Accurate noninvasive methods for the assessment of liver fibrosis are urgently needed. This prospective study evaluated the diagnostic accuracy of diffusion-weighted magnetic resonance imaging (DWI) ...for the staging of liver fibrosis and proposed a diagnostic algorithm using DWI to identify cirrhosis in patients with chronic viral hepatitis.
One hundred twenty-one treatment-naïve patients with chronic hepatitis B or C were evaluated with DWI followed by liver biopsy on the same day. Breath-hold single-shot echo-planar DWI was performed to measure the apparent diffusion coefficient (ADC) of the liver and spleen. Normalized liver ADC was calculated as the ratio of liver ADC to spleen ADC.
There was an inverse correlation between fibrosis stage and normalized liver ADC (p<0.05). For the prediction of fibrosis stage ≥2, stage ≥3, and cirrhosis, the area under the receiver-operating curve of normalized liver ADC was 0.603, 0.704, and 0.847, respectively. The normalized liver ADC value ≤1.02×10-3 mm2/s had 88% sensitivity, 81% specificity, 25% positive predictive value (PPV), and 99% negative predictive value (NPV) for the diagnosis of cirrhosis. Using a sequential approach with the Fibrosis-4 index followed by DWI, normalized liver ADC ≤1.02×10-3 mm2/s in patients with Fibrosis-4 >3.25 yielded an 80% PPV for cirrhosis, and a 100% NPV to exclude cirrhosis in patients with Fibrosis-4 between 1.45 and 3.25. Only 15.7% of patients would require a liver biopsy. This sequential strategy can reduce DWI examinations by 53.7%.
Normalized liver ADC measurement on DWI is an accurate and noninvasive tool for the diagnosis of cirrhosis in patients with chronic viral hepatitis.
Diagnosing intestinal tuberculosis (ITB) is challenging due to the low diagnostic sensitivity of current methods. This study aimed to assess the clinical characteristics and diagnosis of ITB at our ...tertiary referral center, and to explore improved methods of ITB diagnosis.
This retrospective study included 177 patients diagnosed with ITB at Siriraj Hospital (Bangkok, Thailand) during 2009-2020.
The mean age was 49 years, 55.4% were male, and 42.9% were immunocompromised. Most diagnoses (108/177) were made via colonoscopy; 12 patients required more than one colonoscopy. Among those, the sensitivity of tissue acid-fast bacilli (AFB), presence of caseous necrosis, polymerase chain reaction (PCR), and culture was 40.7%, 13.9%, 25.7%, and 53.4%, respectively. Among patients with negative tissue histopathology, 4 (3.7%) and 13 (12.0%) were ITB positive on tissue PCR and culture, respectively. The overall sensitivity when all diagnostic methods were used was 63%. Seventy-six patients had stool tests for mycobacteria. The overall sensitivity of stool tests was 75.0%. However, when analyzing the 31 patients who underwent both endoscopy and stool testing, the sensitivity of stool testing when using tissue biopsy as a reference was 45.8%. Combining stool testing and tissue biopsy did not significantly increase the sensitivity compared to tissue biopsy alone (83.9% vs. 77.4%, respectively).
Despite the availability of PCR and culture for TB, the overall diagnostic sensitivity was found to be low. The sensitivity increased when the tests were used in combination. Repeated colonoscopy may be beneficial. Adding stool mycobacteria tests did not significantly increase the diagnostic yield if endoscopy was performed, but it could be beneficial if endoscopy is unfeasible.
