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Biomedical subjects

John Wong

Publications and source records attributed to John Wong.

At least 19 recordsLinked to original sources
PubMed2007

Tumor size and operative risks of extended right-sided hepatic resection for hepatocellular carcinoma: implication for preoperative portal vein embolization.

HYPOTHESIS: Major hepatic resection for hepatocellular carcinoma (HCC) is associated with high operative morbidity and mortality, especially in patients with underlying chronic liver disease. The present study evaluated the factors associated with increased operative risks in patients who underwent extended right-sided hepatic resection for HCC. DESIGN: Retrospective study. SETTING: Tertiary referral center. PATIENTS: A retrospective study was performed on 172 patients who underwent extended right-sided hepatic resection of more than 4 Couinaud segments for HCC during a 16-year period (January 1, 1989, to December 31, 2004) to evaluate the clinical factors associated with operative morbidity and mortality. MAIN OUTCOME MEASURE: Risk factors associated with hospital mortality and major operative morbidity. RESULTS: The overall major morbidity and hospital mortality rates were 14.0% and 8.1%, respectively. On multivariate analysis, small tumor size, conventional-approach hepatectomy, Child-Pugh grade B cirrhosis, and preexisting tumor rupture were the independent factors significantly associated with an increased risk of operative mortality. Discriminant analysis showed that a tumor size smaller than 10 cm significantly increased the risk of operative mortality compared with larger tumors (17.2% vs 3.5%; P = .046). CONCLUSIONS: Anterior approach is the preferred technique for extended right-sided hepatic resection for HCC. Increased risk of operative mortality was identified in patients who had a small tumor, which was associated with the resection of a large volume of functioning liver parenchyma. Preoperative portal vein embolization should be considered in this group of patients to enhance atrophy of the right lobe and hypertrophy of the future liver remnant to minimize the operative risk.

Adolescent↗
PubMed2007

Identification of hepatitis B virus-specific lymphocytes in human liver grafts from HBV-immune donors.

Both animal and human studies have demonstrated the adoptive transfer of immunity against hepatitis B virus (HBV) through liver transplantation that may be attributed to the presence of HBV-specific immunocompetent cells of donor origin in liver grafts. In this study, we characterized the resident lymphocytes in 41 human liver grafts by immunohistochemical staining and flow cytometry and directly identified the intragraft HBV-specific lymphocytes in relation to the donor's and subsequent recipient's immunity using enzyme-linked immunospot assay. A significant number of HBV-specific T and B cells were detectable in 59.4% (19/32) and 28.1% (9/32), respectively, of liver grafts from HBV-immune donors. The presence of various HBV-specific lymphocytes was closely associated with each other and with a higher serum titer of antibody against hepatitis B surface antigen (anti-HBs) in donors (P < 0.05). After liver transplantation, 17 of 35 (48.6%) patients with chronic HBV infection showed a spontaneous anti-HBs production, which was significantly associated with a higher number of donor-derived T lymphocytes specific for hepatitis B surface antigen (P = 0.043). In conclusion, the presence of considerable numbers of donor-derived HBV-specific immunocompetent cells in grafts may account for the adoptive transfer of HBV immunity through liver transplantation.

Adult↗
PubMed2007

Toward current standards of donor right hepatectomy for adult-to-adult live donor liver transplantation through the experience of 200 cases.

OBJECTIVE: To define the current standards of donor right hepatectomy, including the middle hepatic vein for adult-to-adult live donor liver transplantation. SUMMARY BACKGROUND DATA: Donor morbidity and mortality are inevitable given the ultra-major nature of the donor operation. Results from a matured center could define the true impact of this donor procedure most accurately. PATIENTS AND METHODS: From May 9, 1996 to April 13, 2005, 200 consecutive donors underwent donor right hepatectomy at the University of Hong Kong Medical Center. All right liver grafts except one included the middle hepatic vein. Donor characteristics, operation time, blood loss, hospital stay, laboratory results, and complications graded by Clavien's classification divided into four eras (each consecutive 50 cases) were compared. RESULTS: Donor characteristics of the four eras were generally comparable. Operative outcomes improved progressively through the four eras. From era 1 to era 4, operation time decreased from 598 minutes (range, 378-932 minutes) to 391 minutes (range, 304-635 minutes). Blood loss also decreased from 500 mL (200-1600 mL) of era 1 to 251 mL (range, 95-595 mL) of era 4. Overall complication rate was 20.5% (41 of 200). Complications rates from eras 1 to 4 were 34%, 16%, 16%, and 16%, respectively. The most common complications were of grade I (24 of 41, 58.5%). A late donor death occurred in era 4 from the development of a duodenocaval fistula 10 weeks postoperation, giving a donor mortality of 0.5% (1 of 200). CONCLUSIONS: This study validated the estimated morbidity and mortality of donor right hepatectomy of 20% and 0.5%, respectively. The data provide reference for counseling potential donors and setting the standards of donor right hepatectomy in the current era.

