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Biomedical subjects

J C Sheu

Publications and source records attributed to J C Sheu.

At least 55 records · Page 3Linked to original sources

Seroprevalences of hepatitis B and C viruses and Helicobacter pylori infection in a small, isolated population at high risk of gastric and liver cancer.

The objective of this study was to examine the seroprevalences of chronic infection with hepatitis B and C viruses and Helicobacter pylori in Matzu, a group of small islets with 5,566 civilian residents who have extremely high mortality from cancers of the stomach and liver. The standardized mortality ratios (SMR) of all cancer sites combined, liver cancer and stomach cancer in 1984-1993 were calculated using the general population in Taiwan as the referent (SMR = 100). The SMRs (95% confidence interval) for all cancer sites combined, liver cancer and stomach cancer were 160 (131-195), 252 (170-360) and 351 (229-516), respectively, in Matzu. A health survey was carried out with 1,485 civilian residents aged 30 years or more, giving a response rate of 69% among those who were eligible. Serum samples were tested for antibodies against Helicobacter pylori (anti-HP) by enzyme-linked immunosorbent assay and hepatitis B surface antigen (HBsAg) and antibodies against hepatitis C virus (anti-HCV) by enzyme immunoassay. The seroprevalence was 61% for anti-HP, 24.7% for HBsAg and 1.8% for anti-HCV in Matzu. While mortality rates of liver and stomach cancers were significantly higher in Matzu than in Taiwan, the seroprevalences of anti-HP, HBsAg and anti-HCV in Matzu were similar to or even lower than those in Taiwan. These findings suggest the existence of risk factors other than microbial agents involved in the development of stomach and liver cancers.

Adult↗

Infrequent hMSH2 mutations in sporadic gastric adenocarcinoma with microsatellite instability.

The status of genetic instability was determined with seven microsatellite markers from 40 patients with primary gastric adenocarcinoma. For those cases with microsatellite instability, alterations of hMSH2 were further investigated by direct sequencing of reverse transcription-polymerase chain reaction products. Twelve (30%) of 40 patients were found to have microsatellite instability. Among them, one patient (1/6, 16.7%) was early gastric cancer and 11 (11/34, 32.4%) were advanced gastric cancer. There were seven patients with diffuse type (7/18, 38.7%), while five (5/22, 22.7%) were intestinal type tumors. The entire coding region of the hMSH2 gene in these 12 affected individuals was amplified and sequenced. Only a 41-year-old female patient with diffuse type advanced gastric cancer showed a GCT to TCT missense mutation at codon 207 with predicted protein change from alanine to serine. Our results indicate that genetic instability plays an important role in gastric tumorigenesis and alterations of the hMSH2 gene are related to only a small portion of sporadic gastric adenocarcinoma with microsatellite instability.

Adenocarcinoma↗

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.

Adenomatous Polyposis Coli↗

Bile duct hamartomas. A report of two cases.

Bile duct hamartomas (von Meyenburg's complexes) of the liver are usually detected at laparotomy or autopsy as an incidental finding, and usually they are multiple. We report two cases of proved bile duct hamartomas of the liver. The first was in a 65-year-old man whose initial sepsis and many hepatic lesions were interpreted as microabscess of the liver. The second patient was a 39-year-old man, a hepatitis B surface antigen carrier, in whom an incidental hepatic tumor was found. We suggest that liver biopsy be done in hepatic lesions with uncertain clinical features, because the histologic findings may change the treatment plan.

Adult↗

Molecular mechanism of hepatocarcinogenesis.

