Lister strain vaccinia virus with thymidine kinase gene deletion is a tractable platform for development of a new generation of oncolytic virus.

Vaccinia virus (VV) has many attractive characteristics as a potential cancer therapeutic. There are several strains of VV. The nonvaccine strain Western Reserve VV with deletion of both the thymidine kinase and the viral growth factor genes (known as WRDD) has been reported as the most potent tumor-targeted oncolytic VV. Other strains, such as the European vaccine Lister strain, are largely untested. This study evaluated the antitumor potency and biodistribution of different VV strains using in vitro and in vivo models of cancer. Lister strain virus with thymidine kinase gene deletion (VVΔTK) demonstrated superior antitumor potency and cancer-selective replication in vitro and in vivo, compared with WRDD, especially in human cancer cell lines and immune-competent hosts. Further investigation of functional mechanisms revealed that Lister VVΔTK presented favorable viral biodistribution within the tumors, with lower levels of proinflammatory cytokines compared with WRDD, suggesting that Lister strain may induce a diminished host inflammatory response. This study indicates that the Lister strain VVΔTK may be a particularly promising VV strain for the development of the next generation of tumor-targeted oncolytic therapeutics.

Gene therapy and nasopharyngeal carcinoma.

In 2003, a non-replicating adenoviral gene therapy product received the world`s first government licence for the treatment of head and neck cancer. Two years later approval was granted to a replication-selective adenovirus for the treatment of nasopharyngeal carcinoma in combination with chemotherapy. This review introduces the reader to gene therapy as an emerging treatment modality, and outlines its application to the management of nasopharyngeal carcinoma by examining recent pre-clinical and clinical research.

Lister strain of vaccinia virus armed with endostatin-angiostatin fusion gene as a novel therapeutic agent for human pancreatic cancer.

Survival after pancreatic cancer remains poor despite incremental advances in surgical and adjuvant therapy, and new strategies for treatment are needed. Oncolytic virotherapy is an attractive approach for cancer treatment. In this study, we have evaluated the effectiveness of the Lister vaccine strain of vaccinia virus armed with the endostatin-angiostatin fusion gene (VVhEA) as a novel therapeutic approach for pancreatic cancer. The Lister vaccine strain of vaccinia virus was effective against all human pancreatic carcinoma cells tested in vitro, especially those insensitive to oncolytic adenovirus. The virus displayed inherently high selectivity for cancer cells, sparing normal cells both in vitro and in vivo, with effective infection of tumors after both intravenous (i.v.) and intratumoral (i.t.) administrations. The expression of the endostatin-angiostatin fusion protein was confirmed in a pancreatic cancer model both in vitro and in vivo, with evidence of inhibition of angiogenesis. This novel vaccinia virus showed significant antitumor potency in vivo against the Suit-2 model by i.t. administration. This study suggests that the novel Lister strain of vaccinia virus armed with the endostatin-angiostatin fusion gene is a potential therapeutic agent for pancreatic cancer.

Ethmoidal metastasis as a first presentation of breast cancer: a case report.

Distant metastasis in advanced breast cancer is not uncommon; however, spread to the paranasal sinuses is extremely rare. We present a case of a woman who presented to our ophthalmology colleagues with worsening unilateral proptosis secondary to a tumour mass within her ethmoid sinuses. Biopsy of the ethmoid tumour showed adenocarcinoma of unknown origin. Whole-body positron emission computed tomography demonstrated a breast primary lesion. The patient was treated with palliative chemotherapy, and the patient remains well at this point. The importance of specialist head and neck radiological interpretation of imaging cannot be underestimated. Early tissue diagnosis is essential before ascribing patients with orbital symptoms to non-malignant process.

Gene therapy in head and neck cancer: a review.

Gene therapy for cancer is a rapidly evolving field with head and neck squamous cell cancer being one of the more frequently targeted cancer types. The number of clinical trials in the UK is growing and there is already a commercially available agent in China. Various gene therapy strategies along with delivery mechanisms for targeting head and neck cancer are reviewed.

Viral gene therapy for head and neck cancer.

BACKGROUND: Viral gene therapy is a promising new treatment modality for head and neck cancer. This paper provides the reader with a review of the relevant literature in this field. RESULTS: There are government licensed viral gene therapy products currently in use for head and neck cancer, utilised in conjunction with established treatment modalities. The viruses target tumour-associated genes, with the first licensed virus replacing p53 gene function, which is frequently lost in tumourigenesis. Oncolytic viruses selectively destroy cancer cells through viral replication and can be armed with therapeutic transgenes. CONCLUSION: Despite considerable advances in this field over the last 40 years, further research is needed to improve the overall efficacy of the viruses and allow their widespread utilisation in the management of head and neck cancer.

Tuberculosis presenting as a laryngeal tumour.

As the prevalence of tuberculosis in the U.K. increases, uncommon clinical presentations of the disease may be encountered by the otolaryngologist. We describe just such a case, where a caucasian patient presented with laryngeal lesion, considered to be highly suspicious of a neoplastic process rather than an infective one. We discuss the pathogenesis of tuberculous laryngitis, and review the differential diagnosis and management of the condition.

