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Biomedical subjects

P B Lai

Publications and source records attributed to P B Lai.

At least 19 recordsLinked to original sources
PubMed2001

Immunohistochemical analysis of pro-apoptotic Bid level in chronic hepatitis, hepatocellular carcinoma and liver metastases.

Bid, a member of the Bcl-2 family, mediates apoptosis by inducing the release of proapoptotic factors. The expression of Bid in liver diseases has not been investigated. This study evaluated Bid level in various liver diseases including hepatocellular carcinoma (HCC), liver metastases from colorectal cancer, chronic hepatitis and liver cirrhosis. The expression of Bid in tumorous tissues of HCC was lower than that in their corresponding non-tumorous tissues from the same patient. Heavy staining with Bid antibody was found in some localized tumorous liver tissues from patients with poorly differentiated tumors. In patients with chronic hepatitis and liver cirrhosis, there were gradient tumor-development centers, a gradient increase in reaction with Bid antibody from the middle of the center to its edge. The gradient tumor-development center was also found in non-tumorous tissues of HCC, suggesting that occurrence of this center in chronic hepatitis might be an early pathologic sign of HCC development. Bid was also expressed in the epithelial cells in tissues from liver metastases and their expression was often stronger than in the non-tumorous liver tissues. Heavy nuclear staining of Bid was not uncommon in these metastatic cells. The different patterns of staining between primary and secondary liver tumors may reflect a difference in tumor origin and in cell type. Nuclei of metastatic cells, though positive for Bid, still showed a considerable mitotic activity, indicating that they were in active proliferation rather than on a pathway deemed to be apoptotic. In conclusion, this study shows that the Bid level is decreased in HCC except in poorly differentiated HCC in which cells may undergo a process of apoptosis or necrosis. The existence of gradient tumor-development center in chronic hepatitis, liver cirrhosis and non-tumorous tissues from HCC may serve as a pathologic marker of a carcinogenic change of cell phenotypes.

BH3 Interacting Domain Death Agonist Protein↗
PubMed2001

Induction of Fas and Fas ligand expression on malignant glioma cells by Kupffer cells, a potential pathway of antiliver metastases.

Kupffer cells play an important role in controlling the growth and development of liver metastases. However, the pathway of Kupffer cells against tumor metastases is not clear. In the present study, we set up an experimental model to investigate the mechanisms on how Kupffer cells kill tumor cells which metastasize to the liver. Malignant glioma cells were cocultured with Kupffer cells or treated with culture medium collected from lipopolysaccharide (LPS)-activated Kupffer cells. The results showed that the interaction between Kupffer cells and malignant glioma cells significantly stimulated the generation of tumor necrosis factoralpha (TNFalpha). TNFalpha was mainly produced by Kupffer cells, as its level in culture medium obtained from LPS-treated Kupffer cells was not significantly different from that of malignant glioma cells treated with the same medium. Both Kupffer cells and LPS/Kupffer cell-conditioned supernatants induced expression of Fas and Fas ligand on malignant glioma cells. Subsequently a significant proportion of malignant glioma cells became apoptotic, as evidenced by positive staining of annexin V and propidium iodine and an increase in cellular DNA fragmentation. Therefore, this study supports a novel pathway of Kupffer cells against liver metastases, in which tumor cells were apoptotic via the Fas-Fas ligand system induced by TNFalpha released from Kupffer cells.

Animals↗
PubMed2001

Hypomethylation of chromosome 1 heterochromatin DNA correlates with q-arm copy gain in human hepatocellular carcinoma.

