Overexpression of TSPAN8 in consensus molecular subtype 3 colorectal cancer.

BACKGROUND: Recently, consensus molecular subtypes (CMSs) have been proposed as a robust transcriptome-based classification system for colorectal cancer (CRC). Tetraspanins (TSPANs) are transmembrane proteins. They have been associated with the development of numerous malignancies, including CRC, through their role as "master organizers" for multi-molecular membrane complexes. No previous study has investigated the correlation between TSPANs and CMS classification. Herein, we investigated the expression of TSPANs in patient-derived primary CRC tissues and their CMS classifications. METHODS: RNA samples were derived from primary CRC tissues (n = 100 patients diagnosed with colorectal adenocarcinoma) and subjected to RNA sequencing for transcriptome-based CMS classification and TSPAN-relevant analyses. Immunohistochemistry (IHC) and immunofluorescence (IF) stains were conducted to observe the protein expression level. To evaluate the relative biological pathways, gene-set enrichment analysis was performed. RESULTS: Of the highly expressed TSPAN genes in CRC tissues (TSPAN8, TSPAN29, and TSPAN30), TSPAN8 was notably overexpressed in CMS3-classified primary tissues. The overexpression of TSPAN8 protein in CMS3 CRC was also observed by IHC and IF staining. As a result of gene-set enrichment analysis, TSPAN8 may potentially play a role in organizing signaling complexes for kinase-based metabolic deregulation in CMS3 CRC. CONCLUSIONS: The present study reports the overexpression of TSPAN8 in CMS3 CRC. This study proposes TSPAN8 as a subtype-specific biomarker for CMS3 CRC. This finding provides a foundation for future CMS-based studies of CRC, a complex disease and the second leading cause of cancer mortality worldwide.

Digital image analysis of Ki67 hotspot detection and index counting in gastroenteropancreatic neuroendocrine neoplasms.

The Ki-67 proliferative index plays a pivotal role in the subclassification of neuroendocrine neoplasm (NEN) according to the WHO Classification of Digestive System Tumors (5th edition), which designates neuroendocrine tumor (NET) grades 1, 2, and 3 for Ki-67 proliferative index of <3 %, 3-20 %, and >20 %, respectively. Proliferative index calculation must be performed in the hotspot, traditionally selected by visual scanning at low-power magnification. Recently, gradient map visualization has emerged as a tool for various purposes, including hotspot selection. This study includes 97 cases of gastrointestinal neuroendocrine neoplasms, with hotspots selected by bare eye and gradient map visualization (GM). Each hotspot was analyzed using three methods: eye estimation (EE), digital image analysis (DIA), and manual counting. Of the NENs studied, 91 % were NETs (26 % for G1, 55 % for G2, and 10 % for G3). Only 9 cases were neuroendocrine carcinoma (NEC). Between two hotspot selection methods, GM resulted in a higher grade in 14.77 % of cases, primarily upgrading from NET G1 to G2. Among the counting methods, DIA demonstrated substantial agreement with manual counting, both for pathologist and resident. Grading by other methods tended to result in a higher grade than MC (26.99 % with EE and 8.52 % with DIA). Given its clinical and statistical significance, this study advocates for the application of GM in hotspot selection to identify higher-grade tumors. Furthermore, DIA provides accurate grading, offering time efficiency over MC.

Comparison of blue laser imaging and narrow band imaging for the differentiation of diminutive colorectal polyps: A randomized controlled trial.

BACKGROUND: To compare the diagnostic efficacy of blue laser imaging (BLI)- bright and narrow band imaging (NBI) modes of image enhanced endoscopy (IEE) in differentiating neoplastic and non-neoplastic lesions of diminutive colorectal polyps. METHODS: We conducted a prospective randomized controlled trial from September 2015 to July 2016. The participants were randomly assigned (1:1) for colonoscopy with polyp classification under NBI or BLI-bright mode without magnification. Histopathologic diagnosis was used as the gold standard. RESULTS: Three hundred and twenty-four diminutive polyps in 164 patients were included for analysis (BLI: 162 polyps in 73 patients, NBI: 162 polyps in 91 patients). These polyps were located at colon proximal to sigmoid (61.1 and 58.0%) and rectosigmoid colon (38.9 and 42.0%) in the BLI and NBI groups, respectively. Most polyps (71.9%) were adenomatous with one malignant polyp (0.3%). BLI achieved 86.4% accuracy, 98.3% sensitivity, 55.6% specificity, 85.2% positive predictive value (PPV), and 92.6% negative predictive value (NPV), similar to NBI which exhibited 90.1% accuracy, 99.1% sensitivity, 67.4% specificity, 88.5% PPV, and 96.9% NPV in the diagnosis of adenomatous polyps. Based on the location of the polyp, both modes of IEE provided ≥ 95% NPV for diagnosis of adenomatous polyps at the rectosigmoid colon. CONCLUSIONS: BLI-bright and NBI modes of IEE have similar accuracy in differentiation between neoplastic and non-neoplastic lesions of diminutive polyps. Both modes provided ≥ 90% NPV which allows for the adaptation of the American Society of Gastrointestinal Endoscopy "diagnose-and-leave" recommended strategy for diminutive polyps at the rectosigmoid colon.

