Synchronous chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck using capecitabine: a single-centre, open-label, single-group phase II study.

AIM: To evaluate the efficacy of concurrent oral capecitabine with accelerated hypofractionated radical radiotherapy in locally advanced squamous cell carcinoma of the head and neck (SCCHN). MATERIALS AND METHODS: Between 2001 and 2004, 50 patients with stage III/IV SCCHN (0 to 2 performance status) were enrolled into this study. The capecitabine dose was between 450 and 550 mg/m(2) twice daily, continuously for 28 days. The radiotherapy dose was 5500 cGy in 20 fractions over 4 weeks. No intensity-modulated radiation was used. We evaluated the complete response rate, toxicity, locoregional control, overall survival, disease-free survival and cancer-specific survival. RESULTS: The median age was 55 (range 38-76) years; 72% had stage IV disease. The median follow-up was 6 years on the 30 surviving patients. Eighty-two per cent of patients completed the course of capecitabine and 94% completed prescribed radiotherapy. There were no treatment-related deaths, grade 3/4 haematological or renal toxicity. Five patients developed drug-related grade 3/4 acute toxicity (cardiac, skin, bowel); 47 developed grade 3/4 mucositis from chemoradiotherapy. Twenty-two (44%) patients required tube feeding and the tube dependency rate at 1 year was 6%. The complete response rate at 3 months was 90% (45/50 patients). Relapse occurred in 17/50 (34%) patients by 5 years. The locoregional control, overall survival, cancer-specific survival and disease-free survival rates at 3 years were 78, 72, 82 and 62%, respectively, and at 5 years were 72, 64, 75 and 56%, respectively. CONCLUSION: This schedule of synchronous capecitabine for locally advanced SCCHN is well tolerated. The local control in this series compares favourably with other synchronous chemoradiotherapy reports. Chronic dysphagia and tube dependence is uncommon with this approach. Capecitabine as targeted therapy given with each fraction of radiotherapy and administered orally may have significant advantages over intravenous, 3 weekly cisplatin.

Endovascular management of the carotid blowout syndrome.

Bleeding from the carotid artery or its branches ('carotid blowout') is a well recognized complication following treatment or recurrence of head and neck cancer. The traditional surgical treatment for carotid blowout is often technically difficult and is associated with an unacceptably high morbidity and mortality. The majority of such patients are currently treated conservatively with end of life supportive measures. We report the case of a young patient with recurrent supraglottic carcinoma complicated by carotid blowout on two separate occasions over a five month period, which was successfully treated endovascularly under local anaesthetic, without neurological sequelae. With the continuing development of interventional radiology, endovascular techniques are now emerging as a viable, low morbidity treatment option in selected patients.

Lacrimal gland fluid secretion and lymphocytic infiltration in the NZB/W mouse model of Sjögren's syndrome.

PURPOSE: The fluid secretory impairment of lacrimal and salivary glands in Sjögren's syndrome (SS) is thought to be related to the extent of lymphocytic infiltration (LI) and subsequent loss of glandular tissue. In this study, we examine the correlation between the extent of tear flow reduction and the extent of LI of lacrimal glands in the NZB/W mouse, a model of SS. METHODS: We stimulated tear production by topical application of carbachol onto the gland while fluid was collected from the lacrimal duct. The lacrimal glands were removed after fluid collection for histology. RESULTS: Fluid secretion in response to carbachol was less in the majority of young NZB/W females compared to C57 control animals and none of the glands showed LI. Fluid secretion was also impaired in the majority of old NZB/W females, and the extent of LI was highly variable. Some of the old SW females also showed blunted fluid secretory responses and some degree of focal LI. Young SW females showed no LI and most animals exhibited normal flow responses. Analysis of paired flow and LI measurements showed no correlation between LI and flow impairment in any of the groups or in the pooled data. Carbachol-stimulated protein secretion from lacrimal gland slices in vitro were similar in young and old SW and NZB/W mice. CONCLUSIONS: These results suggest that LI alone is not sufficient to explain the secretory dysfunction in the NZB/W mouse model of Sjögren's syndrome.

Metastatic renal cell carcinoma to the nose and paranasal sinuses.

BACKGROUND: Renal cell carcinoma represents 3% of all malignant tumors. Metastatic deposits of renal cell carcinoma to the head and neck region are infrequent. The objective of this work is to analyze the clinical presentation, radiologic features, surgical and radiotherapy treatment, and outcome of metastatic renal cell carcinoma to the nose and sinuses. METHODS: Retrospective review of 6 patients diagnosed with renal cell carcinoma who had nasal metastasis develop and were seen at the Christie Hospital in Manchester over the past 8 years. RESULTS: Six patients with renal cell carcinoma were seen with recurrent epistaxis, nasal obstruction, and unpleasant nasal crusting. Three patients had orbital involvement. Examination under general anaesthesia and biopsy was performed in all 6 cases. Histologic studies confirmed metastases of renal cell carcinoma in all 6 patients. All patients underwent local external beam radiotherapy. The most common dose used was 35 Gy in 8 daily fractions. All patients had symptomatic control of local nasal disease with a minimum follow-up of 2 years in 4 patients. Two patients died within 6 months of the radiotherapy treatment as a result of their primary tumor. CONCLUSIONS: Metastatic renal cell carcinoma to the nose and paranasal sinuses is rare but has unpleasant symptoms. Local symptomatic control with radiotherapy is excellent.

