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104 CHAPTER 6 to increased muscle wasting due to myocyte apoptosis and decreased regeneration. 34,35 Low SMM may therefore also impair wound healing and increase wound related complications. 36 Success of microvascular free flaps strongly depend on an environment of low thromboge- nicity, favorable endothelialization at the anastomotic sites and a wound microenvironment where essential healing processes such as fibroblast collagen synthesis and the production of reactive oxygen species can be unhindered. 37 An increased inflammatory microenvironment impedes these processes and may consequently be deleterious to the outcomes of micro- surgical flaps. In this study, sarcopenia had a significant prognostic impact on OS but not on disease free survival. A recent study by Tamaki et al. and a study by Grossberg et al. showed also sarco - penia’s negative impact on OS. 31,38 DFS was not found to be affected by sarcopenia. However, both studies found an increase in disease recurrence in sarcopenic patients. This may be attributed to a relatively new insight that skeletal muscle mass may be considered to be an endocrine organ. Different research groups have displayed that skeletal muscle cells secrete cytokines, known as myokines. 39,40 These myokines have been shown induce apoptosis in the cells of some tumors. 40,41 A myokine of specific interest has been interleukin 6. Pedersen et al. demonstrated its antitumorigenic effects in mouse models through increased mobilization of natural killer cells in tumor surveillance. 41 Preventing head and neck cancer-related sarcopenia is challenging, due to high risk of malnu- trition in this patient population secondary to odynophagia, dysphagia, aspiration and prior radiotherapy exposure. Yet, it is of interest to study if interventions aimed at preservation of muscle mass such as multimodal preoperative rehabilitation programs that include physical therapy and nutritional intervention before surgery are effective in improving SMM and out - comes. For instance, exercise and nutrition intervention during and after radiotherapy in HNC patients is shown to be feasible and is effective in diminishing muscle loss. 42 A randomized controlled trial (RCT) in patients with lung cancer undergoing 1-week intensive rehabilitation, which consisted of exercise endurance and resistance training prior to lung cancer lobecto- my, showed a significant decrease in hospital stay after surgery, and less severe pulmonary postoperative complications. Though information on pre-treatment SMMwas not provided. 43 Because of increasing surgical experience and technological advancement, the success rate of microvascular free tissue transfer is reported to be above 95%. 8 Still, flap failures have dreaded consequences for both functional and cosmetic outcomes and can have a devastating psychological impact on patients. The selection of an optimal flap for the reconstruction of a mandibular defect depends on site-specific factors such as the length and location of the segmental defect, extent of the external cutaneous defect and volume of the residual tongue among others. 44 Also, patient specific factors play a role in the decision-making process of optimal flap choice. Determining