Diagnostic role of serum interleukin 6 and CA 19-9 in patients with cholangiocarcinoma

BACKGROUND/AIMS: Cholangiocarcinoma is particularly common in Northeastern Thailand where the liver fluke, O. viverrini, is endemic. Currently there is no sensitive and specific tumor marker for the diagnosis of this cancer. The aim of this study was to investigate the accuracy of carbohydrate antigen 19-9 and interleukin-6 in the diagnosis of cholangiocarcinoma. The first marker represents the commonly used serum marker in cholangiocarcinoma and the second marker is a multi-functional cytokine associated with cancer development. METHODOLOGY: The serum concentrations of carbohydrate antigen 19-9 and interleukin-6 were simultaneously determined in 45 patients with cholangiocarcinoma, 15 with hepatocellular carcinoma, 15 with metastatic liver cancers, 10 with benign biliary disease and 10 healthy controls. RESULTS: The sensitivity of carbohydrate antigen 19-9 value (> or = 37 U/mL) in diagnosing cholangiocarcinoma was 64.4%, while its specificity was 100% and 56.7% when compared with benign biliary disease and other liver cancers, respectively. The sensitivity and specificity of detectable interleukin-6 (> or = 0.18 ng/mL) for differentiating between cholangiocarcinoma and benign biliary disease was 71.1% and 90%, respectively, whereas the specificity for differentiating cholangiocarcinoma from other liver cancers was 26.7%. When higher concentrations of either carbohydrate antigen 19-9 (> or = 100 U/mL) or interleukin-6 (> or = 50 pg/mL) were used as the cut-off points, they provided additional diagnostic sensitivity and accuracy in differentiating between cholangiocarcinoma and other liver cancers to 80% and 76%, respectively. CONCLUSIONS: The combined assays of both serum carbohydrate antigen 19-9 and interleukin-6 could be useful in diagnosing cholangiocarcinoma, particularly in populations where this cancer is prevalent.     

Serum hepatocyte growth factor and clinical outcome in biliary atresia

Purpose

Biliary atresia (BA) remains one of the most intractable liver diseases leading to liver fibrosis. Serum hepatocyte growth factor (HGF) has been shown to increase in cirrhotic patients. The aim of this study was to investigate the possible role of HGF in BA.

Methods

Serum levels of HGF were determined using an enzyme-linked immunosorbent assay from 28 BA patients and 25 healthy children. The patients were categorized into 3 groups according to their clinical outcomes (good, fair, and poor): group A (good), jaundice-free patients (total bilirubin [TB] < 2.0 mg%); group B (fair), patients with mild to moderate jaundice (TB, 2 to 10 mg%); and group C (poor), patients with marked jaundice (TB > 10 mg%). Unpaired t test and analysis of variance (ANOVA) with post-hoc tests were used. Data were expressed as mean and SEM.

Results

Serum HGF levels in BA patients were higher than the controls (P = .02). Subgroup analysis found that there were 12 patients in group A, 8 patients in group B, and 8 patients in group C. The mean age of patients in groups A, B, and C were 5.34 ± 0.52, 7.45 ± 1.98, and 5.49 ± 1.57 years (P > .05). Serum HGF in controls and groups A, B, and C were 0.24 ± 0.03, 0.28 ± 0.04, 0.36 ± 0.09, and 0.56 ± 0.07 ng/mL, respectively. Serum HGF levels in BA patients with poor outcome were higher than patients with good outcome (P = .02). There was no difference in serum HGF of BA patients with fair outcome compared with other groups.

Conclusions

Serum HGF is elevated in BA. Furthermore, BA patients with poor outcome have significantly elevated HGF compared with patients with good outcome. Serum HGF levels may be predictive of prognosis with respect to the progression of liver dysfunction. However, the results of HGF in patients with fair outcome are inconclusive, probably because of the small sample size. Further studies are needed to elucidate the detailed mechanisms.     

Phase III randomized trial comparing LDR and HDR brachytherapy in treatment of cervical carcinoma

PURPOSE: Intracavitary brachytherapy plays an important role in the treatment of cervical carcinoma. Previous results have shown controversy between the effect of dose rate on tumor control and the occurrence of complications. We performed a prospective randomized clinical trial to compare the clinical outcomes between low-dose-rate (LDR) and high-dose-rate (HDR) intracavitary brachytherapy for treatment of invasive uterine cervical carcinoma. METHODS AND MATERIALS: A total of 237 patients with previously untreated invasive carcinoma of the uterine cervix treated at King Chulalongkorn Memorial Hospital were randomized between June 1995 and December 2001. Excluding ineligible, incomplete treatment, and incomplete data patients, 109 and 112 patients were in the LDR and HDR groups, respectively. All patients were treated with external beam radiotherapy and LDR or HDR intracavitary brachytherapy using the Chulalongkorn treatment schedule. RESULTS: The median follow-up for the LDR and HDR groups was 40.2 and 37.2 months, respectively. The actuarial 3-year overall and relapse-free survival rate for all patients was 69.6% and 70%, respectively. The 3-year overall survival rate in the LDR and HDR groups was 70.9% and 68.4% (p = 0.75) and the 3-year pelvic control rate was 89.1% and 86.4% (p = 0.51), respectively. The 3-year relapse-free survival rate in both groups was 69.9% (p = 0.35). Most recurrences were distant metastases, especially in Stage IIB and IIIB patients. Grade 3 and 4 complications were found in 2.8% and 7.1% of the LDR and HDR groups (p = 0.23). CONCLUSION: Comparable outcomes were demonstrated between LDR and HDR intracavitary brachytherapy. Concerning patient convenience, the lower number of medical personnel needed, and decreased radiation to health care workers, HDR intracavitary brachytherapy is an alternative to conventional LDR brachytherapy. The high number of distant failure suggests that other modalities such as systemic concurrent or adjuvant chemotherapy might lower this high recurrence, especially in Stage IIB and IIIB.     