To clarify the relative role of hepatitis C virus (HCV) and hepatitis B virus (HBV) in hepatocarcinogenesis in hepatitis B surface antigen (HBsAg)-negative hepatocellular carcinoma (HCC) in Taiwan, polymerase chain reaction (PCR) was used to detect the HCV-RNA and HBV-DNA sequences in the serum and liver tissues from 31 HBsAg-negative HCC patients. Twenty-one were positive for antibody to HCV (group 1) and 10 were negative (group 2). Hepatitis C virus-RNA was detected by PCR in the serum of 16 group 1 patients and in the liver tissue of 17; while HBV-DNA was found in the liver tissue of only four, and no HBV-DNA was found in the serum. Hepatitis C virus RNA was detected in the serum of one group 2 patient and in the liver tissue of another. In contrast, HBV viral DNA was found in the serum of four group 2 patients and in the liver tissues of five patients. This indicates that HCV plays an important role in hepatocarcinogenesis in HBsAg-negative patients in Taiwan, especially in those with antibody to HCV. In those without antibody to HCV, HBV might still be associated with the development of HCC in a significant proportion of such patients. In order to study the role of the p53 mutation in hepatocarcinogenesis, we investigated the status of the p53 mutation in 61 HCC samples from Taiwan. The exon 5 to 8 of the p53 gene in the tumour tissue of 61 HCC were amplified and sequenced. A total of 20 cases (32.8%) were found to have mutations: 36.6% (15/41) from the HBsAg-positive group and 25.0% (5/20) from the HBsAg-negative group. The corresponding normal liver showed no mutation. The mutation is widely distributed throughout the exon 5 to 8. Only four cases (6.6%), all positive for HBsAg, had a specific hotspot mutation at codon 249 with G to T transversion. These results show that scattered point mutations in p53 are not uncommon in HCC samples from Taiwan and may be important in the development of this cancer. However, the aflatoxin-related specific mutation seems much less related to the genesis of HCC in Taiwan. To study the role of telomerase activity in hepatocarcinogenesis, a total of 39 HCC tissues and the corresponding non-tumour liver tissues were analysed. The results showed that telomerase activity was detected in all the 39 tumour tissues, while it could be detected in six of the 39 non-tumour liver tissues. The high positive rate of telomerase activity in HCC samples suggests that telomerase activity is closely related to the development or progression of HCC. To determine whether exon 1 and exon 2 of the p16 gene are altered in HCC, thirty-four tumours from 30 HCC patients were examined by DNA sequencing analysis of PCR-amplified genomic DNA. Homozygous deletions of MTS1/p16/CDKN2 exon 1 were identified in 1/34 primary tumours (3%), no mutations or rearrangements were found in these specimens. These data suggest that alterations of MTS1/p16/CDKN2 gene are rarely found in HCC, and might play little role in the development of this cancer. To study the clonality of HCC, 18 patients with multiple HCC, most of them small in size, were analysed by DNA fingerprinting. In patients positive for hepatitis B surface antigen, the integration pattern of hepatitis B viral DNA in liver tissue was also analysed. The results by both methods showed that 8/9 hepatitis B surface antigen-positive patients were different in clonality. In the remaining nine patients negative for hepatitis B surface antigen, four had different band patterns in their tumours by DNA fingerprinting. This study indicated that polyclonality of multiple HCC was rather frequent and it highlighted the importance of eliminating the underlying cause of liver injury to improve the survival of these patients. Microsatellite markers were used to study the genetic changes of HCC. Thirty cases of HCC, most of them small in size, were studied. A total of 242 microsatellite markers mapping to 1-22 and X chromosomes was used. The results showed that the range of loss of het

Hepatitis B↗

Prenatal diagnosis, pathology, and genetic study of fetus in fetu.

We report the prenatal diagnosis, pathology, cytogenetics, and molecular studies of a retroperitoneal fetus in fetu. Prenatal ultrasonography of the host fetus in the third trimester showed an anencephalic, acardiac mass with identifiable extremities and spine within an intra-abdominal cystic mass. Pathological examination revealed a fetiform mass weighing 20 g with four extremities, digits, vertebral bodies, an oral cavity with developing teeth, primitive male external genitalia, a urinary bladder, a cloaca with an external opening, large intestines, a membranous capsule, and an umbilical cord with one artery, one vein, and Wharton's jelly. Histological examination demonstrated nerve bundles in the fibrocollagenous tissue below the cuboidal surface epithelium of the membranous capsule, and absence of lamina elastica interna and vasa vasorum in the single artery of the umbilical cord. Both the host infant and the fetus in fetu had a normal 46,XY karyotype. Molecular analysis using informative genetic markers showed no genetic difference between the host infant and the fetiform mass. We report this case as an unusual example of fetus in fetu in co-existence with an amnion-like membrane containing nerve bundles and with a well-formed umbilical cord. We demonstrate that fetus in fetu can be diagnosed prenatally if the fetiform mass has well-developed limbs and spine. We emphasize the necessity for suspicion of fetus in fetu when a well-defined encapsulated cystic mass with calcified solid components is detected prenatally in a fetus by ultrasonography.

