Naruemon Wisedopas

Diagnostic role of serum glypican-3 in differentiating hepatocellular carcinoma from non-malignant chronic liver disease and other liver cancers

Background and Aims:  The role of glypican‐3 (GPC3), a novel serum marker, in differentiating hepatocellular carcinoma (HCC) from non‐malignant chronic liver disease and other malignant space‐occupying lesions in the liver is largely unknown. The aims of this study were to evaluate its diagnostic role and clinical correlations in patients with HCC.

Flexible spectral imaging color enhancement plus probe-based confocal laser endomicroscopy for gastric intestinal metaplasia detection

Probe‐based confocal laser endomicroscope (pCLE) has been applied for the early detection and confirmation of many gastrointestinal neoplasms; however, its use in gastric intestinal metaplasia (GIM) detection has not yet been validated. The objective of this study was to assess the diagnostic yield of magnifying flexible spectral imaging color enhancement (ME‐FICE) plus pCLE for GIM detection.

Helicobacter pylori Infection in Thailand: A Nationwide Study of the CagA Phenotype

Background The risk to develop gastric cancer in Thailand is relatively low among Asian countries. In addition, the age-standardized incidence rate (ASR) of gastric cancer in Thailand varies with geographical distribution; the ASR in the North region is 3.5 times higher than that in the South region. We hypothesized that the prevalence of H. pylori infection and diversity of CagA phenotype contributes to the variety of gastric cancer risk in various regions of Thailand. Methods We conducted a nationwide survey within Thailand. We determined H. pylori infection prevalence by detecting H. pylori, using histochemical and immunohistochemical methods. The anti-CagA antibody and anti-East-Asian type CagA antibody (α-EAS Ab), which showed high accuracy in several East Asian countries, were used to determine CagA phenotype. Results Among 1,546 patients from four regions, including 17 provinces, the overall prevalence of H. pylori infection was 45.9% (710/1,546). Mirroring the prevalence of H. pylori infection, histological scores were the lowest in the South region. Of the 710 H. pylori-positive patients, 93.2% (662) were immunoreactive with the anti-CagA antibody. CagA-negative strain prevalence in the South region was significantly higher than that in other regions (17.9%; 5/28; p < 0.05). Overall, only 77 patients (11.6%) were immunoreactive with the α-EAS Ab. There were no differences in the α-EAS Ab immunoreactive rate across geographical regions. Conclusions This is the first study using immunohistochemistry to confirm H. pylori infections across different regions in Thailand. The prevalence of East-Asian type CagA H. pylori in Thailand was low. The low incidence of gastric cancer in Thailand may be attributed to the low prevalence of precancerous lesions. The low incidence of gastric cancer in the South region might be associated with the lower prevalence of H. pylori infection, precancerous lesions, and CagA-positive H. pylori strains, compared with that in the other regions.

Asymptomatic bilateral giant adrenal myelolipomas: case report and review of literature.

OBJECTIVE To describe an unusual case of bilateral giant adrenal masses caused by a primary adrenal myelolipoma. METHODS We present the clinical, laboratory, and pathologic findings in a 32-year-old man with bilateral adrenal masses. The previous reports of bilateral myelolipomas also were reviewed. RESULTS During a routine examination, a 32-year-old Thai man was found to have an asymptomatic abdominal mass. A computed tomographic scan of the abdomen disclosed bilateral adrenal masses; the one on the left was approximately 27 by 24 by 12 cm, and the one on the right side was 9 by 5 by 5 cm. The computed tomographic scan characteristics showed that both masses consisted mainly of low-density tissues (-30 to -90 Hounsfield units), suggestive of fatty component. An endocrinologic evaluation revealed no evidence of adrenal cortical or medullary functional abnormalities. Bilateral adrenalectomy was performed because of the large size of the lesions and the inability to rule out malignant involvement. CONCLUSION Myelolipoma is a relatively rare benign tumor of the adrenal glands composed of adipose cells and mature hematopoietic elements. Most such lesions are small, asymptomatic, and unilateral; giant or bilateral myelolipomas are quite rare. To our knowledge, our current case may represent the largest bilateral lesions in the literature.

The Learning Curve of Gastric Intestinal Metaplasia Interpretation on the Images Obtained by Probe-Based Confocal Laser Endomicroscopy

Background. Reading the results of gastric intestinal metaplasia (GIM) with probe-based confocal laser endomicroscopy (pCLE) by the expert was excellent. There is a lack of study on the learning curve for GIM interpretation. Therefore, we conducted a study to explore the learning curve in the beginners. Material and Method. Five GI fellows who had no experience in GIM interpretation had been trained with a set of 10 pCLE video clips of GIM and non-GIM until they were able to interpret correctly. Then they were asked to interpret another 80 video clips of GIM and non-GIM. The sensitivity, specificity, accuracy, PPV, NPV, and interobserver agreement on each session were analyzed. Results. Within 2 sessions, all beginners can achieve 80% accuracy with substantial to almost perfect level of interobserver agreement. The sensitivities and specificities among all interpreters were not different statistically. Four out of five interpreters can maintain their high quality of reading skill. Conclusion. After a short session of training on GIM interpretation of pCLE images, the beginners can achieve a high level of reading accuracy with at least substantial level of interobserver agreement. Once they achieve the high reading accuracy, almost all can maintain their high quality of reading skill.