Life-threatening necrotizing fasciitis of the neck: an unusual consequence of a sore throat.

BACKGROUND: Necrotizing fasciitis is life-threatening bacterial infection which spreads with frightening speed along the fascial planes resulting in extensive tissue necrosis and often death. The infection is caused by either Group A streptococci or a combination of aerobic and anaerobic bacteria. Necrotizing fasciitis of the neck is rare and commonly has a dental origin. CASE REPORT: Here we present a unique case of the condition that was preceded by a sore throat in a young immunocompetent woman. We also describe, for the first time, a successful outcome involving primary skin closure and daily irrigation of the wound with hydrogen peroxide.

A rare case of Crohn's disease in head and neck surgery.

Oral manifestations of Crohn's disease may present to the Otolaryngologist in the form of ulceration, glossitis and odynophagia, but rarer examples of presentation are also recognized. In this case a 24-year-old lady presented with cervical lymphadenopathy, the subsequent investigation of which resulted in the identification of the disease both in this node and in the tonsils. It is noted that these lesions may precede the classical intestinal manifestations and so the Otolaryngologist could aid in the initial diagnosis of the disease. The pathogenic possibilities of how Crohn's disease might have arisen in these and other extra-intestinal regions, are discussed.

Oculopharyngeal myopathy with sensorineural hearing loss.

A case is reported of a 59-year-old Caucasian male with oculopharyngeal myopathy and sensorineural hearing loss. He presented with progressive ptosis, sensorineural hearing loss over several years and symptoms of mild dysphagia. Further enquiry into his family history revealed that every male member in his family that lived beyond the age of 60 exhibited identical symptoms. Symptoms of ptosis and dysphagia are consistent with the rare autosomal dominant condition of oculopharyngeal myopathy, believed to be due to mitochondrial disease. The combination of ptosis, dysphagia and sensorineural hearing loss with normal distant muscle group biopsy has not been described before.

Bleeding after tonsillectomy in severe von Willebrand's disease.

A case is reported of a HIV-positive patient with severe von Willebrand's disease describing the bleeding complications during and after tonsillectomy. This patient underwent surgery for asymmetrical tonsillar hypertrophy. The tonsils were spontaneously haemorrhaging and there therefore was a suspicion of neoplasia. Despite close cooperation between the ENT Department and the Haemophilia Centre, involving per-operative Factor VIII monitoring and replacement, the patient suffered both protracted primary and secondary haemorrhages. We report this as a cautionary tale as our previous experience with mild to moderate haemophilia has been uncomplicated, but on this occasion there was massive haemorrhage. We feel that tonsillectomy should not be undertaken in a patient with a severe bleeding disorder without an absolute indicate.

Tele-education: the virtual medical laboratory.

The virtual medical laboratory (VML) was conceived to provide an Internet-accessible resource, offering access for clinicians and scientists to an invaluable data archive at the institute of Laryngology and Otology, London. The Institute is home to the largest collection of temporal bone, laryngeal, skull and sinus sections in Europe. The skull and sinus collections include an extensive section consisting of animal material. These were contributions from zoos around the world. Over the last 50 years, samples have been carefully sectioned and stained by specialized technicians to produce histology slices of most regions of the head and neck. The aim of the project is to create a virtual medical laboratory, which will provide access to archived histological material as well as computerized tomography and magnetic resonance data. Central to this aim is the reconstruction of the internal anatomy of the temporal bone from two-dimensional histology slices, to create three-dimensional views that can be used for anatomical simulation and surgical training in otolaryngology. State-of-the-art three-dimensional reconstruction and rendering technology allows us to develop such a model. Computer-generated simulation could be made available to all hospitals in which otolaryngology is practised, via digital communication networks. We aim to develop core technology in our own specialty that is applicable to other fields of higher education, which have not been exposed to such modern teaching modalities. This has the potential to become an invaluable teaching resource for anatomists, surgeons and other scientists.

ENT aspects of the mummification of the head in ancient Egypt: an imaging study.

This study of a mummified head from the British museum by high resolution computer tomography and 3D reconstruction illustrates, without mutilation of the specimen, some aspects of mummification of the head; namely the extraction of the brain through the nose and filling the cranium with linen like material, packing of the oral cavity and the presence of false eyes. These findings alone allow one to date the mummy to no sooner than the 20th dynasty, a time when this custom was at its peak. ENT aspects of the mummification of the head are discussed.

Treatment of Nelson's syndrome with temozolomide.

A 64-year-old woman was previously treated for Cushing's disease with trans-sphenoidal surgery, external beam radiotherapy and bilateral adrenalectomy. Progression of an aggressive corticotroph adenoma was evident 3 years post-adrenalectomy; involvement of the clivus was treated with surgery and gamma knife radiosurgery. Tumour spread through the skull base, occiput and left ear with persistent facial pain and left ear discharge; progression continued despite second gamma knife treatment. ACTH levels peaked at 2472 and 2265 pmol/l pre- and post-hydrocortisone respectively. Treatment with temozolomide resulted in a significant improvement in symptoms, a reduction of plasma ACTH to 389 pmol/l and regression of tumour on magnetic resonance imaging scan after four cycles of treatment. We propose that temozolomide is an effective and well-tolerated therapeutic tool for the treatment of Nelson's syndrome and a useful addition to the range of therapies available to treat this condition.

