Surasak Leelaudomlipi

TOP2A Amplification and Overexpression in Hepatocellular Carcinoma Tissues

Hepatocellular carcinoma (HCC) is the leading cause of cancer death in men worldwide owing to limited insights into pathogenesis and unsatisfactory efficacy of current therapies. HER2 and TOP2A genes are coamplified in breast and some other cancers. In this study, we investigated gene aberrations of HER2 and TOP2A and protein expressions of HER2, TOP2A, Ki-67, and p53 in tumor and matched nontumor tissues, as well as their associations with clinicopathological features. Gene aberrations were evaluated by FISH and protein expressions by IHC. Neither HER2 overexpression nor HER2 gene amplification was observed in both tumor tissues and matched nontumor tissues. By contrast, TOP2A overexpression was detected in 72.5% of tumor tissues but not detected in matched nontumor tissues. However, TOP2A gene amplification was not observed in both tumor and matched nontumor tissues. TOP2A overexpression was significantly associated with HCC tumor tissues (P < 0.001), hepatitis B surface antigen (HBsAg) in the serum (P = 0.004), and Ki-67 (P = 0.038) but not with age, tumor size, alpha-fetoprotein, TP53, and copy number of TOP2A gene and chromosome 17 centromere. In conclusion, TOP2A overexpression in HCC was not secondary to gene amplification. In addition, neither HER2 amplification nor overexpression could be used as prognostic and predictive marker in HCC.

High coverage and safety of influenza A (H1N1) 2009 monovalent vaccination among health care personnel in Thailand

We aimed to report the coverage and safety of the influenza A (H1N1) 2009 monovalent vaccination (Panenza; Sanofi Pasteur, Val de Reuil Cedex, France) among health care personnel (HCP) in a university hospital setting in Thailand. The hospital set up a system to vaccinate HCP and did surveillance of the adverse effects (AEs). During a 4-week period, 6,210 (78.7%) HCP were vaccinated. There were 82 reported nonserious AEs among 32 HCP. The most common AE was fatigue/uncomfortable feeling (24%).

H1N1 2009 influenza among healthcare workers in a tertiary care hospital in Thailand

resources besides causing inconvenience to patients (staying indoors in an isolation room, visitor restriction, and potential breach of personal confidential clinical information). In view of the above limitations of clinical algorithms and the consequences its implementation may generate, it is imperative that a rational approach is adopted with regard to resource utilisation and infection control needs. Infection control teams of most hospitals are under significant pressure to prevent nosocomial infections to patients, visitors and staff. Understandably under these circumstances it is not uncommon for a safety-first attitude to be adopted, leading to over-utilisation of available resources. Novel swine influenza should not blind us to the fact that there are many other old infections which are equally important and worthy of prevention. The latest data from the World Health Organization show that the basic reproduction rate (R0: mean number of secondary cases a single case will cause) of the novel H1N1 influenza virus is <2 in most European countries and in the USA, which is significantly less than for many common diseases such as measles (R0: 12e18) and mumps (R0: 4e7). 5 Although the preventive measures to contain swine flu are justified (e.g. use of FFP3 mask for aerosol-generating procedures such as endotracheal intubation or suctioning), it is unreasonable not to take such measures for other diseases with potentially serious consequences (e.g. intubation of a patient suspected to have chickenpox or measles). Case definitions are like diagnostic tests. Since case definitions act as a screening tool they are designed to have a high level of sensitivity at the expense of specificity. However, like other diagnostic tests the test for swine flu is likely to have a number of false-negative and false-positive results. It is important that users are aware of its limitations so that when one or more of certain symptoms are absent or additional symptoms/signs are present, the context within which the case definition is being applied is considered. If the consequence of spread of H1N1 virus is higher (inpatient, pregnancy, intubation), a higher level of caution is reasonable, and testing patients or using PPE or other infection control measures can be justified. Clinical algorithms are not tablets of stone. They are rather guide maps akin to the global positioning system. Keeping eyes and ears open is as important as the ability to read these maps.

