hazard ratio (AHR), 1.57, 95% confidence interval (CI), 1.08–2.30; p = 0.02). Furthermore, oncogenic miR-32 and miR-92b were identified to suppress IDH1 expression, leading to the inhibition of cell migration and invasion. We further explored whether reduced expression of IDH1 significantly increases snail expression by activating HIFα (hypoxia-inducible factor-1 alpha) and NFκB (nuclear factor kappa B) signaling. Multivariate Cox regression analysis revealed that the combination of low IDH1 and high snail expression could be an independent risk factor for shorter DSS (AHR, 2.34; 95% CI, 1.32–4.16; p = 0.004) and shorter disease-free survival (AHR, 2.50; 95% CI, 1.39–4.50; p = 0.002) in patients with breast cancer. Conclusion Our findings revealed that a IDH1 low /Snail high molecular signature could serve as an independent biomarker for poor prognosis in breast cancer

DNA methylation at the 5 position of cytosine (5mC) is an epigenetic hallmark in cancer. The 5mC can be converted to 5-hydroxymethylcytosine (5hmC) through a ten-eleven-translocation (TET). We investigated the impact of 5mC, 5hmC, TET1, and TET2 on tumorigenesis and prognosis of breast cancer. Immunohistochemistry was used to assess the levels of 5mC, 5hmC, TET1, and TET2 in the corresponding tumor adjacent normal ( n  = 309), ductal carcinoma in situ (DCIS, n  = 120), and invasive ductal carcinoma (IDC, n  = 309) tissues for 309 breast ductal carcinoma patients. 5mC, 5hmC, TET1-n, and TET2-n were significantly decreased during DCIS and IDC progression. In IDC, the decrease of 5hmC was correlated with the cytoplasmic mislocalization of TET1 ( p  < 0.001) as well as poor disease-specific survival (DSS) (adjusted hazard ratio [AHR] 1.95, p  = 0.003) and disease-free survival (DFS) (AHR 1.91, p  = 0.006). The combined decrease of 5mC and 5hmC was correlated with worse DSS (AHR 2.19, p  = 0.008) and DFS (AHR 1.99, p  = 0.036). Stratification analysis revealed that the low level of 5mC was associated with poor DSS (AHR 1.89, p  = 0.044) and DFS (AHR 2.02, p  = 0.035) for the ER/PR-positive subtype. Conversely, the low level of 5hmC was associated with worse DSS (AHR 2.77, p  = 0.002) and DFS (AHR 2.69, p  = 0.006) for the ER/PR-negative subtype. The decreases of 5mC, 5hmC, TET1-n, and TET2-n were biomarkers of tumor development. The global reduction of 5hmC was a poor prognostic factor for IDC, especially for ER/PR-negative subtype.

Metabolic risk factors, such as obesity, fatty liver, high lipidemia, and diabetes mellitus are associated with increased risk for nonviral hepatocellular carcinoma (HCC); however, few nonviral HCC studies have stratified patients according to underlying etiologies. From 2005 to 2011, 3,843 patients with HCC were recruited into the Taiwan Liver Cancer Network. Of these patients, 411 (10.69%) who were negative for hepatitis B virus (HBV), surface antigen, HBV DNA, and anti‐hepatitis C virus (HCV) antibody were classified as non‐HBV non‐HCV (NBNC)‐HCC. Detailed clinical analyses of these patients were compared with age‐ and sex‐matched patients with HBV‐HCC or HCV‐HCC for the associated metabolic risk factors. For this comparison, 420 patients with HBV‐HCC and 420 patients with HCV‐HCC were selected from the 3,843 patients with HCC. Multivariate analyses showed fatty liver (by echography), high triglyceride levels (>160 mg/dL), and diabetes mellitus history to be significantly associated only with NBNC‐HCC and not with the matched patients with HBV‐ or HCV‐HCC. When the patients with HCC were further divided into four groups based on history of alcoholism and cirrhotic status, the group without alcoholism and without cirrhosis exhibited the strongest association with the metabolic risk factors. Based on trend analyses, patients with NBNC‐HCC with or without alcoholism were significantly different from the matched patients with HBV‐ or HCV‐HCC, except for patients with alcoholism and cirrhosis, in having more than two of the above three risk factors. Conclusion: Metabolic risk factors are significantly associated with nonviral HCC, especially for patients without alcoholism in Taiwan. Because the prevalence of viral HCC is decreasing due to the success of universal vaccination and antiviral therapy, strategies for cancer prevention, prediction, and surveillance for HCC will require modification. (Hepatology Communications 2018;2:747‐759) : Fatty liver (by echography), high triglyceride (>160 mg/dL), and DM history are associated with NBNC‐HCC in Taiwan. The nonalcoholic, noncirrhotic group exhibited the strongest association with the metabolic risk factors.