Colorectal cancer (CRC) is the third most common malignancy cause of cancer-related mortality worldwide. Epithelial-mesenchymal transition (EMT) promotes cancer metastasis and a tumour-based Glasgow ...EMT score was associated with adverse clinical features and poor prognosis. In this study, the impact of using the established five tumour-based EMT markers consisting of E-cadherin (E-cad), β-catenin (β-cat), Snail, Zeb-1, and Fascin in combination with the stromal periostin (PN) on the prediction of CRC patients’ prognosis were invesigated. Formalin-fixed paraffin-embedded tissues of 202 CRC patients were studies the expressions of E-cad, β-cat, Snail, Zeb-1, Fascin, and PN by immunohistochemistry. Individually, cytoplasmic Fascin (Fc), cytoplasmic Snail (Sc), nuclear Snail (Sn), stromal Snail (Ss), and stromal PN (Ps) were significantly associated with reduced survival. A combination of Ps with Fc, Fs, and Sn was observed in 2 patterns including combined Fc, Fs, and Ps (FcFsPs) and Fc, Sn, and Ps (FcSnPs). These combinations enhanced the prognostic power compared to individual EMT markers and were independent prognostic markers. As the previously established scoring method required five markers and stringent criteria, its clinical use might be limited. Therefore, using these novel combined prognostic markers, either FcFsPs or FcSnPs, may be useful in predicting CRC patient outcomes.
Colorectal cancer (CRC) is one of the most fatal cancers with highly invasive properties. The progression of CRC is determined by the driving force of periostin (PN) from cancer‐associated ...fibroblasts (CAFs) in the tumour microenvironment. This present work aims to investigate autophagy‐mediated CRC invasion via the receptor integrin (ITG) by PN. The level of PN in 410 clinical CRC tissues was found increased and was an independent poor prognosis marker (HR = 2.578, 95% CI = 1.218‐5.457, P‐value = .013) with a significant correlation with overall survival time (P‐value < .001). PN activated proliferation, migration and invasion of CRC cells, but with reduced autophagy. Interestingly, the reduction of LC3 autophagic protein corresponded to the increased ability of CRC cell migration. The siITGα5‐treated HT‐29 and siITGβ4‐treated HCT‐116 CRC cells attenuated epithelial‐to‐mesenchymal transitions (EMT)‐related genes and pAKT compared with those in siITG‐untreated cells. The reduction of pAKT by a PI3K inhibitor significantly restored autophagy in CRC cells. These evidences confirmed the effect of PN through either ITGα5β1 or ITGα6β4 and the AKT‐dependent pathway to control autophagy‐regulated cell migration. In conclusion, these results exhibited the impact of PN activation of ITGα5β1 or ITGα6β4 through pAKT in autophagy‐mediated EMT and migration in CRC cells.
Distinguishing intestinal tuberculosis (ITB) from Crohn's disease (CD) is difficult, although studies have reported clinical, endoscopic, imaging, and laboratory findings that help to differentiate ...these two diseases. We aimed to produce estimates of the predictive power of these findings and construct a comprehensive model to predict the probability of ITB vs. CD.
A systematic literature search for studies differentiating ITB from CD was conducted in MEDLINE, PUBMED, and EMBASE from inception until September 2015. Fifty-five distinct meta-analyses were performed to estimate the odds ratio of each predictive finding. Estimates with a significant difference between CD and ITB and low to moderate heterogeneity (I
<50%) were incorporated into a Bayesian prediction model incorporating the local pretest probability.
Thirty-eight studies comprising 2,117 CD and 1,589 ITB patients were included in the analyses. Findings in the model that significantly favored CD included male gender, hematochezia, perianal disease, intestinal obstruction, and extraintestinal manifestations; endoscopic findings of longitudinal ulcers, cobblestone appearance, luminal stricture, mucosal bridge, and rectal involvement; pathological findings of focally enhanced colitis; and computed tomographic enterography (CTE) findings of asymmetrical wall thickening, intestinal wall stratification, comb sign, and fibrofatty proliferation. Findings that significantly favored ITB included fever, night sweats, lung involvement, and ascites; endoscopic findings of transverse ulcers, patulous ileocecal valve, and cecal involvement; pathological findings of confluent or submucosal granulomas, lymphocyte cuffing, and ulcers lined by histiocytes; a CTE finding of short segmental involvement; and a positive interferon-γ release assay. The model was validated by gender, clinical manifestations, endoscopic, and pathological findings in 49 patients (27 CD, 22 ITB). The sensitivity, specificity, and accuracy for diagnosis of ITB were 90.9%, 92.6%, and 91.8%, respectively.
