Prevalence and predictive factors of colorectal sessile serrated lesions in younger individuals.

BACKGROUND: Sessile serrated lesions (SSLs) are obscured lesions predominantly in the right-sided colon and associated with interval colorectal cancer; however, their prevalence and risk factors among younger individuals remain unclear. METHODS: This retrospective study enrolled individuals who underwent index colonoscopy. The primary outcome was the SSL prevalence in the younger (<50 years) and older (≥50 years) age groups, while the secondary outcomes included clinically significant serrated polyps (CSSPs). Multivariable logistic regression was employed to identify predictors. RESULTS: Of the 9854 eligible individuals, 4712 (47.8%) were categorized into the younger age group. Individuals in the younger age group exhibited lower prevalences of adenomas (22.6% vs. 46.2%; P<0.001) and right-sided adenomas (11.2% vs. 27.2%; P<0.001) compared with their older counterparts. However, both groups exhibited a similar prevalence of SSLs (7.2% vs. 6.5%; P=0.16) and CSSPs (10.3% vs. 10.3%;P=0.96). Multivariable analysis revealed that age 40-49 years (odds ratio [OR] 1.81, 95%CI 1.01-3.23), longer withdrawal time (OR 1.17, 95%CI 1.14-1.20, per minute increment), and endoscopist performance (OR 3.35, 95%CI 2.44-4.58) were independent predictors of SSL detection in the younger age group. No significant correlation was observed between adenoma and SSL detection rates among endoscopists. CONCLUSION: SSLs are not uncommon among younger individuals. Moreover, diligent effort and expertise are of paramount importance in SSL detection. Future studies should explore the clinical significance of SSLs in individuals of younger age.

Role of autophagy-related protein in the prognosis of combined hepatocellular carcinoma and cholangiocarcinoma after surgical resection.

BACKGROUND: Autophagy-related proteins may predict postresection overall survival (OS) and disease-free survival (DFS) in patients with combined hepatocellular carcinoma and cholangiocarcinoma (cHCC-CC). METHODS: We prospectively investigated how these proteins affect clinical prognosis in 40 patients who underwent hepatectomy for cHCC-CC from 2011 to 2019 at a Taiwanese hospital. Levels of autophagy-related proteins, namely LC3, Beclin-1, and p62, were immunohistochemically assessed in patient tumor and non-tumor tissues. RESULTS: We noted that LC3 expression was significantly correlated with mild clinicopathological characteristics, including macrovascular invasion, lymph node metastasis, American Joint Committee on Cancer and Barcelona Clinic Liver Cancer stages, recurrence, and mortality. Ten patient showed tumor recurrence, and 15 patients died. Postresection 5-year OS and DFS rates were 43.7 and 57.4%, respectively. Cox regression analysis showed that high intratumoral LC3 expression was significantly associated with improved OS [hazard ratio (HR; 95% confidence interval (CI)): (1.68-26.9), p = 0.007], but multiple tumors and microvascular invasion was significantly correlated with poor OS [HR (95% CI): 0.03 (0.01-0.34), p = 0.004, and 0.07 (0.01-0.46), p = 0.006, respectively]. Furthermore, high LC3 expression and cirrhosis had improved DFS [HR (95% CI): 51.3 (2.85-922), p = 0.008, and 17.9 (1.05-306), p = 0.046, respectively]. The 5-year OS and DFS rates were respectively 61.2 and 74.6% in high LC3 expression patients and 0 and 0% in those with low LC3 expression. CONCLUSION: High LC3 expression in tumors is significantly associated with mild clinicopathological characteristics and favorable clinical prognosis in patients with cHCC-CC after resection.

A prospective, randomized trial of thrombin versus cyanoacrylate injection in the control of acute gastric variceal hemorrhage.