The use of ultrasmall superparamagnetic iron oxide (USPIO) nanoparticles to visualize cells has been applied clinically, showing the potential for monitoring cells in vivo with magnetic resonance imaging (MRI). USPIO conjugated with anti-CD133 antibodies (USPIO-CD133 Ab) that recognize the CD133 molecule, a cancer stem cell marker in a variety of cancers, was studied as a novel and potent agent for MRI contrast enhancement of tumor cells. Anti-CD133 antibodies were used to conjugate with USPIO via interaction of streptavidin and biotin for in vivo labeling of CD133-positive cells in xenografted tumors and N-ethyl-N-nitrosourea (ENU)-induced brain tumors. The specific binding of USPIO-CD133 Ab to CD133-positive tumor cells was subsequently detected by Prussian blue staining and MRI with T2-weighted, gradient echo and multiple echo recombined gradient echo images. In addition, the cellular toxicity of USPIO-CD133 Ab was determined by analyzing cell proliferation, apoptosis, and reactive oxygen species production. USPIO-CD133 Ab specifically recognizes in vitro and labels CD133-positive cells, as validated using Prussian blue staining and MRI. The assays of cell proliferation, apoptosis, and reactive oxygen species production showed no significant differences in tumor cells with or without labeling of USPIO-CD133 Ab. In vivo imaging of CD133-positive cells was demonstrated by intravenous injection of USPIO-CD133 Ab in mice with HT29 xenografted tumors. The MRI of HT29 xenografts showed several clusters of hypotensive regions that correlated with CD133 expression and Prussian blue staining for iron. In rat, brain tumors induced by transplacental ENU mutagenesis, several clusters of hypointensive zones were observed in CD133-expressing brain tumors by MRI and intravenously administered USPIO-CD133 Ab. Combination of USPIO-CD133 Ab and MRI is valuable in recognizing CD133-expressing tumor cells in vitro, extracellularly labeling for cell tracking and detecting CD133-expressing tumors in xenografted tumors as well as ENU-induced rat brain tumors.

This study aimed to compare the performance of gadoxetic acid -enhanced magnetic resonance imaging (MRI) and sonoelastography in evaluating chemopreventive effects of Sho-Saiko-To (SST) in thioacetamide (TAA)-induced early liver fibrosis in rats. Ten of Sprague-Dawley rats receiving TAA (200 mg/kg of body weight) intraperitoneal injection were divided into three groups: Group 1 (TAA only, n = 3), Group 2 (TAA +0.25 g/kg SST, n = 4) and Group 3 (TAA+1 g/kg SST, n = 3). Core needle liver biopsy at week 2 and liver specimens after sacrifice at week 6 confirmed liver fibrosis using histological examinations, including Sirius red staining, Ishak and Metavir scoring systems. Gadoxetic acid-enhanced MRI and shear-wave sonoelastography were employed to evaluate liver fibrosis. The expression of hepatic transporter organic anion transporter 1 (Oatp1), multidrug-resistant protein 2 (Mrp2) and alpha-smooth muscle actin (α-Sma) were also analyzed in each group by immunohistochemistry (IHC) and Western blot. According to histological grading by Sirius red staining, Ishak scores of liver fibrosis in Groups 1, 2 and 3 were 3, 2 and 1, respectively. As shown in gadoxetic acid-enhanced MRI, the ratio of relative enhancement was significantly lower in Group 1 (1.87 ± 0.21) than in Group 2 of low-dose (2.82 ± 0.25) and Group 3 of high-dose (2.72 ± 0.12) SST treatment at 10 minutes after gadoxetic acid intravenous injection (p < 0.05). Sonoelastography showed that the mean difference before and after experiments in Groups 1, 2 and 3 were 4.66 ± 0.1, 4.4 ± 0.57 and 3 ± 0.4 KPa (p < 0.1), respectively. Chemopreventive effects of SST reduced the Mrp2 protein level (p < 0.01) but not Oatp1 and α-Sma levels. Sonoelastography and gadoxetic acid-enhanced MRI could monitor the treatment effect of SST in an animal model of early hepatic fibrosis.