Adult↗

Progressive fetal axillary cystic lymphangioma with coexistent naevus flammeus.

We report the rare occurrence of a progressive fetal axillary cystic lymphangioma coexistent with an overlying naevus flammeus. The fetus at 22 weeks' gestation was found to have a 37 x 35 mm left axillary multiloculated mass without colour-flow imaging. Amniocentesis showed a normal 46,XX karyotype. Multiple fine-needle aspirations of the mass in the second and third trimesters obtained blood-stained chocolate-coloured fluid containing numerous erythrocytes and lymphocytes but proved ineffective in lessening the progressive growth of the mass. The mother underwent caesarean delivery and a healthy neonate was born with a 141 x 81 mm left axillary cystic lymphangioma and a 50 x 35 mm coexistent naevus flammeus. The neonate was well after simple excision of the lesions. Although cystic lymphangiomas arising in the axilla enlarge progressively during fetal life, our case suggests a good prognosis and except for genetic evaluation, no prenatal intervention is required.

Adult↗

A prospective study of transfusion-transmitted GB virus C infection: similar frequency but different clinical presentation compared with hepatitis C virus.

To study the incidence and outcome of GB virus C (GBV-C) infection in blood recipients. Serum samples collected in a prospective study were examined for GBV-C RNA by a nested polymerase chain reaction assay. Among the 400 adults who underwent cardiac surgery, 40 were positive for GBV-C RNA, including six whose pretransfusion sera were already positive and seven coinfected with hepatitis C virus (HCV) during transfusion. The risk of transmission was estimated to be approximately 0.46% per donor. GBV-C viremia was detectable 1 week after transfusion and could persist for 8 years. However, no evident symptoms or signs were noted in the 25 patients infected by GBV-C alone, and the average peak serum alanine aminotransferase activity was 31 IU/L only (range, 12 to 123), with persistently normal levels in 20 patients. In the seven patients coinfected with HCV, the clinical courses of posttransfusion hepatitis were similar to those infected by HCV alone. In eight patients with posttransfusion non-A approximately E hepatitis, only one was positive for GBV-C RNA. Sixty samples were chosen to test hepatitis G virus (HGV) sequences, 26 of the 30 GBV-C positives were positive for HGV RNA in contrast to none of the 30 GBV-C negative samples. In conclusion, GBV-C can be transmitted by transfusion in approximately 9% of patients who underwent cardiac surgery. Nevertheless, this virus does not seem to cause classic hepatitis in most instances.

Acute Disease↗

Long-term outcome after surgery for asymptomatic small hepatocellular carcinoma.

The subjects of this study were 48 asymptomatic patients who had surgery for small hepatocellar carcinoma (HCC). There were 42 men and six women with mean (s.d.) tumour size of 3.31 (1.46) cm and age 55.0 (7.4) years. Follow-up was for a minimum of 10 years. The main concern of this study was a univariate analysis of factors that might affect long-term survival after surgery, which was 50 per cent at 5 years and 31 per cent at 10 years. A high incidence of recurrent HCC (37 of 48 patients) was observed but reoperation further prolonged life in some cases. The significant prognostic factors detected by multivariate analysis were: histological classification, functional liver reserve and histology of the resection margin. Tumour size, gross appearance of tumour, presence of liver cirrhosis, serum alpha-fetoprotein level, age or sex did not affect the prognosis.

Carcinoma, Hepatocellular↗

Pancreatitis in children--experience with 43 cases.