Kinetics of serum HBsAg and intrahepatic cccDNA during pegylated interferon therapy in patients with HBeAg-positive and HBeAg-negative chronic hepatitis B.

This study was aimed at comparing clinical applicability of serum HBsAg quantification in relation to intrahepatic covalently closed‐circular DNA (cccDNA) in patients with HBeAg‐positive and HBeAg‐negative chronic hepatitis B (CHB) treated with pegylated interferon (PEG‐IFN) monotherapy for 48 weeks. Overall, 32 and 36 patients with HBeAg‐positive and HBeAg‐negative CHB, respectively were recruited. Paired liver biopsies at baseline and end of therapy were analyzed for cccDNA. Virological response (VR) at 48 weeks post‐treatment was defined as HBeAg clearance (for HBeAg‐positive CHB) and HBV DNA <2,000 IU/ml (for both groups). The results demonstrated that baseline levels of all viral markers were higher in the HBeAg‐positive group than the HBeAg‐negative group. Baseline HBsAg correlated with cccDNA in the HBeAg‐positive group (r = 0.452, P = 0.009) but not in the HBeAg‐negative group (r = 0.018, P = 0.919). However, the magnitude of cccDNA and HBsAg decline at end of treatment was not different between groups. The reduction of HBsAg showed a positive correlation with cccDNA decline in HBeAg‐positive and HBeAg‐negative CHB (r = 0.544, P = 0.001 and r = 0.364, P = 0.029, respectively). Overall, responders had more decline in cccDNA and HBsAg levels compared with non‐responders. Patients with serum HBsAg decline of >1.0 log10 IU/ml during treatment archived VR and HBsAg clearance of 80% and 30%, respectively. In conclusion, serum HBsAg represented a better surrogate marker of intrahepatic cccDNA in patients with HBeAg‐positive CHB compared to those with HBeAg‐negative CHB. On‐treatment, HBsAg reduction of 1.0 log10 IU/mL was associated with a high probability of subsequent VR and HBsAg clearance in patients receiving PEG‐IFN therapy. J. Med. Virol. 89:130–138, 2017.

A randomized clinical trial of peginterferon alpha‐2b with or without entecavir in patients with HBeAg‐negative chronic hepatitis B: Role of host and viral factors associated with treatment response

Combining peginterferon (PEG‐IFN) and a potent nucleoside/nucleotide analogue might improve treatment response in patients with chronic hepatitis B (CHB). The aims of this study were to compare the efficacy of PEG‐IFN alpha‐2b with or without entecavir in HBeAg‐negative CHB and to investigate predictors of response. A total of 126 treatment‐naïve patients were randomly assigned to receive monotherapy (n = 63) or combination therapy (n = 63) for 48 weeks. Virological response (VR) was defined as HBV DNA level <2000 IU/mL at week 96. Baseline factors including polymorphisms in the IFNL3 (rs12979860) and HLA‐DPA1 (rs3077) genes and on‐treatment viral kinetics were determined. At week 48, rates of undetectable HBV DNA were lower in the monotherapy than combination groups, but rates of HBsAg clearance and decline were comparable. At week 96, there was no difference between the corresponding groups regarding virological response (41.3% vs 38.1%, P = 0.856), HBsAg clearance (9.5% vs 4.8%, P = 0.491) and HBsAg decline. Baseline HBsAg level [odds ratio (OR): 3.14 (1.34–7.69), P = 0.012] and rs3077 polymorphism [OR: 2.78 (1.27–6.11), P = 0.011] were independent predictors of response. Patients carried GG genotype of rs3077 with low baseline HBV (<1000 IU/mL) had high probability of achieving VR (76.5%) and HBsAg clearance (29.4%). None of the patients without decrease in HBsAg combined with <2 log10 HBV DNA decline at week 12 achieved a virological response. In conclusion, the combination therapy lead to greater on‐treatment HBV DNA suppression but did not improve virological response and HBsAg clearance/decline over monotherapy. Host and viral factors could help optimize decision‐making at baseline and during PEG‐IFN‐based therapy.

The Secondary Quality Indicator to Improve Prediction of Adenoma Miss Rate Apart from Adenoma Detection Rate.