BACKGROUND: Acute gastric variceal hemorrhage (AGVH) is a serious complication of portal hypertension. Endoscopic cyanoacrylate glue injection is standard therapy for acute hemostasis; however, it may be associated with serious complications. The role of thrombin injection has not been confirmed. This study compared endoscopic thrombin and glue injections in the hemostasis of AGVH. METHODS: 68 eligible patients with AGVH were randomized to receive thrombin injection (33 patients) or glue injection (35 patients). The primary end point was injection-induced gastric ulcers. Secondary end points were acute hemostasis, rebleeding, and mortality within 42 days. RESULTS: Both groups had comparable baseline data. Hemostasis of active bleeding at endoscopy was 90.0 % (9/10) in the thrombin group and 90.9 % (10/11) in the glue group (P = 0.58), and 48-hour hemostasis was achieved in 93.9 % (31/33) and 97.1 % (34/35), respectively (P = 0.60). Treatment failure at 5 days occurred in two patients (6.1 %) in the thrombin group and two patients (5.7 %) in the glue group (P > 0.99). Gastric ulcers occurred in none of the thrombin group and 11/30 (36.7 %) of the glue group (P < 0.001, 95 % confidence interval [CI] 8 % - 27 %). Complications occurred in 4 (12.1 %) and 18 (51.4 %) patients in the thrombin and glue groups, respectively (P < 0.001, 95 %CI 22 % - 45 %). Two patients who received glue had post-treatment gastric ulcer bleeding. One patient in each group died. CONCLUSIONS: Endoscopic thrombin injection was similar to glue injection in achieving successful hemostasis of AGVH. However, a higher incidence of complications may be associated with glue injection.

Acoustic Radiation Force Impulse Elastography with APRI and FIB-4 to Identify Significant Liver Fibrosis in Chronic Hepatitis B Patients.

INTRODUCTION AND AIM: In chronic hepatitis B (CHB) patients with equivocal indication for antiviral therapy, therapeutic decision currently depends on histopathology of the liver. We aimed to evaluate if acoustic radiation force impulse (ARFI) in conjunction with aspartate transaminase to platelet ratio index (APRI) and fibrosis-4 (FIB-4) score could replace liver biopsy to indicate treatment for CHB. MATERIAL AND METHODS: We prospectively enrolled 101 clinically non-cirrhotic patients whose serum alanine aminotransferase was mildly elevated (1-2 folds above the upper normal limit) despite a high viral load (HBV DNA > 2,000 IU/mL). All participants underwent liver biopsy, and measurement of ARFI, APRI and FIB-4. The ability of the markers to distinguish fibrosis ≥ METAVIR F2 was evaluated. RESULTS: According to histopathology, liver fibrosis was METAVIR F0 in 2 (2.0%), F1 in 43 (42.6%), F2 in 34 (33.7%), F3 in 16 (15.8%), and F4 in 6 (5.9%) patients, and was correlated with ARFI (p = 0.0001), APRI (p = 0.012), and FIB-4 (p = 0.004). The six patients with cirrhosis were included for analysis, and received antiviral therapy. The C statistics of ARFI, APRI, and FIB-4 for fibrosis ≥ F2 were 0.70 (95% confidence interval [CI], 0.59-0.80), 0.62 (95% CI, 0.51-0.73), and 0.64 (0.53- 0.75), respectively. The cut-off values for 95% sensitivity and 95% specificity to identify significant fibrosis were 0.97 m/sec and 1.36 m/sec for ARFI, 0.36 and 1.0 for APRI, 0.63 and 2.22 for FIB-4, respectively. Using a combination of these 3 indices, 44 patients (43.6%) could be spared a liver biopsy procedure. CONCLUSIONS: A combination of ARFI, APRI, and FIB-4 may spare some CHB patients with equivocal indication for antiviral treatment a liver biopsy.

Determinants of hepatocellular carcinoma in cirrhotic patients treated with nucleos(t)ide analogues for chronic hepatitis B.