A Bayesian model based on the meta-analytic results is presented to estimate the probability of ITB and CD calibrated to local prevalence. This model can be applied to patients using a publicly available web application.
Villous adenoma is the one subtype of adenomatous polyp that is very uncommon in the stomach. Data regarding clinical characteristics, natural history, and prognosis were scarce.
This report ...presented an 87-year-old Thai woman with a large gastric villous adenoma incidentally revealed in a computed tomography of chest for the evaluation of right pleural effusion. The esophagogastroduodenoscopy demonstrated a huge, glossy, proliferative polypoid mass involving gastric cardia, fundus, and a lesser curve of the upper body. The pathological report confirmed villous adenoma with low grade dysplasia. Although surgical resection was suggested, the patient denied any treatment due to advanced age and multiple comorbidities. She was generally well after 12 months of clinical and radiologic surveillance.
From literature review, only 14 cases of gastric villous adenoma were reported to date. Most of the lesions were large and symptomatic. Malignancy presented in 43% of the cases. Nevertheless, our patient remained asymptomatic without surgical removal following a 12-month period.
Gastrointestinal (GI) cytomegaloviral (CMV) infection is common among patients with immunocompromised status; however, data specific to GI-CMV infection in immunocompetent patients are comparatively ...limited.
This retrospective study included patients diagnosed with GI-CMV infection at Siriraj Hospital (Bangkok, Thailand) during 2008-2017. Baseline characteristics, presentations, comorbid conditions, endoscopic findings, treatments, and outcomes were compared between immunocompetent and immunocompromised.
One hundred and seventy-three patients (56 immunocompetent, 117 immunocompromised) were included. Immunocompetent patients were significantly older than immunocompromised patients (73 vs. 48.6 years, p < 0.0001). Significantly more immunocompetent patients were in the ICU at the time of diagnosis (21.0% vs. 8.6%, p = 0.024). GI bleeding was the leading presentation in immunocompetent, while diarrhea and abdominal pain were more common in immunocompromised. Blood CMV viral load was negative in significantly more immunocompetent than immunocompromised (40.7% vs. 12.9%, p = 0.002). Ganciclovir was the main treatment in both groups. Significantly more immunocompetent than immunocompromised did not receive any specific therapy (25.5% vs. 4.4%, p ≤ 0.01). Six-month mortality was significantly higher among immunocompetent patients (39.0% vs. 22.0%, p = 0.047). Independent predictors of death were old age and inpatient or ICU clinical setting. Treatment with antiviral agents was the only independent protective factor.
GI-CMV infection was frequently observed among immunocompetent elderly patients with comorbidities or severe concomitant illnesses. GI bleeding was the most common presentation. Blood CMV viral load was not diagnostically helpful. Significantly higher mortality was observed in immunocompetent than in immunocompromised patients, but this could be due to more severe concomitant illnesses in the immunocompetent group.
Cholangiocarcinoma (CCA) has an abundance of tumor stroma which plays an important role in cancer progression via tumor-promoting signals. This study aims to explore the microRNA (miRNA) profile of ...CCA-associated fibroblasts (CCFs) and the roles of any identified miRNAs in CCA progression.
miRNA expression profiles of CCFs and normal skin fibroblasts were compared by microarray. Identified downregulated miRNAs and their target genes were confirmed by real-time PCR. Their binding was confirmed by a luciferase reporter assay. The effects of conditioned-media (CM) of miRNA mimic- and antagonist-transfected CCFs were tested in CCA migration in wound healing assays. Finally, the levels of miRNA and their target genes were examined by real-time PCR and immunohistochemistry in clinical CCA samples.
miR-15a was identified as a downregulated miRNA in CCFs. Moreover, PAI-2 was identified as a novel target gene of miR-15a. Recombinant PAI-2 promoted migration of CCA cells. Moreover, CM from miR-15a mimic-transfected CCFs suppressed migration of CCA cells. Lower expression of miR-15a and higher expression of PAI-2 were observed in human CCA samples compared with normal liver tissues. Importantly, PAI-2 expression correlated with poor prognosis in CCA patients.
