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The optimal therapeutic strategy in nucleoside analogue (NA) experienced chronic hepatitis B (CHB) using peginterferon is still unclear; hence we explored a switch to or add-on peginterferon strategy versus continued NA.We conducted a randomized controlled trial of CHB patients on NA12 months with HBV DNA(-) randomized to switch or add-on peginterferon-alpha2b (1.5 μg/kg/weekly) for 48 weeks versus continuing NA (controls) (allocation 2:2:1; Clinicaltrial.gov: NCT01928511) in tertiary Singapore hospitals. The primary composite endpoint at week 72 was hepatitis B e antigen (HBeAg) loss or quantitative HBsAg (qHBsAg)1 log IU/mL reduction, and secondary endpoints were HBsAg loss, HBsAg seroconversion, qHBsAg200 IU/mL, qHBsAg100 IU/mL, HBV DNA(-), viral relapse, and safety. Analysis was by intention-to-treat (ITT).A total of 253 patients (controls 51, switch 103, add-on 99) were randomized. The primary ITT endpoint was achieved in 3.9% of controls, 33.3% of switch, and 26.7% of add-on (P.0001, switch/add-on versus controls). HBsAg loss occurred in 0% of controls, 7.8% of switch, and 10.1% of add-on (ITT, P.001, switch/add-on versus controls). HBeAg(+) patients on peginterferon had higher HBeAg loss than controls but poor HBsAg responses, whereas HBeAg(-) patients on peginterferon achieved better HBsAg responses than controls. Reduction in qHBsAg in HBeAg(+) was 0.14 log IU/mL versus 0.51 log IU/mL in HBeAg(-) (P.0001) in peginterferon-treated patients. Clinical relapse was higher in switch (13.6% overall, 27% in HBeAg(+)) versus 1% add-on and 0% controls. Adverse events were typically interferon-related symptoms, with one death (myocardial infarction unrelated to therapy).ITT analysis showed that either peginterferon strategies were superior to NA for the primary endpoint and HBsAg loss, but add-on peginterferon is preferred to switch due to improved safety and similar efficacy. ClincialTrials.gov number: NCT01928511.

Detection of pre-neoplastic gastric mucosal changes and early gastric cancer (EGC) by white-light endoscopy (WLE) is often difficult. In this study we investigated whether combined autofluorescence imaging (AFI) and narrow band imaging (NBI) can improve detection of pre-neoplastic lesions and early gastric cancer in high-risk patients.Chinese patients who were 50-years-old or above with dyspepsia were examined by both high-resolution WLE and combined AFI followed by NBI (AFI-NBI), consecutively in a prospective randomized cross-over setting, by two experienced endoscopists. The primary outcome was diagnostic ability of the two methods for patients with pre-neoplastic lesions such as intestinal metaplasia (IM) and mucosal atrophy.Sixty-five patients were recruited. One patient with large advanced gastric cancer was found and excluded from the analysis. Among the remaining 64 patients, 38 (59%) had IM; of these, 26 (68%) were correctly identified by AFI-NBI (sensitivity 68%, specificity 23%) and only 13 (34%) by WLE (sensitivity 34%, specificity 65%). AFI-NBI detected more patients with IM than did WLE (p=0.011). Thirty-one patients (48%) had mucosal atrophy. Ten patients (32%) were identified by AFI-NBI (sensitivity 32%, specificity 79%) and four patients (13%) by WLE (sensitivity 13%, specificity 88%) (p=0.100). No dysplasia or EGC was found.AFI-NBI identified significantly more patients with IM than did WLE. Our result warrants further studies to define the role of combined AFI-NBI endoscopy for detection of precancerous conditions.

