K. Koo

Mapping supramedullary pathways involved in cough using functional brain imaging: Comparison with pain

Several indications suggest that supramedullary brain regions receive sensory information from the airways and provide motor control to the brainstem neurons that control coughing. However, the organization of this circuitry has not been described in any detail. In this short review we will discuss how state-of-the-art functional brain imaging techniques in humans and animals will enable unprecedented insights into the supramedullary brain regions that help control coughing. In addition we will describe the likely similarities between cough-related higher brain networks and those involved in the processing of other aversive sensory modalities, such as pain.

Non-smoking non-drinking elderly females: a clinically distinct subgroup of oral squamous cell carcinoma patients

There is growing interest in non-smoking non-drinking (NSND) patients presenting with oral squamous cell carcinoma (OSCC). There are, however, few published reports of OSCC in the elderly. We describe a subgroup of elderly NSND patients presenting with OSCC. Patients with SCC of the oral cavity were retrospectively assessed from the Head and Neck Oncology Tumour Stream database of the Royal Melbourne Hospital. Epidemiological and clinical data for 169 consecutive patients were reviewed and analysed. NSND patients were more likely to be females with a higher median age at presentation. They were more likely to have maxillary alveolus tumours and oral tongue tumours, with retromolar or mandibular tumours less likely. Second primary tumours for this subgroup were confined to the oral cavity. NSND elderly females experienced a worse disease-specific mortality. We have identified a distinct subgroup of elderly female patients presenting with OSCC not associated with the traditional risk factors of tobacco and alcohol, who have a worse prognosis. Altered management algorithms may prove beneficial for these patients, and further investigation and genetic analysis are required to delineate the aetiology of these carcinomas.

Non-smoking, non-drinking elderly females, a 5 year follow-up of a clinically distinct cohort of oral squamous cell carcinoma patients

To examine differences in survival and clinical outcomes of elderly patients without traditional risk factors presenting with oral squamous cell carcinoma. Retrospective review of 287 consecutive patients divided into 2 treatment period cohorts treated for oral SCC between the 1st Jan 2007 and 31st Dec 2012. Patients were classified as either smoker-drinkers (SD) or non-smoking, non-drinking (NSND). Only patients with oral sub-site primaries according to ICD-10 were included. Carcinomas of the lip, tonsil, base of tongue and oro-pharyngeal subsites were excluded. Of the study population (N = 287), 24.4% were NSND and 9.75% were NSND elderly (older than 70 years) females. >50% of tumours arose from the oral tongue in NSND patients (p = 0.022) and there was a higher rate of recurrent and persistent disease (42.9% vs 27.6%, p = 0.005). Disease specific survival at 5 years was significantly reduced when NSND elderly females were compared to all other patients (p < 0.001) as well as age matched controls (p = 0.006). This effect was verified independently in each cohort.The results of this study suggest that NSND elderly females are a distinct patient population with poorer disease specific survival outcomes.

Predicting the presence of oral squamous cell carcinoma using commonly dysregulated microRNA in oral swirls

Oral swirls are a noninvasive, rapidly collected source of salivary microRNA (miRNA) potentially useful in the early detection of disease states, particularly oral squamous cell carcinoma (OSCC). The aim of this study was to predict the presence of OSCC using a panel of OSCC-related dysregulated miRNA found in oral swirls, identified jointly in data from formalin-fixed paraffin-embedded (FFPE) and fresh-frozen specimens. Next-generation sequencing (NGS) was used to determine miRNA fold changes in FFPE OSCC specimens relative to histologically normal epithelium. These data were placed with NGS of fresh-frozen tissue data of The Cancer Genome Atlas database to select a panel of commonly dysregulated miRNA. This panel was then analyzed by RT-qPCR in RNA extracted from oral swirls collected from 30 patients with OSCC and 30 controls. Upregulation of miR-31 and miR-21 and downregulation of miR-99a, let-7c, miR-125b, and miR-100 were found between OSCC and controls in both FFPE and fresh-frozen samples. These miRNAs were studied in a training set of 15 OSCC versus 15 control oral swirls to develop a dysregulation score [AUC, 0.95; 95% confidence interval (CI), 0.88–1.03] and classification tree. A test cohort of 15 OSCC versus 15 control oral swirls yielded a dysregulation score AUC of 0.86 (95% CI, 0.79–1.00) with the classification tree identifying 100% (15/15) of OSCC and 67% (10/15) of controls. This study debuts the use of OSCC-associated miRNA, commonly dysregulated in both FFPE and frozen specimens, in oral swirls to indicate the presence of OSCC with high accuracy. Cancer Prev Res; 11(8); 491–502. ©2018 AACR.

A role for panendoscopy? Second primary tumour in early stage squamous cell carcinoma of the oral tongue.

BACKGROUND Panendoscopy is routinely used for the identification of occult second primary tumours in head and neck squamous cell carcinoma. However, its role in low risk subgroups, particularly non-smoking, non-drinking patients and patients presenting with early stage oral cavity lesions, is debatable. METHODS The records of 112 patients with T₁ or T₂ oral tongue squamous cell carcinoma were retrospectively reviewed. Demographic, disease characteristics and survival data were collected. RESULTS Average follow-up duration was 71.7 months (range, 3.6-238.3 months). Thirty-five patients died within this period. Thirteen second primary events were identified in 11 patients, with all but 2 tumours in the oral cavity or oropharynx. There was a single synchronous primary - a lung adenocarcinoma; all other events were metachronous. No non-smoking, non-drinking patients re-presented with a second primary tumour; tobacco and alcohol use are clearly risk factors for development of a second primary tumour. CONCLUSION The role of panendoscopy for identifying synchronous primary tumours in patients with early stage oral tongue squamous cell carcinoma should be re-evaluated, particularly in non-smoking, non-drinking patients who are at low risk of second primary development. Close follow up with regular clinical examination including flexible fibre-optic endoscopy may be sufficient in this subgroup.