UNLABELLED: Pancreatitis in children is not common and can be associated with severe morbidity and mortality. We encountered 43 children, ranging in age from 2 to 18 years, with pancreatitis over the past 10 years. The diagnosis of pancreatitis was made in those patients who showed: (1) significant intra-operative pathology or; (2) clinical findings of pancreatic inflammation and laboratory confirmation. More than one third (16 cases) of the cases were due to trauma, other causes included systemic disease (10), structural disease (8), and toxins or drugs (4). Five cases were classified as idiopathic. Most of the patients presented with abdominal pain (95%) and vomiting (56%). Jaundice was found in 7 patients and an abdominal mass in 2. Morbidity included pseudocyst (10), relapse (4), hyperglycaemia (4) and miscellaneous problems. Eight (50%) of the patients with trauma and 6 (86%) of the patients with structural diseases required surgery. Other patients were managed conservatively with bowel rest, gastric decompression, intravenous fluid and total parenteral nutrition. One case had a fatal outcome. All the survivors did well in long term follow up. Relevant literature has been reviewed and the sensitivity of various diagnostic modalities compared and discussed. A lesser known association between pancreatitis and structural anomalies such as choledochal cyst is discussed. To our knowledge, the present review is the first on pancreatitis in Chinese children. CONCLUSION: Pancreatitis can occur from a wide variety of causes and may result in severe complications. Early diagnosis, close monitoring and aggressive intervention are mandatory to reduce morbidity and mortality.

Abdomen, Acute↗

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.

Chronic Disease↗

Surgical treatment of hepatocellular carcinoma originating from the caudate lobe.

Hepatocellular carcinoma (HCC) originating from the caudate lobe is rare, and its surgical management is difficult because of its unique anatomic location. We have seen six such cases at our hospital. For patients with fair to excellent liver reserve, we advocated caudate lobectomy combining other types of hepatic resection. For patients with marked liver cirrhosis and poor liver reserve or a small HCC, we advocated simple partial caudate lobectomy (limited hepatic resection). There was no operative mortality or major operative morbidity. We conclude that such approaches are safer, less time-consuming, and less technique-demanding, and they produce a fair survival result compared with the approaches of other procedures. With such approaches, it is our experience that patients with HCC from the caudate lobe have a prognosis comparable to that of patients with HCC in other parts of the liver.

Adult↗

Experience with distal circular myotomy for long-gap esophageal atresia.

From 1980 to 1994, the authors treated 65 cases of esophageal atresia (with or without tracheoesophageal fistula). Among these patients, 15 (23%) underwent pure proximal circular myotomies and five (8%) underwent both proximal and distal circular myotomies. Of the latter five cases, three were Gross type C and two were Gross type A. The gap ranged from 4.5 cm to 6.5 cm (mean, 5 cm). Surgical complications in these five patients included two anastomotic leaks (40%), one anastomotic stricture (20%), and four gastroesophageal refluxes (80%). Three patients eventually underwent fundoplication as an antireflux procedure. Mucosal outpouching was noted in all cases. The myotomy did not adversely affect the esophageal peristalsis and motility on the esophagogram. Esophageal function was similar to that of other children who had esophageal atresia without myotomy. All patients could eat food typical for their age. This limited experience suggests that distal circular myotomy might be a safe adjuvant procedure to achieve primary anastomosis in long-gap esophageal atresia.

Anastomosis, Surgical↗

Surgical resection for recurrent hepatocellular carcinoma: prognosis and analysis of risk factors.

BACKGROUND: Hepatocellular carcinoma (HCC) is common in Asian countries, and tumor recurrence is the most common cause of treatment failure after curative resection. Repeated hepatectomy is performed only for selected patients because most patients with HCC also have liver cirrhosis and poor liver function reserve. The purposes of this study were to clarify the outcome of the patients after second hepatectomy for recurrent HCC and to evaluate the prognostic factors after second hepatectomy. METHODS: We used retrospective cohort study to examine the disease-free survival, cumulative survival, and possible prognostic factors for recurrence and death in 59 patients who underwent surgical resection for recurrent HCC at the National Taiwan University Hospital from August 1986 to December 1993. Another 64 patients with unresectable recurrent HCC were used as a historical control group. The survival curves between those patients with resectable HCC and those with unresectable HCC were compared. RESULTS: After resection for recurrent HCC, gender and multiplicity (n > 3) of tumor affect recurrence rate (p = 0.046 and 0.021, respectively), whereas gender, age, and tumor invasiveness affect survival rate significantly (p = 0.024, 0.021, and 0.046, respectively). The survival rate of patients with resectable HCC was significantly better than that of those with unresectable HCC. CONCLUSIONS: For recurrent HCC surgical resection is an effective mode of treatment in selected patients. Whether surgery is better than other modes of treatment in the treatment of resectable recurrent HCC demands further investigation.