Molecular characterization and complete genome analysis of human enterovirus 71 and coxsackievirus A16 from children with hand, foot and mouth disease in Thailand during 2008-2011

Hand, foot and mouth disease (HFMD) has mostly been caused by enterovirus 71 (EV71) and coxsackievirus A16 (CA16). CA 16 was the most common cause of HFMD in 2010. EV71 had a high prevalence in 2008-2009 and has been identified with a higher frequency since 2011. Nearly complete genome sequences of three EV71 strains (2008-2009 strains) and two CA16 strains (2010 strains) obtained from outbreaks in Thailand in 2008 to 2010 were characterized. Based on a phylogenetic tree of the complete VP1 region, three EV71 strains grouped into the B5, C1 and C4 genotypes, and two CA16 strains grouped into the C genotype. Based on sequence analysis, nucleotide changes were found to cluster in the internal ribosome entry site (IRES) element of the 5′-untranslated region (5′-UTR). Amino acid differences identified in all strains were located in the non-structural protein. These data also provide the molecular epidemiology of EV71 and CA16 outbreaks in Thailand.     

Molecular epidemiology, genome characterization, and recombination event of human parechovirus

Human Parechovirus (HPeV), a member of the Picornaviridae family, is an infectious agent mostly affecting children. There are 16 recognized genotypes which have globally spread. This study incorporated a total of 2957 nasopharyngeal (NP) swab and 759 fecal samples that were collected from different parts of Thailand. The NP of HPeV was detected in 0.4% of NP swab and 6.1% of fecal samples. The majority of HPeV infections occur in infants below the age of 2 years, while infections were detected in children above the age of 10 years as well. Various genotypes comprising 1A, 1B, 2, 3, 4, 5, 6, 10 and 14 have been characterized. This study revealed recombination events in 16 samples in which HPeV1B was shown as the highest frequency. In conclusion, HPeV can be detected in both the respiratory and GI tract. Moreover, HPeV which circulates in Thailand is highly diverse and subject to recombination.     

Efficacy of pulsed dyed laser (585 nm) in the treatment of molluscum contagiosum subtype 1

Molluscum contagiosum is a common cutaneous disease that may be difficult to treat when there are multiple lesions; especially in children. This study was conducted to determine the efficacy of pulsed dye laser (585 nm) in the treatment of molluscum contagiosum in 20 children. In the treated group, 70.5% of lesions healed after the first treatment; the remaining 10.6% after the second treatment (2 weeks later). The overall cure rate was significantly different from the control group (p< 0.01). The therapy was also well tolerated. Only mild transient hypopigmentation and erythema were observed. None encountered infectious events. In conclusion, pulsed dye laser is a good alternative treatment for molluscum contagiosum due to high efficacy and mild transient side effects.     

A statistical method for forecasting demographic time series counts, with application to HIV/AIDS and other infectious disease mortality in southern Thailand

This study investigated regional and temporal patterns of death reported from infectious diseases (including HIV/AIDS) in 14 provinces of southern Thailand over the period 1999-2004, using data obtained from the Thailand Bureau of Policy and Strategy, Ministry of Public Health. Causes of deaths were identified using the International Classification of Diseases 10th revision (ICD-10), and mortality incidence rates were then calculated using populations obtained from the 2000 population census. Poisson and negative binomial lagged observation-driven regression models for mortality incidence were fitted to the data separately for HIV/ AIDS and other infectious diseases. Overall, the hospital mortality rates started to increase sharply in 2003 - 2004. The in-hospital mortality for HIV/AIDS showed peaks in urban districts and decreased from north to south with mortality for males approximately double that of females. For other infectious diseases, an upward trend in hospital mortality age 40 and over started in 2003-2004, particularly among persons reported as dying from septicemia, while showing a slightly increasing trend for other infectious diseases. Identifying the real cause of hospital deaths recorded as septicemia would substantially improve hospital mortality data quality.     