Missense Mutations in Exons 18–24 of EGFR in Hepatocellular Carcinoma Tissues

Epidermal growth factor receptor (EGFR), a transmembrane tyrosine kinase receptor, plays important roles in various cancers. In nonsmall cell lung cancer (NSCLC), EGFR mutations cluster around the ATP-binding pocket (exons 18–21) and some of these mutations activate the kinase and induce an increased sensitivity to EGFR-tyrosine kinase inhibitors. Nevertheless, data of EGFR mutations in HCC are limited. In this study, we investigated EGFR expression by immunohistochemistry and EGFR mutations (exons 18–24) by PCR cloning and sequencing. EGFR overexpression in HCC and matched nontumor tissues were detected in 13/40 (32.5%) and 10/35 (28.6%), respectively. Moreover, missense and silent mutations were detected in 13/33 (39.4%) and 11/33 (33.3%) of HCC tissues, respectively. The thirteen different missense mutations were p.L730P, p.V742I, p.K757E, p.I780T, p.N808S, p.R831C, p.V851A, p.V897A, p.S912P, p.P937L, p.T940A, p.M947V, and p.M947T. We also found already known SNP, p.Q787Q (CAG>CAA), in 13/33 (39.4%) of HCC tissues. However, no significant association was detected between EGFR mutations and EGFR overexpression, tissue, age, sex, tumor size, AFP, HBsAg, TP53, and Ki-67. Further investigation is warranted to validate the frequency and activity of these missense mutations, as well as their roles in HCC tumorigenesis and in EGFR-targeted therapy.

HER2 expression in breast cancer with nonamplified HER2 and gains of chromosome 17 centromere.

Gains of chromosome 17 centromere (CEP17) may be accompanied by gains of chromosome 17q. To evaluate the effect of CEP17 gains (CEP17>3 copies per tumor nucleus) on the expression of the HER2 gene, which is located on chromosome 17q12-21.32, we analyzed HER2 amplification and expression in breast carcinomas with and without CEP17 gains. We isolated tumor nuclei from frozen tissues of 37 breast carcinomas for analysis of the HER2 gene and CEP17 by fluorescence in situ hybridization. HER2 expression was detected by immunohistochemistry (IHC) performed on formalin-fixed, paraffin-embedded sections of the corresponding tumors. Tumors with amplified HER2 as determined by both HER2 copy number and HER2/CEP17 ratio were detected in 29.7% (11/37). CEP17 gains were significantly associated with HER2 amplification (P=0.005) but not associated with estrogen receptor status, tumor grade, and lymph node status (P>0.05). In contrast, HER2 amplification was significantly associated with estrogen receptor negativity (P=0.020) but not with tumor grade and lymph node status (P>0.05). IHC analysis was performed in 7 HER2-amplified tumors and all of these were IHC 3+, which were used as positive controls. Among HER2–non-amplified tumors with CEP17 gains, only 1 tumor (1/8, 12.5%) was IHC 3+. However, none of the HER2–non-amplified tumors without CEP17 gains was IHC 3+. In HER2–non-amplified tumors, there was no significant association between HER2 protein expression as detected by IHC and CEP17 or HER2 copy number (P=0.999, P=0.785, respectively). These findings indicate that in the absence of HER2 amplification, CEP17 gains do not have a significant effect on HER2 protein expression.

Intrapulmonary vascular dilation in children with chronic liver diseases: pre- and post-liver transplantation.

