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1.
PLoS One ; 12(8): e0183960, 2017.
Article in English | MEDLINE | ID: mdl-28859146

ABSTRACT

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) manifests as chronic abdominal pain. One pathophysiological theory states that the brain-gut axis is responsible for pain control in the intestine. Although several studies have discussed the structural changes in the brain of IBS patients, most of these studies have been conducted in Western populations. Different cultures and sexes experience different pain sensations and have different pain responses. Accordingly, we aimed to identify the specific changes in the cortical thickness of Asian women with IBS and to compare these data to those of non-Asian women with IBS. METHODS: Thirty Asian female IBS patients (IBS group) and 39 healthy individuals (control group) were included in this study. Brain structural magnetic resonance imaging was performed. We used FreeSurfer to analyze the differences in the cortical thickness and their correlations with patient characteristics. RESULTS: The left cuneus, left rostral middle frontal cortex, left supramarginal cortex, right caudal anterior cingulate cortex, and bilateral insula exhibited cortical thinning in the IBS group compared with those in the controls. Furthermore, the brain cortical thickness correlated negatively the severity as well as duration of abdominal pain. CONCLUSIONS: Some of our findings differ from those of Western studies. In our study, all of the significant brain regions in the IBS group exhibited cortical thinning compared with those in the controls. The differences in cortical thickness between the IBS patients and controls may provide useful information to facilitate regulating abdominal pain in IBS patients. These findings offer insights into the association of different cultures and sexes with differences in cortical thinning in patients with IBS.


Subject(s)
Abdominal Pain/physiopathology , Cerebral Cortex/pathology , Gyrus Cinguli/pathology , Irritable Bowel Syndrome/physiopathology , Occipital Lobe/pathology , Prefrontal Cortex/pathology , Abdominal Pain/diagnostic imaging , Abdominal Pain/ethnology , Abdominal Pain/pathology , Adult , Asian People , Brain Mapping , Case-Control Studies , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/physiopathology , Female , Gyrus Cinguli/diagnostic imaging , Gyrus Cinguli/physiopathology , Humans , Image Interpretation, Computer-Assisted , Irritable Bowel Syndrome/diagnostic imaging , Irritable Bowel Syndrome/ethnology , Irritable Bowel Syndrome/pathology , Magnetic Resonance Imaging , Middle Aged , Occipital Lobe/diagnostic imaging , Occipital Lobe/physiopathology , Prefrontal Cortex/diagnostic imaging , Prefrontal Cortex/physiopathology , Severity of Illness Index
2.
Int J Food Sci Nutr ; 67(2): 177-83, 2016.
Article in English | MEDLINE | ID: mdl-26883189

ABSTRACT

Helicobacter pylori is a major risk factor for gastritis, gastric ulcers and gastric cancer. Traditional therapy with proton pump inhibitor and antibiotics is regarded as optimal for H. pylori eradication whereas, the eradication rate is unsatisfactory. Studies have reported that cranberry may inhibit H. pylori adhesion to the human gastric mucus but lack of other berry extracts have been evaluated in clinical study. Thus, a 9-week add-on randomised controlled trial was conducted to explore the impact of blueberry and grape seed extract (BGE) combinations traditional therapy for H. pylori eradication. In results, we found that there was no significant difference of eradication rate between the berry extract group and placebo group in the intention-to-treat analysis and in the per-protocol analysis (94.64% versus 84.62%, p = 0.085). Diarrhoea, constipation and epigastric pain were observed increasing during ingestion of the berry extract in some cases. In conclusion, this study indicated that no significant difference existed between the BGE extract group and placebo group in eradication rate under triple therapy.


Subject(s)
Amoxicillin/therapeutic use , Blueberry Plants/chemistry , Clarithromycin/therapeutic use , Esomeprazole/therapeutic use , Grape Seed Extract/pharmacology , Helicobacter Infections/drug therapy , Adult , Aged , Amoxicillin/administration & dosage , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Anti-Ulcer Agents/administration & dosage , Anti-Ulcer Agents/therapeutic use , Bacterial Adhesion , Clarithromycin/administration & dosage , Drug Therapy, Combination , Esomeprazole/administration & dosage , Female , Grape Seed Extract/chemistry , Helicobacter pylori , Humans , Male , Middle Aged
3.
Nanoscale Res Lett ; 10: 224, 2015.
Article in English | MEDLINE | ID: mdl-26019699

ABSTRACT

We report a first-of-its-kind, unique approach for generating a self-aligned, gate-stacking heterostructure of Ge quantum dot (QD)/SiO2/SiGe shell on Si in a single fabrication step. The 4-nm-thick SiO2 layer between the Ge QD and SiGe shell fabricated during the single-step process is the result of an exquisitely controlled dynamic balance between the fluxes of oxygen and silicon interstitials. The high-quality interface properties of our "designer" heterostructure are evidenced by the low interface trap density of as low as 2-4 × 10(11) cm(-2) eV(-1) and superior transfer characteristics measured for Ge-based metal-oxide-semiconductor field-effect transistors (MOSFETs). Thanks to the very thin interfacial SiO2 layer, carrier storage within the Ge QDs with good memory endurance was established under relatively low-voltage programming/erasing conditions. We hope that our unique self-aligned, gate-stacking heterostructure provides an effective approach for the production of next-generation, high-performance Ge gate/SiO2/SiGe channel MOSFETs.