Diagnostic yield of esophagogastroduodenoscopy, colonoscopy, and small bowel endoscopy in Thai adults with chronic diarrhea.

BACKGROUND: Gastrointestinal endoscopy is frequently recommended for chronic diarrhea assessment in Western countries, but its benefit in the Southeast Asia region is not well established. METHODS: Medical records of consecutive patients undergoing esophagogastroduodenoscopy (EGD), colonoscopy, and small bowel endoscopy for chronic diarrhea from 2008 to 2018 were reviewed. Small bowel endoscopy included push enteroscopy, balloon-assisted enteroscopy (BAE), and video capsule endoscopy (VCE). The diagnostic yield of each endoscopic modality and predictors for positive small bowel endoscopy were analyzed. RESULTS: A total of 550 patients were included. The mean age was 54 years, and 266 (46.3%) patients were male. The mean hemoglobin and albumin levels were 11.6 g/dL and 3.6 g/dL, respectively. EGD and colonoscopy were performed in 302 and 547 patients, respectively, and the diagnostic yield was 24/302 (7.9%) for EGD and 219/547 (40.0%) for colonoscopy. EGD did not reveal positive findings in any patients with normal colonoscopy. Fifty-one patients with normal EGD and colonoscopy underwent small bowel endoscopy. Push enteroscopy, BAE, and VCE were performed in 28, 21, and 19 patients with a diagnostic yield of 5/28 (17.9%), 14/21 (66.7%), and 8/19 (42.1%), respectively. Significant weight loss, edema, and hypoalbuminemia were independent predictors for the positive yield of small bowel endoscopy. CONCLUSION: Colonoscopy was an essential diagnostic tool in identifying the cause of chronic diarrhea in Thai patients, whereas EGD provided some benefits. Small bowel endoscopy should be performed when colonoscopy and EGD were negative, particularly in patients with significant weight loss, edema, and hypoalbuminemia.

Periostin regulates autophagy through integrin α5ß1 or α6ß4 and an AKT-dependent pathway in colorectal cancer cell migration.

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 siITGß4-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 ITGα5ß1 or ITGα6ß4 and the AKT-dependent pathway to control autophagy-regulated cell migration. In conclusion, these results exhibited the impact of PN activation of ITGα5ß1 or ITGα6ß4 through pAKT in autophagy-mediated EMT and migration in CRC cells.

Prospective comparison of transient elastography, point shear wave elastography, APRI and FIB-4 for staging liver fibrosis in chronic viral hepatitis.

Ultrasound-based elastography and serum indexes have been individually validated as noninvasive methods for staging liver fibrosis in chronic viral hepatitis. We aimed to compare the accuracy of transient elastography (TE), shear wave elastography (SWE), aspartate aminotransferase to platelet index (APRI) and Fibrosis-4 index (FIB-4) with the METAVIR liver fibrosis staging in viral hepatitis patients. We enrolled 121 treatment-naïve chronic hepatitis B and C monoinfected patients. All underwent liver biopsy had biochemistry tests and liver stiffness measurements by TE using M and XL probes followed by point SWE performed on the same day. The accuracy of each method for predicting different fibrosis stages was demonstrated as an area under the receiver operating characteristic (AUROC) curves. The AUROCs of TE using M and XL probes, SWE, APRI and FIB-4 were 0.771, 0.761, 0.700, 0.698 and 0.697, respectively, for significant fibrosis; 0.974, 0.973, 0.929, 0.738 and 0.859, respectively, for advanced fibrosis; and 0.954, 0.949, 0.962, 0.765 and 0.962, respectively, for cirrhosis. TE using the M probe was comparable to the XL probe in detecting all fibrosis stages. TE was superior to SWE for assessing significant fibrosis and advanced fibrosis. For cirrhosis, the performances of TE, SWE and FIB-4 were similar. APRI was least accurate in liver fibrosis staging. To conclude, for patients with viral hepatitis, TE using either M or XL probe is an effective noninvasive test for assessing liver fibrosis, particularly advanced fibrosis and cirrhosis, while SWE and FIB-4 possess an excellent accuracy in predicting cirrhosis.

