Teh-Hong Wang

Growth rate of asymptomatic hepatocellular carcinoma and its clinical implications.

The growth rate of 31 asymptomatic hepatocellular carcinomas (diameter less than or equal to 5 cm) discovered in 28 patients by a prospective screening program was determined by real-time ultrasonography over 36-860 days. Except for one tumor that shrank on follow-up, the doubling time ranged from 29 to 398 days, with a median of 117 days, an arithmetic mean of 136 days, and a geometric mean of 110 days. In 17 tumors with more than two measurements, the growth rate remained exponential in nine, declined in growth in seven, and showed an initial lag period in one. Doubling time correlated with initial tumor diameter but was independent of the patients age, sex, hepatitis B surface antigen status, tumor location, liver function tests, stage of liver cirrhosis, histologic type, or grade of malignancy. Although initial alpha-fetoprotein levels did not correlate well with growth rate, in 14 patients with an exponential increase of serum alpha-fetoprotein, the alpha-fetoprotein doubling time was closely related to the tumor doubling time. Based on the above data, the median detectable subclinical period of hepatocellular carcinoma was deduced to be 3.2 yr, and the suitable screening interval for its early detection in our area was 4-5 mo.

Early detection of hepatocellular carcinoma by real-time ultrasonography. A prospective study

For early detection of hepatocellular carcinoma (HCC), real‐time ultrasonography (US) was performed prospectively in 528 patients, including 236 with cirrhosis, 81 with chronic hepatitis, 168 asymptomatic hepatitis B surface antigen carriers, and 43 with a family history of HCC. Simultaneous measurement of serum alpha‐fetoprotein (AFP) level was also done. In addition, 233 patients had regular controls at 3‐ to 6‐month intervals, with an average follow‐up period of 1.4 years. On initial screening, a total of 17 patients were found to have HCC: 13 in the cirrhotic group, 3 in the HCC family group, and 1 in the asymptomatic carriers. Of these HCCs, 7 were smaller than 3 cm, 6 were between 3 to 5 cm, and 4 were larger than 5 cm. In patients with tumors smaller than 5 cm, the AFP levels were normal in 46.2%, between 20 to 400 ng/ml in another 46.2%, and only 7.6% were over 400 ng/ml. On follow‐up, another seven patients, all in the cirrhotic group, were found to have HCCs varying from 1.6 to 4.7 cm; three of them had normal serum AFP level. The authors conclude that real‐time US is more sensitive than AFP assay in early detection of HCC, and the high‐risk subjects should receive this procedure at regular intervals.

Genetic alterations in gastric cancer: relation to histological subtypes, tumor stage, and Helicobacter pylori infection

BACKGROUND & AIMS A different spectrum of genetic changes including p53, c-erbB-2, c-met, adenomatous polyposis coli (APC), and deleted in colorectal cancer (DCC) is involved in gastric cancer (GC). The aim of this study was to correlate these alterations with histological subtypes, tumor stages, and Helicobacter pylori infection. METHODS Specimens of 163 patients with GC were immunostained for p53, c-erbB-2, and c-met, and polymerase chain reaction was performed in them to determine loss of heterozygosity (LOH) of APC and DCC. RESULTS Overexpression of p53 was more frequent in early intestinal than early diffuse GC and was noted in the stage progression of diffuse but not intestinal GC. Overexpression of c-erbB-2 occurred more commonly in intestinal GC and advanced GC of both types. Overexpression of c-met was greater in diffuse GC, particularly at advanced stage. LOH of APC was more common in intestinal GC irrespective of the stage but rarely in diffuse GC. LOH of DCC occurred primarily in advanced intestinal GC and infrequently in early GC or advanced diffuse GC. Alterations of these five genes were not correlated with H. pylori infection. CONCLUSIONS A distinct genetic pathway exists in gastric carcinogenesis of different histological subtypes and their tumor progression, in which H. pylori infection may play an equal role or no role.

Ultrasound-guided cutting biopsy for the diagnosis of hepatocellular carcinoma — a study based on 420 patients

BACKGROUND/AIMS To evaluate ultrasound-guided cutting biopsy for hepatocellular carcinoma, we report findings from 10 years of experience. METHODS We performed 455 ultrasound-guided cutting biopsies of hepatic tumors in 420 patients with hepatocellular carcinoma from 1981 to 1990. RESULTS Liver tissues were adequately sampled for a histological diagnosis of hepatocellular carcinoma in the initial biopsy in 391 sessions. The remaining 64 were proved to have hepatocellular carcinoma after subsequent studies. Ultrasound-guided biopsy changed the initial diagnosis in 9 of the 420 patients: three had been diagnosed with liver abscess, and six with metastatic liver tumors. Complications of the biopsy were rare: the tumor had spread to the chest wall in nine, and internal bleeding was noted in five patients. There was no mortality and no other sequelae. CONCLUSIONS Ultrasound-guided biopsy of hepatic tumors is important in the diagnosis of liver cancer, but this technique should be applied only when the image diagnosis and results of fine needle biopsy are equivocal to minimize possible complications. For patients with small HCCs, who are candidates for surgical resection of hepatocellular carcinoma or liver transplantation, it should not be considered as a first-step invasive procedure.

Transfusion-transmitted HBV infection in an endemic area: the necessity of more sensitive screening for HBV carriers.

