Immunohistochemical analyses of gastric stromal tumors in Taiwanese.

BACKGROUND AND PURPOSE: Gastrointestinal stromal tumors (GISTs), identified by the presence of CD117 (KIT), were previously classified as gastric and intestinal smooth muscle tumors prior to the availability of immunohistochemical methods. This study evaluated the percentage of GISTs previously diagnosed as gastric smooth muscle tumors in our hospital during an 11-year period. METHODS: A total of 81 surgically resected gastric smooth muscle tumor specimens from 81 patients were collected from January 1986 to December 1997. Immunohistochemical studies were performed on these tumors with antibodies of CD34, CD117, smooth muscle actin (SMA), S-100, and desmin. RESULTS: Among the 81 tumors, 74 (91.4%) were CD117-positive and were classified as GISTs. Among the 74 GISTs, CD34 was positive in 72 tumors (97.3%), SMA was positive in 12 tumors (16.2%), desmin was positive in 5 tumors (6.7%), and S-100 was positive in 4 tumors (5.4%). The 7 tumors classified as non-GISTs had the following immunohistochemical characteristics: 1 was a CD117-negative CD34-positive stromal tumor (GINST) [1/81, 1.2%]; 3 were schwannomas with strong S-100-positive characteristics (3/81, 3.7%); and 3 were smooth muscle tumors with both SMA- and desmin-positive status (3/81, 3.7%). No clear relationship between CD117 or CD34 expression and prognosis was found for these tumors. CONCLUSIONS: The majority (91.4%) of gastric tumors originally diagnosed as gastric smooth muscle tumors were GISTs, except for small groups of smooth muscle tumors and schwannomas.     

Increased endostatin/collagen XVIII expression correlates with elevated VEGF level and poor prognosis in hepatocellular carcinoma.

Liver is the primary source for collagen XVIII, the precursor of angiogenesis inhibitor, endostatin. However, the role of endostatin/collagen XVIII expression during liver carcinogenesis remains elusive. Therefore, we studied its expression in five hepatoma cell lines and 105 hepatocellular carcinoma specimens. The poorly differentiated hepatoma cell lines exhibited increased endostatin/collagen XVIII levels compared with the well-differentiated ones. In hepatoma tissues, endostatin/collagen XVIII expression was detected in various types of liver cells and was significantly stronger in adjacent nontumor tissues than that in tumors (P<0.001). Endostatin/collagen XVIII expression in nontumor tissues correlated with tumor stages (P=0.014) and expression of vascular endothelial growth factor (P=0.007), but not the stages of hepatic fibrosis (P>0.05). Kaplan-Meier analysis showed that patients with higher endostatin/collagen XVIII expression had significantly shorter overall survival (P=0.011) and disease-free survival (P=0.0034). Moreover, endostatin/collagen XVIII level was an independent prognostic factor for tumor recurrence (P=0.034) by multivariate analysis. In conclusion, increased endostatin/collagen XVIII expression correlated with hepatoma progression and predicted poor prognosis for patients with hepatocellular carcinoma.     

Endoscopic findings and management of dengue patients with upper gastrointestinal bleeding

There are 100 million cases of dengue infection, 500,000 cases of dengue hemorrhagic fever, and 25,000 deaths annually due to dengue worldwide. Gastrointestinal bleeding is the most common type of severe hemorrhage in dengue fever. However, there are no reports about the clinical applications of endoscopic therapy for upper gastrointestinal bleeding (UGI) in dengue patients. From June 17, 2002 to January 30, 2003, 1,156 patients with confirmed dengue virus infection were treated at Kaohsiung Chang Gung Memorial Hospital in Taiwan. We analyzed those patients who had received endoscopic therapy for UGI. The characteristic endoscopic findings, therapeutic courses, and amount of blood component transfused were collected from their charts for statistical analysis. Among the 1,156 dengue patients, 97 (8.4%) had complications of UGI bleeding during hospitalization. The endoscopic findings included hemorrhagic (and/or erosive) gastritis in 67% of the patients, gastric ulcer in 57.7%, duodenal ulcer in 26.8%, and esophageal ulcer in 3.1%. Of the 73 patients with peptic ulcer, 42 (57.5%) met the endoscopic criteria (recent hemorrhage) for endoscopic hemostasis therapy. Peptic ulcer patients with recent hemorrhage required more transfusions with packed red blood cells (P = 0.002) and fresh frozen plasma (P = 0.05) than those without recent hemorrhage. Among these 42 patients with recent hemorrhage, endoscopic injection therapy was conducted in 15 patients (group A). The other 27 patients (group B) did not receive endoscopic therapy. After endoscopy, patients in group A required more transfusions with packed red blood cells (P = 0.03) and fresh frozen plasma (P = 0.014) than did patients in group B. There were no significant differences between groups A and B in duration of hospital stay and amounts of transfused platelet concentrate after endoscopy. Medical treatment with blood transfusion is the mainstay of management of UGI bleeding in dengue patients. Patients having peptic ulcer with recent hemorrhage require more transfusions with packed red blood cells and fresh frozen plasma for management of UGI bleeding than those without recent hemorrhage. However, when peptic ulcer with recent hemorrhage is encountered during the endoscopic procedure, endoscopic injection therapy is not an effective adjuvant treatment of hemostasis in dengue patients with UGI bleeding.     

