Detection of Lymphatic Micrometastases in Patients With Stages I and II Colorectal Cancer: Impact on Five-Year Survival

PURPOSE: Despite having removed the whole macroscopic disease (curative intent surgery), one of five patients with Stages I and II colorectal cancer will develop recurrence. Lymphatic micrometastases detected by immunohistochemistry could be one of explanation for recurrence and cancer-related death in patients without lymph node involvement at light microscopy. However, the biologic importance of micrometastases remains unclear. This study was designed to determine the impact of micrometastases in five-year survival in patients with Stages I and II colorectal cancer.METHODS: This retrospective study included patients operated on between May 1989 and January 1999 for colorectal cancer without histopathologic lymph node involvement. Patients who received any adjuvant therapy were excluded. Immunohistochemical staining of the lymph nodes was performed with antipancytokeratin antibodies. Follow-up data were obtained from the clinical database and death certificates. Survival was estimated by the Kaplan-Meier method and compared by the log-rank test.RESULTS: Micrometastases were observed in 26 of 90 patients (28.9 percent). The mean follow-up time was 90.7 (range, 11–160) months. Seventeen cancer-related deaths occurred during follow-up (18.9 percent), 6 of them in patients with micrometastases (23.1 percent) and 11 in patients without micrometastases (17.2 percent; P = 0.559). Cancer-specific five-year survival was 87 percent in the whole group and 81 percent in patients positive for micrometastases vs. 90 percent in negative patients (P = 0.489).CONCLUSIONS: The presence of micrometastases in patients with Stages I and II colorectal cancer seems not to have any impact on cancer-specific survival.Supported by the Apertus Research Program (Andromaco Pharmaceutical Company) and by The National Public Grant (FONDECYT #1000556).     

Factors Influencing the Rate of Fibrosis Progression in Chronic Hepatitis C

Alcohol consumption, age at infection, and male gender have been identified as risk factors for faster fibrosis progression in patients with chronic hepatitis C (CHC). Yet the influence of liver steatosis, light to moderate alcohol consumption, or iron overload on this progression remains controversial. To analyze the effect of individual risk factors and their interaction on fibrosis progression in a group of patients with CHC and a definite date of infection, we studied 133 consecutive untreated patients. Covariates included were age, body mass index (BMI), gender, age at infection, alcohol intake, serum lipids, glycemia, serum ALT, AST, GGT, iron, and ferritin, grade and stage (METAVIR and Scheuer), and hepatic stainable iron (Perl's stain). The rate of fibrosis progression was inferred from the METAVIR score. By logistic regression analysis, hepatic steatosis (odds ratio [OR], 3.035; 95% confidence interval [CI], 1.16-7.93), serum ferritin levels higher than 290 ng/ml (OR, 5.5; 1.6-18.65), and light to moderate ethanol intake (1-50 g/day) (OR, 5.22; 1.5-17.67) were independently associated with faster fibrosis progression. There was no effect of interaction between these variables on the rate of fibrosis progression. Liver steatosis, serum ferritin levels, and light to moderate alcohol intake are associated with faster fibrosis progression in chronic hepatitis C. Combination of these factors did not further accelerate this progression. The impact of modification of these factors on progression should be tested in longitudinal studies.     

Coronary endarterectomy and bypass grafting without cardiopulmonary bypass

We prospectively analyzed patients who underwent simultaneous off-pump coronary artery bypass grafting and endarterectomy between March 1, 1997 and February 28, 2002. The incidence of perioperative myocardial infarction, need for inotropic support, morbidity, long-time functional class, and mortality were evaluated.Nine endarterectomies were performed in eight patients, more frequently in the right coronary artery. Dopamine was used in four patients. One perioperative myocardial infarction (12.5%) occurred. No deaths occurred and all patients are now functional class I. Tests for ischemia have been negative in all patients.Coronary endarterectomy is an alternative procedure that has little morbidity and enables complete myocardial revascularization without cardiopulmonary bypass.     

Beyond superquenching: hyper-efficient energy transfer from conjugated polymers to gold nanoparticles

Gold nanoparticles quench the fluorescence of cationic polyfluorene with Stern-Volmer constants (KSV) approaching 1011 M-1, several orders of magnitude larger than any previously reported conjugated polymer-quencher pair and 9-10 orders of magnitude larger than small molecule dye-quencher pairs. The dependence of KSV on ionic strength, charge and conjugation length of the polymer, and the dimensions (and thus optical properties) of the nanoparticles suggests that three factors account for this extraordinary efficiency: (i) amplification of the quenching via rapid internal energy or electron transfer, (ii) electrostatic interactions between the cationic polymer and anionic nanoparticles, and (iii) the ability of gold nanoparticles to quench via efficient energy transfer. As a result of this extraordinarily high KSV, quenching can be observed even at subpicomolar concentrations of nanoparticles, suggesting that the combination of conjugated polymers with these nanomaterials can potentially lead to improved sensitivity in optical biosensors.     

Results after the adoption of a MELD/PELD‐based liver allocation policy in Argentina

In July 2005, Argentina switched from a categorical liver allocation system to a MELD/PELD‐based policy for patients with CLD. To analyze WL outcomes and survival after LT in children. From January 2000 to December 2010, 923 children were registered. Two consecutive five‐yr periods were analyzed and compared: Era I (January 2000–July 2005) (n = 379) and Era II (July 2005–December 31, 2010) (n = 544). All data were prospectively collected and analyzed using the Kaplan–Meier method. After adopting the MELD/PELD system, WL registrations increased by 44% (from 379 to 544) and the number of LT increased by only 24% (from 278 to 365). However, three‐month WL mortality rate (32% to 18%, p < 0.0001, HR 2.002 CI 95% 1.5–2.8) decreased significantly. No significant differences were observed between Era 1 and II in one‐yr post‐LT survival (77.5% vs. 84.1%, p = 0.3053) and in acute re‐LT rate (9% vs. 5%, p = 0.1746). Under the MELD/PELD‐based allocation system in Argentina, mortality on the WL significantly decreased in children with CLD without affecting post‐LT survival, although reduced access to LT was observed.     

Microarray analysis of endothelial differentially expressed genes in liver of cirrhotic rats

BACKGROUND & AIMS: There is a long-standing interest in the identification of endothelial-specific pathways for therapeutic targeting in cirrhosis. Therefore, the aim of this study was to evaluate differences in gene expression patterns between liver endothelial cells (LECs) from control and cirrhotic rats by using microarrays. METHODS: LECs were obtained by isopycnic centrifugation. LECs gene expression was then analyzed on high-density oligonucleotide microarrays. RESULTS: Analysis of gene expression revealed that most of the differentially expressed mRNA in cirrhosis are associated with extracellular matrix remodeling, inflammation, antioxidant/stress response, and cell signaling. CONCLUSIONS: The collective expression changes observed within some functional groups of genes indicate that LECs in cirrhotic livers may contribute to lymphangiogenesis, enhancement of fibrogenesis and inflammatory processes, changes in cell-cell interaction with up-regulation of adherens junction proteins, and alterations in the intrahepatic vascular tone because of the down-regulation of genes involved in vasodilatation.