Adolescent↗
PubMed2007

Difference in tumor invasiveness in cirrhotic patients with hepatocellular carcinoma fulfilling the Milan criteria treated by resection and transplantation: impact on long-term survival.

SUMMARY BACKGROUND DATA: Some previous studies demonstrated better survival after transplantation for small hepatocellular carcinoma (HCC) compared with resection, but the influence of differences in tumor invasiveness between transplanted and resected patients has not been studied. This study compared the tumor characteristics of patients with HCC within the Milan criteria treated by resection or transplantation, and elucidated their impact on long-term survival. PATIENTS AND METHODS: Tumor characteristics and long-term survival of 204 cirrhotic patients with resection and 43 cirrhotic patients with transplantation for HCC within the Milan criteria were compared. A multivariate analysis was performed to determine the prognostic factors of survival in all patients with resection or transplantation. RESULTS: Tumors in the transplanted group were associated with lower incidence of high-grade tumors, microscopic venous invasion, and microsatellite nodules. The overall 5-year survival was better in the transplantation group than the resection group (81% vs. 68%, P = 0.017). However, there were no significant differences in survival between the two groups when stratified according to presence or absence of venous invasion. Multivariate analysis showed that hepatitis C virus serology, tumor size, tumor number, and microscopic venous invasion, but not resection or transplantation, were of prognostic significance. CONCLUSIONS: There were significant differences in tumor invasiveness in HCC treated by transplantation and resection as a result of selection bias, even in patients with the tumors fulfilling the Milan criteria. When the different tumor invasiveness was taken into account, there was no significant difference in the long-term survival after resection or transplantation.

Adolescent↗
PubMed2006

Liver intestine-cadherin (CDH17) haplotype is associated with increased risk of hepatocellular carcinoma.

PURPOSE: Hepatocellular carcinoma (HCC), the most common form of liver cancer, is a leading cause of cancer death worldwide. We previously showed that aberrant mRNA splicing of the liver intestine-cadherin gene CDH17 in liver tissues was triggered by the specific constellation of two CDH17 single nucleotide polymorphisms (651T and IVS6+35G). CDH17 aberrant splicing was highly associated with tumor dissemination and shorter survival of HCC patients. Consequently, it is highly relevant to assess whether the presence of these single nucleotide polymorphisms in the general population represents a risk to the development of HCC. EXPERIMENTAL DESIGN: We conducted a case-control study including 164 HCC and 99 cirrhosis patients and 293 healthy controls. Genotyping was done by PCR and direct sequencing. Odds ratio (OR) and chi2 analysis were used to analyze genotypes and haplotypes. RESULTS: Genotypes 651TT [OR, 2.62; 95% confidence interval (95% CI), 1.34-5.03] and IVS6+35 GG (OR, 1.95; 95% CI, 1.04-3.62) were highly associated with HCC disease. The 651T (C>T) and IVS6+35G (A>G) alleles were also overrepresented in HCC patients and, in particular, the T-G haplotype was the most prevalent in HCC patients when compared with healthy controls (OR, 1.57; 95% CI, 1.167-2.109; P=0.004), which was in agreement with the aberrant splicing observed in tumor tissues. There was no significant difference in genotype and allele frequencies between cirrhosis patients and controls. CONCLUSION: The functional T-G haplotype of CDH17 (651 C>T and IVS6+35A>G) is a genetic susceptibility factor for the development of HCC in a Chinese population.

Alleles↗
PubMed2006

The management of ductal carcinoma in situ of the breast: a screened population-based analysis.