OBJECTIVES: We aimed to identify determinants of hepatocellular carcinoma (HCC) in cirrhotic patients who received nucleos(t)ide analogues for chronic hepatitis B (CHB). PATIENTS AND METHODS: This retrospective-prospective study screened all patients (n = 1630) who received antiviral therapy for CHB between 1 September 2007 and 31 March 2013 at the E-Da Hospital and enrolled 210 consecutive cirrhotic patients with pretreatment viral DNA >2000 IU/mL. Those who developed HCC within 3 months of treatment were excluded. All participants were observed until occurrence of HCC, death or 1 January 2014. The incidence and determinants of HCC were estimated using competing risk analyses adjusted for mortality. RESULTS: Thirty-five (16.7%) patients developed HCC during a median follow-up of 25.2 months (IQR, 16.3-37.3 months), with a cumulative incidence of 24.1% (95% CI, 16.3%-32.0%) at 5 years. Multivariate-adjusted analyses identified age >55 years [adjusted hazard ratio (HR), 2.19; 95% CI, 1.03-4.66], male gender (adjusted HR, 3.07; 95% CI, 1.05-9.02), model for end-stage liver disease (MELD) score >12 points (adjusted HR, 2.16; 95% CI, 1.10-4.23) and diabetes mellitus (DM; adjusted HR, 3.49; 95% CI, 1.54-7.91) as independent risk factors after adjusting for multiple covariates, including antidiabetes medication. A scoring formula that used information on age, gender, MELD score, DM and antidiabetes regimen significantly discriminated patients at high or low risk of HCC, with sensitivity and specificity of 82.9% and 62.3%, respectively. CONCLUSIONS: Age, gender, hepatic dysfunction, DM and medication for DM are baseline factors that stratify the risk of HCC in cirrhotic patients who receive nucleos(t)ide analogues for CHB.

Heavy alcohol consumption increases the incidence of hepatocellular carcinoma in hepatitis B virus-related cirrhosis.

BACKGROUND & AIMS: Taiwan has a high prevalence of hepatitis B viral (HBV) infection and hepatocellular carcinoma (HCC) with increasing consumption of alcohol. We investigated the impact of heavy alcohol consumption and HBV infection on HCC in cirrhotic patients. METHODS: 966 cirrhotic patients (132 with HBV infection and alcoholism, 632 with HBV infection, and 202 patients with alcoholism) were enrolled between 2000 and 2009 and followed until 2011. The primary end point was newly developed HCC. RESULTS: Within the three patient groups (cirrhotic patients with HBV infection and alcoholism, HBV infection alone, and alcoholism alone) 38 (28.8%), 100 (15.8%), and 21 (10.4%) showed newly developed HCC, respectively. The 10-year cumulative (52.8% vs. 39.8% vs. 25.6%, p <0.001) and annual incidences (9.9%, 4.1%, and 2.1%) of HCC were significantly higher in cirrhotic patients with HBV infection and alcoholism than those in patients with HBV infection or alcoholism alone. For patients with HBV infection and alcoholism, baseline serum HBV DNA (OR=16.8, p=0.025), antiviral nucleos(t)ides analogues (NUCs) therapy (OR=0.01, p=0.035), and serum α-fetoprotein (OR=1.18, p=0.045) were risk predictors of HCC by multivariate logistic regression models. The cumulative incidence of HCC was higher in patients with higher baseline serum HBV DNA. Antiviral NUCs therapy reduced the incidence of HCC. CONCLUSIONS: Heavy alcohol consumption significantly increased the risk of HCC in HBV-related cirrhotic patients. Elevated baseline serum HBV DNA was a strong risk predictor of HCC and antiviral NUCs therapy reduced the incidence of HCC in cirrhotic patients with HBV infection and alcoholism.

A retrospective comparative study of histoacryl injection and banding ligation in the treatment of acute type 1 gastric variceal hemorrhage.