Relationship between vascular reactivity and lipids in Mexican-Americans with type 2 diabetes treated with pioglitazone

CONTEXT: Vascular dysfunction and insulin resistance precede atherosclerosis in type 2 diabetes (T2DM). Better knowledge of the interaction between these is of considerable clinical interest. OBJECTIVE: The objective of this study was to examine the association between inflammation, glucose, and lipid metabolism and vascular dysfunction. DESIGN AND SETTING: We conducted a randomized, double-blind, controlled trial of pioglitazone vs. placebo and other therapies aimed at equal glycemic control for 24 wk at an academic tertiary referral clinic. PATIENTS AND INTERVENTIONS: Mexican-American subjects with T2DM and no complications were randomly assigned to pioglitazone 45 mg daily (PIO, n=16) or placebo (CON, n=15) and matched for age, gender, body mass index, diabetes duration, and glycemic control. All subjects completed the study. MAIN OUTCOME MEASURE: We looked for improved vascular reactivity independent of glycemic control but closely related to plasma adiponectin, lipids, and insulin sensitivity. RESULTS: After 24 wk, there was an equal decrease in fasting plasma glucose (approximately 135 mg/dl), glycosylated hemoglobin (approximately 7.0%), and glucose production (approximately 15%). The decrease in free fatty acids (30 vs. 10%) and increase in glucose disposal (40 vs. 25%) were greater in PIO vs. CON (P<0.05). In PIO, plasma high-density lipoprotein rose by 15% (P<0.05), and low-density lipoprotein and high-density lipoprotein particle size rose significantly (P<0.01). Plasma adiponectin doubled in PIO (from 6.1+/-0.8 to 12.7+/-2.1 microg/ml). Forearm blood flow rose equally (approximately 130%) during reactive hyperemia in both groups, although after therapy, the increase was greater (P<0.001) in PIO (153%) than in CON (137%); vasodilation was greater (P=0.01) in PIO (92, 160, and 204%) than in CON with acetylcholine (74, 130, and 144%) and with sodium nitroprusside (PIO=164 and 253% vs. 116 and 230%; P=0.04). The elevation in diameter was also greater in PIO (13 vs. 10%; P<0.05). Vascular responses correlated with plasma free fatty acids, adiponectin, and low-density lipoprotein particle size but not with glycemic control. CONCLUSION: These data indicate that pioglitazone improves vascular reactivity irrespective of glycemic control and suggest a close association with changes in fat cell metabolism.     

Effect of acute exercise on AMPK signaling in skeletal muscle of subjects with type 2 diabetes: a time-course and dose-response study

Activation of AMP-activated protein kinase (AMPK) by exercise induces several cellular processes in muscle. Exercise activation of AMPK is unaffected in lean (BMI approximately 25 kg/m(2)) subjects with type 2 diabetes. However, most type 2 diabetic subjects are obese (BMI >30 kg/m(2)), and exercise stimulation of AMPK is blunted in obese rodents. We examined whether obese type 2 diabetic subjects have impaired exercise stimulation of AMPK, at different signaling levels, spanning from the upstream kinase, LKB1, to the putative AMPK targets, AS160 and peroxisome proliferator-activated receptor coactivator (PGC)-1alpha, involved in glucose transport regulation and mitochondrial biogenesis, respectively. Twelve type 2 diabetic, eight obese, and eight lean subjects exercised on a cycle ergometer for 40 min. Muscle biopsies were done before, during, and after exercise. Subjects underwent this protocol on two occasions, at low (50% Vo(2max)) and moderate (70% Vo(2max)) intensities, with a 4-6 week interval. Exercise had no effect on LKB1 activity. Exercise had a time- and intensity-dependent effect to increase AMPK activity and AS160 phosphorylation. Obese and type 2 diabetic subjects had attenuated exercise-stimulated AMPK activity and AS160 phosphorylation. Type 2 diabetic subjects had reduced basal PGC-1 gene expression but normal exercise-induced increases in PGC-1 expression. Our findings suggest that obese type 2 diabetic subjects may need to exercise at higher intensity to stimulate the AMPK-AS160 axis to the same level as lean subjects.     

Primary vesicoureteral reflux mediated renal scarring after urinary tract infection in Thai children

AIM: To evaluate the association between primary vesicoureteral reflux (VUR) and renal scarring in children using 99 m Technetium-labelled dimercaptosuccinic acid (DMSA). METHODS: Children attending at Songklanagarind Hospital from 1987 to 2002 were evaluated. RESULTS: Ages at diagnosis of VUR in 46 boys and 52 girls were 1.1+/-1.6 and 2.9+/-2.5 years, median 0.6 and 2.3 years, respectively (P<0.001). DMSA scans were performed at 4.1+/-3.6 years. Renal parenchymal damage was detected in 34 kidneys (22%) of 154 demonstrated refluxing ureters, and one kidney (2%) of 42 non-refluxing ureters (P=0.002). Of 79 refluxing ureters in boys and 75 refluxing ureters in girls, there were 25 and nine renal scars, respectively (32% and 12%, P=0.003). Renal scars in VUR grades I-V were 11%, 7%, 12%, 44% and 64%, respectively (P<0.001). Multivariate analysis revealed that high grade VUR (P<0.001), age of diagnosis of VUR greater than 5 years (P=0.001), and male gender (P=0.002) were the most significant risk factors for renal scarring. CONCLUSION: High-grade VUR, age of diagnosis of VUR greater than 5 years and male gender were the most significant risk factors for renal scarring.