BACKGROUND: A recent SEER study identified significant variations in the care of women with DCIS, yet several potential confounding variables were not included. We report a patterns of care study of women with DCIS to better understand the gap between evidence-based knowledge and the management of DCIS. METHODS: We studied all cases of DCIS diagnosed through the Ontario Breast Screening Program from 1991 to 2000. Data was obtained by database linkage and chart abstraction. A logistic regression model using generalized estimating equations to adjust for clustering was used. RESULTS: About 320,236 women were screened and 727 individuals were diagnosed with DCIS. The rate of mastectomy was 30% and was associated with multifocality (OR: 3.5 [1.7, 7.1], P = 0.0005), tumor size (OR: >2 cm vs. 1 cm (OR: 2.4 [1.3, 4.4], P = 0.006). Half of cases with margins <1 cm did not receive XRT. CONCLUSIONS: Our study corroborates previous reports on the persistent rates of mastectomy and axillary nodal dissection and the limited use of XRT in the treatment of DCIS.

Age Distribution↗
PubMed2006

Esomeprazole with aspirin versus clopidogrel for prevention of recurrent gastrointestinal ulcer complications.

BACKGROUND AND AIMS: The role of clopidogrel in patients at risk for gastrointestinal complications is uncertain, although it has been recommended for patients who have gastrointestinal intolerance to aspirin. We tested the hypothesis that clopidogrel is as effective as esomeprazole and aspirin in preventing recurrences of ulcer complications. METHODS: This was a prospective, double-blind, randomized, controlled study of 170 patients who developed ulcer bleeding after the use of low-dose aspirin between November 2002 and January 2005. After healing of ulcers and eradication of Helicobacter pylori, if present, patients were assigned randomly to treatment with esomeprazole 20 mg/day and aspirin 100 mg/day (n = 86) or clopidogrel 75 mg/day (n = 84) for 52 weeks. The primary end point was recurrent ulcer complications. RESULTS: During a median follow-up period of 52 weeks, no patient in the esomeprazole group, as compared with 9 patients in the clopidogrel group, developed recurrent ulcer complications. The cumulative incidences of recurrent ulcer complications were 0% in patients receiving esomeprazole and aspirin and 13.6% in patients receiving clopidogrel (absolute difference, 13.6%; 95% confidence interval for the difference, 6.3-20.9; log-rank test, P = .0019). CONCLUSIONS: The combination of esomeprazole and aspirin is superior to clopidogrel in preventing ulcer complications in patients who have a past history of aspirin-related peptic ulcer bleeding.

Aged↗
PubMed2006

Highly efficacious nontoxic preclinical treatment for advanced metastatic breast cancer using combination oral UFT-cyclophosphamide metronomic chemotherapy.

Metronomic antiangiogenic chemotherapy, the prolonged administration of relatively low drug doses, at close regular intervals with no significant breaks, has been mainly studied at the preclinical level using single chemotherapeutic drugs, frequently in combination with a targeted antiangiogenic drug, and almost always evaluated on primary localized tumors. We tested a "doublet" combination metronomic chemotherapy treatment using two oral drugs, UFT, a 5-fluorouracil (5-FU) prodrug administered by gavage, and cyclophosphamide, for efficacy and toxicity in a new mouse model of advanced, terminal, metastatic human breast cancer. The optimal biological dose of each drug was first determined by effects on levels of circulating endothelial progenitor cells as a surrogate marker for angiogenesis, which was assessed to be 15 mg/kg for UFT and 20 mg/kg for cyclophosphamide. A combination treatment was then evaluated in mice with advanced metastatic disease using a serially selected metastatic variant of the MDA-MB-231 breast cancer-cell line, 231/LM2-4. UFT or cyclophosphamide treatment showed only very modest survival advantages whereas a combination of the two resulted in a remarkable prolongation of survival, with no evidence of overt toxicity despite 140 days of continuous therapy, such that a significant proportion of mice survived for over a year. In contrast, this striking therapeutic effect of the combination treatment was not observed when tested on primary orthotopic tumors. We conclude that combination oral low-dose daily metronomic chemotherapy, using cyclophosphamide and UFT, is superior to monotherapy and seems to be a safe and highly effective experimental antimetastatic therapy, in this case, for advanced metastatic breast cancer.

