High thymidylate synthase gene expression predicts poor outcome after resection of hepatocellular carcinoma.

INTRODUCTION: Prognosis after resection of hepatocellular carcinoma (HCC) is highly variable. Compared to clinicopathologic factors, the use of molecular markers to predict outcome has not been well studied. We investigated the prognostic importance of thymidylate synthase (TS) gene expression and polymorphisms in patients after resection of HCC. METHODS: Patients who underwent complete resection of HCC for whom tissue was available were identified. TS gene expression level and polymorphisms were determined in HCC specimens. Prognostic factors were evaluated using Kaplan-Meier curves and Cox proportional hazard models. RESULTS: The study included 67 patients. In univariate analysis, variables that negatively influenced survival included TNM stage, microvascular invasion, and high TS expression. For the high TS expression group, median survival was 54 months and 5-year actuarial survival was 47%. For the low TS expression group, median survival was not reached and the 5-year actuarial survival was 91%. In multivariate analysis, only high TS expression remained an independent predictor of poor survival (HR = 10.77, 95% CI 1.36-84.91; P = 0.02). TS gene polymorphisms were not associated with TS expression or overall survival. CONCLUSIONS: High TS expression predicts poor outcome after resection of HCC. Molecular markers might be robust predictors of patient outcome after resection of HCC.

Mitogen Inducible Gene-6 Is a Prognostic Marker for Patients with Colorectal Liver Metastases.

PURPOSE: Prognostic schemes that rely on clinical variables to predict outcome after resection of colorectal metastases remain imperfect. We hypothesized that molecular markers can improve the accuracy of prognostic schemes. METHODS: We screened the transcriptome of matched colorectal liver metastases (CRCLM) and primary tumors from 42 patients with unresected CRCLM to identify differentially expressed genes. Among the differentially expressed genes identified, we looked for associations between expression and time to disease progression or overall survival. To validate such associations, mRNA levels of the candidate genes were assayed by qRT-PCR from CRCLM in 56 additional patients who underwent hepatectomy. RESULTS: Seven candidate genes were selected for validation based on their differential expression between metastases and primary tumors and a correlation between expression and surgical outcome: lumican; tissue inhibitor metalloproteinase 1; basic helix-loop-helix domain containing class B2; fibronectin; transmembrane 4 superfamily member 1; mitogen inducible gene 6 (MIG-6); and serpine 2. In the hepatectomy group, only MIG-6 expression was predictive of poor survival after hepatectomy. Quantitative PCR of MIG-6 mRNA was performed on 25 additional hepatectomy patients to determine if MIG-6 expression could substratify patients beyond the clinical risk score. Patients within defined clinical risk score categories were effectively substratified into distinct groups by relative MIG-6 expression. CONCLUSIONS: MIG-6 expression is inversely associated with survival after hepatectomy and may be used to improve traditional prognostic schemes that rely on clinicopathologic data such as the Clinical Risk Score.

Color Doppler echocardiographic assessment of valvular regurgitation in normal infants.

BACKGROUND/PURPOSE: Despite valvular regurgitation being a common finding in children, its prevalence in infants is unclear. The aim of this study was to determine the presence and severity of valvular regurgitation in normal infants using echocardiographic screening. METHODS: Two-dimensional (2D) color Doppler echocardiography was performed on 420 consecutive infants (aged 1-12 months) with structurally normal hearts. Pulsed, continuous-wave, and color Doppler imaging techniques were used to detect and evaluate regurgitant blood flow at each valve. RESULTS: Valvular regurgitation was present in 258 infants (61.4%). Among these, 41 (15.9%) were found to have a heart murmur. Tricuspid regurgitation was found in 237 (56.4%) infants, pulmonary regurgitation in 71 (16.9%), mitral regurgitation in 51 (12.1%), and aortic regurgitation in nine (2.1%). Regurgitation of one valve occurred in 161 (38.3%) infants, of two valves in 84 (20%), and of three valves in 13 (3.1%). Right-sided regurgitation was significantly more common than left-sided regurgitation (p < 0.05). The degree of regurgitation was trivial or mild in 97.3% of infants and the peak velocities of the regurgitant jets were < or = 2.5 m/sec in all the valves, by Doppler echocardiography. CONCLUSION: The prevalence of inaudible valvular regurgitation is high in infants with structurally normal hearts. Multiple-valve involvement with regurgitation is not uncommon. Mild severity and low velocity on color Doppler, and the structural information provided by 2D imaging strongly suggest that these regurgitant flows are physiologically normal in infancy.

