Shou-Dong Lee

Efficacy of non-selective β-blockers as adjunct to endoscopic prophylactic treatment for gastric variceal bleeding: A randomized controlled trial

BACKGROUND & AIMS Gastric variceal obturation (GVO) therapy is the current treatment of choice for gastric variceal bleeding (GVB). However, the efficacy of non-selective β-blockers (NSBB) in the secondary prevention of GVB is still debatable. This study aimed at evaluating the efficacy of additional NSBB to repeated GVO in the secondary prevention of GVB. METHODS From April 2007 to March 2011, 95 patients with GVB after primary hemostasis using GVO were enrolled. Repeated GVO were performed until GV eradication. Forty-eight and 47 patients were randomized into the GVO alone group (Group A) and the GVO+NSBB group (Group B), respectively. Primary outcomes in terms of re-bleeding and overall survival were analyzed by multivariate analysis. RESULTS After a mean follow-up of 18.10 months in group A, 26 patients bled and 20 died. In group B, 22 patients bled and 22 died after a mean follow-up of 20.29 months. The overall re-bleeding and survival rates analyzed by the Kaplan-Meier method were not different between the two groups (p=0.336 and 0.936, respectively). The model of end-stage liver disease (MELD) score and main portal vein thrombosis (MPT) were independent determinants of re-bleeding while MPT and re-bleeding were independent factors of mortality by time-dependent Cox-regression model. Asthenia was the most common adverse event and was higher in group B (p<0.001). CONCLUSIONS Adding NSBB therapy to repeated GVO provides no benefit for the secondary prevention of bleeding and mortality in patients with GVB.

The influence of verapamil and nifedipine on hepatic indocyanine green clearance in patients with HBsAg-positive cirrhosis and ascites

The influence of verapamil and nifedipine on hepatic indocyanine green kinetics was studied in 12 patients with HBsAg‐positive cirrhosis and ascites. Hepatic clearance and its two biologic determinants, hepatic blood flow and metabolic activity (intrinsic clearance [maximum velocity/metabolite elimination rate constant, or Vmax/km]), were determined from hepatic indocyanine green elimination at steady state in patients with cirrhosis. Acute intravenous administration 10 mg verapamil significantly increased the hepatic indocyanine green blood flow (p < 0.05), but significantly decreased the hepatic clearance (p < 0.05), extraction ratio (p < 0.05) and Vmax/km (p < 0.05). However, acute sublingual administration of 10 mg nifedipine resulted in no significant change in any parameters of hepatic elimination function. These results show that verapamil, but not nifedipine, might impair the transhepatic extraction activity of hepatocytes in patients with HBsAg‐positive cirrhosis and ascites.

Intracerebroventricular Ghrelin Enhances Non-Nutrient Semiliquid Gastric Emptying in Fasted Conscious Rats

Background and Aims: Although peripheral and central impacts of ghrelin on food intake as well as the peripheral influence of ghrelin on gut motility are well known, the central effect of acyl ghrelin on gastric motility in rats remains uninvestigated. We aimed, first, to establish a stable, conscious rat model to measure non-nutrient, semiliquid gastric emptying, and second, to investigate the effect of intracerebroventricular (ICV) injection of acyl ghrelin on gastric emptying. Methods: We investigated the temporal effects of charcoal, non-nutrient, semiliquid gastric emptying in 16-h food-deprived, conscious rats chronically implanted with ICV cannula. Then, we studied the dose-response effect of ICV acyl ghrelin on charcoal, non-nutrient, semiliquid gastric emptying in fasted conscious rats. Results: Stable, temporal effects of charcoal, non-nutrient, semiliquid gastric emptying in chronically ICVcannulated, conscious rats were created first, and 30-min non-nutrient, semiliquid gastric emptying was selected among them for the subsequent experiments. ICV-injected ghrelin (0.1, 0.3 and 1.0 nmol/rat) enhanced 30-min nonnutrient, semiliquid gastric emptying in fasted conscious rats. Conclusions: We established a reliable, in vivo animal model to measure the effects of peptides or chemicals in the forebrain on gastric motility. ICV administration of ghrelin effectively enhances 30-min non-nutrient, semiliquid gastric emptying in fasted conscious rats. The optimal doses of ghrelin at 0.1 and 0.3 nmol on gastric emptying could be chosen in the future to study the interactions between ghrelin and other gut motility inhibitory peptides, such as corticotropin-releasing factor peptide families and cholecystokinin.

