Ruey-Chang Lin

Current trends and recent advances in diagnosis, therapy, and prevention of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) has been one of the most fatal malignant tumors worldwide and its associated morbidity and mortality remain of significant concern. Based on in-depth reviews of serological diagnosis of HCC, in addition to AFP, there are other biomarkers: Lens culinaris agglutinin-reactive AFP (AFP-L3), des- carboxyprothrombin (DCP), tyrosine kinase with Ig and eprdermal growth factor (EGF) homology domains 2 (TIE2)-espressing monocytes (TEMs), glypican-3 (GPC3), Golgi protein 73 (GP73), interleukin-6 (IL-6), and squamous cell carcinoma antigen (SCCA) have been proposed as biomarkers for the early detection of HCC. The diagnosis of HCC is primarily based on noninvasive standard imaging methods, such as ultrasound (US), dynamic multiphasic multidetector-row CT (MDCT) and magnetic resonance imaging (MRI). Some experts advocate gadolinium diethyl-enetriamine pentaacetic acid (Gd-EOB-DTPA) MRI and contrast-enhanced US as the promising imaging madalities of choice. With regard to recent advancements in tissue markers, many cuting-edge technologies using genome-wide DNA microarrays, qRT-PCR, and proteomic and inmunostaining studies have been implemented in an attempt to identify markers for early diagnosis of HCC. Only less than half of HCC patients at initial diagnosis are at an early stage treatable with curative options: local ablation, surgical resection, or liver transplant. Transarterial chemoembolization (TACE) is considered the standard of care with palliation for intermediate stage HCC. Recent innovative procedures using drug-eluting-beads and radioembolization using Yttrium-90 may exhibit beneficial effects in HCC treatment. During the past few years, several molecular targeted agents have been evaluated in clinical trials in advanced HCC. Sorafenib is currently the only approved systemic treatment for HCC. It has been approved for the therapy of asymptomatic HCC patients with well-preserved liver function who are not candidates for potentially curative treatments, such as surgical resection or liver transplantation. In the USA, Europe and particularly Japan, hepatitis C virus (HCV) related HCC accounts for most liver cancer, as compared with Asia-Pacific regions, where hepatitis B virus (HBV) may play a more important role in HCC development. HBV vaccination, while a vaccine is not yet available against HCV, has been recognized as a best primary prevention method for HBV-related HCC, although in patients already infected with HBV or HCV, secondary prevention with antiviral therapy is still a reasonable strategy. In addition to HBV and HCV, attention should be paid to other relevant HCC risk factors, including nonalcoholic fatty liver disease due to obesity and diabetes, heavy alcohol consumption, and prolonged aflatoxin exposure. Interestingly, coffee and vitamin K2 have been proven to provide protective effects against HCC. Regarding tertiary prevention of HCC recurrence after surgical resection, addition of antiviral treatment has proven to be a rational strategy.

Increase of Resting Levels of Superoxide Anion in the Whole Blood of Patients With Decompensated Liver Cirrhosis

The aim of this study is to investigate the relationship between the resting level of superoxide anion (O2.) and liver cirrhosis (LC). The resting levels of superoxide anion in the whole blood of healthy controls and patients with compensated or decompensated LC were measured, by an ultra-sensitive chemiluminescence (CL) analyzer and lucigenin amplification. The assay system can be performed in the absence of leukocyte isolation and stimulant administration. The results showed that the blood CL levels of compensated cirrhotic patients (381.0 +/- 201.5 counts/10 s, mean +/- SD, n = 24) were similar to that of healthy controls (467.9 +/- 299.5 counts/10 s, n = 24). However, the blood CL levels of decompensated cirrhotic patients (2083.5 +/- 1462.4 counts/10 s, n = 24) were significantly greater than that of healthy controls and patients with compensated LC (both p < .001, Students t-test). The correlation analysis revealed that the blood CL levels in cirrhotic patients were significantly correlated with serum concentrations of albumin (r = -0.65, p < .001) and total bilirubin (r = +0.42, p < .005). However, there was no significant correlation between the blood CL levels and serum levels of transaminases (GOT and GPT). These results suggest that blood levels of superoxide of decompensated cirrhotic patients were greater than those of healthy controls or compensated cirrhotic patients. Moreover, the increase of blood levels of superoxide in decompensated cirrhotic patients is related to the impairment of liver function but not to the inflammation.

