Familial Nasopharyngeal Carcinoma 6

282 S. S. Lo, J. J. Lu, and L. Kongradiosensitivity of parenchymal cells. Most recently,molecular pathways are implicated in the developmentof radiation-induced fibrosis. Irradiation of softtissue causes tissue injury, which leads to activationof monocytes, macrophages, and platelets, which inturn causes release cytokine and growth factors(O’Sullivan and Levin 2003). This results in recruitmentand proliferation of fibroblasts, increased synthesisof extracellular matrix, and decreased degradationof extracellular matrix and all these events contributeto eventual fibrosis.22.4.2Clinical Manifestation and DiagnosisFor neck soft tissue fibrosis, the earliest feature isthe loss of tissue elasticity and mild induration(O’Sullivan and Levin 2003). More severe degree offibrosis will result in rigidity of surface layers of tissueand loss of normal surface contours. Other associatedchanges any include hyperpigmentation, skin dryness,epilation, loss of vascularity, and changes in the epidermis.In the most severe case, necrosis or ulceration mayoccur. Trismus is result of fibrosis of the temporomandibularjoints and the muscles of mastication. The dentalgap may be narrowed to an extent such that feedingbecomes difficult (Lee 1999). Dysphagia can be a resultof swallowing dysfunction caused by radiation fibrosis.However, damage to the IX and X nerves from radiotherapyand/or late lymphedema may also contributeto dysphagia (Murphy and Gilbert 2009).The diagnosis of radiation-induced fibrosis ismainly clinical. A combination of a history of radiotherapyfor NPC and one or more of the above symptomsand signs substantiates the diagnosis. For patientswith dysphagia, the physician should have a high indexof suspicion for potential aspiration if there are symptomslike coughing or clearing of the throat prior to,during, and after eating (Murphy and Gilbert 2009).An official swallowing assessment should be performedby certified speech- language pathologists. Themost common tests used include modified bariumswallow study (MBSS) and flexible endoscopic evaluationof swallowing safety (FEES). MBSS allows for evaluationof oral and pharyngeal function whereas FEESallows for direct visualization of the upper aerodigestivetract and evaluation of vital functions includingmanagement of secretions, sensory function, and muscularfunction of the pharyngeal muscles. It also allowsfor direct visualization of the larynx and evaluation ofany dysfunction of the larynx.22.4.3ManagementThere are several strategies that have been used forthe treatment of radiation fibrosis. Several pharmacologicagents have been used. Pentoxifylline hasbeen used alone or together with vitamin E with fairresults (O’Sullivan and Levin 2003). In a study byChua et al., 16 NPC patients who developed severeradiation-induced trismus that resulted in a dentalgap of 25 mm or less. Pentoxifylline 400 mg 2–3 timesa day was given for 8 weeks. Ten (62.5%) patients hadmeasured increase in dental gap ranging from 2 to25 mm and six (37.5%) had an increase of dental gapof 5 mm or more (Chua et al. 2001). In a study byDelanian et al., where 40 patients with radiationinducedfibrosis were treated with pentoxifylline andvitamin D, 24 (60%) patients showed at least 50%regression and the mean surface area regression was53% (Delanian et al. 1999). Liposomal Cu/Zn superoxidedismutase has also been used for the treatmentof radiation-induced fibrosis with impressive results.Among the 34 patients treated with twice weeklyintramuscular injections of 5 mg for a total dose of30 mg, all showed some clinical regression of fibrosisafter 3 weeks with maximal effect observed after 2months (Delanian et al. 1994). However, this agentis not available as an approved treatment. The role ofcorticosteroid in the management of radiationinducedfibrosis is uncertain.Apart from pharmacologic measures, hyperbaricoxygen, physical therapy, and microcurrent therapyhave also been used (O’Sullivan and Levin 2003).Hyperbaric oxygen works by increasing oxygen diffusibility,collagen synthesis, and neo-angiogenesis,thus allowing healing of damaged soft tissue. However,there has not been conclusive evidence that hyperbaricoxygen can significantly affect the degree offibrosis (O’Sullivan and Levin 2003). Physical therapy,namely jaw exercise, may be useful in decreasingthe degree of trismus when it is done during and afterradiotherapy. Microcurrent therapy has been demonstratedto improve range of motion of the neck in81%–92% of 26 patients with established radiationfibrosis of the neck in a study and the effect was sustainedfor more than 3 months (Lennox et al. 2002).However, no other confirmatory studies are available.In patients with radiation-induced dysphagia, thegoals of swallowing therapy are avoiding aspiration,improving swallowing function over time, and modificationsin diet to render safe oral intake possible.The techniques used in swallowing therapy include