Radiotherapy is Effective in the Treatment of Hepatocellular Carcinoma with Right Atrium Invasion - Report of A Case

Hepatocellular carcinoma (HCC) is a common malignant neoplasm in East Asia. HCC has the tendency to invade vessels, mainly the portal venous system. Right atrium metastasis through venous invasion is a rare condition with grave prognosis. Surgical resection of intra-atrial tumors is technically difficult and it is too invasive for the seriously ill patients. Here, we present a 58-year-old male patient of HCC with hepatic veins, inferior vena cava, and right atrium invasion, who received well-designed three-dimensional conformal radiotherapy (totally 60 Gy 33 fractions), followed by one course of intra-arterial chemotherapy with cisplatin (65 mg/m2 infusion for 6 hours) and 5-fluorouracil (2,200 mg/m2 infusion for 24 hours). Serum alpha-fetoprotein was markedly decreased, and size of tumor thrombus was shrinkage. This patient survived for 15 more months. Therefore, for HCC patients with right atrium metastasis, three-dimensional conformal radiotherapy plus chemotherapy may be an effective salvage treatment.

Splanchnic Hyposensitivity to Glypressin in a Hemorrhage-Transfused Rat Model of Portal Hypertension: The Role of Tumor Necrosis Factor-α

Introduction: Vasopressin and its long-acting analogue, glypressin given during hemorrhage are less effective than when given during a stable state in portal hypertensive or cirrhotic conditions, that is, the so-called hyposensitivity phenomenon. According to the previous studies, nitric oxide has been ascribed to participate in the hyposensitivity. Tumor necrosis factor-α stimulates nitric oxide synthesis and is enhanced during acute hemorrhage. However, its role in portal hypertension with acute hemorrhage and vascular hyporesponsiveness remains unclear. Materials and Methods: Portal hypertension was induced by partial portal vein ligation (PVL) on male Spraque-Dawley rats. Fourteen days after PVL, portal and systemic hemodynamic parameters were evaluated then rats were divided into without-bleeding and with-bleeding groups. In rats with a hypotensive hemorrhage, 4.5ml of blood was withdrawn with an infusion/withdrawal pump, of which 50% was re-infused. The without-bleeding groups received no manipulation during the same period of time. Forty-five minutes later, the second hemodynamic measurement was performed, followed by glypressin (0.07mg/kg) infusion. Ten minutes after glypressin administration, the third hemodynamic study was done, followed by heparinized blood sampling for TNF-α measurements. Results: splanchnic hyposensitivity to glypressin was noted in portal hypetensive rats during acute hemorrhage. The level of tumor necrosis factor tended to be higher in rats with bleeding but not statistically significant (P=0.087). Conclusion: Tumor necrosis factor did not seem to play a significant role in splanchnic hyposensitivity to glypressin in portal hypertensive rats during acute hemorrhage. The influences of other endogenous vasoactive substances should also be considered.