BACKGROUND : By NAT, HBV DNA is occasionally detectable in blood donors with past HBV infection but negative for HBsAg. Whether or not these donors can cause transfusion‐transmitted HBV infections is uncertain.

Clinical study on primary carcinoma of the liver in Taiwan

T IS COMMON knowledge that pr imary carcinoma of the liver has been much more prevalent in the Orient and South Africa than anywhere else. Th is carcinoma is very well known not only to every doctor in practice in Taiwan, but also to the people living there. T h e purpose of this paper is to report the result of a clinical study of a series of 151 histologically proved cases of pr imary carcinoma o[ the liver.

Chronic hepatitis C without anti-hepatitis C antibodies by second-generation assay. A clinicopathologic study and demonstration of the usefulness of a third-generation assay.

To study the clinicopathologic features of hepatitis C viremic patients negative for hepatitis C antibodies (anti-HCV) by current second-generation assay, we categorized 139 consecutive histologically verified patients with chronic non-A, non-B hepatitis into three groups: 121 (87%) were positive for second-generation anti-HCV (group A); 10 (7%) were negative for second-generation anti-HCV but positive for HCV RNA (group B); and 8 (6%) were negative for both antibodies and viremia (group C). Six (60%) of group B patients could be further detected by a new third-generation assay, but none of group C patients was third-generation anti-HCV-positive. The demographic features, mean peak serum alanine aminotransferase levels, HCV genotype distribution, and histologic changes were comparable among the three groups. The study indicates that most patients with chronic hepatitis C in Taiwan could be identified by current second-generation assay, and viremic but antibody seronegative patients were clinicopathologically similar to the seropositives. Most patients of the latter group could be diagnosed by a third-generation assay, indicating the usefulness of this assay.

Icteric type hepatocellular carcinoma: Revisited 20 years later

Abstract: Icteric type hepatocellular carcinoma is rare, and a poor prognosis has been demonstrated in the past. We performed this study to re-evaluate prognosis since the availability of modern diagnostic modalities. Of 3921 patients with hepatocellular carcinoma in our hospital, 9 patients who presented with tumor fragments in common bile duct and had a patent portal vein were submitted for analysis. Cholangiocarcinoma was suspected in 7 patients before the study was completed, and icteric type hepatocellular carcinoma was diagnosed in all 9 patients after serial studies that included serum alpha-fetoprotein levels, computed tomography, angiography, and histology. The prognosis was better in the 4 resectable patients (survival time 16, 31, 33, and 63 months, respectively), and was extremely poor for the 5 patients who received palliative treatment only (mean survival time, 4.5 months). Because of the apparently discrepant outcomes, this specific type of hepatocellular carcinoma should be kept in mind in areas where hepatocellular carcinomas are prevalent, and the suspected cases should be thoroughly investigated, because prognosis may be improved when resection is done at an earlier stage.

Effective Prevention and Treatment of Helicobacter pylori Infection Using a Combination of Catechins and Sialic Acid in AGS Cells and BALB/c Mice

The increasing emergence of Helicobacter pylori strains resistant to antibiotics may cause unsuccessful treatment. An alternative agent or mixture with anti-H. pylori effect is urgently required to reduce H. pylori infection. We explored the preventive and therapeutic potential of a combination of catechins and sialic acid on H. pylori-infected human gastric cells in vitro and in mice in vivo. We evaluated the anti-H. pylori activity of catechins and/or sialic acid using the agar dilution and checkerboard methods. The effect of catechins and/or sialic acid on H. pylori infection-induced oxidative stress and apoptosis/autophagy in cell culture was explored using an ultrasensitive chemiluminescence analyzer, immunocytochemistry, and Western blotting. Specific pathogen-free BALB/c mice were divided into uninfected control, infected control, pretreated, and post-treated groups. The effects of catechins/sialic acid were determined by histology and immunocytochemistry. The combination of catechins and sialic acid showed synergistic or additive anti-H. pylori activity and significantly reduced inducible nitric oxide synthase expression and Bax/Bcl-2-mediated apoptosis but enhanced Beclin-1-mediated autophagy. All mice infected with H. pylori displayed gastritis and accumulation of 3-nitrotyrosine and 4-hydroxynonenal. Pretreatment with catechins/sialic acid completely prevented H. pylori infection and resulted in normal histology. Post-treatment with catechins/sialic acid decreased the bacterial load and gastritis score and eradicated up to 60% of H. pylori infections in a dose-dependent manner. This is the first demonstration to our knowledge of a nonprobiotic, nonantibiotic treatment that is 100% effective in preventing and has promising possibilities for treating H. pylori infection. Further studies are needed to confirm this result in humans.

Low-power Laserthermia for the Treatment of Small Hepatocellular Carcinoma

Laserthermia by a novel interstitial probe adapted to low power Nd-YAG laser machine was used to treat small hepatocellular carcinoma (HCC). The set condition was 43-45 degrees C in thermocouple with power of 2-3 W and the duration 20-30 min. In the 5 cases studied, 1 had a good result with total necrosis of the tumour without recurrence in 16 months. 1 died of liver failure 2.5 months later although death was not related to the procedure. 1 patient died of progressive disease 18 months later. The remaining 2 had recurrent tumours 5 and 12 months later, although the treated small tumours showed good response. Histological examination showed cell degeneration and necrosis. It is concluded that laserthermia is potentially useful in the treatment of the patients with small HCC.