Using comparative genomic hybridization (CGH) analysis, we, and others, have shown that there is a high and consistent incidence of chromosome 1q copy gain in human hepatocellular carcinoma (HCC). Chromosome 1 rearrangements, that involved peri-centromeric breakpoints, have also been frequently reported in karyotypic studies of HCC. Satellite DNA hypomethylation has been postulated as the mechanism underlying the induction of chromosome 1 peri-centromeric instability in many human cancers and in individuals with the rare recessive disorder ICF (immunodeficiency, centromeric heterochromatin instability, facial anomalies). In this study, we have investigated the role of DNA hypomethylation in 1q copy gain in HCC by examining the methylation status of chromosome 1 heterochromatin DNA (band 1q12). Thirty-six histologically confirmed samples of HCC were studied (24 paired tumor and adjacent nontumorous liver tissues, and 12 tumor only). Hypomethylation of satellite 2 (Sat2) DNA in 1q12 was analyzed by Southern blotting using methyl-sensitive enzyme digestion. In parallel, all cases were analyzed by CGH. A strong correlation between hypomethylated Sat2 sequences and 1q copy gain with a 1q12 breakpoint was found (P < 0.001). We postulate that such hypomethylation alters the interaction between the CpG-rich satellite DNA and chromatin proteins, resulting in heterochromatin decondensation, breakage and aberrant 1q formation. Spectral karyotyping further supported the presence of fragile 1q12 in HCC. Of particular interest was the finding of Sat2 DNA hypomethylation in 5 of 24 adjacent nontumorous liver tissues examined. These tissues showed no evidence of malignancy on histological examination nor did they display any CGH abnormalities. Our findings suggest a role for Sat2 demethylation in the early stages of the stepwise progression of liver carcinogenesis.

Adult↗
PubMed2001

Does patient position during liver surgery influence the risk of venous air embolism?

BACKGROUND: It is generally believed that positioning of the patient in a head-down tilt (Trendelenberg position) decreases the likelihood of a venous air embolism during liver resection. METHODS: The physiological effect of variation in horizontal attitude on central and hepatic venous pressure was measured in 10 patients during liver surgery. Hemodynamic indices were recorded with the operating table in the horizontal, 20 degrees head-up and 20 degrees head-down positions. RESULTS: There was no demonstrable pressure gradient between the hepatic and central venous levels in any of the positions. The absolute pressures did, however, vary in a predictable way, being highest in the head-down and lowest during head-up tilt. However, on no occasion was a negative intraluminal pressure recorded. CONCLUSION: The effect on venous pressures caused by the change in patient positioning alone during liver surgery does not affect the risk of venous air embolism.

Adult↗
PubMed2001

Decreased expression of Bid in human hepatocellular carcinoma is related to hepatitis B virus X protein.

As a mitochondrial membrane death ligand, Bid oligomerises Bak to release cytochrome C and its deficiency renders hepatocytes resistant to apoptosis induced by Fas. The Bid level in hepatocellular carcinoma (HCC) is unknown. In this report, we examined the expression of Bid protein and mRNA in HCC cancerous tissues and their corresponding non-cancerous ones. The effect of the hepatitis B x protein (HBx) on the expression of Bid was also evaluated by transfecting hepatoma cells with the HBx gene. The results showed that the expression of Bid was significantly lower in cancerous tissues than that in their corresponding non-cancerous tissues. Immunohistochemical study revealed that Bid molecule was mainly localised in hepato-cytoplasm. Some nuclei were also positive for Bid antigen though to a lesser degree. In vitro experiments demonstrated that the expression of Bid in cells transfected with HBx was significantly lower than that in the cells without HBx transfection. This finding suggests that HBx may play a causative role in the reduction of Bid expression in HCC. This in vitro result is, to some degree, supported by clinical data that all the HCC examined are positive for hepatitis B virus (HBV). We conclude from this data that the expression of Bid in HCC is significantly decreased and the reduction of Bid may result from a mechanism associated with HBx, a major hepatocarcinogenic product from HBV. The imbalance of increased anti-apoptosis and decreased pro-apoptosis seen in HCC is a critical mechanism leading to the uncontrolled growth of tumour cells. Therefore, this study suggests that a deficiency in the expression of Bid may contribute to the development of such an imbalance in HCC.

BH3 Interacting Domain Death Agonist Protein↗
PubMed2001

Incidence of deep vein thrombosis after colorectal surgery in a Chinese population.

