Advances in molecular,genetic and immune signatures of gastric cancer: Are we ready to apply them in our patients’ decision making?

In the last few years we have witnessed a vast expansion of our knowledge regarding the molecular and genetic profile of gastric cancer. The molecular subtypes described have shed light on the pathogenesis of the disease, thus prompting the development of new therapeutic strategies and favoring a more individualized approach for treatment. Most of the clinical trials for so called targeted therapies could be considered, at best, partially successful. In addition, checkpoint inhibitors have recently been added to our armamentarium in later stages of the disease, and combinations with chemotherapy and targeted agents are currently under development. In view of the rapid advances of molecular oncology, a new challenge for the clinical oncologist arises: The appropriate patient selection for each new therapy, which can be made possible only through the implementation of predictive biomarkers in our therapy decision making.     

The use of thymidylate synthase inhibitors in the treatment of advanced colorectal cancer: current status

The combination of 5-fluorouracil (5-FU) and leucovorin has been the unofficial "standard" therapy for patients with colorectal cancer for over a decade. Recently, however, a number of new agents targeted against the enzyme thymidylate synthase have been synthesized and are in various stages of development. The currently available thymidylate synthase inhibitors are discussed. Enormous efforts have been made over the years to improve the efficacy of 5-FU, the most popular of these agents. Biochemical modulation by leucovorin has been the most successful so far. Continuous infusion schedules also appear to be advantageous over bolus administration. However, marked intra- and interpatient variability, combined with nonlinear elimination kinetics and erratic oral bioavailability are relative limitations to further development of 5-FU. New oral 5-FU prodrugs such as UFT, S-1, and Capecitabine may help to overcome some of these difficulties. Eniluracil, a potent inhibitor of the enzyme dihydropyrimidine dehydrogenase, may also help by overcoming potential 5-FU resistance mechanisms, in addition to increasing its bioavailability. Of the antifolate-based inhibitors, Tomudex is in the most advanced stage of development. Similar efficacy with 5-FU and a convenient schedule may suggest a role in future combination regimens. It is quite likely that even the most optimal thymidylate synthase inhibition will have limitations in terms of clinical efficacy. Novel combinations of 5-FU or its analogs with agents that have different mechanisms of action (e.g., oxaliplatin, irinotecan) could provide important new opportunities for improving the outlook of patients with colorectal cancer.     

Monte Carlo simulation of the energy loss of low-energy electrons in liquid water

A Monte Carlo code that performs detailed (i.e. event-by-event) simulation of the transport and energy loss of low-energy electrons (approximately 50-10 000 eV) in water in the liquid phase is presented. The inelastic model for energy loss is based on a semi-empirical dielectric-response function for the valence-shells of the liquid whereas an exchange corrected semi-classical formula was used for K-shell ionization. Following a methodology widely used for the vapour phase, we succeeded in parametrizing the dielectric cross-sections of the liquid in accordance with the Bethe asymptote, thus providing a unified approach for both phases of water and greatly facilitating the computations. Born-corrections at lower energies have been implemented in terms of a second-order perturbation term with a simple Coulomb-field correction and the use of a Mott-type exchange modification. Angular deflections were determined by empirical schemes established from vapour data. Electron tracks generated by the code were used to calculate energy- and interaction-point-kernel distributions at low electron energies in liquid water. The effect of various model assumptions (e.g., dispersion, Born-corrections, phase) on both the single-collision and slowing-down distributions is examined.     

Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology,European Society of Coloproctology,International Society of Geriatric Oncology,and American College of Surgeons Commission on Cancer

With an expanding elderly population and median rectal cancer detection age of 70 years, the prevalence of rectal cancer in elderly patients is increasing. Management is based on evidence from younger patients, resulting in substandard treatments and poor outcomes. Modern management of rectal cancer in the elderly demands patient-centered treatment, assessing frailty rather than chronological age. The heterogeneity of this group, combined with the limited available data, impedes drafting evidence-based guidelines. Therefore, a multidisciplinary task force convened experts from the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology and the American College Surgeons Commission on Cancer, with the goal of identifying the best practice to promote personalized rectal cancer care in older patients.A crucial element for personalized care was recognized as the routine screening for frailty and geriatrician involvement and personalized care for frail patients. Careful patient selection and improved surgical and perioperative techniques are responsible for a substantial improvement in rectal cancer outcomes. Therefore, properly selected patients should be considered for surgical resection. Local excision can be utilized when balancing oncologic outcomes, frailty and life expectancy. Watch and wait protocols, in expert hands, are valuable for selected patients and adjuncts can be added to improve complete response rates. Functional recovery and patient-reported outcomes are as important as oncologic-specific outcomes in this age group. The above recommendations and others were made based on the best-available evidence to guide the personalized treatment of elderly patients with rectal cancer.     

Blood lymphocyte blastogenesis in patients with thyroid dysfunction: ex?vivo response to mitogen activation and cyclosporin?A

Objective  

To evaluate lymphocyte activation following mitogen and cyclosporin A (CsA) administration in peripheral blood of hyperthyroxinaemic and hypothyroid patients.