4.
BMC Gastroenterol ; 15: 22, 2015 Feb 15.
Article in English | MEDLINE | ID: mdl-25886887

ABSTRACT

BACKGROUND: Non-alcoholic steatohepatitis (NASH) is associated with hepatic fibrogenesis. Despite well-known cholesterol-lowering action of statins, their mechanisms against NASH-mediated fibrogenesis remain unclear. This study aimed at investigating the in vitro and in vivo anti-fibrotic properties of fluvastatin (Flu). METHODS: Palmitate (PA)-induced changes in intracellular hydrogen peroxide levels in primary rat hepatocytes (PRHs) and human hepatoma cell line (HepG2) were quantified by dichlorofluorescein diacetate (DCF-DA) dye assay, whereas changes in expressions of NADPH oxidase gp91 (phox) subunit, α-smooth muscle actin (α-SMA), and NFκB p65 nuclear translocation were quantified with Western blotting. Quantitative real-time polymerase chain reaction (q-PCR) was used to investigate mRNA expressions of pro-inflammatory genes (ICAM-1, IL-6, TNF-α). Conditioned medium (CM) from PA-treated PRHs was applied to cultured rat hepatic stellate cell line, HSC-T6, with or without Flu-pretreatment for 2 h. Pro-fibrogenic gene expressions (COL1, TIMP-1, TGF-ß1, α-SMA) and protein expression of α-SMA were analyzed. In vivo study using choline-deficient L-amino acid defined (CDAA) diet-induced rat NASH model was performed by randomly assigning Wistar rats (n = 28) to normal controls (n = 4), CDAA diet with vehicles, and CDAA diet with Flu (5 mg/kg or 10 mg/kg) (n = 8 each) through gavage for 4 or 8 weeks. Livers were harvested for histological, Western blot (α-SMA), and q-PCR analyses for expressions of pro-inflammatory (IL-6, iNOS, ICAM-1) and pro-fibrogenic (Col1, α-SMA, TIMP-1) genes. RESULTS: In vitro, Flu (1-20 µM) inhibited PA-induced free-radical production, gp91 (phox) expression, and NFκB p65 translocation in HepG2 and PRHs, while CM-induced α-SMA protein expression and pro-fibrogenic gene expressions in HSC-T6 were suppressed in Flu-pretreated cells compared to those without pretreatment. Moreover, α-SMA protein expression was significantly decreased in HSC-T6 cultured with CM from PA-Flu-treated PRHs compared to those cultured with CM from PA-treated PRHs. Flu also reduced steatosis and fibrosis scores, α-SMA protein expression, mRNA expression of pro-inflammatory and pro-fibrogenic genes in livers of CDAA rats. CONCLUSIONS: We demonstrated PA-induced HSC activation through paracrine effect of hepatocyte in vitro that was significantly suppressed by pre-treating HSC with Flu. In vivo, Flu alleviated steatosis-induced HSC activation and hepatic fibrogenesis through mitigating inflammation and oxidative stress, suggesting possible therapeutic role of Flu against NASH.


Subject(s)
Fatty Acids, Monounsaturated/pharmacology , Hepatic Stellate Cells/physiology , Hepatocytes/drug effects , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Indoles/pharmacology , Liver Cirrhosis/prevention & control , Paracrine Communication/drug effects , Actins/genetics , Actins/metabolism , Animals , Choline/administration & dosage , Collagen Type I/genetics , Culture Media, Conditioned/pharmacology , Diet , Fatty Acids, Monounsaturated/therapeutic use , Fluvastatin , Gene Expression/drug effects , Hep G2 Cells , Hepatocytes/physiology , Humans , Hydrogen Peroxide/metabolism , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Indoles/therapeutic use , Intercellular Adhesion Molecule-1/genetics , Interleukin-6/genetics , Liver Cirrhosis/etiology , Liver Cirrhosis/pathology , Male , Membrane Glycoproteins/metabolism , NADPH Oxidase 2 , NADPH Oxidases/metabolism , Nitric Oxide Synthase Type II/genetics , Non-alcoholic Fatty Liver Disease/complications , Non-alcoholic Fatty Liver Disease/pathology , Oxidative Stress/drug effects , Palmitic Acid/pharmacology , RNA, Messenger/metabolism , Rats , Rats, Wistar , Tissue Inhibitor of Metalloproteinase-1/genetics , Transcription Factor RelA/metabolism , Transforming Growth Factor beta1/pharmacology , Tumor Necrosis Factor-alpha/genetics
5.
Case Rep Gastroenterol ; 8(1): 77-81, 2014 Jan.
Article in English | MEDLINE | ID: mdl-24748862

ABSTRACT

Lung cancer is one of the leading causes of cancer deaths worldwide. Metastatic spreads of lung cancer are often found in the adrenal glands, bone, liver, brain and kidneys; the gastrointestinal tract is less commonly involved. However, according to some reports in the literature, the incidence of gastrointestinal metastases, most of them asymptomatic, might be as frequent as 11% in autopsy studies of lung cancer, which suggests that this condition is not as rare as it was previously considered. We report a very rare case of small cell lung cancer with a solitary gastric metastasis mimicking an adrenal tumor which was belatedly diagnosed due to its unusual presentation and treated actively with surgery and chemotherapy, achieving a relatively favorable outcome.