Objectives:Adenoma detection rate (ADR) cannot distinguish between endoscopists who detect one adenoma and those who detect ≥2 adenomas. Hypothetically, adenoma miss rate (AMR) may be significant for endoscopists with high ADRs who examine the rest of colon with less care after detecting first polyp. Our objective was to evaluate other quality indicators plus ADR vs. ADR alone in prediction of AMR.Methods:We conducted a cross-sectional study of asymptomatic participants aged 50–75 years who underwent back-to-back screening colonoscopies by four faculty endoscopists. Each round of colonoscopy was performed by two of the endoscopists in a randomized order. During each round of colonoscopy, all detected polyps were removed. The second endoscopist was blinded to the results of the first. The total number of adenomas per positive participant (APP), the total number of adenomas per colonoscopy (APC), the additional adenomas found after the first adenoma per colonoscopy (ADR-Plus), and ADR were calculated for prediction of AMR.Results:In all, 200 participants underwent back-to-back colonoscopies. There were no significant differences in ADRs of four endoscopists (44, 50, 54, and 46%). APPs were 1.91, 2.12, 2.19, and 2.43. APCs were 0.84, 1.06, 1.18, and 1.12. ADR-Plus were 0.40, 0.56, 0.64, and 0.66, respectively. AMRs differed significantly between the endoscopists (36, 27, 21, and 13%; P=0.01). There was no correlation between ADR and AMR (r=−0.25; P=0.75). Whereas APP exhibited a strong inverse correlation with AMRs (r=−0.99; P<0.01). APC and ADR-Plus appeared to be inversely correlated with AMR, however this was not statistically significant (r=−0.82; P=0.18 and r=−0.93; P=0.07, respectively).Conclusions:Among high-ADR endoscopists, AMRs still varied. APP may be a promising secondary indicator for distinguishing between the one-and-done polyp endoscopist and the meticulous endoscopist. The evaluation of influence of new metrics on colorectal cancer (CRC) prevention requires a larger population-based study.

The Optimal Cut-Off Level of The Fecal Immunochemical Test For Colorectal Cancer Screening in a Country with Limited Colonoscopy Resources: A Multi-Center Study from Thailand

Background: Selecting the cut-off point for the fecal immunochemical test (FIT) for colorectal cancer (CRC) screening programs is of prime importance. The balance between the test performance for detecting advanced neoplasia and the available colonoscopy resources should be considered. We aimed to identify the optimal cut-off of FIT for advanced neoplasia in order to minimize colonoscopy burden. Methods: We conducted a multi-center study in 6 hospitals from diverse regions of Thailand. Asymptomatic participants, aged 50-75 years, were tested with one-time quantitative FIT (OC-SENSOR, Eiken Chemical Co.,Ltd., Tokyo, Japan) and all participants underwent colonoscopy. We assessed test performance in detecting advanced neoplasia (advanced adenoma and CRC) and measured the burden of colonoscopy with different cut-offs [25 (FIT25), 50 (FIT50), 100 (FIT100), 150 (FIT150), and 200 (FIT200)ng/ml]. Results: Among 1,479 participants, advanced neoplasia and CRC were found in 137 (9.3%) and 14 (0.9%), respectively. From FIT25 to FIT200, the positivity rate decreased from 18% to 4.9%. For advanced neoplasia, an increased cut-off decreased sensitivity from 42.3% to 16.8% but increased specificity from 84.2% to 96.3%. The increased cut-off increased the positive predictive value (PPV) from 21.5% to 31.5%. However, all cut-off points provided a high negative predictive value (NPV) (>90%). For CRC, the miss rate for FIT25 to FIT 150 was the same (n=3, 21%), whereas that with FIT200 increased to 35% (n=5). Conclusions: In a country with limited-colonoscopy resources, using FIT150 may be preferred because it offers both high PPV and NPV for advanced neoplasia detection. It could also decrease colonoscopy workload, while maintaining a CRC miss rate similar to those with lower cut-offs.

Colon Cancer Prevention by Detection of APC Gene Mutation in a Family with Attenuated Familial Adenomatous Polyposis

BACKGROUND Genetic mutation is a significant factor in colon CA pathogenesis. Familial adenomatous polyposis (FAP) is an autosomal dominant hereditary disease characterized by multiple colorectal adenomatous polyps affecting a number of cases in the family. This report focuses on a family with attenuated familial adenomatous polyposis (AFAP) with exon 4 mutation, c.481C>T p.Q161X of the APC gene. METHODS We analyzed 20 members of a family with AFAP. Clinical and endoscopic data were collected for phenotype determination. Genetic analysis was also performed by direct sequencing of the APC gene. RESULT Five patients with a phenotype of AFAP were found. Endoscopic polyposis was demonstrated among the second generation with genotype mutation of the disease (age > 50 years) consistent with delayed phenotypic adenomatous polyposis in AFAP. APC gene mutation was identified in exon 4 of the APC gene, with mutation points of c.481C>T p.Q161X. Laparoscopic subtotal colectomy was performed to prevent carcinogenesis. CONCLUSION A family with attenuated familial adenomatous polyposis of APC related to exon 4 mutation, c.481C>T p.Q161X, was reported and the phenotypic finding was confirmed by endoscopic examination. Genetic mutation analysis might be advantageous in AFAP for long term colon cancer prevention and management due to subtle or asymptomatic phenotype presentation in early adulthood.