Hock-Liew Eng

Smooth muscle tumors of the gastrointestinal tract: Analysis of prognostic factors

BACKGROUND The survival rates and therapeutic approaches to gastrointestinal leiomyoma and leiomyosarcoma vary widely. This review analyzes the clinical symptoms and signs, the results of the pathologic examination, and the DNA makeup of these tumors and determines the factors that affect the prognosis of patients who have leiomyosarcoma. METHODS Flow cytometric DNA analysis was performed in 80 patients with gastrointestinal smooth muscle tumors to establish the correlation of DNA ploidy with tumor size and stage and histologic grade. Using univariate and multivariate analyses, we investigated tumor size, histologic grade, association with gastrointestinal bleeding, DNA makeup, operative procedure, age, gender, and tumor necrosis as they affect the long-term survival of 45 patients with leiomyosarcoma. The Kaplan-Meier method was used to determine the survival rates and the log-rank method was used to compare survival rates between the two groups. RESULTS Between 1986 and 1992, operations were performed on the 80 gastrointestinal smooth muscle tumors--esophageal 1, stomach 32, intestinal 33, colonic 2, and rectal 12. The most common symptoms and signs were gastrointestinal bleeding (43.8%), abdominal mass (37.5%), and abdominal pain (21.3%), and the tumors were classified as leiomyoma 35, low-grade leiomyosarcoma 24, and high-grade leiomyosarcoma 21, according to the cellular atypia and mitotic rate. DNA ploidy correlated with histology grade (r = 0.70, p < 0.01) and tumor size (r = 0.31, p < 0.01) but not with localized or advanced tumors. Only one patient with leiomyoma died of liver metastasis during the follow-up period. In univariate analysis of the 45 patients with leiomyosarcoma, the survival rate was poor in men with tumor sizes greater than 5 cm, incomplete resections, advanced tumors, and high-grade tumors. With multivariate Cox regression analysis only advanced tumors (p < 0.01) and high-grade tumors (p < 0.01) were the independent factors that affected survival. CONCLUSIONS Leiomyosarcomas usually measure more than 10 cm. In univariate analysis the significant factors affecting the survival rate of patients with leiomyosarcoma are maleness, size greater than 5 cm, inadequate resection, and advanced-stage and high-grade disease. In multivariate Cox regression analysis advanced-stage and high-grade leiomyosarcoma are the only independent factors affecting survival. DNA ploidy correlates with the size and the grade of gastrointestinal smooth muscle tumors but not with tumor stage. DNA ploidy does not affect independently the survival of leiomyosarcoma.

Right Lobe Living Donor Liver Transplantation—Addressing the Middle Hepatic Vein Controversy

Objective To describe our approach in the decision-making for taking the middle hepatic vein with the graft or leaving it with the remnant liver in right lobe live donor liver transplantation. Summary Background Data Right lobe living donor liver transplantation has been successfully performed. However, the extent of donor hepatectomy is still a subject of debate and the main considerations in the decision making are graft functional adequacy and donor safety. Methods An algorithm based on donor-recipient body weight ratio, right lobe-to-recipient standard liver volume estimate, and donor hepatic venous anatomy was used to decide the extent of donor hepatectomy. This algorithm was applied in 25 living donor liver transplant operations performed between January 1999 and January 2002. In grafts taken without the middle hepatic vein, anterior segment tributaries draining into it were not reconstructed. Outcomes between right lobe liver transplants with (Group I) and without (Group II) the middle hepatic vein were compared. Results Ten grafts included the middle hepatic vein and 15 did not. The mean graft to recipient standard liver volume ratio was 58% and 64% in Groups I and II, respectively, and the difference was not statistically significant. Donors from both groups had comparable recovery, with 2 complications, 1 from each group, requiring a percutaneous drainage procedure. The recipient outcomes were, likewise, comparable and there was 1 case of structural outflow obstruction in Group I, which required venoangioplasty and stenting. There were 2 recipient mortalities, 1 due to a biliary complication and the other to recurrent hepatitis C. Another patient required retransplantation for secondary biliary cirrhosis. The overall actuarial graft and patient survival rates are 84% and 96%, respectively, at a median follow-up of 16 months. Conclusion Based on certain preoperative criteria, a right lobe graft can be taken with or without the middle hepatic vein with equally successful outcomes in both the donors and recipients. The decision, therefore, of the extent of right lobe donor hepatectomy should be tailored to the particular conditions of each case.