INTRODUCTION: Contemporary studies indicate that the incidence of deep vein thrombosis (DVT) is increasing in the Asian population. The present study aims to evaluate the incidence of postoperative DVT in Chinese patients undergoing surgery for colorectal malignancies. METHODS: Fifty-one consecutive patients with carcinoma of the rectum or sigmoid colon scheduled for resection were included in the study. None of the study subjects were given any form of DVT prophylaxis. Serial duplex ultrasound of both lower limbs were examined in the preoperative and postoperative periods. RESULTS: Three patients were excluded from the study because of the presence of DVT noted preoperatively. A total of 20/48 (41.7%) patients developed asymptomatic calf vein thrombosis. One out of 20 patients required anticoagulation because of thrombus propagation. None of the subjects showed signs or symptoms of DVT or pulmonary embolism. A total of 7/20 thrombi resolved completely at 4 weeks after operation. Only old age and smoking were identified as being associated with a higher incidence of DVT. Disseminated disease, type of operation, duration of operation and postoperative complications did not appear to be risk factors for DVT. CONCLUSION: A high incidence of asymptomatic calf vein thrombosis occurred after colorectal surgery for malignancies in Chinese. The majority did not progress even without anticoagulation.

Age Factors↗
PubMed2001

Selection of patients for laparoscopic repair of perforated peptic ulcer.

BACKGROUND: Although randomized and non-randomized studies have evaluated the safety of laparoscopic repair for perforated peptic ulcer, no definite guidelines have been published on selection of patients for laparoscopic repair. This cohort study aimed to define patients who may not benefit from laparoscopic techniques. METHODS: The data from 374 consecutive patients with perforated peptic ulcer treated by simple repair were collected prospectively and analysed. RESULTS: From January 1992 to December 1998, 219 patients were treated by open suture repair, 109 by laparoscopic sutureless (fibrin glue) repair and 46 by laparoscopic suture repair. The overall leak rate after laparoscopic suture and sutureless repair was 6 and 16 per cent respectively. Leakage was noted to be associated with a significantly higher rate of wound infection, intra-abdominal abscess formation, prolonged ileus (P < 0.001) and longer hospital stay (11 versus 5 days; P < 0.001). Multivariate analysis demonstrated that Acute Physiology and Chronic Health Evaluation (APACHE) II score on admission predicted the likelihood of a leak after laparoscopic fibrin glue repair (P = 0.006). CONCLUSION: APACHE II score may be a useful index for selecting patients for laparoscopic fibrin glue repair.

APACHE↗
PubMed2001

Necrosis of the nasal ala after improper taping of a nasogastric tube.

Inserting a nasogastric tube during various abdominal procedures is a common maneuver to decompress the upper gastrointestinal tract. Improper placement and taping of the nasogastric tube results in excessive pulling on the nasal ala and subsequent pressure necrosis. This complication not only carries serious cosmetic morbidity, it is also preventable if a proper taping technique is employed.

Adult↗
PubMed2001

Circulating Epstein-Barr virus DNA in the serum of patients with gastric carcinoma.

PURPOSE: We investigated the detectability of EBV DNA in the serum of gastric carcinoma patients in Hong Kong. Previous data have shown that approximately 10% of gastric carcinomas in Hong Kong are associated with EBV. EXPERIMENTAL DESIGN: We recruited 51 patients with gastric carcinoma, 30 patients with gastritis, and 197 apparently healthy controls. For gastric carcinoma patients, blood samples were obtained before surgery. After surgery, the resected tumor samples from the cancer cases were subjected to in situ hybridization for small EBV-encoded RNA (EBER). Serum EBV DNA in all cases was measured by real-time quantitative PCR. RESULTS: Serum EBV DNA was detectable in 5 of 5 (100%) EBER-positive gastric carcinoma cases (median concentration, 1063 copies/ml), in 13 of 14 (93%) EBER-negative gastric carcinoma cases with EBER-positive infiltrating lymphocytes (median concentration, 50 copies/ml), and in 0 of 32 (0%) EBER-negative cases. In the nontumor controls, serum EBV DNA was detectable in 7 of 30 (23%) gastritis cases (median concentration, 0 copies/ml) and in 7 of 197 (3.6%) apparently healthy individuals (median concentration, 0 copy/ml). CONCLUSIONS: Our data indicate that serum EBV DNA reflects tumoral EBER status and opens up the possibility that circulating EBV DNA may be used as a tumor marker for the EBER-positive gastric carcinomas. The biological and clinical significance of the presence of low levels of circulating EBV DNA in the minority of gastritis patients and healthy individuals remains to be elucidated.