Radiotherapy for carcinoma of the posterior pharyngeal wall.

Posterior pharyngeal carcinoma has an extremely poor prognosis regardless of the method of treatment. The purpose of this study was to assess the local control and survival in patients with carcinoma of the posterior pharyngeal wall treated with definitive radiotherapy and to determine prognostic factors which may be relevant to the current UICC staging classification. Between January 1991 and December 1995, 22 patients with a mean age of 60 years (range 44-82) received definitive radiotherapy, using a homogeneous technique, for carcinoma of the posterior pharyngeal wall. The median follow-up was 42 months (range 25-66). The overall 3-year survival and local control for the whole group was 50% and 73% respectively. Patients with early stage (T1 and T2) disease had a significantly better overall 3-year survival rate of 77% compared to 11% for patients with advanced stage (T3 and T4) disease (p=0.0010). Similarly, patients with early stage disease had a significantly improved 3-year local control rate compared to patients with more advanced stage disease (92% and 44% respectively, p=0.0080). Patients with node positive disease had an inferior survival rate of 29% compared to 60% for those with node negative disease though the difference did not reach statistical significance. In addition only one patient with initial node negative disease had isolated nodal relapse. There was no significant late morbidity. For patients with early stage disease we have obtained local control and survival rates comparable to other groups with a once daily, short fractionation radiotherapy scheme but with reduced morbidity. In late stage disease altered fractionation schemes should be considered in order to achieve better local control and survival. Isolated nodal relapse was not a significant problem in this cohort of patients. Outcome correlates with primary tumour size and this is reflected in the current UICC staging classification.

The diagnostic value of positron emission tomography (PET) with radiolabelled fluorodeoxyglucose (18F-FDG) in head and neck cancer.

Positron emission tomography (PET) scanning has recently been introduced into clinical practice but its usefulness in the management of head and neck cancer is not well defined. The aim of this prospective preliminary study was to examine the clinical value of fluorodeoxyglucose (FDG)--PET in patients with head and neck cancer treated by radiotherapy with surgery in reserve by (i) relating quantitative uptake of isotope to tumour type and histological grade and (ii) comparing the imaging findings of PET and magnetic resonance imaging (MRI) in post-radiotherapy assessment of tumour response. Twenty-one patients had pre-treatment PET and MRI scans and these were repeated four and eight months after treatment if there was no clinical relapse. Pre-treatment uptake of FDG using tumour to cerebellar ratio parameters was significantly related to the histological grade of squamous cancer (p = 0.04) but not to tumour type. Discordance of post-treatment PET/MRI findings in one case indicates a possible role for PET in the early detection of tumour recurrence. Other potential uses of PET scanning in the management of head and neck cancer are discussed.

Submandibular gland carcinoma; an audit of local control and survival following adjuvant radiotherapy.

Carcinoma of the submandibular gland is a rare diagnosis, accounting for less than 2% of cases of salivary gland tumours. We have examined the treatment and outcome of a total of 30 patients treated with radiotherapy at the Christie Hospital, Manchester between 1980 and 1993. In most cases this followed radical surgery, though 12 patients were referred following either incomplete excision or biopsy only. Adenoid-cystic histology accounted for 19 cases (63%). Standard radiotherapy was delivered using a beam directed technique to treat the whole submandibular compartment. Doses prescribed were most commonly from 50 to 55 Gy in 16 fractions over three weeks. Cancer specific survival was 79% and 57% at 5 and 10 yr respectively, the continued fall at 10 yr reflected late recurrence seen in patients with adenoid-cystic histology. Local control was 85% and 73%, respectively. Nine of twelve patients with incomplete excision or biopsy only had local control with radiotherapy. Six patients developed lung metastases, all of whom had adenoid-cystic histology. Radiotherapy was well-tolerated acutely, and only one patient experienced osteoradionecrosis requiring surgical intervention. The incidence of adenoid-cystic carcinoma is higher in the submandibular than the parotid gland. This typically results in late recurrence, and a high incidence of lung metastases and this was confirmed in our study. However, overall survival was very similar to that of parotid carcinoma.

A comparison of surgery and radiotherapy in the management of post-cricoid carcinoma.