Animals↗
PubMed2006

The influence of technical complications on postoperative outcome and survival after esophagectomy.

BACKGROUND: The dismal survival associated with esophagectomy for cancer has led to the search for potentially correctable factors responsible for this poor prognosis. Although it is intuitive that technical complications could increase postoperative mortality, the effect on long-term survival is controversial. METHODS: From 1990 to 2002, 434 patients underwent resection for squamous cell carcinoma of the intrathoracic esophagus. Prospectively collected data were reviewed for the presence of technical complications. Patient, tumor, and operative variables, postoperative outcome, and survival were compared between patients with technical complications and those without. Prognostic factors were assessed by multivariate analysis. RESULTS: Technical complications occurred in 98 (22.6%) patients. Patients with technical complications had a higher prevalence of cardiac disease, more proximal tumors, and more cervical anastomoses. Technical complications were associated with an increased rate of pulmonary complications (37.8% vs. 10.7%; P<.001) and increased hospital mortality (9.2% vs. 3.3%; P=.025), but no difference in 30-day mortality (2% vs. 1.2%; P=.6). Poor-prognostic factors for survival included male sex, stage III/IV disease, cirrhosis, proximal tumors, and R1/R2 resection, but not technical complications. CONCLUSIONS: Although immediate postoperative outcome and hospital mortality rates were increased, no effect on long-term survival was seen in patients with complications related to errors in surgical technique.

Adult↗
PubMed2006

The effects of neoadjuvant chemoradiation on pTNM staging and its prognostic significance in esophageal cancer.

For esophageal cancer, it is not clear if pathologic TNM staging after chemoradiation and resection will have the same prognostic significance compared with patients who undergo resection only. From 1995 to 2004, prospectively collected data from 279 patients with intrathoracic squamous cell cancers were analyzed. Patients were given chemoradiation either as part of a randomized trial comparing neoadjuvant chemoradiation with surgical resection alone, or because of advanced disease at presentation. One hundred seventy patients had surgical resection only (surgery), and 109 had neoadjuvant chemoradiation (CRT plus surgery). In the surgery group, pT1, 2, 3, and 4 disease was found in 15, 17, 104, and 34 patients, respectively; their respective pN1 rates were 13.3%, 29.4%, 57.7%, and 64.7%, P < 0.01. In CRT plus surgery, pT0, T1, 2, 3, and 4 were found in 48, 12, 23, 21, and 5 patients, respectively; their respective pN1 rates were 31.3%, 16.7%, 21.7%, 52.4%, and 20%, P = 0.44. Logistic regression analysis of factors predictive of pN1 showed that pT stage correlated with pN1 status (P = 0.005) in the surgery group, but not for the CRT plus surgery group. Cox regression analysis demonstrated that in the surgery group, pT, pN, and R category, and overall pTNM stage, were independent prognostic factors, whereas pN, R category, and gender were identified as relevant for CRT plus surgery. After chemoradiation, pT and overall pTNM stage groupings were not as clearly prognostic as in patients without prior therapy. Nodal status remains an important prognostic factor.

Adult↗
PubMed2006

Operative outcomes of adult-to-adult right lobe live donor liver transplantation: a comparative study with cadaveric whole-graft liver transplantation in a single center.

OBJECTIVE: To evaluate and compare the operative and survival outcomes of patients who underwent right lobe live donor liver transplantation (RLDLT) and cadaveric whole-graft liver transplant (CWLT) recipients in a single institution. SUMMARY BACKGROUND DATA: Current data suggest that RLDLT has an inferior graft survival outcome when compared with CWLT. PATIENTS AND METHODS: A prospective study was performed on 180 consecutive adult patients who underwent primary liver transplantation from January 2000 to February 2004. The operative and survival outcomes of RLDLT (n = 124) were compared with those of CWLT (n = 56). RESULTS: Fifty-five (44%) and 16 (29%) patients were on high-urgency list in the RLDLT group and the CWLT group, respectively (P = 0.045). The preoperative Model for End-Stage Liver Disease scores were comparable in both groups. The waiting time for liver transplantation was significantly shorter in the RLDLT group. The graft weight to estimated standard liver weight ratio was significantly lower in the RLDLT group. The postoperative hospital stay and hospital mortality were comparable in the RLDLT group (1.6%) and the CWLT group (5.4%). Thirty-one (25%) patients in the RLDLT group and 3 (5%) patients in the CWLT group developed biliary stricture on follow-up (P = 0.002). At a median follow-up of 27 months, the actuarial graft and patient survival rates were 88% and 90%, respectively, in the RLDLT group, and both were 84% in the CWLT group. CONCLUSION: RLDLT results in favorable operative outcomes comparable with those of CWLT. However, there is a significantly higher incidence of biliary stricture associated with RLDLT.

