Combined portal vein embolization and preoperative chemotherapy prior to liver resection for colorectal cancer metastases

Abstract Objective. Compare perioperative course and long-term mortality after liver resection for colorectal cancer (CRC) metastases between patients who had preoperative treatment with portal vein embolization (PVE) and chemotherapy or chemotherapy alone. Methods. Among patients undergoing liver resection for CRC metastases following preoperative chemotherapy treatment, 17 patients who had received preoperative PVE (group A) were compared with 17 matched controls who had no PVE (group B). Perioperative course and long-term mortality were compared between groups A and B and between group A and the entire group of 75 cases with preoperative chemotherapy (group C). Results. Baseline characteristics for the matched groups A and B were similar. Group C included less major resections. Median intraoperative bleeding was 1600 ml in group A, 1200 ml in group B, and 1000 ml in group C (p < 0.05 vs. group A). Median postoperative stay was comparable in all groups (8-9 days). Operation time was 542 min in group A and 464 min in group B (p < 0.01). Mortality after 30 days and 1, 2, and 5 years was similar in all groups. Conclusion. Perioperative outcome and long-term survival did not differ when comparing liver resection for CRC liver metastases preceded by PVE and chemotherapy or chemotherapy alone, except for the operation time. The study supports the safety of this "aggressive" combination approach in patients in need of tumor "downstaging" by chemotherapy and PVE to increase the remnant liver volume.     

Selection of antibodies that regulate phenotype from intracellular combinatorial antibody libraries

A method is presented that uses combinatorial antibody libraries to endow cells with new binding energy landscapes for the purpose of regulating their phenotypes. Antibodies that are expressed in cells infected with a lentiviral combinatorial antibody library are selected directly for function rather than only for binding. The potential diversity space can be very large because more than one lentivirus can infect a single cell. Thus, the initial combinatorial diversity of ∼1.0 × 10¹¹ members generated by the random association of antibody heavy and light chains is greatly increased by the reassortment of the antibody Fv domains themselves inside cells. The power of the system is illustrated by its ability to select unusual antibodies. Here, the selected antibodies are potent erythropoietin agonists whose ontogeny depends on recombination at the protein level of pairs of antibodies expressed in the same cell to generate heterodimeric bispecific antibodies. The obligate synergy between the different binding specificities of the antibody’s monomeric subunits appears to replicate the asymmetric binding mechanism of authentic erythropoietin.     

Myopia

Myopia has emerged as a major health issue in east Asia, because of its increasingly high prevalence in the past few decades (now 80-90% in school-leavers), and because of the sight-threatening pathologies associated with high myopia, which now affects 10-20% of those completing secondary schooling in this part of the world. Similar, but less marked, changes are occurring in other parts of the world. The higher prevalence of myopia in east Asian cities seems to be associated with increasing educational pressures, combined with life-style changes, which have reduced the time children spend outside. There are no reported major genes for school myopia, although there are several genes associated with high myopia. Any genetic contribution to ethnic differences may be small. However, to what extent many genes of small effect and gene-environment interactions contribute to variations in school myopia within populations remains to be established. There are promising optical and pharmacological interventions for preventing the development of myopia or slowing its progression, which require further validation, and promising vision-sparing treatments for pathological myopia.     

Minimizing inappropriate medications in older populations: a 10-step conceptual framework

The increasing burden of harm resulting from the use of multiple drugs in older patient populations represents a major health problem in developed countries. Approximately 1 in 4 older patients admitted to hospitals are prescribed at least 1 inappropriate medication, and up to 20% of all inpatient deaths are attributable to potentially preventable adverse drug reactions. To minimize this drug-related iatrogenesis, we propose a quality use of medicine framework that comprises 10 sequential steps: 1) ascertain all current medications; 2) identify patients at high risk of or experiencing adverse drug reactions; 3) estimate life expectancy in high-risk patients; 4) define overall care goals in the context of life expectancy; 5) define and confirm current indications for ongoing treatment; 6) determine the time until benefit for disease-modifying medications; 7) estimate the magnitude of benefit versus harm in relation to each medication; 8) review the relative utility of different drugs; 9) identify drugs that may be discontinued; and 10) implement and monitor a drug minimization plan with ongoing reappraisal of drug utility and patient adherence by a single nominated clinician. The framework aims to reduce drug use in older patients to the minimum number of essential drugs, and its utility is demonstrated in reference to a hypothetic case study. Further studies are warranted in validating this framework as a means for assisting clinicians to make more appropriate prescribing decisions in at-risk older patients.