BACKGROUND. Esophageal varices extending along lesser curvature side of stomach is classified as GOV1. The optimal therapy for GOV1 bleeding is still undetermined. METHODS. One hundred and sixty-two patients diagnosed as acute hemorrhage from GOV1 were enrolled. At endoscopists' discretion, 118 patients received glue injection (Glue group) and 44 patients received ligation to arrest bleeding [endoscopic variceal ligation (EVL) group]. This study aimed to compare hemostasis, rebleeding, complications and mortality within 42 days. RESULTS. Both groups were comparable in baseline data. In 109 patients (92%) in the Glue group and 36 patients (82%) in the EVL group (p = 0.07) 48-h hemostasis was achieved . Hemostasis of active bleeding was achieved in 49 of 55 patients (89%) in the Glue group and 24 of 28 patients (85%) in the EVL group (p = 0.70). Treatment failure was noted in 14% of the Glue group and 23% in the EVL group (p = 0.22). Eight patients in the Glue group and four patients in the EVL group rebled between 5 and 42 days (p = 0.73). A total of 48 and 19 adverse events occurred in the Glue and EVL groups, respectively (p = 0.85). Six patients in the Glue group and seven patients in the EVL group encountered posttreatment gastric ulcer bleeding (p = 0.04). Seventeen patients (14%) in the Glue group and 10 (23%) patients in the EVL group died within 42 days (p < 0.001). CONCLUSIONS. Banding ligation was similar to glue injection in achieving successful hemostasis of acute bleeding from GOV1. However, a higher incidence of posttreatment ulcer bleeding and mortality may be associated with banding ligation.

Controlled trial of ligation plus vasoconstrictor versus proton pump inhibitor in the control of acute esophageal variceal bleeding.

BACKGROUND: Endoscopic therapy combined with vasoconstrictor was generally recommended to treat acute variceal bleeding. However, up to 30% of patients may still encounter treatment failure. OBJECTIVES: This trial was to evaluate the efficacy of combination with endoscopic variceal ligation (EVL) and proton pump inhibitor (PPI) infusion in patients with acute variceal bleeding. METHODS: Cirrhotic patients presenting with acute esophageal variceal bleeding were rescued by emergency EVL. Soon after arresting of bleeding varices, eligible subjects were randomized to two groups. Vasoconstrictor group received either somatostatin or terlipressin infusion. PPI group received either omeprazole or pantoprazole. End points were initial hemostasis, very early rebleeding rate, and adverse events. RESULTS: Sixty patients were enrolled in vasoconstrictor group and 58 patients in PPI group. Both groups were comparable in baseline data. Initial hemostasis was achieved in 98% in vasoconstrictor group and 100% in PPI group (P = 1.0). Very early rebleeding within 48-120 h occurred in one patient (2%) in vasoconstrictor group and one patient (2%) in the PPI group (P = 1.0). Treatment failure was 4% in vasoconstrictor group and 2% in PPI group (P = 0.95). Adverse events occurred in 33 patients (55%) in vasoconstrictor group and three patients (6%) in PPI group (P < 0.001). Two patients in vasoconstrictor group and one patient in PPI group encountered esophageal ulcer bleeding. CONCLUSIONS: After successful control of acute variceal bleeding by EVL, adjuvant therapy with PPI infusion was similar to combination with vasoconstrictor infusion in terms of initial hemostasis, very early rebleeding rate, and associated with fewer adverse events.

Diallyl sulfide protects against ultraviolet B-induced skin cancers in SKH-1 hairless mouse: analysis of early molecular events in carcinogenesis.

BACKGROUND: Diallyl sulfide (DAS) has been shown to have a preventive effect against various cancers. AIMS AND OBJECTIVES: We evaluated the protective effects of DAS in regression of ultraviolet B (UVB)-induced skin tumor formation in SKH-1 hairless mice and its underlying early molecular biomarkers. METHODS: We examined the efficacy of DAS in UVB light-induced skin lesion in SKH-1 hairless mice and the associated molecular events. RESULTS: Mice irradiated with UVB at 180mJ/cm(2) twice per week elicited 100% tumor incidence at 20 weeks. The topical application of DAS before UVB irradiation caused a delay in tumor appearance, multiplicity, and size. The topical application of DAS before and immediately after a single UVB irradiation (180mJ/cm(2) ) resulted in a significant decrease in UVB-induced thymine dimer-positive cells, expression of proliferative cell nuclear antigen (PCNA), terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling, and apoptotic sunburn cells, together with an increase in p53 and p21/Cip1-positive cell population in the epidermis. Simultaneously, DAS also significantly inhibited nuclear factor-κB (NF-κB), cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and nitric oxide (NO) levels. CONCLUSIONS: The protective effect of DAS against photocarcinogenesis is accompanied by the down-regulation of cell-proliferative controls, involving thymine dimer, PCNA, apoptosis, transcription factors NF-κB, and of inflammatory responses involving COX-2, PGE2, and NO, and up-regulation of p53, p21/Cip1 to prevent DNA damage and facilitate DNA repair.

