Sarcopenia is an important public health problem, characterized by age-related loss of muscle mass and muscle function. It is a precursor of physical frailty, mobility limitation, and premature death. Muscle loss is mainly due to the loss of type II muscle fibres, and progressive loss of motor neurones is thought to be the primary underlying factor. Anterior thigh muscles undergo atrophy earlier, and the loss of anterior thigh muscle function may therefore be an antecedent finding. The aim of this review is to provide an in-depth (and holistic) neuromusculoskeletal approach to sarcopenia. In addition, under the umbrella of the International Society of Physical and Rehabilitation Medicine (ISPRM), a novel diagnostic algorithm is proposed, developed with the consensus of experts in the special interest group on sarcopenia (ISarcoPRM). The advantages of this algorithm over the others are: special caution concerning disorders related to the renin-angiotensin system at the case finding stage; emphasis on anterior thigh muscle mass and function loss; incorporation of ultrasound for the first time to measure the anterior thigh muscle; and addition of a chair stand test as a power/performance test to assess anterior thigh muscle function. Refining and testing the algorithm remains a priority for future research. LAY ABSTRACT Sarcopenia is an important public health problem, characterized by age-related loss of muscle mass and muscle function. The diagnostic recommendations published to date have addressed total or appendicular muscle mass. However, under the umbrella of the International Society of Physical and Rehabilitation Medicine (ISPRM), experts in the special interest group on sarcopenia (ISarcoPRM) developed a new algorithm, based on regional measurements and functional evaluations of the anterior thigh muscle, which is the most commonly and initially affected condition in sarcopenia. Unlike other suggestions, diseases associated with the renin-angiotensin system are emphasized in this algorithm, and ultrasound has been used for measurement of anterior thigh muscle mass.

Background:Dihydropyrimidine dehydrogenase (DPD) catabolises ∼85% of the administered dose of fluoropyrimidines. Functional DPYD gene variants cause reduced/abrogated DPD activity. DPYD variants analysis may help for defining individual patients’ risk of fluoropyrimidine-related severe toxicity.Methods:The TOSCA Italian randomised trial enrolled colon cancer patients for 3 or 6 months of either FOLFOX-4 or XELOX adjuvant chemotherapy. In an ancillary pharmacogenetic study, 10 DPYD variants (*2A rs3918290 G>A, *13 rs55886062 T>G, rs67376798 A>T, *4 rs1801158 G>A, *5 rs1801159 A>G, *6 rs1801160 G>A, *9A rs1801265 T>C, rs2297595 A>G, rs17376848 T>C, and rs75017182 C>G), were retrospectively tested for associations with ⩾grade 3 fluoropyrimidine-related adverse events (FAEs). An association analysis and a time-to-toxicity (TTT) analysis were planned. To adjust for multiple testing, the Benjamini and Hochberg’s False Discovery Rate (FDR) procedure was used.Results:FAEs occurred in 194 out of 508 assessable patients (38.2%). In the association analysis, FAEs occurred more frequently in *6 rs1801160 A allele carriers (FDR=0.0083). At multivariate TTT analysis, significant associations were found for *6 rs1801160 A allele carriers (FDR<0.0001), *2A rs3918290 A allele carriers (FDR<0.0001), and rs2297595 GG genotype carriers (FDR=0.0014). Neutropenia was the most common FAEs (28.5%). *6 rs1801160 (FDR<0.0001), and *2A rs3918290 (FDR=0.0004) variant alleles were significantly associated with time to neutropenia.Conclusions:This study adds evidence on the role of DPYD pharmacogenetics for safety of patients undergoing fluoropyrimidine-based chemotherapy.