Serum concentration of tumor necrosis factor in patients with breast cancer

Background: The outcome of breast cancer is usuallydetermined by multiple factors. Serum tumor necrosis factoralpha concentration has been found to be increasedin the circulation of patients with malignancy. Thisstudy was designed with the aim to investigateany correlation between the serum tumor necrosis factoralpha and the clinicopathological fetures and furthermore evaluatethe prognostic significance of serum tumor necrosis factoralpha concentration in breast cancer. Methods: Forty consecutivepatients with invasive breast cancer undergoing modified radicalmastectomy were prospectively included and evaluated. Venous bloodsamples were collected before the surgery. Sera wereobtained by centrifugation, and stored at − 70°C until assayed. The control group consisted 30healthy, age-matched subjects. Serum concentrations of tumor necrosisfactor alpha were measured by the quantitative sandwichenzyme immunoassay technique. The data on tumor size,age, estrogen receptor status, lymph node status andTNM staging were reviewed and recorded.Results: The mean value of serum tumor necrosis factor alphain patients with invasive breast cancer was 1.47± 0.58 pg/ml and that of the controlgroup was 0.98 ± 0.37 pg/ml, and thedifference was significant (P < 0.01). With univariableanalysis, patients with maximum tumor size of 5cm or larger (P=0.03), more advancedTNM staging (P < 0.01); and more advancedlymph node status (P < 0.01) were shownto have significantly higher serum concentrations of tumornecrosis factor alpha. However, with multivariable analysis, TNMstaging appeared as the only independent factor (P< 0.01) predicting the significant, higher serum concentrationsof tumor necrosis factor alpha. Conclusion: Preoperative evaluationof serum tumor necrosis factor alpha concentrations maybe a valuable parameter for reflecting the severityof staging for invasive breast cancer.

Impact of artificial sunlight therapy on the progress of non-alcoholic fatty liver disease in rats.

BACKGROUND & AIMS Non-alcoholic steatohepatitis (NASH) is recognized as the most severe form of non-alcoholic fatty liver disease, with likely progression to liver cirrhosis and hepatocellular carcinoma. However, there is no unified standard for diagnosis and therapeutics. This study aimed to characterize lipid transfer/metabolic proteins as non-invasive diagnostic markers, and to evaluate the therapeutic effects of phototherapy on the progression of NASH in rats. METHODS Lewis rats given a choline-deficient and iron-supplemented l-amino acid-defined (CDAA) diet and Zucker fa/fa rats were used as a diet-induced and an obesity-related NASH models, respectively, with or without phototherapy. RESULTS Serum apolipoprotein E and low molecular weight-adiponectin levels were gradually reduced and reached the lowest level at fatty liver/NASH stage both in CDAA diet-induced NASH model and in genetically obese model. Total-adiponectin levels were dramatically elevated after NASH was established in CDAA diet-induced NASH model. Phototherapy ameliorated hepatocyte apoptosis, inflammation, fibrosis, and insulin/leptin resistance caused by CDAA diet with alteration of the levels of lipid transfer/metabolic proteins and elevation of the circulating active form of vitamin D(3). Vitamin D(3) supplementation ameliorated NASH progression in CDAA diet-induced NASH model. However, phototherapy failed to ameliorate the obesity and steatosis, suggesting that phototherapy may possess anti-inflammatory/fibrotic activity rather than anti-obesity/steatotic activity. CONCLUSIONS These results suggest that serum lipid transfer/metabolic proteins and vitamin D(3) status may be effective biomarkers for non-invasive diagnosis of NASH progression, and that phototherapy may be a good complementary therapy for NASH because of its regulation of lipid transfer/metabolic proteins and vitamin D(3).