Patient characteristics, clinical manifestations, prognosis, and factors associated with gastrointestinal cytomegalovirus infection in immunocompetent patients.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Asymptomatic Histoplasma Pylephlebitis in an Orthotopic Liver Transplant Recipient: A Case Report and Literature Review.

Histoplasma capsulatum is one of the most common pathogenic dimorphic fungi in Thailand. Its usual clinical syndrome is progressive disseminated histoplasmosis, whereas isolated hepatic histoplasmosis is extremely rare. Here, we report the world's first reported case of hepatic histoplasmosis with pylephlebitis in a 45-year-old Thai male who underwent orthotopic liver transplantation due to hepatitis B cirrhosis. Histopathology of the recipient's liver showed infiltration of fungal organisms in portal vein and hepatic granulomas. Serum H. capsulatum antibody was positive, and molecular identification from the liver revealed the DNA of H. capsulatum.

The microRNA-15a-PAI-2 axis in cholangiocarcinoma-associated fibroblasts promotes migration of cancer cells.

BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: These findings highlight the miR-15a/PAI-2 axis as a potential therapeutic target in CCA patients.

Meta-Analytic Bayesian Model For Differentiating Intestinal Tuberculosis from Crohn's Disease.

OBJECTIVES: 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. METHODS: 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 (I2<50%) were incorporated into a Bayesian prediction model incorporating the local pretest probability. RESULTS: 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. CONCLUSIONS: 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.

The prevalence of steatohepatitis in chronic hepatitis B patients and its impact on disease severity and treatment response.

BACKGROUND & AIMS: The clinical significance of steatohepatitis in chronic hepatitis B remains unclear. This study aimed to determine the prevalence and risk factors for steatohepatitis in chronic hepatitis B, and to determine its correlation with liver fibrosis and response to antiviral therapy. METHODS: Liver histopathology of 256 consecutive chronic hepatitis B patients with serum hepatitis B virus DNA >2000 IU/mL were analysed with clinical and laboratory characteristics. Virological and biochemical responses were prospectively assessed in the 112 patients treated with antiviral monotherapy. RESULTS: Hepatic steatosis was observed in 38% of the entire cohort, and steatohepatitis was diagnosed in 18% of patients with hepatic steatosis according to Brunt's classification. The presence of steatohepatitis was associated with overweight/obese (odds ratio, 5.99; 95% CI, 1.32-27.2) and hypertriglyceridaemia (odds ratio, 2.95; 95% CI, 1.07-8.15). None of the viral characteristics including HBeAg status, genotypes and viraemia levels was associated with the presence of steatohepatitis. Steatohepatitis was an independent predictor of significant fibrosis (odds ratio, 10.0; 95% CI, 2.08-48.5) and advanced fibrosis (odds ratio, 3.45; 95% CI, 1.11-10.7) after adjusting for viraemia levels and features of the metabolic syndrome. The rates of suppression of serum hepatitis B virus DNA <20 IU/mL combined with aminotransferase normalization at week 48 of antiviral therapy were not different between the steatohepatitis and non-steatohepatitis groups (43% vs 53%; P=.475). CONCLUSIONS: Steatohepatitis is not uncommon in chronic hepatitis B patients. It is associated with metabolic syndrome but not viral factor. This study demonstrates that steatohepatitis is related to the severity of liver fibrosis but it does not affect response to antiviral therapy.

Non-insulinoma Pancreatogeneous Hypoglycemia Syndrome with False-Positive Somatostatin Receptor Scintigraphy: A Case Report and Review of Literature.