One hundred and forty-three patients with post-cricoid squamous cell carcinoma are described. Twenty-nine patients (20%) underwent pharyngolaryngoesophagectomy with gastric transposition. Forty-four patients (31%) were treated with radical radiotherapy and 70 (49%) had palliative therapy. Kaplan Meier 5-year survival following surgery was 45% and radiotherapy was 23%. The presence of nodal disease at presentation was the most significant prognostic factor. The 5-year survival of patients undergoing surgery with no palpable lymph node spread at presentation was 63% which compared with 25% following radiotherapy. This difference was statistically significant (P = 0.0153, Logrank test stratified by nodal status). Patients with palpable metastatic nodal spread at presentation had 5-year survivals of 10% and 0% in the surgical and radiotherapy groups respectively. This study demonstrates that patients with post-cricoid carcinoma who present without palpable lymph node spread have a significant improved 5-year survival following surgery when compared with radiotherapy.

Neuroendocrine carcinoma of the larynx.

Neuroendocrine carcinomas (NEC) of the larynx are rare. The key to diagnosis is therefore an increased awareness of such lesions amongst otolaryngologists and pathologists. A precise histological diagnosis is crucial, as the management is different for each NEC sub-type. Advances in immunohistochemistry have been a great help in this respect. We report a typical case of large cell NEC (atypical carcinoid) and highlight the clinical pointers to the histological diagnosis.

External ear canal cholesteatoma. Case report.

External ear canal cholesteatoma is a rare condition in otologic practice. A case in a 43-year-old woman is presented in which despite the extensive nature of the lesion, minimal symptoms and absence of signs delayed diagnosis. The cause of the lesion and its treatment are discussed.

Ménière's disease.

Even more than a century after the first description of Ménière's disease, Portmann (1927) said: 'Ménière's is one of the least understood disorders both by doctors in general and specialists. It is variable in clinical presentation, imprecise in diagnosis, and because the effectiveness of treatment is doubtful, leaves the clinician disillusioned, depriving the patient of the potential cure that has become the rule.'

Recurrent respiratory papillomatosis--the Manchester experience, 1974-1992.

A series of 59 patients of all ages with recurrent respiratory papillomatosis (RRP) treated over an 18-year period is presented. A number of these patients were initially diagnosed in childhood but required treatment throughout adult life. The frequency of laser treatment was not related to either disease duration or age at onset. In 28 patients, the HPV type was identified, showing that HPV type 11 was more common in children and ran a more protracted clinical course. The requirement for tracheostomy in this series was small, whereas the incidence of malignant change in adult patients was significant.

An extensive vestibular schwannoma with both intracranial spread and lateral extension to the external auditory canal.

An extensive schwannoma in a 54-year-old woman is described. There was extension intracranially to involve the brain stem, laterally to fill the middle ear and external meatus, and inferiorly into the infratemporal fossa. Initially the intracranial portion of the tumour was excised. Later a second operation was undertaken to remove the residual tumour from the temporal bone and infratemporal fossa.

Reconstruction of discharging mastoid cavities using the temporalis myofascial flap.

Muscle obliteration of the troublesome mastoid cavity is one method of achieving a permanently dry ear, although long-term results are often disappointing. An operation is described, which is a modification of existing techniques and utilizes a temporalis myofascial flap. This procedure has been used on 46 discharging mastoid cavities and produced encouraging results. It provides a simple, safe and reliable solution to the problem.

Intralabyrinthine schwannoma shown by magnetic resonance imaging.

Intralabyrinthine schwannomas are rare benign tumours which present with progressive or fluctuant audiovestibular symptoms and may mimic Meniéres disease. The size and position of these lesions make preoperative diagnosis unusual and most are discovered incidentally at labyrinthectomy. A case is reported which was diagnosed on magnetic resonance imaging and confirmed at surgery.

Vomiting in pregnancy resulting in oesophageal perforation in a 15-year-old.

Spontaneous perforation of the oesophagus is extremely rare in children, as is perforation due to vomiting in pregnancy. We report the case of a 15-year-old in whom vomiting in early pregnancy resulted in oesophageal perforation with subcutaneous emphysema causing marked facial swelling in the absence of other signs. The more common clinical presentation of spontaneous oesophageal rupture (Boerhaave's syndrome) is discussed.

Primary synovial sarcoma of the middle ear.

Synovial sarcoma is a soft tissue malignancy which most commonly affects the lower limbs of young adults and rarely occurs in the head and neck region. The term synovial sarcoma may be a misnomer as most of these tumours occur in tissues not known to contain synovial tissue. There has only been one previously reported case affecting the middle ear, which was metastatic, and we report the first case of primary synovial sarcoma of the middle ear.

Cerebellopontine angle lipoma.

A case of a cerebellopontine angle lipoma is presented with a typical clinical, audiometric and radiological features of an acoustic neuroma. The correct pre-operative diagnosis was elusive even with the aid of magnetic resonance imaging.