6.
World J Gastroenterol ; 19(45): 8366-72, 2013 Dec 07.
Article in English | MEDLINE | ID: mdl-24363529

ABSTRACT

AIM: To determine the role of the fecal immunochemical test (FIT), used to evaluate fecal hemoglobin concentration, in the prediction of histological grade and risk of colorectal tumors. METHODS: We enrolled 17881 individuals who attended the two-step colorectal cancer screening program in a single hospital between January 2010 and October 2011. Colonoscopy was recommended to the participants with an FIT of ≥ 12 ngHb/mL buffer. We classified colorectal lesions as cancer (C), advanced adenoma (AA), adenoma (A), and others (O) by their colonoscopic and histological findings. Multiple linear regression analysis adjusted for age and gender was used to determine the association between the FIT results and colorectal tumor grade. The risk of adenomatous neoplasia was estimated by calculating the positive predictive values for different FIT concentrations. RESULTS: The positive rate of the FIT was 10.9% (1948/17881). The attendance rate for colonoscopy was 63.1% (1229/1948). The number of false positive results was 23. Of these 1229 cases, the numbers of O, A, AA, and C were 759, 221, 201, and 48, respectively. Regression analysis revealed a positive association between histological grade and FIT concentration (ß = 0.088, P < 0.01). A significant log-linear relationship was found between the concentration and positive predictive value of the FIT for predicting colorectal tumors (R(2) > 0.95, P < 0.001). CONCLUSION: Higher FIT concentrations are associated with more advanced histological grades. Risk prediction for colorectal neoplasia based on individual FIT concentrations is significant and may help to improve the performance of screening programs.


Subject(s)
Adenoma/blood , Biomarkers, Tumor/analysis , Colorectal Neoplasms/blood , Feces/chemistry , Hemoglobins/analysis , Adenoma/pathology , Biopsy , Colonoscopy , Colorectal Neoplasms/pathology , False Positive Reactions , Female , Humans , Immunohistochemistry , Linear Models , Male , Middle Aged , Neoplasm Grading , Predictive Value of Tests , Retrospective Studies , Risk Factors
7.
J Chin Med Assoc ; 76(6): 325-9, 2013 Jun.
Article in English | MEDLINE | ID: mdl-23602215

ABSTRACT

BACKGROUND: The Taiwanese government has proposed a population-based colorectal tumor detection program for the average-risk population. This study's objectives were to understand the outcomes of these screening policies and to evaluate the effectiveness of the program. METHODS: We compared two databases compiled in one medical center. The "policy-promoted cancer screening" (PPS) database was built on the basis of the policy of the Taiwan Bureau of National Health Insurance for cancer screening. The "health promotion service" (HPS) database was built to provide health check-ups for self-paid volunteers. Both the PPS and HPS databases employ the immunochemical fecal occult blood test (iFOBT) and colonoscopy for colorectal tumor screening using different strategies. A comparison of outcomes between the PPS and HPS included: (1) quality indicators-compliance rate, cecum reaching rate, and tumor detection rate; and (2) validity indicators-sensitivity, specificity, positive, and negative predictive values for detecting colorectal neoplasms. RESULTS: A total of 10,563 and 1481 individuals were enrolled in PPS and HPS, respectively. Among quality indicators, there was no statistically significant difference in the cecum reaching rate between PPS and HPS. The compliance rates were 56.1% for PPS and 91.8% for HPS (p < 0.001). The advanced adenoma detection rates of PPS and HPS were 1.0% and 3.6%, respectively (p < 0.01). The carcinoma detection rates were 0.3% and 0.4%, respectively (p = 0.59). For validity indicators, PPS provides only a positive predictive value for colorectal tumor detection. HPS provides additional validity indicators, including sensitivity, specificity, positive predictive value, and negative predictive value, for colorectal tumor screening. CONCLUSION: In comparison with the outcomes of the HPS database, the screening efficacy of the PPS database is even for detecting colorectal carcinoma but is limited in detecting advanced adenoma. HPS may provide comprehensive validity indicators and will be helpful in adjusting current policies for improving screening performance.


Subject(s)
Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Health Promotion , Aged , Colonoscopy , Humans , Middle Aged , Occult Blood , Retrospective Studies
8.
BMC Gastroenterol ; 12: 124, 2012 Sep 14.
Article in English | MEDLINE | ID: mdl-22978826