Diabetes mellitus is associated with gastroesophageal variceal bleeding in cirrhotic patients

Diabetes mellitus (DM) has been reported to increase the risk of complications of liver cirrhosis of any etiology and subsequent survival. However, the impact of DM on the development of gastroesophageal variceal bleeding (GEVB) remains unclear. We aimed to elucidate whether DM is an independent risk factor for GEVB among cirrhotic patients. A total of 146 consecutive patients with liver cirrhosis (Child-Pugh Class A, n = 75; Class B, n = 40; and Class C, n = 31) were prospectively enrolled. Data on clinical and biochemical characteristics and history of ascites, GEVB, hepatic encephalopathy, and spontaneous bacterial peritonitis were retrospectively reviewed. Of these 146 patients, 37 (25%) had DM. Patients with DM had significantly higher ratio of Child-Pugh Class B/C (p = 0.043), renal insufficiency (p = 0.002), and history of GEVB (p = 0.006) compared with non-DM patients. GEVB was associated with Child-Pugh Class B/C (p = 0.001), ascites (p = 0.002), hepatic encephalopathy (p = 0.023), and low platelet counts (p < 0.001). Based on stepwise multiple logistic regression analysis, Child-Pugh class B/C [odds ratio (OR) = 4.90, p = 0.003] and DM (OR = 2.99, p = 0.022) were identified as independent predictors of GEVB. In the subgroup analysis, DM significantly correlated with GEVB in patients with Child-Pugh Class A (p = 0.042), but not in patients with Child-Pugh Class B/C (p = 0.128). DM is independently associated with GEVB in cirrhotic patients, especially in those with Child-Pugh Class A.     

Recurrent gastric varices bleeding after living-related liver transplantation successfully eradicated by splenic artery embolization

Living related liver transplantation (LRLT) may not be the only treatment for recurrent bleeding due to severe gastric varices secondary to left-side portal hypertension and splenic vein thrombosis. Splenectomy is the preferred long-term standard treatment for non-orthotopic liver transplantation patients, but additional treatments such as post-transplantation partial splenic arterial embolization to preserve the immunological function of the spleen and thus prevent the occurrence of post LRLT severe infection are suggested for these patients.     

Telbivudine and adefovir combination therapy for patients with chronic lamivudine-resistant hepatitis B virus infections

We evaluated second-line salvage therapy with adefovir + telbivudine (group 1), adefovir followed by adefovir + telbivudine (group 2), or lamivudine + adefovir followed by adefovir + telbivudine (group 3) in hepatitis B patients with an inadequate virologic response to lamivudine treatment. Simple linear regression analysis showed that for each additional month of treatment, the most significant reduction in viral load occurred in group 1 (HBV DNA [Log₁₀ IU/mL]: group 1, ?0.149; group 2, -0.081; group 3, ?0.123). Generalized estimating equation analysis revealed that compared to group 1, hepatitis B virus (HBV) DNA levels were 1.203 and 0.443 Log₁₀ IU/mL higher in groups 2 and 3, respectively. Overall, a significant reduction in viral load (?0.060 Log₁₀ IU/mL) was observed for each additional month of treatment. Adefovir + telbivudine treatment resulted in a significant reduction in HBV DNA levels. Moreover, telbivudine treatment resulted in a significant reduction in viral load (?0.050 Log₁₀ IU/mL) compared to lamivudine treatment after the emergence of lamivudine resistance.     