Artificial Neural Network Model Is Superior to Logistic Regression Model in Predicting Treatment Outcomes of Interferon-Based Combination Therapy in Patients with Chronic Hepatitis C

Background/Aims: Patients with chronic hepatitis C (CHC) can achieve a sustained virologic response if they received pegylated interferon plus ribavirin therapy; however, some of them do not respond or relapse after treatment. The aim of this study was to compare the ability of two statistical models to predict treatment outcomes. Methods: Clinical data, biochemical values, and liver histological features of 107 patients with CHC were collected and assessed using a logistic regression (LR) model and an artificial neural network (ANN) model. Both the LR and ANN models were compared by receiver-operating characteristics curves. Results: Aspartate aminotransferase (p = 0.017), prothrombin time (p = 0.002), body mass index (BMI; p = 0.003), and fibrosis score of liver histology (p = 0.002) were found to be significant predictive factors by univariate analysis. The independent significant predicting factor was BMI by multivariate LR analysis (p = 0.0095). The area under receiver-operating characteristics of the ANN model was larger than that of the LR model (85 vs. 58.4%). Conclusions: It was found that BMI is an independent factor for identifying patients with favorable treatment response. A useful ANN model in predicting outcomes of standard treatment for CHC infection was developed and showed greater accuracy than the LR model.

Predicting Therapeutic Results of Interferon Based Treatment by Modeling the First Week Viral Kinetics in Patients with Chronic Hepatitis C

Background: The present study aimed to develop an optimal model predictive of the treatment response one week after initiating antiviral therapy. Patients and Methods: In all, 166 patients completed the treatment and were followed up for six months. Results: A viral response was achieved in 14 (8.4%) genotype 1 (G1) and 32 (19.3%) non-genotype 1 (G0) patients at week one after initiation of therapy and 45 (27.1%) G1 and 90 (54.2%) G0 patients at week four. A sustained viral response (SVR) was achieved in 50 (30.1%) G1 and 83 (50.0%) G0 patients, in 13 (29.5%) G1 and 31 (70.5%) G0 patients whose antiviral response was achieved at one week, and in 37 G1 (32.2%) and 78 G0 (67.8%) patients whose antiviral response was achieved at four weeks. The HCV viral kinetic parameter π (i.e., 1: α, α was defined as the area under the line y [viral load]=– a[x{time}] between week 0 and week 1) was found to be the best performing test for predicting SVR (p<0.0001). Regression analysis identified π as the only independent predictor of SVR (p=0.043). Conclusions: The use of bio-mathematical models of HCV kinetics can reliably predict SVR one week after starting therapy.

Empiric antibiotic choices for community-acquired biliary tract infections

The study was conducted to reveal the most appropriate empiric antibiotics for the treatment of community‐acquired biliary tract infections (CA‐BTI) at a regional hospital in Taiwan.

Pyogenic Liver Abscess-Comparison between Diabetic Patients and Non-Diabetic Patients

Background and Aims: Pyogenic liver abscess (PLA) is a rare and life threatening disease. Diabetes is also known as the most common risk factor for PLA. The objective of this study is to compare the nature of PLA between patients with diabetes and without. We also tried to identify if diabetes was an independent predictor for mortality in patients with PLA. Methods: We conducted a retrospective study of 120 patients who presented with PLA from January 2003 to May 2009. Patients were divided into two groups depending on whether they had diabetes or not. Characteristics of these patients were analyzed by two-sample test for interval and categorical data. Significant predictors of mortality in patients with PLA were investigated by multivariate logistic regression. Results: Fifty percent of the 120 studied PLA patients were found with diabetes mellitus. Those PLA patients with diabetes were more likely to have a culture result of Klebsiella pneumonia and hypertension. In contrast, more PLA patients without diabetes had concomitant biliary stones, a history of hepatobiliary procedures, and elevated alkaline phosphatase level. These patients also received more treatment of catheter drainage. Diabetes was not an independent predictor for mortality in PLA. Impaired renal function with creatinine＞1.5 g/dl (adjusted OR 5.4, 95% CI 1.4-20.8) and hypoalbuminemia with albumin＜3.0 g/dl (adjusted OR 11.6, 95% CI 1.4-98.3) were independent predictors for mortality in PLA. Conclusion: There were several different characteristics between diabetic and non-diabetic PLA. Initial presentations with renal insufficiency and hypoalbuminemia were associated with poor prognosis in patients with PLA.

Small Cell Carcinoma of Rectum: Report of a case

Small cell carcinoma of rectum is a rare tumor， since the majority of small cell carcinomas are of primary pulmonary origin. This tumor manifested highly aggressive behavior. We reported a 63 year-old male patient who had bloody stool. Colonoscopy revealed a rectal mass with ulcerated surface. Endoscopic ultrasound miniprobe image showed a homogenous, hypoechoic rectal tumor invading into the muscularis propria layer. The diagnosis of small cell carcinoma was made after colonoscopic biopsy, and patient received surgical resection of tumor, followed by chemotherapy and radiotherapy.

Primary Malignant Melanoma of The Esophagus: Report of a Case

原發性食道惡性黑色素瘤是罕見的疾病。本例報告一名60歲女性患者，最近二個月來因吞嚥固體食物特別困難而至本院求診。食道攝影及內視鏡檢查發現在食道中下部有一息肉樣的腫瘤，經手術切除。病理診斷證實為惡性黑色素瘤，由於此病預後極差，手術治療目前仍是緩解症狀及延長生命的主要治療方法。