ABSTRACT

BACKGROUND: Gastric subepithelial tumors are usually asymptomatic and observed incidentally during endoscopic examination. Although most of these tumors are considered benign, some have a potential for malignant transformation, particularly those originating from the muscularis propria layer. For this type of tumor, surgical resection is the standard treatment of choice. With recent advent of endoscopic resection techniques and devices, endoscopic submucosal dissection (ESD) has been considered as an alternative way of treatment. The aim of this study is to demonstrate the feasibility of a modified ESD technique with enucleation for removal of gastric subepithelial tumors originating from the muscularis propria layer, and to evaluate its efficacy and safety. METHODS: From November 2009 to May 2011, a total of 16 patients received a modified ESD with enucleation for their subepithelial tumors. All tumors were smaller than 5 cm and originated from the muscularis propria layer of the stomach, as shown by endoscopic ultrasonography (EUS). The procedure was conducted with an insulated-tip knife 2. Patient's demographics, tumor size and pathological diagnosis, procedure time, procedure-related complication, and treatment outcome were reviewed. RESULTS: Fifteen of the sixteen tumors were successful complete resection. The mean tumor size measured by EUS was 26.1 mm (range: 20-42 mm). The mean procedure time was 52 minutes (range: 30-120 minutes). Endoscopic features of the 4 tumors were pedunculated and 12 were sessile. Their immunohistochemical diagnosis was c-kit (+) stromal tumor in 14 patients and leiomyoma in 2 patients. There was no procedure-related perforation or overt bleeding. During a mean follow up duration of 14.8 months (range: 6-22 months), there was no tumor recurrence or metastasis. CONCLUSIONS: Using a modified ESD with enucleation for treatment of gastric subepithelial tumors originating from the muscularis propria layer and larger than 2 cm, complete resection can be successfully performed without serious complication. It is a safe and effective alternative to surgical therapy for these tumors of 2 to 5 cm in size.


Subject(s)
Dissection/methods , Gastrointestinal Stromal Tumors/surgery , Gastroscopy/methods , Leiomyoma/surgery , Stomach Neoplasms/surgery , Adult , Aged , Endosonography/methods , Female , Gastrointestinal Stromal Tumors/diagnostic imaging , Gastrointestinal Stromal Tumors/pathology , Humans , Immunohistochemistry , Leiomyoma/diagnostic imaging , Leiomyoma/pathology , Male , Middle Aged , Operative Time , Stomach Neoplasms/diagnostic imaging , Stomach Neoplasms/pathology , Treatment Outcome
9.
Case Rep Gastroenterol ; 6(2): 254-9, 2012 May.
Article in English | MEDLINE | ID: mdl-22679414

ABSTRACT

Pancreatic pseudoaneurysm is a rare vascular complication of chronic pancreatitis resulting from erosion of the pancreatic or peripancreatic artery into a pseudocyst that is identified as a pulsating vascular malformation which may lead to lethal complications if left untreated. Many publications in the literature consider angiography as the first step in the management of pancreatic pseudoaneurysm to stabilize the patient's critical condition; it should be followed by surgical intervention as the definite treatment. We report a rare case of pancreatic pseudoaneurysm rupture with hemodynamic embarrassment in a critical patient with multiple comorbid conditions and poor risk for surgery who responded dramatically to angiographic management as a single therapeutic modality without further surgical intervention. The results observed in our patient suggest that pancreatic pseudoaneurysm may be successfully managed with angiography only and that not all cases require surgical intervention. This is particularly relevant in critically ill patients in whom surgical intervention would be unfeasible.

10.
Hepatol Res ; 42(8): 774-81, 2012 Aug.
Article in English | MEDLINE | ID: mdl-22469194

ABSTRACT

AIM: In spite of numerous studies on the association between diabetes mellitus (DM) and hepatocellular carcinoma (HCC), the results are inconsistent and whether and how the effect of DM on the risk for HCC is modified or synergistically exerted by hepatitis virus infection are still unclear. We aimed to elucidate and quantify the effect modification and synergism between hepatitis B and C virus (HBV and HCV, respectively) and DM leading to the risk for HCC and also assess the independent contribution of DM to the risk for HCC at population level (population attributable fraction) in a high prevalence area of hepatitis virus infection. METHODS: A hospital-based case-control study was conducted from one medical center. Information on hepatitis B and C virus infection and DM status (defined by 8-h fasting blood glucose level ≥126 mg/dL, current use of oral hyperglycemic agent or insulin injection) was collected to assess interaction of hepatitis virus infection with DM on the risk for HCC. RESULTS: The association between DM and the risk for HCC was significant regardless of the presence of HBV infection, whereas a significant positive association was noted for HCV negativity. Synergistic interactions between DM and HBV infection were significant. In the absence of both hepatitis virus infections, the independent effect of DM accounted for 7.5% risk for HCC from the underlying population. CONCLUSION: The effect of DM on the risk for developing HCC is higher in HCV negative patients and synergistic with HBV infection. The independent effect of DM provides a new insight to the prevention of HCC other than virus-related mechanism.

11.
Case Rep Gastroenterol ; 5(3): 597-601, 2011 Sep.
Article in English | MEDLINE | ID: mdl-22110421

ABSTRACT

Enteroclysis was first used to diagnose small bowel obstruction in 1996. However, nasojejunal intubation required during enteroclysis causes discomfort to the patient. Triphasic computed tomography (CT) enterography, a noninvasive procedure that does not require intubation, was found to be an efficient method to diagnose small bowel lesions. We describe our experience of using triphasic CT enterography with polyethylene glycol (PEG) for diagnosing renal cell carcinoma (RCC) metastases to the small intestine. RCC can metastasize to many organs and can cause variable clinical presentations. We report the case of a 56-year-old man with RCC who had psoas muscle involvement and lung metastasis. The patient presented with melena and intermittent abdominal pain. Two conventional CT and small bowel series examinations had shown no obstructive lesion in the small intestine. However, triphasic CT enterography with PEG detected two enhanced masses suggestive of small bowel metastasis. The patient underwent laparotomy and segmental resection of the jejunum with primary anastomosis. Histologic examination was compatible with RCC. This is the first report where RCC metastasis to the small bowel was diagnosed using triphasic CT enterography. Our study emphasizes the importance of triphasic CT enterography in cases of obscure gastrointestinal bleeding, especially in patients suspected of having small bowel metastasis.