Prospective survey for the etiology and outcome of peptic ulcer bleeding: a community based study in southern Taiwan.

BACKGROUND/PURPOSE: Helicobacter pylori infection and drugs are the two major risk factors for peptic ulcer bleeding. The role of these two factors may change with changes in the prevalence of H pylori and use of NSAIDs. This study aimed to determine the cause, endoscopic features, and outcome of peptic ulcer bleeding in a community hospital in southern Taiwan. METHODS: Patients who received esophagogastroduodenoscopy on arrival at the emergency department and were found to have actively bleeding ulcers or ulcers with stigmata of recent hemorrhage were included. H pylori infection was documented by the rapid urease test, histology, and/or C-13 urease breath test. Medication history, comorbidities, requirement for endoscopic therapy, blood transfusion, hospitalization days, and rebleeding rates were analyzed. RESULTS: A total of 204 patients were enrolled with a mean age of 64.8 ± 15.2 years, with 58.3% of the subjects being female. There were 62 patients (30.4%) with H pylori infection only, 40 patients (19.6%) with drug use only, 67 patients (32.8%) with H pylori infection and drug use, and 37 patients (17.2%) without H pylori or drug use. A total of 107 patients (52.5%) were found to have had drug exposure. Drug exposure had an odds ratio (OR) of 2.34 [95% Confidence Interval (CI) = 1.30-4.20] for gastric ulcer bleeding and H pylori had an OR of 2.64 (95% CI = 1.17-5.97) for combined gastric and duodenal ulcer bleeding. The mean hospitalization period was 5.7 ± 4.0 days and the overall re-bleeding rate was 4.0%. The H pylori negative and drug negative subjects needed more endoscopic therapy (p < 0.05). CONCLUSION: Drug use, especially NSAIDs, aspirin, and clopidogrel has become an important cause of peptic ulcer bleeding in southern Taiwan.

Short-course vasoconstrictors are adequate for esophageal variceal bleeding after endoscopic variceal ligation: A systematic review and meta-analysis.

Endoscopic variceal ligation (EVL) with vasoconstrictors has been recommended for acute esophageal variceal bleeding. However, the optimal duration of vasoconstrictors after EVL is controversial. This systematic review and meta-analysis was conducted to explore the efficacy of short-course vasoconstrictors (≤3 days) versus standard combination (3-5 days). A comprehensive literature review was conducted using the PubMed, Embase, and Cochrane library databases with subsequent meta-analysis. The primary outcomes were 5-day rebleeding, mortality, and treatment failure rates. A risk ratio (RR) with 95% confidence interval is used for outcome comparison. Nine randomized studies with 838 patients were included. The initial hemostasis (96.8% vs 97.4%, p = 0.919), 5-day rebleeding (11.2% vs 8.3%, RR = 1.05, 95% CI = 0.62-1.76), mortality (0 vs 1.3%, RR = 0.48, 95% CI = 0.10-2.39), and treatment failure (7.4% vs 5.9%, RR = 1.10, 95% CI = 0.48-2.49) were similar in both groups. Subgroup analysis suggested EVL alone had no significant difference of 5-day re-bleeding (15.9% vs 7.1%, RR = 2.25, 95% CI = 0.87-5.77), mortality (0 vs 0.7%, RR = 0.71, 95% CI = 0.08-6.03), treatment failure (9.6% vs 6.7%, RR = 1.43, 95% CI = 0.54-3.75) compared to standard combination. Clinical heterogeneity was found for the rebleeding rate for the subgroup during sensitivity analysis. EVL with short-course vasoconstrictors is highly efficacious for esophageal variceal bleeding. Further studies are required to determine the genuine need of subsequent vasoconstrictor after successful EVL.

Esophagogastric varices predict mortality in hospitalized patients with alcoholic liver disease in Taiwan.