This prospective cohort study investigated the impact of Helicobacter pylori infection on the development of various gastric malignancies. We prospectively followed up 1,225 dyspeptic Taiwanese who had nonulcer dyspepsia, gastric ulcers, or duodenal ulcers at enrollment. Among them, 618 (50.4%) had H. pylori infection and 607 (49.6%) did not. Patients underwent endoscopy at enrollment and at 1- to 3-yr intervals thereafter. During a mean follow-up of 6.3 yr, gastric adenocarcinoma developed in 7 of the 618 H. pylori-infected patients, but in none of the 607 uninfected patients (1.1%vs 0.0%, P= 0.015). The incidence of gastric lymphoma was 0.2% (1/618) and 0% in H. pylori-infected and uninfected patients. Taken together, the development rate of gastric malignancy in H. pylori-infected patients was significantly higher than that in uninfected patients (1.3%vs 0%, P= 0.007). Among H. pylori-infected subjects, the incidence of gastric malignancy was similar between those receiving and not receiving eradication therapy (1.4%vs 1.2%). Multivariate analysis showed that intestinal metaplasia was the only independent factor predicting subsequent development of gastric malignancy in H. pylori-infected subjects with an odds ratio of 4.5 (95% CI 1.1-19.1). In this prospective cohort study, all gastric malignancies, including adenocarcinoma and lymphoma, developed in H. pylori-infected patients. The finding implies that H. pylori is a necessary cause of most gastric malignancies. Follow-up for H. pylori-infected patients who have intestinal metaplasia is indicated.

This prospective, randomized, controlled, head-to-head study was conducted to compare the efficacies of esomeprazole- and pantoprazole-based triple therapies for Helicobacter pylori eradication. From January 2002 to October 2003, 200 H. pylori-infected patients were randomly assigned to undergo twice daily treatment with esomeprazole 40 mg (n = 100) or pantoprazole 40 mg (n = 100) combined with clarithromycin 500 mg and amoxicillin 1 g for 1 wk (ECA and PCA groups, respectively). Follow-up endoscopy was performed at 8 wks after the end of treatment to assess the treatment response. Intention-to-treat analysis demonstrated a significantly higher eradication rate for the ECA group than for the PCA group (94%vs 82%, respectively, p= 0.009). Per-protocol analysis also showed similar results (97%vs 84%, p= 0.003). Both groups had similar frequencies of adverse events (15%vs 24%) and drug compliance (97%vs 96%). Multivariate analysis disclosed that the use of esomeprazole (OR: 1.56, 95% CI, 1.11-2.19) and good compliance 7.39 (95% CI, 1.27-42.95) were independent predictors of treatment success. Alcohol drinking was an independent predictor of eradication failure (OR: 0.18; 95% CI, 0.06-0.54). Esomeprazole-based triple therapy demonstrated a higher eradication rate than pantoprazole-based regimen. The differences in eradiation efficacies between the two study groups may be related to the more powerful acid inhibition effect and stronger anti-H. pylori activity of esomeprazole compared to pantoprazole.

Aims. To investigate the impact of blood type, functional polymorphism (T-1676C) of the COX-1 gene promoter, and clinical factors on the development of peptic ulcer during cardiovascular prophylaxis with low-dose aspirin. Methods. In a case-control study including 111 low-dose aspirin users with peptic ulcers and 109 controls (asymptomatic aspirin users), the polymorphism (T-1676C) of the COX-1 gene promoter was genotyped, and blood type, H pylori status, and clinical factors were assessed. Results. Univariate analysis showed no significant differences in genotype frequencies of the COX-1 gene at position -1676 between the peptic ulcer group and control group. Multivariate analysis revealed that blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID were the independent risk factors for the development of peptic ulcer with the odds ratios of the 2.1, 3.1, 27.6, and 2.9, respectively. Conclusion. The C-1676T polymorphism in the COX-1 gene promoter is not a risk factor for ulcer formation during treatment with low-dose aspirin. Blood type O, advanced age, history of peptic ulcer, and concomitant use of NSAID are of independent significance in predicting peptic ulcer development during treatment with low-dose aspirin.