**7. References**

148 Carcinogenesis, Diagnosis, and Molecular Targeted Treatment for Nasopharyngeal Carcinoma

administered and the total dose, damage to the germinal epithelium and the supporting Sertoli cells, with consequent oligo-or azoo-spermia, occurs in 20-90% of patients following chemotherapy. Recovery of spermatogenesis is not unusual and can be seen several years after chemotherapy (Howell & Shalet, 2005). In patients treated for testicular cancer, for example, variable degrees of recovery of spermatogenesis are seen in 50-80% after 2 to 5 years following completion of cisplatinum-based chemotherapy (Howell & Shalet, 2005). However, patients who have fully preserved or recovered spermatogenesis still have reduced sperm count compared with healthy men. Damage to the germinal epithelium causes gradual atrophy of the testes with reduced volume, reduced inhibin B and increased

Although less vulnerable to the cytotoxic effects of chemotherapy than the germinal epithelium, Leydig cell dysfunction following chemotherapy is well described. It is often fully compensated with normal testosterone levels and significantly increased LH levels (Howell & Shalet, 2001). The effects of chemotherapy on the production of testosterone from Leydig cells are only seen at much higher doses. The doses required to cause Leydig cell failure will invariably have resulted in damage to the germinal epithelium. However, subtle degrees of Leydig cell dysfunction may be seen in the presence of normal spermatogenesis (Howell & Shalet, 2001). Co-existing radiation-induced gonadotrophin deficiency may impair the extent

The impact of mild/subclinical Leydig cell insufficiency is unclear (Howell et al., 1999). However, the manifestations of severe degrees of Leydig cell dysfunction depend upon the age of the patient. Loss of Leydig cell function before the onset of, or during puberty will be associated with failure to enter puberty spontaneously or arrest of pubertal development. Leydig cell failure following the development of normal secondary sexual characteristics manifests clinically with reduced libido, erectile dysfunction, fatigue and mood changes. In the long-term, Leydig cell failure may adversely affect skeletal, muscular, cardiovascular, and metabolic health as well as cognitive functions (Bhasin et al., 2010). If not contraindicated, testosterone replacement therapy is recommended for symptomatic men with classical androgen deficiency aimed at inducing and maintaining secondary sex characteristics and at improving their sexual function, sense of well-being, and bone mineral density. Clinical monitoring of testosterone therapy at regular intervals to assess response, compliance and adverse effects is important. Assessment of bone density every 1-2 years in osteoporotic men and annual monitoring of the haematocrit and the PSA (in men 40 yr of

of compensation and result in combined primary and secondary hypogonadism.

age or older) are also important particularly in the long-term (Bhasin et al., 2010).

and hormonal manipulation are largely experimental (Howell & Shalet, 2002).

With regard to fertility preservation, cryopreservation of spermatozoa before sterilizing chemotherapy (sperm banking) in the sexually mature male is currently the only established clinical option. In men with spermatogenic arrest, sperm extraction for intracytoplasmic sperm injection (ICSI) is a potentially successful approach. Other fertility preservation techniques such as cryopresvation of testicular tissues, germ cell transplantation, testis tissue xenografting

Treatment of NPC with radiotherapy is associated with a high risk of radiation-induced hypothalamic-pituitary dysfunction. More than 80% of NPC survivors will have at least one

FSH secretion.

**6. Conclusions** 


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**9** 

*Singapore* 

**Ear-Related Issues in Patients** 

**with Nasopharyngeal Carcinoma** 

*Department of Otolaryngology, Singapore General Hospital* 

Wong–Kein Christopher Low and Mahalakshmi Rangabashyam

Nasopharyngeal carcinoma (NPC) is the sixth most common cancer in Singapore amongst males. Each year, there are 300-400 new cases diagnosed **(**Singapore cancer registry 2005- 2009). NPC is endemic in Southeast Asia, North Africa, and parts of the Mediterranean basin, with the highest prevalence in Southern China where an average of 80 cases per

The nasopharynx is at a point where the ear, nose and upper pharynx converge. NPC is relevant to the Otologist although the nasopharynx is located outside the precincts of the anatomical confines of the ear, since it frequently manifests itself in the form of ear-related symptoms. The ear deserves special attention not only during diagnosis, but also in treatment and follow-up of patients with NPC. NPC is extremely radiosensitive and potentially curable provided the diagnosis is made early. As ear structures are often included in the radiation fields, ear-related complications of radiotherapy are common as

Early diagnosis is important as it has better treatment outcomes. Patients with early stages of the disease may present with ear-related complaints. In advanced disease, adjuvant chemotherapy may become necessary. Chemotherapy usually involves using Cisplatin (CDDP), which is potentially ototoxic. It is of concern that only 10% of patients are diagnosed early at stage I (van Hasselt and Woo, 2008). According to Leong et al.(1999), patient factors identified which contributed to delayed diagnosis included deferment in seeking medical help, defaulting follow up visits and refusing investigations. Other factors contributing to further delay in diagnosis were Clinicians not considering a diagnosis of NPC and Clinicians suspecting NPC but misled by the results of investigations. These factors contributed to nearly a fifth of patients with NPC having delayed diagnosis. Many of the factors responsible for the delays appear to be preventable by better patient education and counseling, doctors having sharper clinical acumen and skills in NPC diagnosis and the hospital administration having a system of tracking down high risk patients who default. Therefore, Clinicians should be familiar with the ear-related manifestations of NPC, which

This review aims to highlight ear-related issues in NPC patients from 2 perspectives: 1) as a manifestation of the disease itself and 2) ear-related complications arising from treatment of

100,000 populations is reported each year **(**Loong et al., 2008).

**1. Introduction** 

well.

may help in its early diagnosis