Background & Aims It is not clear how the duration of upper endoscopy affects the detection of cancer or premalignant lesions that increase the risk for gastric cancer. We investigated whether the length of time spent performing esophagogastroduodenoscopy (EGD) affects the detection of important pathologic features of the stomach. Methods We collected data from 837 symptomatic patients, during a 3-month period in 2010, who underwent a first diagnostic EGD at a tertiary university hospital in Singapore. Endoscopists were classified as fast or slow based on the mean amount of time it took them to perform a normal EGD examination. We used logistic regression to compare between groups the numbers of intestinal metaplasias, gastric atrophies, dysplasias, and cancers detected, using histologic analysis of biopsy samples collected during endoscopy as the standard. Results Of 224 normal endoscopies, the mean duration was 6.6 minutes (range, 2–32 min). When we used 7 minutes as the cut-off time, 8 endoscopists were considered to have short mean examination times (mean duration, 5.5 ± 2.1 min; referred to as fast endoscopists ), and 8 endoscopists were considered to have long mean examination times (mean duration, 8.6 ± 4.2 min; referred to as slow endoscopists ). Eleven cancers and 81 lesions considered to pose risks for cancer were detected in 86 patients; 1.3% were determined to be cancer, 1.0% were determined to be dysplasia, and 8.7% were determined to be intestinal metaplasia and/or gastric atrophy. Slow endoscopists were twice as likely to detect high-risk lesions as fast endoscopists (odds ratio, 2.50; 95% confidence interval, 1.52–4.12), regardless of whether they were endoscopy staff or trainees. The slow endoscopists also detected 3-fold more neoplastic lesions (cancer or dysplasia; odds ratio, 3.42; 95% confidence interval, 1.25–10.38). Conclusions Endoscopists with mean EGD examination times longer than 7 minutes identified a greater number of high-risk gastric lesions than faster endoscopists. Examination time may be a useful indicator of quality assessment for upper endoscopy. Studies are required to test these findings in different populations.

Background & Aims: VEGF is a key stimulator of angiogenesis and promotes the growth colon tumors via increased nutrient and oxygen supply. A recent study demonstrated that colorectal cancer (CRC) cells have increased expression of VEGF and its receptors VEGFR1 & VEGF-R2, which indicates a possibility of direct stimulation of CRC cell growth by VEGF. However, the role of VEGF in CRC cell proliferation by an autocrine mechanism has not been fully explored in depth. We hypothesized that VEGF secreted by CRC cells binds to VEGF-R1 & VEGF-R2 on CRC cells and: 1) promotes proliferation of these cells through an autocrine pathway, 2) inhibits CRC apoptosis. Methods: We used: (1) human CRC cell lines HCT116 & HT29 and (2) normal colonic epithelial cells NCM356 & NCM460 cultured in nutrient media. Studies: 1) VEGF, VEGF-R1 & VEGF-R2 mRNA and protein expression of by Real-Time RT-PCR and immunoblotting; 2) VEGF165 secretion into the culture media by ELISA; 3) cell proliferation by BrdU assay; 4) apoptosis by TUNEL staining and assessment of activated caspases 3 and 9; 5) Inhibition of VEGF receptor function using AAL993 inhibitor, which blocks function of VEGF-R1 and VEGF-R2; 6) assessment of phosphorylation of EGF receptor (EGF-R) to test its transactivation by VEGF. Results: 1) Normal colonic cells do not secrete VEGF (< 35 pg/ml culture media) while CRC cells express and secrete high levels of VEGF (840 1500 pg/ml culture media); 2) Normal colonic epithelial cell lines expressed no or minimal VEGF-R1 & VEGF-R2 mRNA and protein while CRC cell lines exhibit strong expression of VEGF-R1 & VEGF-R2 vs. normal colonic epithelial cells by 14and 24-fold, respectively (all p < 0.001); 3) CRC cell lines have significantly increased cell proliferation by 31% (p < 0.01) and decreased apoptosis vs. normal colonic epithelial cells; 3) Inhibition of both VEGF-R1 & VEGF-R2 receptors using AAL-993 significantly decreased CRC cell proliferation by (2.2-fold) ; 4) Treatment of CRC cells with AAL-993 decreased phosphorylation of EGF-R by 1.9-fold (p < 0.01). Conclusions: 1) VEGF and its VEGF-R1 & VEGF-R2 receptors are increased in CRC cell lines; 2) CRC cells secrete VEGF, which stimulates CRC cell proliferation via an autocrine mechanism by its VEGF-R1 & VEGF-R2 receptors and also inhibits apoptosis; 3) VEGF receptor signaling pathway is critical for activating EGF-R in CRC cells; 4) These studies suggest a cross-talk between VEGF receptor and EGF-R signaling in CRC cells, which promotes these cells' proliferation.