Clinical Significance of Hepatitis B Virus (HBV) Genotypes and Precore and Core Promoter Mutations Affecting HBV e Antigen Expression in Taiwan

ABSTRACT To assess the prevalence and clinical significance of hepatitis B virus (HBV) genotypes and precore and core promoter mutations in Taiwan, a cohort of 200 Taiwanese chronic hepatitis B patients was analyzed. The HBV genotypes and sequences of the precore and the core promoter regions were determined in 66 asymptomatic carriers and 134 patients who had liver biopsy-verified chronic hepatitis and liver cirrhosis. The HBV e-antigen (HBeAg)-negative patients had a higher frequency of mutations at core promoter nucleotides 1753 and 1773 and precore nucleotides 1846, 1896, and 1899 than HBeAg-positive patients. Among the 200 patients, the frequencies of genotype C, T1762 and A1764, C1753, T1766 and A1768, and A1896 mutations increased and the frequencies of T or G1752, T1773, G1799, and C1858 mutations decreased with advancing liver diseases. These factors were different between those with HBeAg-positive status and those with HBeAg-negative status. Based on multiple logistic regression analysis, the risk factors of liver cirrhosis for 200 patients were the presence of T1762 and A1764 mutations (odds ratio [OR] = 11.11; 95% confidence interval [CI] = 3.91 to 31.25; P < 0.001), age ≥35 years (OR = 3.42; 95% CI = 1.33 to 8.77; P = 0.011), and genotype C (OR = 2.87; 95% CI = 1.21 to 6.81; P = 0.017). Further categorical analysis found that 62.1% of patients with genotype C, T1762 and A1764 mutations and age ≥35 years had liver cirrhosis. None of the 55 patients infected with the genotype B, A1762 and G1764 wild type and age <35 years showed liver cirrhosis. In conclusion, our data suggest that pathogenic differences between HBeAg-positive and -negative patients may exist. In Taiwan, HBV genotype C and the T1762 and A1764 mutations may play a role in HBV-related liver cirrhosis, and these could serve as molecular markers for prediction of the clinical outcomes of chronic HBV patients.

Living Donor Liver Transplantation for Biliary Atresia: A Single-Center Experience with First 100 Cases

The aim of this study is to present our institutional experience in living donor liver transplantation (LDLT) as a treatment for end‐stage liver disease in children with biliary atresia (BA). A retrospective review of transplant records was performed. One hundred BA patients (52 males and 48 females) underwent LDLT. The mean follow‐up period was 85.5 months. The mean age was 2.4 years. The mean preoperative weight, height, and computed GFR were 12.2 kg, 82.5 cm, and 116.4 ml/min/1.73 m2, respectively. Twenty‐seven patients were below 1 year of age, and 49 patients were below 10 kg at the time of transplantation. Ninety‐six had had previous Kasai operation prior to transplant. The mean recipient operative time was 628 min. The mean recipient intraoperative blood loss was 176 ml. Thirty‐five did not require blood or blood component transfusion. The left lateral segment (64) was the most common type of graft used. There were 27 operative complications which included 3 reoperations for postoperative bleeding, 9 portal vein, 4 hepatic vein, 4 hepatic artery, and 7 biliary complications. There was one in‐hospital mortality and one retransplantation. The overall rejection rate was 20%. The overall mortality rate was 3%. The 6‐month, 1‐year and 5‐year actual recipient survival rates were 99%, 98% and 98%, respectively.

Correlation of pandemic (H1N1) 2009 viral load with disease severity and prolonged viral shedding in children.

Younger children may require a longer isolation period and more aggressive treatment.

Lamivudine for the treatment of hepatitis B virus reactivation following chemotherapy for non-Hodgkin's lymphoma.