12.
Case Rep Gastroenterol ; 5(2): 267-71, 2011 May.
Article in English | MEDLINE | ID: mdl-21887127

ABSTRACT

Although gastric polyp is usually an incidental endoscopic finding, large-sized polyps can cause symptoms ranging from epigastralgia to bleeding from ulcerated polyps and gastric outlet obstruction. Although the gold standard of treatment is removal of the polyp either through endoscopic polypectomy or surgical excision, complications associated with these procedures cannot be ignored. The risk becomes a major concern for patients at high risk for surgery when complications arise. We describe a debilitated 74-year-old woman who presented with early satiety, intermittent postprandial nausea and vomiting for three months. Upper endoscopy revealed a 2.5 cm pedunculated polyp over the gastric antrum causing intermittent obstruction. Considering her high risk for polypectomy, detachable snaring was performed without polypectomy in an outpatient setting. The patient was complication-free with complete relief of obstructive symptoms one week after the procedure. Subsequent follow-ups showed satisfactory healing without signs of mucosal disruption or recurrence. The results suggest that detachable snaring without polypectomy may be a therapeutic option for high-risk patients with benign symptomatic gastric polyps.

13.
Phytother Res ; 25(7): 990-9, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21213358

ABSTRACT

Triptolide (C38H42O6N2, TP, a diterpene triepoxide derived from Tripterygium wilfordii Hook F.), is a potent immunosuppresive and antiinflammatory agent. The present study investigated whether TP exerted antihepatofibrotic effects in vitro and in vivo. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with tumor necrosis factor-α (TNF-α) or transforming growth factor (TGF)-ß1. The inhibitory effects of TP on the nuclear factor-κB (NFκB) signaling cascade and fibrosis markers, including α-smooth muscle actin (α-SMA) and collagen, were assessed. An in vivo therapeutic study was conducted in dimethylnitrosamine (DMN)-treated rats. The rats were randomly assigned to one of three groups: control rats, DMN rats receiving vehicle only and DMN rats receiving TP (20 µg/kg). Treatment was given by gavage twice daily for 3 weeks starting 1 week after the start of DMN administration. TP (5-100 nM) concentration-dependently inhibited the NFκB transcriptional activity induced by TNF-α, lipopolysaccharide and phorbol 12-myristate 13-acetate in HSC-T6 cells. In addition, TP also suppressed TNF-α and TGF-ß1-induced collagen deposition and α-SMA secretion in HSC-T6 cells. In vivo, TP treatment significantly reduced hepatic fibrosis scores, collagen contents, IL-6 and TNF-α levels, and the number of α-SMA and NFκB-positive cells in DMN rats. The results showed that TP exerted antifibrotic effects in both HSC-T6 cells and DMN rats.


Subject(s)
Diterpenes/pharmacology , Hepatic Stellate Cells/drug effects , Liver Cirrhosis, Experimental/drug therapy , Phenanthrenes/pharmacology , Actins/metabolism , Animals , Cell Line , Collagen/metabolism , Dimethylnitrosamine/adverse effects , Epoxy Compounds/pharmacology , Interleukin-6/metabolism , Liver/drug effects , Liver/pathology , Liver Cirrhosis, Experimental/pathology , Male , NF-kappa B/metabolism , Rats , Rats, Sprague-Dawley , Transforming Growth Factor beta1/pharmacology , Tripterygium/chemistry , Tumor Necrosis Factor-alpha/pharmacology
14.
Int J Radiat Oncol Biol Phys ; 78(1): 188-93, 2010 Sep 01.
Article in English | MEDLINE | ID: mdl-20133077

ABSTRACT

PURPOSE: We report our preliminary experience of combining sunitinib and helical tomotherapy in patients with advanced HCC. METHODS AND MATERIALS: Records of patients with advanced hepatocellular carcinoma (HCC) treated with helical tomotherapy and sunitinib after radiation therapy (RT) from March 2007 to August 2008 were retrospectively reviewed. We report acute toxicities, radiologic response, serial alpha-fetoprotein (AFP) kinetics, and survival. RESULTS: Of 23 evaluable patients, 60% had >or=2 hepatic lesions, extrahepatic disease was present in 5 (21.7%), and all received 2 tablets (25 mg) of sunitinib at least 1 week before, during, and 2 weeks after RT. Thirteen patients continued maintenance sunitinib after RT until disease progression. Hypofractionated RT with a median target dose of 52.5 Gy/15 fractions was delivered. An objective response was achieved in 74% of patients. The 1-year survival rate was 70%, with median survival of 16 months. Multivariate analysis showed that maintenance sunitinib was the most significant factor for survival. The time to progression was 10 months in the maintenance group compared with 4 months in the control group. Eighteen out of 21 patients with elevated AFP (85.7%) had >or=50% decline of AFP within 2 months after RT. There were three episodes of upper gastrointestinal bleeding and one episode of pancreatitis; 10 patients had >or=Grade 2 elevation of liver enzymes, and 15 had >or=Grade 2 thrombocytopenia. CONCLUSIONS: These preliminary results suggest that sunitinib and helical tomotherapy yield high Response Evaluation Criteria in Solid Tumors (RECIST) and AFP response rates in advanced HCC with an acceptable safety profile. Maintenance sunitinib after RT potentially prolongs survival. A randomized trial is warranted.