Non-insulinoma pancreatogeneous hypoglycemia syndrome (NIPHS) is a rare cause of hypoglycemia in adults. The cause of NIPHS is diffuse hyperinsulinism. As a result, computed tomography (CT) of pancreas, endoscopic pancreatic ultrasonography (EUS), and somatostatin receptor scintigraphy (SSRS), which are usually performed to locate an insulinoma, are not able to diagnose NIPHS. Moreover, SSRS can give a false-positive result. In this case report, we introduce a 22-year-old Thai woman who presented with fasting and postprandial hyperinsulinemic hypoglycemia. Accordingly, an insulinoma was suspected. She underwent several studies to locate the lesion. Pancreatic CT and EUS failed to locate a lesion; however, SSRS showed a faint focus of increased uptake at the pancreatic head. The suspected insulinoma was not identified during a first operation. Thereafter other diagnostic methods were performed in an effort to locate the suspected insulinoma, including selective arterial calcium stimulation test. The result of the selective arterial calcium stimulation test was negative. Intraoperative ultrasonography during a second operation also failed to locate a tumor. Finally, a pancreatic head resection was performed according to SSRS result, yet capillary blood glucose levels did not increase after resection. In response, a 95% pancreatectomy was performed. The pathology report was consistent with diffuse hyperinsulinism. This report emphasizes that SSRS can give false positive result in NIPHS.

Comparison between disease free survival of hepatocellular carcinoma after hepatic resection in chronic hepatitis B patients with or without cirrhosis.

BACKGROUND: Hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) patients can develop in those with cirrhotic and non-cirrhotic liver Not only impairment of liver status, but also the extension of tumor and difference of pathogenesis may also affect characteristics of patient and tumor including survival and recurrence. OBJECTIVE: To evaluate the disease free survival, prognostic factors and features of HCC after hepatic resection in CHB patients with and without cirrhosis. MATERIAL AND METHOD: Two hundred fifteen HBV-related HCC patients underwent hepatic resection and were analyzed. Cirrhotic and non-cirrhotic groups were compared for differences inpatient and tumor characteristics, disease-free survival including prognostic factors. RESULTS: In comparison with cirrhotic patients, non-cirrhotic patients had more family history of HCC, more preserved liver function, were less HBeAg positive, and had lower HBV viral load. HCC characteristics in non-cirrhotic groups showed significantly larger (5.8 ± 3.7 vs. 4.9 ± 3.9 cm, p = 0.036) and operative data revealed that non-cirrhotic patients underwent more major surgery (50.7 vs. 18.3%, p < 0.001), and had shorter hospital stay (10.8 ± 8.9 vs. 8.1 ± 4.3 days, p = 0.006) than cirrhotic ones. Operative time, blood loss and requirement of PRC transfusion were similar in both groups. Pathological profiles of HCC and liver parenchyma were comparable in both cirrhotic and non-cirrhotic patients. The disease-free survival of non-cirrhotic patients was longer than cirrhotic patients (Median disease free survival were 21 and 11 months respectively, p = 0.022). The independent predictive factor of lower disease-free survival of non-cirrhotic CHB patients who underwent hepatic resection was lymph node involvement (Hazard ratio (HR), 4.598. 95% confidence interval (CI), 1.1-19.212; p = 0.037) while of cirrhotic patients, factors were age > 50 years old (HR, 2.998; 95% CI, 1.298-6.925; p = 0.01), multifocal tumor (HR, 5.835; 95% CI, 1.122-30.342; p = 0.036) andportal vein involvement (HR, 3.722; 95% CI, 1.121-12.353; p = 0.032). HBV treatment after HCC diagnosis was a significant predictor in the cirrhotic group by univariate analysis (p = 0.04). CONCLUSION: Imaging and histological findings of HCC in cirrhotic and non-cirrhotic CHB patients were not different, except for larger tumor size in non-cirrhotic patients. Lymph node involvement is the predictor of HCC recurrence in non- cirrhotic CHB patients. Age > 50 year old and multifocal tumor and portal vein involvement are the predictors of HCC recurrence in cirrhotic CHB patients. These groups may need surveillance that is more intensive after hepatic resection. Antiviral therapy may lower the risk of HCC recurrence among CHB cirrhotic patients.

Comparative study on the characteristics of Meckel's diverticulum removal from asymptomatic and symptomatic patients: 18-year experience from Thailand's largest university hospital.

