Association between postoperative muscle wasting and survival in older patients undergoing surgery for non-metastatic colorectal cancer

BACKGROUND: Preoperative sarcopenia in older patients is a risk factor for adverse outcomes after colorectal cancer (CRC) surgery. Longitudinal changes in muscle mass in this group have not been studied previously although muscle wasting may have prognostic significance regarding survival. We aimed to determine the association between muscle wasting and overall survival (OS) in older patients who underwent surgery for CRC.METHODS: Patients ≥70 years who underwent surgery for non-metastatic CRC in Gelre hospitals, The Netherlands, between 2011 and 2015 were included. Cross-sectional area of skeletal muscle was measured at the level of the 3rd lumbar vertebra on preoperative and postoperative abdominal CT-scans. Patients who had &gt;1 standard deviation decrease in muscle mass were considered to have muscle wasting. Cox regression analysis was used to evaluate associations between muscle wasting and OS.RESULTS: 233 patients were included (40% female, median age 76 years). Thirty-four patients had muscle wasting. After a median follow-up of 4.7 years, 53 (23%) patients died. The 3-year mortality rate was higher in patients with muscle wasting (27% vs 14%, p = .05). In multivariable analysis adjusted for age, recurrent disease and preoperative muscle mass, muscle wasting was associated with reduced OS (HR 2.8, 95% CI 1.5-5.4, p = .002).CONCLUSION: Muscle wasting predicted poorer survival in older patients who underwent CRC surgery. Measuring changes in muscle mass may improve risk prediction in this patient group. Future studies should address the etiology of muscle wasting in older patients with CRC. Whether perioperative exercise interventions can prevent muscle wasting also warrants further study.</p

Validation of a clinicopathological and gene expression profile model for sentinel lymph node metastasis in primary cutaneous melanoma

Background: The Clinicopathological and Gene Expression Profile (CP-GEP) model was developed to accurately identify patients with T1–T3 primary cutaneous melanoma at low risk for nodal metastasis. Objectives: To validate the CP-GEP model in an independent Dutch cohort of patients with melanoma. Methods: Patients (aged ≥ 18 years) with primary cutaneous melanoma who underwent sentinel lymph node biopsy (SLNB) between 2007 and 2017 at the Erasmus Medical Centre Cancer Institute were eligible. The CP-GEP model combines clinicopathological features (age and Breslow thickness) with the expression of eight target genes involved in melanoma metastasis (ITGB3, PLAT, SERPINE2, GDF15, TGFBR1, LOXL4, CXCL8 and MLANA). Using the pathology result of SLNB as the gold standard, performance measures of the CP-GEP model were calculated, resulting in CP-GEP high risk or low risk for nodal metastasis. Results: In total, 210 patients were included in the study. Most patients presented with T2 (n = 94, 45%) or T3 (n = 70, 33%) melanoma. Of all patients, 27% (n = 56) had a positive SLNB, with nodal metastasis in 0%, 30%, 54% and 16% of patients with T1, T2, T3 and T4 melanoma, respectively. Overall, the CP-GEP model had a negative predictive value (NPV) of 90·5% [95% confidence interval (CI) 77·9–96.2], with an NPV of 100% (95% CI 72·2–100) in T1, 89·3% (95% CI 72·8–96·3) in T2 and 75·0% (95% CI 30·1–95·4) in T3 melanomas. The CP-GEP indicated high risk in all T4 melanomas. Conclusions: The CP-GEP model is a noninvasive and validated tool that accurately identified patients with primary cutaneous melanoma at low risk for nodal metastasis. In this validation cohort, the CP-GEP model has shown the potential to reduce SLNB procedures in patients with melanoma

Cathepsin L, target in cancer treatment?

Cathepsin L a cysteine protease, is considered to be a potential therapeutic target in cancer treatment. Proteases are involved in the development and progression of cancer. Inhibition of activity of specific proteases may slow down cancer progression. In this review, we evaluate recent studies on the inhibition of cathepsin L in cancer. The effects of cathepsin L inhibition as a monotherapy on apoptosis and angiogenesis in cancer are ambiguous. Cathepsin L inhibition seems to reduce invasion and metastasis, but there is concern that selective cathepsin L inhibition induces compensatory activity by other cathepsins. The combination of cathepsin L inhibition with conventional chemotherapy seems to be more promising and has yielded more consistent results. Future research should be focused on the mechanisms and effects of this combination therapy. (C) 2009 Elsevier Inc. All rights reserve