Objective: The efficacy of bevacizumab in metastatic colorectal cancer (mCRC) could be related not only to its well-known antiangiogenetic properties but also to a hypothetical effect on the immune system of the host. Methods: We enrolled mCRC patients treated with a bevacizumab-based first-line therapy. Lymphocyte and dendritic cell subsets were evaluated at baseline, 3rd and 6th cycle. The clinical efficacy was estimated as response rate and progression-free survival. Forty healthy subjects were used as reference. Results: Fifty-one patients were enrolled. In comparison with healthy subjects, they showed a decrease of T and B cell compartments. Bevacizumab ameliorated the impairment of lymphocyte subsets, especially for T cells. Responders showed a trend toward an increase of CD3 (p = 0.07) and CD4 (p = 0.05). Among patients with a progression-free survival >1 year, only CD19 (p = 0.033) and CD20 (p = 0.013) showed a significant increase. No baseline impairment and no significant modification of dendritic cells were found. Conclusion: Bevacizumab-based therapy is able to increase B and T cell compartments. The expansion of T lymphocytes could imply an amelioration of dendritic cell-presenting capacity. These effects correlate with a more favourable clinical outcome and could be taken into account in clinical protocols aimed at combining antiangiogenetic-therapy with immunotherapy in mCRC.

This review focuses on the personalized treatment of mCRC and discusses the potential of new prognostic and predictive biomarkers in selecting patients treated with anti-EGFR therapy.

Background: Despite therapeutic innovations, metastatic colorectal cancer (mCRC) is still characterized by poor prognosis and few molecular markers predict the risk of progression. Polycomb group genes (PcGs) are epigenetic modifiers involved in tumor suppressor gene silencing. PcG member EZH2 mediates gene silencing through histone-H3 lysine-27 methylation. In colorectal cancer (CRC), EZH2 overexpression predicts shorter survival. Recently, four EZH2 single-nucleotide polymorphisms (SNPs) have been described. The present study was aimed at evaluating the correlation between EZH2 SNPs and outcome parameters in mCRC patients.Patients and methods: DNA was extracted from blood samples of 110 mCRC patients treated with first-line 5-fluorouracil, folinic acid, irinotecan (FOLFIRI) and bevacizumab. Genotyping was carried out by real-time PCR. Genotype was used to predict objective response, progression-free survival (PFS) and overall survival (OS). EZH2 messenger RNA levels were evaluated on lymphocytes of a parallel cohort of 50 CRC patients.Results: One allelic variant (rs3757441 C/C versus C/T or T/T) was significantly associated with shorter PFS and OS (P < 0.01 and P < 0.05, respectively). At multivariate analysis, the same variant resulted an independent predictor of PFS and OS (P < 0.05). The C/C variant was associated with significantly higher EZH2 expression (P < 0.05).Conclusion: An EZH2 SNP may be useful to predict clinical outcome in mCRC patients.

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Approximately 213,380 new cases of non-small-cell lung cancer (NSCLC) were estimated to occur in the USA in 2007, which caused 160,390 NSCLC-related deaths. The majority of patients will be diagnosed with nonoperable, advanced-stage disease. Although combination chemotherapy remains the standard treatment, median survival with these regimens is only 8-10 months. Recent advances in our understanding of lung cancer on a molecular level have led to the introduction of targeted therapies. The EGF receptor (EGFR) was the first receptor to be proposed for cancer therapy and two EGFR-targeted pharmacologic approaches have been successfully developed: monoclonal antibodies (mAbs) and small-molecule inhibitors of the EGFR tyrosine kinase enzymatic activity. Erlotinib is a quinazoline derivative that selectively and reversibly inhibits the tyrosine kinase activity of the EGFR. Here, we review the mechanism(s) of action of erlotinib, as well as the results of Phase I, II and III trials with this drug in NSCLC, which have led to the worldwide approval of erlotinib treatment as monotherapy for therapy-refractory, advanced NSCLC patients.

Ultrasound appears to be the most useful imaging tool in the diagnosis and guided treatment of musculoskeletal disorders. However, ultrasonography has been criticized for being user dependent. Therefore, medical professionals should be familiar with the basic principles of ultrasound imaging (e.g., physics and technical skills) to diminish artifacts and avoid misinterpretation. In this review, we focused on the physics of common artifacts, their clinical significance, and the ways to tackle them in daily practice during musculoskeletal imaging. In particular, artifacts pertaining to the focal zone, beam attenuation, path and side lobe of the beam, speed of the sound, and range ambiguity were described.