These findings highlight the miR-15a/PAI-2 axis as a potential therapeutic target in CCA patients.
Data on external validation of models developed to distinguish Crohn's disease (CD) from intestinal tuberculosis (ITB) are limited. This study aimed to validate and compare models using clinical, ...endoscopic, and/or pathology findings to differentiate CD from ITB.
Data from newly diagnosed ITB and CD patients were retrospectively collected from 5 centers located in Thailand or Hong Kong. The data was applied to Lee, et al., Makharia, et al., Jung, et al., and Limsrivilai, et al. model.
Five hundred and thirty patients (383 CD, 147 ITB) with clinical and endoscopic data were included. The area under the receiver operating characteristic curve (AUROC) of Limsrivilai's clinical-endoscopy (CE) model was 0.853, which was comparable to the value of 0.862 in Jung's model (p = 0.52). Both models performed significantly better than Lee's endoscopy model (AUROC: 0.713, p<0.01). Pathology was available for review in 199 patients (116 CD, 83 ITB). When 3 modalities were combined, Limsrivilai's clinical-endoscopy-pathology (CEP) model performed significantly better (AUROC: 0.887) than Limsrivilai's CE model (AUROC: 0.824, p = 0.01), Jung's model (AUROC: 0.798, p = 0.005) and Makharia's model (AUROC: 0.637, p<0.01). In 83 ITB patients, the rate of misdiagnosis with CD when used the proposed cutoff values in each original study was 9.6% for Limsrivilai's CEP, 15.7% for Jung's, and 66.3% for Makharia's model.
Scoring systems with more parameters and diagnostic modalities performed better; however, application to clinical practice is still limited owing to high rate of misdiagnosis of ITB as CD. Models integrating more modalities such as imaging and serological tests are needed.
ObjectiveThe decision regarding whether to perform a liver biopsy in patients with cirrhosis and clinically suspected autoimmune hepatitis (AIH) remains a challenge. This study aimed to assess the ...utility and complications of percutaneous liver biopsy in cirrhosis for differentiating AIH from other liver conditions.MethodsA clinicopathological database of patients undergoing percutaneous liver biopsies for suspected AIH (unexplained hepatitis with elevated γ-globulin and autoantibody seropositivity) was reviewed to identify patients presenting with cirrhosis. Biopsy slides were reviewed by an experienced hepatopathologist who was blinded to clinical data.ResultsIn 207 patients who underwent liver biopsy for suspected AIH, 59 patients (mean age: 59.0±12.0 years, 83.1% female) had clinically diagnosis of cirrhosis. Mean Child-Turcotte-Pugh score was 6.6±1.6, and 44% of patients had a Child-Turcotte-Pugh score≥7. According to the revised International AIH Group (IAIHG) criteria, histology assessment combined with clinical information facilitated a diagnosis of AIH or overlap syndrome of AIH and primary biliary cholangitis (PBC) in 81.4% of cases. Liver biopsy identified other aetiologies, including PBC (n=2), non-alcoholic steatohepatitis (n=6) and cryptogenic cirrhosis (n=3). A reliable diagnosis of AIH could be made using histological category of the simplified criteria in 69.2% and 81.8% of cases using IAIHG scores before biopsy of <10 and 10–15, respectively. Three patients with cirrhosis (5.1%) experienced bleeding following biopsy, but none of 148 patients with non-cirrhosis had bleeding complication (p=0.022).ConclusionLiver biopsy provides important diagnostic information for the management of patients with cirrhosis and suspected AIH, but the procedure is associated with significant risk.
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