Subject(s)
Angiogenesis Inhibitors/therapeutic use , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular , Indoles/therapeutic use , Liver Neoplasms , Pyrroles/therapeutic use , Radiotherapy, Intensity-Modulated/methods , Adult , Aged , Analysis of Variance , Angiogenesis Inhibitors/adverse effects , Antineoplastic Agents/adverse effects , Carcinoma, Hepatocellular/blood supply , Carcinoma, Hepatocellular/drug therapy , Carcinoma, Hepatocellular/radiotherapy , Combined Modality Therapy/adverse effects , Combined Modality Therapy/methods , Dose Fractionation, Radiation , Female , Gastrointestinal Hemorrhage/etiology , Humans , Indoles/adverse effects , Liver Neoplasms/blood supply , Liver Neoplasms/drug therapy , Liver Neoplasms/radiotherapy , Male , Middle Aged , Pyrroles/adverse effects , Radiotherapy, Intensity-Modulated/adverse effects , Retrospective Studies , Sunitinib , Survival Analysis , Treatment Outcome , alpha-Fetoproteins/metabolism
15.
J Gastroenterol Hepatol ; 24(8): 1375-9, 2009 Aug.
Article in English | MEDLINE | ID: mdl-19467140

ABSTRACT

BACKGROUND AND AIM: Our aim was to determine associations between metabolic risk factors and erosive esophagitis. METHODS: In this retrospective case-control study, diagnosis of erosive esophagitis was based on the Los Angeles classification. Endoscopic findings in subjects with erosive esophagitis were reviewed by two experienced endoscopists and those with agreement of diagnosis were enrolled for study. Body mass index (BMI), abdominal girdle, blood pressure, and serum triglyceride, glucose, and beta-lipoprotein levels were compared between individuals with and without erosive esophagitis. Multivariate binary logistic regression analysis was used to identify independent metabolic risk factors associated with erosive esophagitis. RESULTS: Between October 2004 and April 2006, 518 of 4206 subjects who underwent endoscopic examination were diagnosed as having erosive esophagitis. After expert review, 427 (male : female = 365:62) individuals met the study criteria of having erosive esophagitis (10.5%). Compared with age- and gender-matched controls, patients with erosive esophagitis had significantly higher BMI, abdominal girdle, blood pressure, and triglyceride levels, and lower levels of high density lipoprotein (HDL) cholesterol (P < 0.05). More subjects with metabolic syndrome had erosive esophagitis than without metabolic syndrome (OR: 1.76, 95% CI: 1.27-2.44, P = 0.001). Multivariate logistic regression analysis revealed that central obesity (OR: 1.41, 95% CI: 05-1.89, P = 0.023) and hypertriglyceridemia (OR: 1.57, 95% CI: 1.19-2.13, P = 0.004) were significantly associated with erosive esophagitis. CONCLUSIONS: Obesity and hypertriglyceridemia, which are key components of metabolic syndrome, are moderate independent risk factors for erosive esophagitis.


Subject(s)
Esophagitis/etiology , Hypertriglyceridemia/complications , Metabolic Syndrome/complications , Obesity/complications , Adult , Biomarkers/blood , Blood Pressure , Body Mass Index , Case-Control Studies , Cholesterol, HDL/blood , Esophagitis/blood , Esophagitis/epidemiology , Esophagitis/pathology , Esophagitis/physiopathology , Esophagoscopy , Female , Humans , Hypertension/complications , Hypertension/physiopathology , Hypertriglyceridemia/blood , Hypertriglyceridemia/epidemiology , Logistic Models , Male , Metabolic Syndrome/blood , Metabolic Syndrome/epidemiology , Metabolic Syndrome/physiopathology , Middle Aged , Obesity/epidemiology , Obesity/physiopathology , Odds Ratio , Prevalence , Retrospective Studies , Risk Assessment , Risk Factors , Taiwan/epidemiology , Triglycerides/blood , Waist Circumference
16.
Mol Carcinog ; 48(5): 420-31, 2009 May.
Article in English | MEDLINE | ID: mdl-18767070

ABSTRACT

Phloretin (Ph), which can be obtained from apples, apple juice, and cider, is a known inhibitor of the type II glucose transporter (GLUT2). In this study, real-time PCR analysis of laser-capture microdissected (LCM) human hepatoma cells showed elevated expression (>5-fold) of GLUT2 mRNA in comparison with nonmalignant hepatocytes. In vitro and in vivo studies were performed to assess Ph antitumor activity when combined with paclitaxel (PTX) for treatment of human liver cancer cells. Inhibition of GLUT2 by Ph potentiated the anticancer effects of PTX, resensitizing human liver cancer cells to drugs. These results demonstrate that 50-150 microM Ph significantly potentiates DNA laddering induced in Hep G2 cells by 10 nM PTX. Activity assays showed that caspases 3, 8, and 9 are involved in this apoptosis. The antitumor therapeutic efficacy of Ph (10 mg/kg body weight) was determined in cells of the SCID mouse model that were treated in parallel with PTX (1 mg/kg body weight). The Hep G2-xenografted tumor volume was reduced more than fivefold in the Ph + PTX-treated mice compared to the PTX-treated group. These results suggest that Ph may be useful for cancer chemotherapy and chemoprevention.