Cronkhite-Canada Syndrome Associated with Gastric Carcinoid Tumor: Report of a Case

Cronkhite-Canada syndrome associated with gastric carcinoid tumor is very rare. We report a 76-year-old male presented with the chief complaints of epigastric pain and abdominal distention. His abnormal physical findings included alopecia, splitting of nail bed and generalized hyperpigmentation. Both upper gastrointestinal endoscopy and small intestinal series revealed multiple polypoid lesions in the stomach and the small intestine. In addition, a submucosal mass was also noted over the antrum. The histopathologic diagnosis of his gastric polyps was inflammatory polyps. Nervertheless, his gastric submucosal lesion was proved to be a carcinoid tumor. In addition, several sessile polyps were also found by colonoscopy. Although high serum level of gastrin-17, other special endocrine studies including levels of 24-hours urinary 5-HIAA excretion, plasma metanephrines, catecholamines, vanillylmandelic acid were all within normal limits. Surgical intervention was suggested, but he refused and was lost to follow-up for two years. Finally, he died from aspiration pneumonia with multiple organ failure due to protein-losing enteropathy and severe malnutrition.

Study of Salivary Function in Patients with Gastroesophageal Reflux Disease

Background and Aims: Saliva is one of the protective factors against gastroesophageal reflux. However, its actual role in patients with gastroesophageal reflux disease (GERD) particularly in terms of mucosal protection requires elucidation. Present study attempted to know the distinct protective role of saliva in esophageal mucosal protection. Materials and Methods: Fifty-four patients with typical GERD symptoms were consecutively enrolled. Personal history for non-steroidal anti-inflammatory drugs (NSAIDs) use, drinking tea, coffee and alcohol and smoking status was recorded. Stimulated saliva secretion was collected from each subject and its epidermal growth factor (EGF) and prostaglandin (PG) PGE1/PGE2 were determined. Upper gastrointestinal (GI) panendoscopy was performed to determine which patients had erosive esophagitis (EE) (n=27) and non-erosive reflux disease (NERD) (n=27). Helicobacter pylori (Hp) infection was checked and gastric juice pH was also assessed. Additionally, 27 non-GERD dyspeptic subjects were enrolled as controls for comparisons. Results: No significant differences were noted between EE patients and NERD patients in all variables including: age; gender; consumptions of tea, coffee or alcohol; smoking status; use of NSAIDs; Hp infection; gastric juice pH; rate of hiatal hernia; saliva secretion amount; salivary concentrations of PGE1/PGE2 and EGF, and salivary PGE1/ PGE2 and EGF output. However, EE patients had a significantly higher likelihood of hiatal hernia (48% vs. 19%), higher saliva secretion amount (1.82±0.67 vs. 1.33±0.36 ml/min) and salivary EGF output (3.8±1.5 vs. 2.5±0.9 ng/min) than controls (P＜0.05). Unlike EE patients, NERD patients did not have any significant differences from the control group for these variables. Conclusion: Patients with endoscopically evident EE had significantly increased salivary output. The result could not support that saliva play a critical role in protecting against the formation and severity of erosive esophagitis in our study model.

Combination Interferon α-2b Plus Ribavirin Therapy in Patients with Chronic Hepatitis C with Resistance to or Relapse after Interferon Monotherapy

Backgrounds and Objective: Previous studies in Caucasian patients showed treatment of chronic hepatitis C (CHC) patients with interferon and ribavirin was well tolerated, and produced a higher response rate in patients non-responded or relapsed to previous interferon monotherapy. However, it is unknown whether this conclusion can be extrapolated to patients with Chinese ethnic origin. The objective of this clinical trial is to evaluate the efficacy and tolerability of the combination of interferon α-2b plus Ribavirin in CHC patients who relapsed from or not responding to previous interferon therapy. Methods: Twenty-one Chinese CHC patients (19 males, 2 females, mean age: 47.5±9.2 years) who were non-responded or relapsed from previous interferon treatment received 3 MU of interferon α-2b, three times a week. plus ribavirin (1000 mg/day if body weight ＜75kg or 1200mg/day if body weight ＞75kg) for 24 weeks. Sustained virological response was defined as disappearance of serum HCV RNA at 24 weeks after the end of treatment by polymerase chain reaction assay. Results: Among 21 CHC patients, 20 patients completed the treatment and one withdrew from the study due to adverse event. Using intent-to-treat analysis, 11 patients (52%) had undetectable HCV RNA at the end of treatment. However, the sustained virological response was achieved in 2 patients (9.5%) 24 weeks after stopping of treatment. These two patients with sustained virological response were both genotype non-1 and pretreatment serum HCV RNA level ＜5 million copies/mL by branched DNA signal amplification assay, while the other 19 patients without sustained virological response were either HCV genotype 1 or pretreatment serum HCV RNA level ＞5 million copies/mL (P＜0.01). Conclusions: The sustained virological response rate was 9.5% in CHC patients non-responded or relapsed from previous interferon therapy and re-treated with interferon α-2b and ribavirin. HCV genotype and pretreatment HCV RNA level were important factors in predicting the retreatment sustained virological response.