Image-enhanced surgical navigation for endoscopic sinus surgery: evaluating calibration, registration and tracking.

BACKGROUND: Endoscopic sinus surgery (ESS) is generally applied to treat sinusitis when medication is not effective in eliminating the symptoms. Images captured by the endoscope are viewed on a monitor placed near the surgeon. Due to the separation of the handling of the endoscope from the viewing of the image, ESS requires surgeons to have well-trained hand-eye coordination. Unlike the use of the stereo surgical microscope in ENT, the endoscope does not provide the stereo cue for depth perception, hence a surgeon can only perceive depth through motion and shading, which may affect the accuracy of tool placement. Whilst the skill and experience of the surgeon are important factors to the success of ESS, the assistance of image-enhanced surgical navigation (IESN) can further reassure the surgeon's judgement and enhance surgical performance. METHODS: We developed and validated an IESN system (ARView) for a rigid zero-degree endoscope, typically used for ESS. We present the interface, and calibration and registration (pre-operative and intra-operative) methods of the system. We then quantitatively assess the performance of each of the steps needed to generate the overlay of a real endoscope image with its 'virtual' counterpart, obtained from computed tomography (CT) image data of a real skull. These steps include calibration, registration, motion tracking and final overlay. RESULTS: Calibration results using a planar calibration object displayed optimized object space errors of 0.025 +/- 0.013 mm, whilst a non-planar calibration object displayed errors of 0.12 +/- 0.08 mm. Target registration errors (TREs) near the region of interest (ROI), using our pre-operative registration method with the calibration object located near the mouth of the patient (skull), were 2.3 +/- 0.4 mm. The proposed photo-consistency method for intra-operative registration has not yet yielded satisfactory results for ESS-based IESN. (RMS) values for tracking accuracy were found to be around 1.2 mm in a typical workspace of 400 x 400 mm. Object space overlay errors in a small measurement volume of 10 x 10 x 10 mm were found to be around 0.4 +/- 0.02 mm. CONCLUSIONS: We conclude that, in agreement with individual experiments, the current overall overlay accuracy is of the order of 2-3 mm in the x-y plane, which is in line with current conventional SN systems. The method which is most in need of improvement is registration, hence we wish to investigate the application of the proposed photo-consistency method further.

PET scanning and Gamma Knife radiosurgery in the early diagnosis and salvage "cure" of locally recurrent nasopharyngeal carcinoma.

"Gamma Knife radiosurgery" is high-dose conformal radiation therapy used for the treatment of small target lesions in the head. It is a minimally invasive technique of multiple fixed, precisely aimed cobalt beams, and relies upon strict patient immobilization via a pinned stereotactic frame to deliver treatment to a precisely located target within a coordinated mapping system. This technique has been widely validated for the treatment of intra-cranial neoplasms and arteriovenous malformations. In this manuscript, two cases of early diagnosed, locally recurrent (persistent) nasopharyngeal carcinoma, successfully treated by Gamma Knife, are described. In one of these, early diagnosis by PET scanning may have improved the chance of cure.

Are sleep studies worth doing?

AIMS: To evaluate a sleep study service for children suspected of having sleep related upper airway obstruction (SRUAO). DESIGN: Prospective survey. SETTING: Paediatric and ear, nose, and throat clinics of the Royal Free Hampstead NHS Trust. SUBJECTS: Consecutively referred children with SRUAO symptoms. MAIN OUTCOME MEASURES: Sleep study data, referring clinician's impression, and completed symptom questionnaires. RESULTS: A total of 120 children (aged 6 months to 15.5 years) were studied. Study scores showed that 24 were classified as normal, 42 as mild, 33 as moderate, and 21 as severe SRUAO. In the 106 cases with matching data between clinician's impression and study score, 71 had good agreement, 18 were underestimated by the clinician, and 17 were over estimated. No cases reported as moderate or severe sleep apnoea by the study were referred by the clinician as normal. There were no important associations between parental symptom scores and sleep study scores. CONCLUSION: In children with suspected SRUAO, sleep studies do contribute to assessing the need for operation, the likelihood of postoperative respiratory failure, or as a baseline or outcome measure in intervention studies.

Peri-umbilical superficial fascial graft myringoplasty--a simple alternative.

We present new material in the surgical repair of the perforated tympanic membrane. Forty-two patients with a unilateral tympanic membrane perforation and eight patients with bilateral perforations had their perforations closed with peri-umbilical superficial fascia via a transtympanic route. Of the 58 tympanic membranes repaired, 51 were successful while seven failed. The technique is cost-effective and quick, making bilateral repairs possible under the same anaesthetic.