Summary. Chemotherapy for non‐Hodgkins lymphoma (NHL) patients with chronic hepatitis B virus (HBV) infection may be accompanied by severe hepatitis. Of 86 consecutive NHL patients, 11 (12·8%) exhibited a positive serum HBsAg. Six of these patients (54·5%) developed acute exacerbation of chronic HBV infection following chemotherapy and received lamivudine. Five of the six patients demonstrated a clinical improvement, one patient died from fulminant hepatic failure owing to delayed lamivudine therapy and poor compliance. These data suggest that HBsAg screening is necessary before commencing chemotherapy for NHL patients in a hyperendemic area and that lamivudine is effective in treating hepatitis B reactivation during chemotherapy.

Failure to Detect Human Papillomavirus DNA in Malignant Epithelial Neoplasms of Conjunctiva by Polymerase Chain Reaction

To elucidate the putative role of human papillomavirus (HPV) infection in the etiology of conjunctival tumors, 44 formalin-fixed, paraffin-embedded specimens of conjunctival tumors (24 patients with papillomas and 20 patients with dysplastic and/or malignant tumors) were screened for HPV infection using 4 different polymerase chain reactions (PCRs). Of the 24 samples of papilloma, 14 (58%) displayed positive results by applying nested PCR using primer sets of HPV consensus L1 region. HPV type 6 or 11 was detected in 9 cases of papilloma by type-specific primer sets, but none of them were positive for HPV type 16 or 18. However, by using the highly sensitive PCR technique, we failed to demonstrate the HPV DNA of HPV types 6, 11, 16, and 18 in any of the 20 malignant epithelial tumors of conjunctiva. We conclude that HPV-6 or HPV-11 is present in a substantial percentage of conjunctival papillomas, which is in accordance with findings of previously reported studies. In contrast, malignant conjunctival carcinomas are not associated with HPV infection; other pathogenic mechanisms, such as UV light, probably are more important in the cause of these malignant lesions.

Serum Levels of Hepatocyte Growth Factor in Patients with Breast Cancer

Objective: Hepatocyte growth factor (HGF) has been reported the cause of many biological events, including cell proliferation, movement, invasiveness, morphogenesis, and angiogenesis. Elevated hepatocyte growth factor content in tumor tissue was reported to predict a more aggressive biology in non–small cell lung cancer patients. However, there is still limited knowledge about the role of HGF in breast cancer. This study was designed with the aim to elucidate the possible relationship between the preoperative circulating soluble HGF and breast cancer. Materials and Methods: One hundred twenty-four consecutive patients with invasive breast cancer undergoing surgery were prospectively included and evaluated. Venous blood samples were collected before the surgery. Sera were obtained by centrifugation and stored at −70°C until assayed. The control group consisted of 35 patients with benign breast tumor (20 with fibrocystic disease and 15 with fibroadenoma). Serum concentrations of soluble HGF were measured by the quantitative sandwich enzyme immunoassay technique. The data on primary tumor staging, age, estrogen receptor status, lymph node status, distant metastases status, histologic grading, and tumor-node-metastasis (TNM) staging were reviewed and recorded. Results: The mean value of serum soluble HGF in patients with invasive breast cancer was 529.05 ± 123.33 pg/mL and that of control group was 343.00± 31.03 pg/mL and the difference was significant (P < 0.001). Furthermore, there were significantly higher serum levels of soluble HGF in patients with negative estrogen receptor (P = 0.035), in patients with poorer differentiated tumor (P < 0.001), in patients with more advanced primary tumor staging (P < 0.001), in patients with more advanced lymph node status (P < 0.001), in patients with distant metastases (P < 0.001), and in patients with more advanced TNM staging (P < 0.001). In multivariate analysis by the multiple linear regression method, TNM staging (P < 0.001) seemed an independent factor regarding the significant higher serum levels of soluble HGF. Conclusion: Patients with more advanced TNM staging were shown to have higher serum soluble HGF. Thus, preoperative serum soluble HGF levels might reflect the severity of invasive breast cancer and deserve further evaluation.