Gastric Adenocarcinoma with Distant Cutaneous Metstasis: Report of a Case

We present a case of gastric adenocarcinoma with distant cutaneous metastasis initially on the neck. In the literature, the stomach has been shown to be a very rare source for metastatic tumors of the skin. Generally, skin metastasis most frequently occurs in the vicinity of the primary tumor. The neck is an unusual area for cutaneous metastasis of gastric adenocarcinoma. Primary skin tumors and a variety of dermal or subcutaneous lesions need to be differentially diagnosed. A definite diagnosis is made by performing tissue biopsy. Although skin metastasis indicates a very bad prognosis with rapid death, a high index of suspicion of cutaneous metastasis in various malignancies will enable the clinician to provide a more effective curative or palliative treatment.

Comparison of Different Ascitic Fluid Collection Methods for the Diagnosis of Spontaneous Bacterial Peritonitis in Cirrhotic Rats

To test for the best method of collecting ascitic fluid for the diagnosis of spontaneous bacterial peritonitis, carbon tetrachloride was administered in 120 rats for 6-18 weeks to induce infected cirrhotic ascites. Only 58 cirrhotic rats survived with ascitic fluid ≥3 ml for cell counts and cultures. These rats were randomly divided into 4 groups to compare the methods of ascitic fluid collection: group A, paracentesis; group B, direct laparotomy; group C, rapid decapitation followed by laparotomy; and group D, the intubation method. In 13 rats in which paracentesis was performed, ascitic fluid ≥3 ml was only successfully withdrawn in 7 rats and the amount of ascitic fluid was much less than they really had. Among 52 cirrhotic rats from which ascitic fluid was successfully withdrawn, 10 had infected ascites and 42 had sterile ascites. Of 42 rats with sterile cirrhotic ascites, ascitic fluid red cell counts were significantly greater in group B (3.88±4.12xl0^5cells/mm^3) than in group A (0.14±0.31x10^5cells/mm^3, p＜0.01), C (0.18±0.l9xl0^5cells/mm^3, p＜0.01) orD (0.12±0.1410^5cells/mm^3, p＜0.01). Ascitic fluid neutrophil counts and ratio were significantly greater in group B(1667±2336cells/mm^3, 15.0±19.3%) than in group C (76±103cells/mm^3, 4.2±3.0%, p＜0.05)orD (36±33 cells/mm^3, 3.8±2.8%, p＜0.05). Of 42 rats with sterile cirrhotic ascites, ascitic fluid neutrophil counts were greater than 250 cells / mm^3 in 0, 6, 1 and 0 of group A, B, C and D (p ＜0.01), respectively; and greater than 500 cells/mm^3 in 0, 5, 0and 0 (p＜0.0l). In conclusion, rapid decapitation followed by laparotomy and the intubation method are the two best methods in collecting ascitic fluid for the rat model of spontaneous bacterial peritonitis. Since blood specimens obtained from rapid decapitation followed by laparotomy are not aseptic, the intubation method may be the best way for further experiments when simultaneous collection of aseptic blood and ascitic fluid specimens is needed.