BACKGROUND/AIMS: Alcoholic liver disease (ALD) is a major cause of morbidity and mortality in Western countries. The present study investigated the status and the risk factors for predicting mortality of ALD in Taiwan. METHODOLOGY: We retrospective studied 100 consecutive in patients with ALD between 1992 and 2000. All patients had a history of alcohol consumption exceeding 80 g per day for at least 5 years. RESULTS: The study comprised 93 men and 7 women with a mean age of 45.4 years. The ALD included fatty liver (21%), alcoholic hepatitis (15%), alcoholic hepatitis superimposed on alcoholic cirrhosis (24%), and alcoholic cirrhosis (40%). Forty-four percent of patients had esophagogastric varices. Thirty-three percent of patients were mortality. The presence of esophagogastric varices was the only parameter identified by univariate and multivariate analyses and had a statistically significant association with increased mortality (OR: 8.603; 95% CI: 2.009-36.864; p = 0.004). The cumulative survival for ALD patients with varices was significantly lower than for patients without varices. CONCLUSIONS: The presence of esophagogastric varices had a statistically significant relationship with increased mortality. This study strongly implicates esophagogastric varices were a valuable poor prognostic factor with mortality. Upper gastrointestinal endoscopy is a simple clinical available tool for the assessment of the occurrence of varices to predict the disease severity and mortality in hospitalized patients with ALD.

Anti-proliferative activity of biochanin A in human osteosarcoma cells via mitochondrial-involved apoptosis.

Biochanin A is a major isoflavone in red clover and a potent chemopreventive agent against cancer. However, the effects of biochanin A on human osteosarcoma cells have never been clarified. This study investigated the anti-proliferative potential of biochanin A in osteosarcoma cells. The results indicate that biochanin A inhibited cell growth and colony formation in a dose-dependent manner with a minimal toxicity to normal cells. The combination of doxorubicin and biochanin A could synergistically inhibit osteosarcoma cell growth. The cytotoxic effect of biochanin A via the induction of apoptosis as evidenced by formation of apoptotic bodies, externalization of phosphatidylserine, accumulation of sub-G1 phase cells, caspase 3 activation, and cleavage of PARP. Apoptosis was associated with loss of the mitochondrial membrane potential, release of cytochrome c, caspase 9 activation, increased Bax expression, and reduced Bcl-2 and Bcl-XL expression. Pre-treatment with a caspase-9 specific inhibitor (Z-LEHD-FMK) partially attenuated cell death, suggesting involvement of the intrinsic mitochondrial apoptotic cascade. However, pre-treatment with the JNK inhibitor SP600125, the MEK inhibitor PD-98059, and the p38 MAPK inhibitor SB203580 or the antioxidants vitamin E, N-acetylcysteine, and glutathione failed to prevent biochanin A-induced cell death. Our results suggest that biochanin A inhibits cell growth and induces apoptosis in osteosarcoma cells by triggering activation of the intrinsic mitochondrial pathway and caspase-9 and -3 and increasing the Bax: Bcl-2/Bcl-XL ratio.

Esophageal adenocarcinoma arising from Barrett's epithelium in Taiwan.

The prevalence of Barrett's esophagus (BE) in Eastern countries is rising to match the prevalence in the West. However, a corresponding trend of BE-associated adenocarcinoma has yet to be observed in Asia. Historically, adenocarcinoma complicating BE has been considered a rare event in Taiwan. In the present report, we collected three Taiwanese cases of esophageal adenocarcinoma arising from BE. The first case was a 37-year-old man with an advanced cancer that developed on pre-existing BE after a 3-year interval without endoscopic surveillance. The second case was a 63-year-old man who presented with odynophagia and was found to have an ulcerative tumor centered on the characteristic Barrett's mucosa. The final case was a 44-year-old man who presented with gradual-onset dysphagia and weight loss, without typical reflux symptom. Our report emphasizes the need for an updated epidemiologic study to determine the incidence of BE-associated adenocarcinoma in Taiwan.

Discovery of a novel anti-cancer agent targeting both topoisomerase I and II in hepatocellular carcinoma Hep 3B cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde.