Adolescent↗
PubMed2006

Anterior approach versus conventional approach right hepatic resection for large hepatocellular carcinoma: a prospective randomized controlled study.

OBJECTIVE: To evaluate whether major right hepatectomy using the anterior approach technique for large hepatocellular carcinoma (HCC) results in better operative and long-term survival outcomes when compared with the conventional approach technique. SUMMARY BACKGROUND DATA: The anterior approach technique has been advocated recently for large right liver tumors. However, its beneficial effects on the operative and survival outcomes of the patients have not been evaluated prospectively. METHODS: A prospective randomized controlled study was performed on 120 patients who had large (> or =5 cm) right liver HCC and underwent curative major right hepatic resection during a 57-month period. The patients were randomized to undergo resection of the tumor using the anterior approach technique (AA group, n = 60) or the conventional approach technique (CA group, n = 60). The anterior approach technique involved initial vascular inflow control, completion of parenchymal transection, and complete venous outflow control before the right liver was mobilized. Operative and long-term survival outcomes of the two groups were analyzed. Quantitative assessments of markers of circulating tumor cells at various stages of surgery of the two techniques were also assessed by plasma albumin-mRNA. RESULTS: The overall operative blood loss, morbidity, and duration of hospital stay were comparable in both groups. Major operative blood loss of > or =2 L occurred less frequently in the AA group (8.3% vs. 28.3%, P = 0.005). As a result, blood transfusion requirement and number of patients requiring blood transfusion were significantly lower in the AA group. Hospital mortality occurred in 1 patient in the AA group and 6 patients in the CA group (P = 0.114). Median disease-free survival was 15.5 months in the AA group and 13.9 months in the CA group (P = 0.882). Overall survival was significantly better in the AA group (median >68.1 months) than in the CA group (median = 22.6 months, P = 0.006). The survival benefit appeared more obvious in patients with stage II disease and patients with lymphovascular permeation of the tumor. The anterior approach was also found to associate with significantly lower plasma albumin-mRNA levels at various stages of surgery compared with the CA technique. On multivariate analysis, tumor staging, anterior approach hepatic resection, and resection margin involved by the tumor were independent factors affecting overall survival. CONCLUSION: The anterior approach results in better operative and survival outcomes compared with the conventional approach. It is the preferred technique for major right hepatic resection for large HCC.

Blood Loss, Surgical↗
PubMed2006

Human cytomegalovirus attenuates interleukin-1beta and tumor necrosis factor alpha proinflammatory signaling by inhibition of NF-kappaB activation.

Viral infection is associated with a vigorous inflammatory response characterized by cellular infiltration and release of the proinflammatory cytokines interleukin-1 (IL-1) and tumor necrosis factor alpha (TNF-alpha). In the present study, we identified a novel function of human cytomegalovirus (HCMV) that results in inhibition of IL-1 and TNF-alpha signaling pathways. The effect on these pathways was limited to cells infected with the virus, occurred at late times of infection, and was independent of cell type or virus strain. IL-1 and TNF-alpha signaling pathways converge at a point upstream of NF-kappaB activation and involve phosphorylation and degradation of the NF-kappaB inhibitory molecule IkappaBalpha. The HCMV inhibition of IL-1 and TNF-alpha pathways corresponded to a suppression of NF-kappaB activation. Analysis of IkappaBalpha phosphorylation and degradation suggested that HCMV induced two independent blocks in NF-kappaB activation, which occurred upstream from the point of convergence of the IL-1 and TNF-alpha pathways. We believe that the ability of HCMV to inhibit these two major proinflammatory pathways reveals a critical aspect of HCMV biology, with possible importance for immune evasion, as well as establishment of infection in cell types persistently infected by this virus.