BACKGROUND AND STUDY AIMS Chronic liver disease (CLD) can cause hepatopulmonary syndrome (HPS), defined as triad of liver disease, hypoxemia, and intrapulmonary vascular dilation (IPVD). The aim of this study was to determine the evidence of IPVD in a cohort of pediatric patients with CLD pre- and post-liver transplantation (LT). MATERIAL AND METHODS All pediatric patients with CLD listed for LT were studied. Pulse oxygen saturation (SpO(2)), technetium-99m-labeled macroaggregated albumin ((99m)Tc- MAA) perfusión scan (positive test: uptake of the isotope ≥ 6% in the brain), and echocardiography with saline bubble test (SBT) were performed. SBT was re-evaluated at 3-6 months after LT. Grading of SBT included grade 0 (no bubble), I (1-9 bubbles), grade II (10-20 bubbles), and grade III (> 20 bubbles). RESULTS Eighteen patients, median age 22.5 months (8-108), were enrolled. Most had biliary atresia (77.8%). Pre-LT, all patients had SpO(2) of 100% and none had positive (99)mTc- MAA perfusion scan. Two patients (11%) had negative SBT (grade 0), 1 (5.5%) had grade I, 3 (16.5%) had grade II, and 12 (67%) had grade III, respectively. Post-LT SBT became negative in all survivors (n = 16), (p = 0.0001). CONCLUSIONS Most cirrhotic children in this cohort study had evidence of IPVD by positive SBT. However, none of these met the criteria for diagnosis of HPS. This evidence of IPVD subsided after LT.BACKGROUND AND STUDY AIMS Chronic liver disease (CLD) can cause hepatopulmonary syndrome (HPS), defined as triad of liver disease, hypoxemia, and intrapulmonary vascular dilation (IPVD). The aim of this study was to determine the evidence of IPVD in a cohort of pediatric patients with CLD pre- and post-liver transplantation (LT). MATERIAL AND METHODS All pediatric patients with CLD listed for LT were studied. Pulse oxygen saturation (SpO2), technetium-99m-labeled macroaggregated albumin (99mTc- MAA) perfusion scan (positive test: uptake of the isotope ≥ 6% in the brain), and echocardiography with saline bubble test (SBT) were performed. SBT was re-evaluated at 3-6 months after LT. Grading of SBT included grade 0 (no bubble), I (1-9 bubbles), grade II (10-20 bubbles), and grade III (> 20 bubbles). RESULTS Eighteen patients, median age 22.5 months (8-108), were enrolled. Most had biliary atresia (77.8%). Pre-LT, all patients had SpO2 of 100% and none had positive 99mTc- MAA perfusion scan. Two patients (11%) had negative SBT (grade 0), 1 (5.5%) had grade I, 3 (16.5%) had grade II, and 12 (67%) had grade III, respectively. Post-LT SBT became negative in all survivors (n = 16), (p = 0.0001). CONCLUSIONS Most cirrhotic children in this cohort study had evidence of IPVD by positive SBT. However, none of these met the criteria for diagnosis of HPS. This evidence of IPVD subsided after LT.

Dual Kidney Transplantation: A Single-Center Experience in Thailand

BACKGROUND Dual kidney transplants (DKTs) from expanded criteria donors (ECDs) have been performed in our hospital since 2014. We needed to review our clinical outcome and update criteria to selected ECDs for DKTs. MATERIALS AND METHODS Between January 2014 and December 2016, 4 DKTs and 269 deceased donor kidney transplants were performed. The outcome of DKTs was reviewed. The literature was reviewed for surgical technique and indication for DKT. RESULTS Four DKTs were performed between 2014 and 2016. One-year graft survival rate was 100%. One patient developed delayed graft function. No morbidity or mortality occurred. CONCLUSIONS DKTs in our center were safe and had good outcome with optimized selected criteria. DKT can improve the rate of kidney transplant in a developing country.

The First Case Series of Combined Liver-Kidney Transplantation (CLKT) fromThailand

From the hospital database, four patients underwent CLKT. Three patients had ESRD and cirrhosis. Causes of cirrhosis were chronic hepatitis B and chronic hepatitis C in two and one patient. The fourth patient underwent CLKT due to subfulminant liver failure and prolonged acute renal failure with severely damaged kidney and required hemodialysis for 5 weeks. The waiting time ranged from 6 to 1988 days. After CLKT, one patient required hemodialysis for 45 days because of prolonged acute tubular necrosis. Mild early liver graft dysfunction occurred in one patient. Induction regimens were IL2-receptor blockers, steroids and tacrolimus in three patients, and steroids combining with tacrolimus in one patient. Maintenance regimens included tacrolimus, mycophenolate mofetil (with or without low-dose prednisolone). One-year graft and patient survival rate was 100%. Median follow-up time was 2.2 years. None developed liver or renal graft rejection. At 6 and 12 months, median creatinine levels were 1.30 and 1.13 mg/dl. At the last visits, median creatinine level was 1.05 mg/dl with median eGFR of 76.45 ml/min. CLKT may be done in the patients with ESRD and viral hepatitis-related cirrhosis even without portal hypertension. Other indication is for patients with acute liver failure with severely damaged ARF.