Radiofrequency catheter ablation of idiopathic left ventricular tachycardia in a child.

Ventricular tachycardia occurring in apparently normal heart is rare in children. A 9-year-old boy presented with recurrent palpitations and syncope was found to have idiopathic ventricular tachycardia with a right bundle branch block morphology and left axis deviation. Pace mapping and activation mapping were used to localize the site of ventricular tachycardia origin. Radiofrequency catheter ablation successfully abolished this arrhythmia at a site of the midportion of the inferoseptal region of the left ventricle. This boy was free of tachycardia over follow-up of 2 years.

Predictive value of clinical features in differentiating group A beta-hemolytic streptococcal pharyngitis in children.

Identifying children with acute pharyngitis caused by group A beta-hemolytic Streptococcus (GABHS) is an important task for pediatricians. This study examined the value of certain clinical symptoms and signs in predicting a positive culture result. A total of 442 children who presented at the outpatient department with pharyngeal erythema were enrolled. The clinical features of patients with positive throat cultures for GABHS were compared to those with negative culture results. Throat cultures were positive for GABHS in 120 (27%) patients. Patients aged between 5 and 10 years had a higher prevalence of GABHS pharyngitis. Significant differences between the groups with and without GABHS pharyngitis were noted for the presence of sore throat (p < 0.001), tonsillar swelling (p < 0.001), anterior cervical adenopathy (p = 0.004), and scarlatiniform rash (p < 0.001), but not for the presence of fever, cough, rhinorrhea, abdominal pain, headache, tonsillar exudate, or palatal petechiae. Despite these strong associations, none of these symptoms or signs had both high sensitivity and specificity, and the positive predictive values of these individual findings were never greater than 50%. The results indicate that diagnosis based on clinical grounds alone is unreliable although there are certain individual symptoms and signs that are associated with GABHS pharyngitis. These symptoms and signs may be helpful in modifying estimates of probability of infection with GABHS. Throat cultures in suspected patients remain mandatory.

Epidemiological and clinical features of group A Streptococcus pharyngitis in children.

In order to understand the prevalence of childhood streptococcal pharyngitis, isolation of group A Streptococcus (GAS) was attempted from throat swabs of pharyngitis patients. Children aged between 1 and 15 years presenting to the outpatient department with pharyngeal erythema were prospectively enrolled in the study. Demographic data and presenting symptoms and signs for each patient were recorded and a throat swab was taken. Of 1175 throat cultures obtained, GAS was isolated in 252 cases (21.4%). Of these, 142 (56.3%) were boys and 110 (43.7%) girls. A higher proportion of boys was found with GAS pharyngitis (1.29: 1). The mean age of GAS culture-positive patients was 7.8 +/- 2.3 years old. Patients aged between 6 and 11 years were more prevalent in GAS pharyngitis. Ninety (35.7%) of our GAS pharyngitis patients occurred between March and May. A second smaller peak occurred between October and December. The following factors showed independent positive correlation with GAS infection: sore throat (p < 0.001), no coryza (p = 0.011), tonsillar swelling (p < 0.001), anterior cervical adenopathy (p = 0.029) and scarlatiniform rash (p < 0.001). However, GAS was found in less than half of the patients who had these clinical manifestations. In conclusion, pharyngeal infection with GAS in children is not uncommon. The prevalence of GAS pharyngitis is related to patient gender, age, and month of the year. Diagnosis of GAS pharyngitis based on clinical features alone is unreliable.