Cinnamomum verum has been used as a traditional Chinese herbal medicine. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, in hepatocellular carcinoma Hep 3B cells. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by an up-regulation of pro-apoptotic bax and bak genes and down-regulation of anti-apoptotic bcl-2 and bcl-XL genes, mitochondrial membrane potential loss, cytochrome c release, activation of caspase 3 and 9, increase in the DNA content in sub G1, and morphological characteristics of apoptosis. 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments (VAC), suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against Hep 3B cells is accompanied by downregulations of NF-κB binding activity, inflammatory responses involving COX-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and VAC. Our data suggest that 2-MCA could be a potential agent for anticancer therapy.

Predictive factors for anti-HBs status after 1 booster dose of hepatitis B vaccine.

In Taiwan, infants need to receive 3 doses of hepatitis B virus (HBV) vaccine under the public health policy from the government. However, there are many young adults who even though received complete HBV vaccination in their childhood would lose the positive response of anti-hepatitis B surface antibody (HBs) and need the booster dose of HBV vaccine. The aim of our study is to determine the powerful predictive factor for screening the candidates who need only 1 booster dose of HB vaccine then they can regain positive postbooster anti-HBs status (≧10 mIU/mL) or protective postbooster anti-HBs status (≧100 mIU/mL).We recruited 103 university freshmen who were born after July 1986 with complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels at their health examinations upon university entry. They received 1 booster dose of HB vaccine, and their anti-HBs titers were rechecked 4 weeks after the booster administration. Multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL, model 1) and protective postbooster anti-HBs status (≧100 mIU/mL, model 2) was done with predictive factors of prebooster anti-HBs level, body mass index, serum glutamate pyruvate transaminase level, and sex.Twenty-four students got positive postbooster anti-HBs status (10-100 mIU/mL) and 50 students got protective postbooster anti-HBs status (≧100 mIU/mL). In the model of multivariate analysis logistic regression for positive postbooster anti-HBs status (≧10 mIU/mL), prebooster anti-HBs level was the strongest predictive factor. The odds ratio was 218.645 and the P value was 0.001. Even in the model of multivariate analysis logistic regression for protective postbooster anti-HBs status (≧100 mIU/mL), prebooster anti-HBs level was still the strongest predictive factor, but the odds ratio of a protective booster effect was 2.143, with 95% confidence interval between 1.552 and 2.959, and the P value was less than 0.001.Prebooster anti-HBs level can be the powerful predictive factor for positive postbooster anti-HBs status (≧10 mIU/mL) and protective postbooster anti-HBs status (≧100 mIU/mL). According to the result of this study, if someone received complete HBV vaccination in childhood, but displayed negative results for hepatitis B surface antigen and anti-HBs levels around 2 decades later, 1 booster dose of HBV vaccine could help him or her to regain positive postbooster anti-HBs status (≧10 mIU/mL) under the strong predictive factor of prebooster anti-HBs level higher than 1 mIU/mL. The other 2 HBV vaccines could be saved and the case could also save money and time.

Discovery of a novel anticancer agent with both anti-topoisomerase I and II activities in hepatocellular carcinoma SK-Hep-1 cells in vitro and in vivo: Cinnamomum verum component 2-methoxycinnamaldehyde.

Cinnamomum verum is used to make the spice cinnamon and has been used as a traditional Chinese herbal medicine for various applications. We evaluated the anticancer effect of 2-methoxycinnamaldehyde (2-MCA), a constituent of the bark of the plant, and its underlying molecular biomarkers associated with carcinogenesis in human hepatocellular carcinoma SK-Hep-1 cell line. The results show that 2-MCA suppressed proliferation and induced apoptosis as indicated by mitochondrial membrane potential loss, activation of caspase-3 and caspase-9, increase in the DNA content in sub-G1, and morphological characteristics of apoptosis, including blebbing of plasma membrane, nuclear condensation, fragmentation, apoptotic body formation, and long comet tail. In addition, 2-MCA also induced lysosomal vacuolation with increased volume of acidic compartments, suppressions of nuclear transcription factors NF-κB, cyclooxygenase-2, prostaglandin E2 (PGE2), and both topoisomerase I and II activities in a dose-dependent manner. Further study reveals the growth-inhibitory effect of 2-MCA was also evident in a nude mice model. Taken together, the data suggest that the growth-inhibitory effect of 2-MCA against SK-Hep-1 cells is accompanied by downregulations of NF-κB-binding activity, inflammatory responses involving cyclooxygenase-2 and PGE2, and proliferative control involving apoptosis, both topoisomerase I and II activities, together with an upregulation of lysosomal vacuolation and volume of acidic compartments. Similar effects (including all of the above-mentioned effects) were found in other tested cell lines, including human hepatocellular carcinoma Hep 3B, lung adenocarcinoma A549, squamous cell carcinoma NCI-H520, colorectal adenocarcinoma COLO 205, and T-lymphoblastic MOLT-3 (results not shown). Our data suggest that 2-MCA could be a potential agent for anticancer therapy.