Adult↗

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.

Adolescent↗

Prenatal diagnosis and perinatal aspects of abdominal wall defects.

We retrospectively reviewed 27 cases of omphalocele and 15 cases of gastroschisis occurring among 62, 572 deliveries between 1987 and 1994. All cases had undergone prenatal sonographic examinations at a mean gestational age of 28 weeks. In cases of omphalocele, 59.3% (16/27) of fetuses were associated with multiple malformations and 16% (4/25) had chromosomal abnormalities. Among the 4 cases with an abnormal karyotype, three cases were associated with extracorporeal livers and two cases were associated with umbilical cord cysts. Prenatal ultrasound examinations during the second and third trimesters were able to detect 66.7% (18/27) of the cases of omphalocele and 66.7% (10/15) of the cases of gastroschisis. Failure in correctly diagnosing abdominal wall defects by prenatal ultrasound occurred mostly in cases associated with small defects, ruptured omphalocele, multiple fetal anomalies, intrauterine fetal death, twin pregnancies, or cases referred in late gestation. A comparison of perinatal data between omphalocele and gastroschisis reveals fetuses with omphalocele carry higher risks of associated malformations, chromosomal abnormalities, prematurity, and neonatal death. Although fetuses with gastroschisis have higher incidences of oligohydramnios and small for gestational age, the fetal prognosis after pediatric surgery is good.

Abdominal Muscles↗

Intragenic homozygous deletions of MTS1 gene in gastric cancer in Taiwan.

The multiple tumor suppressor 1 (MTS1) and 2 (MTS2) genes, located on chromosome 9p21, have been reported to be deleted or mutated in many malignant cell lines and in a high percentage of some primary carcinomas. To determine whether these genes are altered, and if so, what is the nature of the alterations, in human gastric adenocarcinoma, we investigated their frequency of mutation by Southern blotting, polymerase chain reaction (PCR) and direct sequencing in 55 patients. Furthermore, loss of heterozygosity (LOH) of chromosome 9p21 at the IFNA locus and D9S171 was assessed. Homozygous deletions of exon 1 of the MTS1 gene were identified in 5 of 55 (9.1%) primary tumors. No deletion of MTS2 gene was noted. LOH was observed in 7 (14.3%) of 49 informative cases (5 cases at IFNA locus, 2 cases at D9S171 and one case with combined LOH at D9S171 and homozygous deletion at exon 1 of MTS1). Direct sequencing of PCR products of the MTS1 and MTS2 gene did not reveal any point mutation in these 55 patients. These data indicate that alterations of the MTS1 and MTS2 genes are infrequently encountered. Additional studies of LOH with more microsatellite markers near 9p21 are mandatory to elucidate whether another tumor suppressor gene exists in the vicinity of MTS1 in primary gastric adenocarcinoma.

Blotting, Southern↗

Lack of critical domains in the beta-chain of hepatocyte growth factor.

Hepatocyte growth factor (HGF) is a cytokine with pleiotropic effects on many different cell types. Its biological activities depend on the disulfide-linked alpha beta heterodimeric molecule. To study the functions of the beta-chain of HGF, insect cell-expressed HGFs prepared from nested deletions from C-terminus of beta-chain were studied for their biological activities and ligand-binding functions. The results demonstrated that the functions of HGF are dependent on the intactness of its beta-chain. The loss of HGF activities is correlated with the progressive deletion of beta-chain. There is not a single critical domain in the beta-chain that is essential for the functions of HGF. We propose that beta-chain may act to stabilize the ligand-receptor binding or contribute to the proper conformation of HGF to interact with its receptor.

Animals↗