Subject(s)
Antineoplastic Agents, Phytogenic/pharmacology , Apoptosis/drug effects , Malus/chemistry , Paclitaxel/pharmacology , Phloretin/pharmacology , Animals , Base Sequence , Caspases/metabolism , Cell Line, Tumor , DNA Primers , Enzyme Activation , Glucose Transporter Type 2/genetics , Humans , Immunohistochemistry , Mice , Mice, SCID , Phloretin/isolation & purification , Polymerase Chain Reaction , RNA, Messenger/antagonists & inhibitors , RNA, Messenger/genetics
17.
J Gastrointestin Liver Dis ; 17(2): 203-6, 2008 Jun.
Article in English | MEDLINE | ID: mdl-18568143

ABSTRACT

We report two cases of hepatobiliary cystadenoma. Case 1. A 58-year-old male presented with dull abdominal pain and recurrent jaundice. Abdominal echo revealed biliary tracts dilatation; ERCP revealed amorphous filling defect inside the dilated CBD, a cystic tumor in the left lobe communicated with bile duct was disclosed by MRI/MRCP. He received left lobectomy and microscopic findings proved hepatobiliary cystadenoma. Case 2. Abdominal ultrasound detected a huge cystic tumor over the left hepatic lobe in a 69-year-old male. Abdominal CT revealed a large cystic mass lesion over the left hepatic lobe with septations and multiple papillary projections. A liver biopsy was performed and microscopic findings proved biliary cystadenoma. An abdominal ultrasound 6 months later revealed intrahepatic spread of cystadenocarcinoma over both lobes. Hepatobiliary cystadenoma is a rare benign cystic tumor of the liver. It usually occurs in middle-aged women and can undergo malignant change and become lethal. It is frequently misdiagnosed and should be suspected when a uni- or multilocular cystic lesion with papillary infoldings is detected in the liver by CT or ultrasound. ERCP/MRCP have a role in pre-operative evaluation. Elevated serum and cystic fluid tumor markers CA19-9 are only seen in some patients; cystic fluid cytology does not provide adequate diagnostic aid. Its morphologic features maybe confused with biliary papillomatosis or IPMN of bile duct. Its prognosis is excellent after complete resection.


Subject(s)
Bile Ducts, Intrahepatic , Biliary Tract Neoplasms/diagnosis , Cystadenoma/diagnosis , Liver Neoplasms/diagnosis , Aged , Biliary Tract Neoplasms/surgery , Biopsy , Cholangiopancreatography, Endoscopic Retrograde , Cholecystectomy , Cystadenoma/surgery , Diagnosis, Differential , Follow-Up Studies , Hepatectomy , Humans , Liver Neoplasms/surgery , Magnetic Resonance Imaging , Male , Middle Aged , Tomography, X-Ray Computed
18.
World J Gastroenterol ; 12(43): 7029-32, 2006 Nov 21.
Article in English | MEDLINE | ID: mdl-17109500

ABSTRACT

AIM: To elucidate the different serological reactions to H pylori using the immunoblotting technique for further understanding of its pathogenic role in gastric cancer. METHODS: A total of 54 patients were divided into two groups after upper gastrointestinal endoscopy: normal control group (25 patients) and gastric cancer group (29 patients). Both groups were further divided into H pylori (+) and H pylori (-) subgroups based on the results of CLO test, Giemsa staining and culture. Sera were further analyzed with the immunoblotting technique (HelicoBlot 2.0, Genelabs Diagnostics, Singapore). RESULTS: The positive rate of the immunoblotting test was as high as 88.9% in the H pylori (-) gastric cancer group and only 14.3% in the H pylori (-) normal control group with a statistically significant difference. CONCLUSION: The prevalence of H pylori infection is higher in gastric cancer patients than in the normal controls, suggesting that H pylori may play a role in the pathogenesis of gastric cancer.


