Mark D. Wilkie

Transoral laser microsurgery for oropharyngeal squamous cell carcinoma: A paradigm shift in therapeutic approach.

The contemporary treatment of oropharyngeal squamous cell carcinoma (SCC) is an area of debate. We report outcomes of a minimally invasive approach involving transoral laser microsurgery (TLM).Background The contemporary treatment of oropharyngeal squamous cell carcinoma (SCC) is an area of debate. We report outcomes of a minimally invasive approach involving transoral laser microsurgery (TLM). Methods A consecutive series of patients (n = 153) undergoing primary TLM for oropharyngeal SCC from 2006 to 2013 was studied. Human papillomavirus (HPV) status was determined by p16 immunohistochemistry and high-risk HPV DNA in situ hybridization. Survival analyses were evaluated using Kaplan–Meier statistics. Results Tumor subsites included tonsil (n = 94; 61.5%), tongue base (n = 38; 24.8%), and soft palate (n = 21; 13.7%), with the majority being American Joint Committee on Cancer (AJCC) stage III/IVa (n = 124; 81.0%) and HPV-positive (n = 101; 66.0%). Three-year overall survival (OS), disease-specific survival (DSS), and disease-free survival (DFS) were 84.5%, 91.7%, and 78.2%, respectively. HPV-positivity portended favorable oncologic outcomes. One-year gastrostomy tube (G-tube) dependency was 1.3%. Conclusion To the best of our knowledge, this is the largest single-center TLM oropharyngeal SCC series to date. Our data suggest that TLM +/− postoperative radiotherapy (PORT) results in at least as good oncologic outcomes as chemoradiotherapy (CRT), while conferring swallowing function advantages.

Pott's puffy tumour: an unforgettable complication of frontal sinusitis

First described by Sir Percival Pott in 1768, Potts puffy tumour is a subperiosteal abscess of the frontal bone associated with underlying frontal osteomyelitis. It occurs most frequently as an adverse sequelae of head trauma but can also arise in the setting of frontal sinusitis, as a postoperative complication following craniotomy, or from the spread of infection from adjacent sites, such as dental sepsis.1 Since the advent and widespread prescription …

Trichilemmal carcinoma: an unusual presentation of a rare cutaneous lesion

Trichilemmal carcinoma (TC) is a rare cutaneous neoplasm which is derived from adnexal keratinocytes, is histologically invasive, contains cytologically atypical clear cell neoplasm and is in continuity with the epidermis and/or follicular epithelium. However, the diagnostic criteria and even the existence of TC have been contentious. We report the case of a 92-year-old woman with TC of the head and neck region who presented with an unusually long history. She was treated successfully with wide local excision. Important aspects in presentation, differential diagnosis, including histopathological features and management are discussed.

Relative expression of vascular endothelial growth factor isoforms in squamous cell carcinoma of the head and neck.

Alternative splicing of the vascular endothelial growth factor (VEGF) gene results in a family of antiangiogenic isoforms (VEGFxxxb), not yet investigated in squamous cell carcinoma of the head and neck (SCCHN). We examined, therefore, the prognostic value of the relative expression of VEGF isoforms in SCCHN.

Tumour metabolism in squamous cell carcinoma of the head and neck: an in-vitro study of the consequences of TP53 mutation and therapeutic implications

BACKGROUND Survival for squamous cell carcinoma of the head and neck (SCCHN) has not improved substantially in recent years. Since radiotherapy is a cornerstone of treatment, it is crucial to identify ways to augment its efficacy, for which tumour metabolism is an attractive target. p53 is a metabolic mediator, and TP53 mutations are common in this disorder. We sought to investigate metabolic changes in SCCHN, to elucidate any correlation with TP53 status, and to determine whether targeted metabolic therapy might be used to potentiate the effects of radiation. METHODS Extracellular acidification and oxygen consumptions rates, respective measures of glycolytic flux and mitochondrial respiration, were assayed in real time for a panel of wild-type (wt) and mutant (mut) TP53 SCCHN cell lines in an extracellular flux analyser (XF24, Seahorse Bioscience, Billerica, MA, USA) during specifically designed stress tests. Sensitivity to radiation with or without 25mM 2-deoxyglucose (glycolytic inhibitor) was evaluated in clonogenic assays. FINDINGS MutTP53 SCCHN cell lines showed a distinct metabolic phenotype from that of wtTP53 cells: wtTP53 cells maintained metabolic diversity, displaying robust mitochondrial and glycolytic reserve capacities, whereas mutTP53 cells displayed glycolytic dependence with markedly reduced mitochondrial and glycolytic reserve, functioning near capacity under basal conditions. This metabolic shift, in turn, correlated with radiation response after administration of 2-deoxyglucose, which significantly (p<0·05) potentiated effects of radiation in mutTP53 but not wtTP53 cells. INTERPRETATION TP53 mutation in SCCHN seems to correlate with a metabolic shift away from mitochondrial respiration towards glycolysis, resulting in sensitivity to the potentiating effects of glycolytic inhibition on radiation. Consequently, TP53 status could be applied clinically as a marker of metabolic phenotype in SCCHN, enabling a more tailored therapeutic approach, which would also specifically target the typically treatment-resistant disease associated with TP53 mutation. FUNDING Cancer Research UK, Royal College of Surgeons of England.

Metabolic signature of squamous cell carcinoma of the head and neck: Consequences of TP53 mutation and therapeutic perspectives

There is a pressing need to identify ways of sensitising squamous cell carcinomas of the head and neck (SCCHN) to the effects of current treatments, both from oncological and functional perspectives. Alteration to cellular metabolism is now widely considered a hallmark of the cancer phenotype; presents a potentially attractive therapeutic target in this regard; and as such has received renewed research interest in recent years. However, whilst metabolic disruption may occur to some degree in all tumours, there is undoubtedly heterogeneity and detailed study of individual tumour types is paramount if effective therapeutic strategies targeting metabolism are to be developed and effectively deployed. In this review we outline current understanding of altered tumour metabolism and how these adaptations promote tumorigenesis generally. We relate this specifically to SCCHN by focusing on several recent key studies specific to SCCHN, and by discussing the role TP53 mutation may play in this metabolic switch, given the fundamental role of this oncogenic event in SCCHN tumorigenesis. Finally, we also offer insight into the potential therapeutic implications this may have in the clinical setting and make recommendations for future study.

Prognostic implications of pathologically determined tumour volume in glottic carcinomas treated by transoral laser microsurgery.

The TNM classification system for squamous cell carcinoma (SCC) of the head and neck neglects to incorporate volumetric analysis of the primary tumour. Tumour volume (TV) has been implicated prognostically in laryngeal SCC treated by primary radiotherapy (RT), but data for patients treated surgically are lacking. We evaluated such for glottic SCCs resected by transoral laser microsurgery (TLM).

Capillary haemangioma of the ethmoid sinus.

A middle-aged male presented with unilateral nasal blockage, reduced sense of smell and daily nosebleeds. He had a history of nasal polyps, and had undergone a left-sided polypectomy and ethmoidectomy some 10 years previously. A large polpypoid mass was visible within the right nasal cavity upon examination, with CT and MRI imaging confirming the presence of a large soft tissue abnormality with no intracranial extension. Following biopsy suggestive of angioma, the patient underwent embolisation of the mass prior to endoscopic resection. Subsequent pathology revealed the mass to be a capillary haemangioma. The man made good postoperative progress and was asymptomatic at early follow-up.