OBJECTIVE: To report an experience with Meckel's diverticulum (MD) from a University Hospital in Thailand, and to compare the characteristics of MD removal from asymptomatic patients and symptomatic patients. MATERIAL AND METHOD: The authors retrospectively reviewed the medical records of patients undergoing the resection of MD between January 1994 and July 2011 at the Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok. The patients were subsequently divided into two groups. The asymptomatic group included individuals with MD that were found incidentally during the course of laparotomy performed for reasons not related to the complications of the MD. The symptomatic group included individuals presenting with complications related to the MD. Data were recorded including patient's demographics, clinical presentation, histopathologic findings, and postoperative outcomes. RESULTS: The present study included 84 patients (53 males, 63%). Of whom, 60 patients (71%) were pediatric (age < 16 years) and 51 patients (61%) were symptomatic. The most common presentation of symptomatic MDs in pediatric and adult patients was lower gastrointestinal bleeding and mechanical small bowel obstruction, respectively. The correct preoperative diagnosis of MD was made in only 20 patients (39%) of the symptomatic group, all with 99mTc-pertechnetate scanning. The MDs in the symptomatic group were significantly longer with a wider base than those in the asymptomatic group, 3.2 vs. 2.0 cm in length (p = 0.001) and 1.8 vs. 1.0 cm in width (p < 0.001). Ectopic tissue was present more significant in the symptomatic group than in the asymptomatic group (51% vs. 12%; p < 0.001). None of the resected MDs contained neoplasm. There was no significant difference in the morbidity or mortality rate between the symptomatic and asymptomatic groups. CONCLUSION: The MDs in the symptomatic patients were significantly longer with a wider base than those in the asymptomatic patients. Symptomatic MDs contained ectopic tissue more frequently than asymptomatic MDs.

Benefit of double contrast MRI in diagnosis of hepatocellular carcinoma in patients with chronic liver diseases.

OBJECTIVE: To assess the benefit on diagnosis of hepatocellular carcinoma (HCC) in patients with chronic liver disease or cirrhosis with double contrast MR imaging compared to the routine gadolinium-based MR imaging. MATERIAL AND METHOD: Seventy-one consecutive patients with cirrhosis or chronic hepatitis underwent multiphase, gadolinium-enhanced liver MRI examination and sequentially superparamagnetic iron oxide (SPIO)-enhanced images. The presence signal intensities of lesions on non-contrast sequences, dynamic gadolinium-enhanced images and delayed 10-min post-SPIO T2*-weighted images were recorded. RESULTS: Among 27 patients, 15 HCCs from 12 patients were diagnosed by surgical (n = 7) and non-surgical (n = 8) proofs. The overall sensitivity, specificity, positive predictive value, and negative predictive value of double contrast-enhanced images in 12 patients were 83.3% (95% CI: 58.5, 96.2), 33.3% (95% CI: 5.4, 88.4), 88.2% (95% CI: 63.5, 98.2), and 25% (95% CI: 4.1, 79.6) and these of gadolinium-enhanced images were 72.2% (95% CI: 46.5, 90.2), 33.3% (95% CI: 5.4, 88.4), 86.6% (95% CI: 59.5, 97.9), and 16.6% (95% CI: 2.7, 63.9), respectively. There were two benign hepatic nodules (1 adenoma, 1 dysplastic nodule) suspected as HCCs on MR images and two surgically proven-HCCs, invisible on gadolinium-enhanced images, detected as defect on only delayed 10-min post-SPIO T2*-weighted images. CONCLUSION: SPIO-enhanced images in double contrast-enhanced MR imaging had an additional value on HCC detection, compared to gadolinium-enhanced MR imaging, in patients with chronic liver disease or cirrhosis.

The combined tumour-based Fascin/Snail and stromal periostin reveals the effective prognosis prediction in colorectal cancer patients.

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), ß-catenin (ß-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, ß-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.

Detection of centroblast cells in H&E stained whole slide image based on object detection.