Subject(s)
Blotting, Western/methods , Helicobacter Infections/complications , Helicobacter pylori/pathogenicity , Stomach Neoplasms/microbiology , Adult , Aged , Antibodies, Bacterial/immunology , Case-Control Studies , Female , Helicobacter Infections/diagnosis , Helicobacter Infections/epidemiology , Helicobacter pylori/immunology , Humans , Immunoglobulin G/immunology , Male , Middle Aged , Prevalence , Stomach Neoplasms/diagnosis
19.
Cancer J ; 12(3): 194-200, 2006.
Article in English | MEDLINE | ID: mdl-16803677

ABSTRACT

PURPOSE: This study aimed to quantify the full clinical courses characterized by alternating transitions between remission and relapses for small hepatocellular carcinomas treated by percutaneous ethanol injection, and to ascertain the significant predictors for the remission, relapse, and finally to metastasis or death. PATIENTS AND METHODS: A three-state Markov process was used to depict full clinical course. A total of 108 patients who underwent nonsurgical therapy as the first choice of treatment were derived from consecutive clinical series of patients registered in one medical center renowned for their use of percutaneous ethanol injection. RESULTS: We found that approximately 57.19% (95% confidence interval [CI]: 39.82%, 74.56%) patients were promptly responsive to initial treatment, whereas 43.81% had delayed response or were resistant to treatment. The rate of relapse (per month) was higher than the rate of remission (19.20% [95% CI: 15.36%, 23.04%] vs. 13.82% [95% CI: 10.72%, 16.93%]). The results from the multivariate analysis indicate that the significant predictors for the full clinical courses are total bilirubin, alpha-fetoprotein, prothrombin time, globulin, tumor morphology, and alkaline phosphatase. CONCLUSIONS: A three-state remission-relapse-death model was proposed to quantify and ascertain the predictors for the multistate disease progression of small hepatocellular carcinomas treated by percutaneous ethanol injection. This model captures the risk of recurrence of tumor as well as the primary endpoint of death.


Subject(s)
Carcinoma, Hepatocellular/drug therapy , Central Nervous System Depressants/therapeutic use , Ethanol/therapeutic use , Liver Neoplasms/drug therapy , Neoplasm Recurrence, Local/drug therapy , Administration, Cutaneous , Aged , Antineoplastic Agents/therapeutic use , Carcinoma, Hepatocellular/mortality , Carcinoma, Hepatocellular/pathology , Female , Humans , Liver Neoplasms/mortality , Liver Neoplasms/pathology , Male , Markov Chains , Middle Aged , Neoplasm Metastasis , Neoplasm Recurrence, Local/pathology , Prognosis , Remission Induction , Survival Rate , Treatment Outcome , alpha-Fetoproteins/analysis
20.
J Biomed Sci ; 13(3): 403-18, 2006 May.
Article in English | MEDLINE | ID: mdl-16604421

ABSTRACT

Tumor necrosis factor-alpha (TNF-alpha) plays a central role in cellular necrosis, apoptosis, organ failure, tissue damage, inflammation and fibrosis. These processes, occurring in liver injury, may lead to cirrhosis. Thalidomide, alpha-N-phthalidoglutarimide, (C(13)H(10)N(2))(4), has been shown to have immunomodulatory and anti-inflammatory properties, possibly mediated through its anti-TNF-alpha effect. In this study, we investigated the in vitro and in vivo effects of thalidomide on hepatic fibrosis. A cell line of rat hepatic stellate cells (HSC-T6) was stimulated with transforming growth factor-beta1 (TGF-beta1) or TNF-alpha. The inhibitory effects of thalidomide on the NFkappaB signaling cascade and fibrosis markers including alpha-smooth muscle actin (alpha-SMA) and collagen, were assessed. An in vivo therapeutic study was conducted in dimethylnitrosamine (DMN)-treated rats, which were randomly assigned to 1 of 4 groups: vehicle (0.7% carboxyl methyl cellulose, CMC), thalidomide (40 mg/kg), thalidomide (200 mg/kg), or silymarin (50 mg/kg), each given by gavage twice daily for 3 weeks starting after 1 week of DMN administration. Thalidomide (100-800 nM) concentration-dependently inhibited NFkappaB transcriptional activity induced by TNF-alpha, including IKKalpha expression and IkappaBalpha phosphorylation in HSC-T6 cells. In addition, thalidomide also suppressed TGF-beta1-induced alpha-SMA expression and collagen deposition in HSC-T6 cells. Fibrosis scores of livers from DMN-treated rats receiving high dose of thalidomide (0.89 +/- 0.20) were significantly reduced in comparison with those of DMN-treated rats receiving vehicle (1.56 +/- 0.18). Hepatic collagen contents of DMN rats were also significantly reduced by either thalidomide or silymarin treatment. Immunohistochemical double staining results showed that alpha-SMA- and NFkappaB-positive cells were decreased in the livers from DMN rats receiving either thalidomide or silymarin treatment. In addition, real-time PCR analysis indicated that hepatic mRNA expressions of TGF-beta1, alpha-SMA, collagen 1alpha2, TNF-alpha and iNOS genes were attenuated by thalidomide treatment. In conclusion, our results showed that thalidomide inhibited activation of HSC-T6 cells by TNF-alpha and ameliorated liver fibrosis in DMN-intoxicated rats.


Subject(s)
Dimethylnitrosamine/pharmacology , Liver/drug effects , Thalidomide/pharmacology , Actins/metabolism , Animals , Collagen/metabolism , Fibrosis/pathology , I-kappa B Proteins/metabolism , Immunosuppressive Agents/pharmacology , Liver/cytology , Liver Cirrhosis, Experimental/therapy , Muscle, Smooth/metabolism , NF-KappaB Inhibitor alpha , NF-kappa B/metabolism , Rats , Transforming Growth Factor beta/metabolism , Transforming Growth Factor beta1 , Tumor Necrosis Factor-alpha/metabolism
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