DNA, Viral↗
PubMed2001

Local renin-angiotensin system in the pancreas: the significance in acute pancreatitis.

Acute pancreatitis is a complex disease entity of which the pathogenesis is still not completely known. Research into the initiation and propagation of the diseases would hopefully help to design new treatment strategies for patients, especially those with severe acute pancreatitis. The novel observation of the activation of the local pancreatic renin-angiotensin system in experimental pancreatitis opens up new horizons for research regarding the pathogenesis of acute pancreatitis.

Acute Disease↗
PubMed2000

Laparoscopic-assisted abdominoperineal resection for low rectal adenocarcinoma.

BACKGROUND: Laparoscopic-assisted resection for colorectal lesions is feasible, but most reported series are heterogeneous and noncomparative. The aim of this study was to investigate whether laparoscopic-assisted resection was better than open abdominoperineal resection for low rectal adenocarcinoma. METHODS: Twenty-five (study group) of 59 consecutive patients who were considered suitable were selected for laparoscopic-assisted abdominoperineal resection based on the availability of informed consent, laparoscopic instruments, and experienced surgeons. The results in these patients were compared with the other 34 patients operated on by the open method (control group). RESULTS: The median follow-up times for the study and control groups were 30.1 and 28.3 months, respectively. The operation time was significantly longer (t-test, p < 0.001), while operative blood loss (Mann-Whitney U test, p = 0.02), postoperative analgesic requirement (Mann-Whitney U test, p = 0.02), time to resume normal diet (Mann-Whitney U test, p = 0.04), and total hospital stay (Mann-Whitney U test, p = 0.02) were significantly less in the study than in the control group. The oncological clearance, complication rate, disease-free interval, and survival were comparable in the two groups. CONCLUSIONS: Laparoscopic-assisted abdominoperineal resection allowed earlier postoperative recovery, with equal oncological clearance, morbidity, mortality, disease-free interval, and survival.

Adenocarcinoma↗
PubMed2000

A comprehensive karyotypic analysis on a newly developed hepatocellular carcinoma cell line, HKCI-1, by spectral karyotyping and comparative genomic hybridization.

A continuously growing human hepatocellular carcinoma (HCC) cell line was established from a Chinese male, carrier of the hepatitis B virus (HBV). This cell line, designated HKCI-1, grows as an adhering monolayer of polygonal epithelial cells that embody one or more nuclei. HKCI-1 secretes alpha-fetoprotein but shows no evidence of HBV carriage. Conventional banding analysis of the short-term cultured primary tumor and the propagated HKCI-1 revealed a chromosome modal number of near-triploidy. It was, however, impossible to derive their complete karyotype due to the complex nature of chromosomal rearrangements and many marker chromosomes of uncertain origin. Spectral karyotyping (SKY) is a newly developed molecular cytogenetic technique that allows the unprecedented discernment of chromosomal abnormalities. Spectral karyotyping analysis on HKCI-1 and the primary tumor elucidated all aberrant chromosomes and revealed complex karyograms. Recurring aberrations detected in both primary tumor and HKCI-1 included der(X)t(X;11)(q10;p10), der(1)t(1;10)(q10;?pq), der(4)t(4;16)(p10;q10), i(5p), del(5)(q13), der(7)t(7;21)(q32q10::q10), der(8)t(8;17)(q10;p10), and der(9)t(9;22)(q34;?pq). Comparative genomic hybridization (CGH) was employed to monitor the culture evolution in vitro. Genomic imbalances in HKCI-1 involved chromosomal losses on 4q, 5q13-qter, 8p, 9pter-q33, 10q, 11q, 13q, 16q, 17q12-qter, and 22, and low-level gains on 6pter-q22, 7p, 8q, 9q34, 10p, 11p, 12, 17pter-q11.2, 18, 19, 20, 21, and Y. High-level amplifications were also detected on 5pter-q12, 7q11.2-qter, and Xq. The corresponding CGH finding on the primary tumor indicated similar imbalances. TP53 mutational analysis showed that both HKCI-1 and the primary tumor had the aflatoxin-associated mutation in codon 249 and an additional TP53 polymorphism in codon 72. Our present study demonstrates the value of combined SKY and CGH study in defining complex rearrangements and identifying cryptic translocations, and provides a comprehensive analysis on the chromosomal abnormalities in HKCI-1.