Expression and prognostic role of tumor suppressor gene PTEN/MMAC1/TEP1 in hepatocellular carcinoma

BACKGROUND: Inactivation of the tumor suppressor gene PTEN/MMAC1/TEP1, located on chromosome 10q23, is a common event in advanced stages of diverse human malignancies. However, the prognostic role of PTEN expression in patients with hepatocellular carcinoma (HCC) has not been characterized. METHODS: One hundred five resected specimens were collected from patients with HCC. Expression levels of PTEN and p53 in clinical samples were analyzed by immunohistochemistry. RESULTS: Immunohistochemical analysis of 105 HCC tissue specimens revealed that decreased or absence of PTEN immunostaining was found in 43 specimens (40.9%). Reduced PTEN expression levels were correlated with increased tumor grade (P = 0.017), advanced disease stage (P = 0.016), and elevated serum alpha-fetoprotein (alphaFP) levels (P = 0.001). Kaplan-Meier analysis indicated that patients with reduced PTEN levels had shorter overall survival (P = 0.001) and higher recurrence rates (P = 0.0007) compared with patients who had intact PTEN expression. Examining p53 expression unveiled an inverse correlation between p53 overexpression and reduced PTEN expression in patients with HCC (P = 0.004). In addition, patients with p53 overexpression had shorter overall survival compared with patients who were without p53 overexpression (P = 0.0014). Univariate and multivariate analyses revealed that reduced PTEN expression was an independent prognostic factor for survival in patients with HCC. CONCLUSIONS: The current study demonstrated that reduced PTEN expression levels are involved in the pathogenesis of HCC. Moreover, decreased PTEN expression was correlated with tumor progression, high alphaFP levels, p53 overexpression, and poor prognosis in patients with HCC.     

Predictors of rebleeding after initial hemostasis with epinephrine injection in high-risk ulcers

AIM: To identify the predictors of rebleeding after initial hemostasis with epinephrine injection (EI) in patients with high-risk ulcers. METHODS: Recent studies have revealed that endoscopic thermocoagulation, or clips alone or combined with EI are superior to EI alone to arrest ulcer bleeding. However, the reality is that EI monotherapy is still common in clinical practice. From October 2006 to April 2008, high-risk ulcer patients in whom hemorrhage was stopped after EI monotherapy were studied using clinical, laboratory and endoscopic variables. The patients were divided into 2 groups: sustained hemostasis and rebleeding. RESULTS: A total of 175 patients (144, sustainedhemostasis; 31, rebleeding) were enrolled. Univariate analysis revealed that older age (≥ 60 years), advanced American Society of Anesthesiology (ASA) status (category Ⅲ , Ⅳ and Ⅴ ), shock, severe anemia (hemoglobin < 80 g/L), EI dose ≥ 12 mL and severe bleeding signs (SBS) including hematemesis or hematochezia were the factors which predicted rebleeding. However, only older age, severe anemia, high EI dose and SBS were independent predictors. Among 31 rebleeding patients, 10 (32.2%) underwent surgical hemostasis, 15 (48.4%) suffered from delayed hemostasis causing major complications and 13 (41.9%) died of these complications. CONCLUSION: Endoscopic EI monotherapy in patients with high-risk ulcers should be avoided. Initial hemostasis with thermocoagulation, clips or additional hemostasis after EI is mandatory for such patients to ensure better hemostatic status and to prevent subsequent rebleeding, surgery, morbidity and mortality.     

Insulin resistance is associated with hepatocellular carcinoma in chronic hepatitis C infection

AIM:To elucidate the role of insulin resistance(IR) and serum adiponectin level in hepatocellular carcinoma(HCC) associated with chronic hepatitis C.METHODS:Clinical and biochemical characteristics were collected from 165 consecutive patients with newly diagnosed HCC.Homeostasis model assessment of IR(HOMA-IR) and serum adiponectin level were investigated in 188 patients with different stages of hepatitis C virus(HCV) infection.RESULTS:Among HCC patients,type 2 diabetics(DM) was more prevalent in HCV subjec...