Comparison of 13C-urea breath test values in gastric cancer, peptic ulcer and gastritis.

BACKGROUND/AIMS: Results of urea breath test (UBT) are related to the severity of atrophic gastritis and the density of Helicobacter pylori (H. pylori). Recently, it has been reported that low UBT values should be considered to suggest the possibility of gastric cancer. This study compares UBT results in gastric cancer patients with those of peptic ulcer and gastritis patients. METHODOLOGY: Between October 1998 and May 2000, we have consecutively collected 564 H. pylori-positive patients: 128 gastritis patients, 72 gastric cancer patients, 64 gastric ulcer patients and 300 duodenal ulcer patients. Peptic ulcers were classified into active (A), healing (H), and scar (S) stages. Gastric cancer was classified into early stage (EGCA) and advanced stage (AGCA). The dose of 13C-urea was 50mg, and breath samples were analyzed with a mass spectrometer and the data was evaluated by Mann-Whitney test. The cut-off value was 3.5 per thousand. RESULTS: The mean UBT values of gastric cancer, gastric ulcer (GU), duodenal ulcer (DU) and gastritis were 16.95 +/- 12.2 per thousand, 16.3 +/- 9.3 per thousand, 15.13 +/- 9.9 per thousand and 20.07 +/- 13.5 per thousand. There were no significant differences in UBT values between gastric cancer and gastric ulcer (p = 0.745), duodenal ulcer (p = 0.3831), or gastritis (p = 0.2953). There were also no significant differences between subgroups of gastric cancer and gastric ulcer. There were significantly higher UBT values in the DU scar stage (p = 0.001) and healing stage (p = 0.0484) than in the active stage. CONCLUSIONS: We conclude that the UBT value is not a good method for the prediction of gastric cancer. In addition, based on the results of our study, the UBT values may explain the relationship between the natural course of duodenal ulcer and H. pylori infection.

The role of radiotherapy in the treatment of hepatocellular carcinoma with portal vein tumor thrombus.

The aim of this study was to evaluate the role of radiotherapy in the treatment of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVT) and to determine the prognostic factors for overall survival. Altogether, 106 patients with HCC and PVT referred for radiotherapy between 2004 and 2009 were retrospectively reviewed. A total of 60 Gy in 30 daily fractions was delivered with intensity-modulated radiotherapy techniques. Patient-related and treatment-related factors were analyzed to evaluate their prognostic significance for the overall survival rate. Complete response was noted in 10 patients and partial response in 55 patients. The liver lesions had become resectable after the completion of radiotherapy in 12 patients, and surgery was subsequently performed. One or two courses of transarterial chemoembolization (TACE) were administered to 19 patients following radiotherapy. The 1-year and 2-year overall survival rates were 34.7% and 11%, respectively, and the median survival was 7 months for the entire cohort of patients. Post-radiotherapy treatment modality, response to radiotherapy and JIS score were demonstrated as independent prognostic factors for overall survival (P = 0.003, P < 0.001, P < 0.001, respectively). For patients who received surgical intervention after radiotherapy, the median survival was 30 months and the 2-year overall survival rate was 67%. Radiotherapy achieved a 61.5% objective response rate and prolonged survival in patients with PVT. The liver tumors had become resectable after radiotherapy in 11% of patients. Our results suggested that radiotherapy could offer survival benefits and should be considered as a treatment option for patients with PVT. Radiotherapy could also be considered as a preoperative treatment modality in patients with HCC and PVT.