Adult↗
PubMed2000

Effects of hepatic blood inflow occlusion on liver regeneration following partial hepatectomy in an experimental model of cirrhosis.

BACKGROUND: Hepatic blood inflow occlusion during hepatectomy may influence postoperative liver regeneration. The aim of this study was to investigate the influence of hepatic blood inflow occlusion on liver regeneration following partial hepatectomy in thioacetamide-induced cirrhotic rats. METHODS: Forty-three cirrhotic Wistar-Furth rats were randomly assigned to three groups. Rats in group 1 underwent 64 per cent hepatectomy alone, those in group 2 were subjected to 15 min hepatic blood inflow occlusion followed by 64 per cent hepatectomy, and animals in group 3 were subjected to 30 min inflow occlusion followed by 64 per cent hepatectomy. Liver function, 5-bromo-2'-deoxyuridine (BrdU) labelling index and percentage of initial liver weight on days 1, 2 and 7 posthepatectomy were assessed. RESULTS: Rats in groups 1 and 2 had a significantly higher serum albumin level and a markedly lower alanine aminotransferase level than animals in group 3 on day 1 posthepatectomy (P < 0.05). There was no significant difference in the serum level of total bilirubin of the three groups on days 1, 2 and 7. The BrdU labelling index was significantly higher in groups 1 and 2 than in group 3 animals on day 1 posthepatectomy (P < 0.01 and P < 0.05 respectively). Percentages of initial liver weight were similar in groups 1, 2 and 3 on days 1, 2 and 7 after hepatectomy. CONCLUSION: Hepatic blood inflow occlusion for up to 30 min suppressed DNA synthesis and hepatocyte proliferation at an early posthepatectomy stage and consequently delayed recovery of liver function in cirrhotic rats. However, it did not affect restoration of liver mass or survival after 64 per cent hepatectomy.

Animals↗
PubMed2000

Systemic cytokine response after laparoscopic-assisted resection of rectosigmoid carcinoma: A prospective randomized trial.

OBJECTIVE: To compare the systemic cytokine response in patients after laparoscopic-assisted resection with those after open resection of rectosigmoid carcinoma. SUMMARY BACKGROUND DATA: Laparoscopic resection of colorectal carcinoma is technically feasible, but objective evidence of its benefit is scarce. Systemic cytokines are accepted as markers of postoperative tissue trauma and mediators of the host immune response. METHODS: Thirty-four patients with rectosigmoid carcinoma, without evidence of metastatic disease and suitable for laparoscopic resection, were randomized to undergo either laparoscopic (n = 17) or conventional open (n = 17) resection of the tumor. Clinical parameters were recorded. Sera were collected before surgery and at appropriate time points afterward and assayed for interleukin-1beta, tumor necrosis factor-alpha, interleukin-6, and C-reactive protein. The primary end points were the cytokine and C-reactive protein levels. Data were analyzed by intention to treat. RESULTS: The demographic data of the two groups were comparable. The clinical outcome of both groups was satisfactory, with no surgical deaths and a reasonable complication rate. Both interleukin-1beta and interleukin-6 levels peaked 2 hours after surgery, with the responses in the laparoscopic group significantly less than those in the open group. C-reactive protein levels peaked at 48 hours, and the difference was also statistically significant. Levels of tumor necrosis factor-alpha were not elevated after surgery, and there was no difference between the groups. CONCLUSIONS: Tissue trauma, as reflected by systemic cytokine response, was less after laparoscopic resection than after open resection of rectosigmoid carcinoma. The difference in the systemic cytokine response may have implications on the long-term survival.

Aged↗