Introduction: Detection and counting of Centroblast cells (CB) in hematoxylin & eosin (H&E) stained whole slide image (WSI) is an important workflow in grading Lymphoma. Each high power field (HPF) patch of a WSI is inspected for the number of CB cells and compared with the World Health Organization (WHO) guideline that organizes lymphoma into 3 grades. Spotting and counting CBs is time-consuming and labor intensive. Moreover, there is often disagreement between different readers, and even a single reader may not be able to perform consistently due to many factors. Method: We propose an artificial intelligence system that can scan patches from a WSI and detect CBs automatically. The AI system works on the principle of object detection, where the CB is the single class of object of interest. We trained the AI model on 1,669 example instances of CBs that originate from WSI of 5 different patients. The data was split 80%/20% for training and validation respectively. Result: The best performance was from YOLOv5x6 model that used the preprocessed CB dataset achieved precision of 0.808, recall of 0.776, mAP at 0.5 IoU of 0.800 and overall mAP of 0.647. Discussion: The results show that centroblast cells can be detected in WSI with relatively high precision and recall.

The specimen handling of GI mucosal biopsy: a simple and effective quality improvement initiative.

OBJECTIVE: Histologic diagnostic foci on GI mucosal biopsy may be patchy. Therefore, slides with good orientation of mucosal tissue in a perpendicular plane and demonstrating an entire layer of mucosa will increase the diagnostic yield. Department of Pathology Faculty of Medicine Siriraj Hospital has launched the two steps quality improvement program and a parallel research aiming to demonstrate the importance of tissue orientation of GI biopsy. MATERIAL AND METHOD: Step 1: quality improvement was introduced at the pathology laboratory. Embedding technicians were trained to embed tissue in perpendicular plane. Step 2: quality improvement at endoscopy unit, endoscopic nurses were trained to spread the biopsy tissues on a mesh with upward mucosal surface before fixing them into formalin. Three sets of 50 consecutive cases of GI mucosal biopsy were retrieved from before, after step 1, and after step 2. The number of high quality slides, diagnostic discrepancy, and diagnostic confidence of the pathologists were compared between the three sets. RESULTS: High quality slides were significantly increased from 23 (46%) before quality improvement to 30 (60%) after step 1, and 37 (74%) after step 2 (p-value = 0.017). Diagnostic discrepancy was decreased while diagnostic confidence was increased after quality improvement. CONCLUSION: The quality of GI mucosal biopsy slides were significantly improved after a simple and feasible program indicating that both educating and training of medical personnel for tissue procurement and tissue processing are crucial. Higher quality of slide can lead to more accurate diagnosis and fewer laboratory resources used.

Gastric villous adenoma: a case report and review of the literature.

BACKGROUND: 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. CASE PRESENTATION: 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. CONCLUSION: 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.

Prognostic Relevance of Metabolic Dysfunction-associated Steatohepatitis for Patients with Chronic Hepatitis B.

Background and Aims: Metabolic dysfunction-associated fatty liver disease (MAFLD) is prevalent in patients with chronic hepatitis B (CHB). The effect of the histologic MAFLD phenotype on long-term CHB outcomes is unknown. We performed a longitudinal study to determine the prognostic relevance of biopsy-proven hepatic steatosis and steatohepatitis for CHB patients. Methods: Clinical and laboratory data were obtained from CHB patients who underwent liver biopsy during 2002-2008 and were treated with antiviral drugs. A hepatopathologist reviewed the biopsy specimens. Cox proportional hazards regression was used to estimate the adjusted hazard ratio (aHR) of outcomes, including all-cause mortality, liver transplantation, and liver-related events. Results: In accordance with Brunt's classification, 408 patients had steatohepatitis (n=34), "steatosis but not steatohepatitis" (n=118), or "non-steatosis" (n=256). All steatohepatitis patients had features of metabolic dysfunction. Over a mean follow-up of 13.8±3.1 years, 18 patients died or underwent liver transplantation. In multivariate-adjusted analysis, steatohepatitis (aHR, 6.37; 95% confidence interval [CI]: 1.59-25.5) compared with non-steatosis and advanced fibrosis (aHR, 11.3; 95% CI: 1.32-96.3) compared with no fibrosis were associated with overall mortality/liver transplantation. Thirty-five patients developed 43 liver-related events, among which 32 were hepatocellular carcinoma. These events were associated with steatohepatitis (aHR, 5.55; 95% CI: 2.01-15.3) compared with non-steatosis and advanced fibrosis (aHR, 6.23; 95% CI: 1.75-22.2) compared with no fibrosis. The steatosis but not steatohepatitis group had a non-significantly higher risk of overall mortality and liver-related events. Conclusions: Metabolic dysfunction-associated steatohepatitis increased the risk of long-term mortality/transplantation and liver-related events in CHB patients.