Cytomegalovirus↗
PubMed2006

Co-occurrence and comorbidities in patients with immune-mediated inflammatory disorders: an exploration using US healthcare claims data, 2001-2002.

OBJECTIVE: Research in immune-mediated inflammatory disorders (IMIDs) suggests that several diseases share disruptions in key cytokines. A common pathogenesis may present as similar patterns of disease co-occurrence and comorbidity, which could be observed through the analysis of healthcare claims datasets. METHODS: Adult patients continuously enrolled from 2001-2002 were identified in two US healthcare datasets containing medical and drug claims from health plans and self-insured employers. Patients with treatment records indicating an IMID were selected (e.g., rheumatoid arthritis, psoriasis, Crohn's disease); controls for each disorder were matched 3:1 based on age, gender, region, and previous insurance coverage. IMID cohorts and comorbidities were identified using International Classification of Diseases, 9th revision codes. Prevalence relative risk was used to assess co-occurrence and comorbidity rates in IMID cohorts and controls. Medical and drug utilization patterns were also explored. RESULTS: Findings were similar across the two datasets. IMID patients represented about 4% of the population; specific IMID prevalence matched the epidemiology literature. Patients with at least one IMID had a higher risk for another IMID when compared to controls. The risk for infectious, renal, liver, and ulcerative comorbidities was also elevated. Selected drug utilization patterns confirmed comorbidity findings. IMID patients used more healthcare resources compared to controls; findings were robust under sensitivity analyses. CONCLUSIONS: IMID patients were generally more likely than controls to have another IMID, supporting the concept that the diseases are related. These patients also had higher comorbidity rates. Findings may be limited by the nature of claims datasets and the confounding effect of current treatments. Prospective studies are needed to determine whether IMIDs have a common pathogenesis.

Adult↗
PubMed2006

Transforming capacity of two novel genes JS-1 and JS-2 located in chromosome 5p and their overexpression in human esophageal squamous cell carcinoma.

Esophageal squamous cell carcinoma (ESCC) has a high mortality rate and geographic differences in incidence. Previous studies of comparative genomic hybridization (CGH) showed that chromosomal 5p is frequently amplified in cell lines and primary ESCC of Hong Kong Chinese origin. In this report, attempt was made to study two novel genes, named as JS-1 and JS-2, which are located in chromosome 5p15.2 and are 5' upstream to delta catenin for their roles in molecular pathogenesis of ESCC. Eleven cell lines, 27 primary ESCC cases and multiple human tissue cDNA panels (MTC) of digestive system were studied for the expression level of JS-1 and JS-2 by RT-PCR. The full-length cDNA sequences of JS-1 and JS-2 were determined from a non-tumor esophageal epithelial cell line by 3' and 5' rapid amplification of cDNA ends (RACE). The transforming capacity of JS-1 and JS-2 was also investigated by transfecting NIH 3T3 cells with the expression vector pcDNA3.1(-) cloned with the full coding sequences and it was followed by the study of foci formation of the transfected cells under confluence growth and the anchorage-independent growth in soft agar. Forty-five percent (5/11) and 18% (2/11) of the ESCC cell lines showed overexpression of JS-1 and JS-2 respectively, while 55% (15/27) and 14% (3/22) primary ESCC cases showed overexpression of JS-1 and JS-2 respectively. JS-1 overexpression was most common in patients with stage II ESCC (6/27; 22%) whereas JS-2 was only overexpressed in a dysplastic lesion (1/22; 4%) and stage III tumors (2/22; 9%). The expression levels of JS-1 and JS-2 are both low in normal esophageal tissues. Overexpression of JS-1 in NIH 3T3 cells caused foci formation in confluence growth and colony formation in soft agar but not for JS-2. A high grade sarcoma was formed in the athymic nude mice when NIH 3T3 cells overexpressing JS-1 were injected subcutaneously. Our results thus indicate that the frequent overexpression of JS-1 in ESCC and its transforming capacity in normal cells may play a critical role in the molecular pathogenesis of ESCC. The present study also forms the ground work for further identification of novel mechanisms of molecular carcinogenesis in ESCC and other cancers.

Aged↗