Management of the neck in T1 and T2 buccal squamous cell carcinoma.

Buccal squamous cell carcinoma (SCC) appears to behave more aggressively than other oral subsites, in particular with regards to regional disease at presentation and regional recurrence. Adequate management of the neck is of the utmost importance but is still the subject of debate. An international multicentre retrospective review of 101 patients treated for T1-T2 buccal SCC was performed. Twenty-four were staged clinical node positive (cN+) and underwent therapeutic neck dissection, while 77 were node negative (cN0), with 32 undergoing elective neck dissection (END), with an occult nodal metastasis rate of 28.1%. Depth of invasion (DOI) < 4 mm was associated with a significantly lower rate of cervical nodal metastasis (87.5% versus 12.5%; P = 0.033). END demonstrated a non-significantly lower regional recurrence rate compared to observation (6.3% versus 8.9%, P = 0.670). Regional recurrence was more common in pN+ (24%) and undissected cases (8.9%) than in pN0 patients (0%) (P = 0.011) and was associated with DOI > 5 mm (P = 0.002). Regional recurrence resulted in a reduction in survival (24 versus 93 months, P < 0.001). In the pT2cN0 group, END improved survival (123 versus 26 months, P = 0.009). It is suggested that END be performed in cT2N0 buccal SCC, particularly for tumours with DOI > 4 mm.

Surgery for maxillary oral squamous cell carcinoma: the effect of surgical resection margins and elective neck dissection on oncological outcomes.

Maxillary oral squamous cell carcinoma (OSCC) is uncommon. Surgical resection is challenging due to the anatomy, and the role of elective neck dissection (END) is not well-defined. A retrospective cohort study of patients with maxillary OSCC treated with primary surgery between 2007 and 2019 was conducted. Primary tumours of sinonasal origin with extension into the oral cavity were excluded. Survival analysis was performed using Kaplan-Meier and Cox proportional hazards models. Sixty-seven patients were included; mean follow-up was 55 months. On univariate analysis, clear (≥5 mm) margins were associated with higher disease-free (68% vs 36%, P = 0.019) and overall survival (75% vs 36%, P = 0.004) than close/involved (<5 mm) margins. In clinically node-negative patients, the risk of occult cervical metastasis in tumours with depth of invasion (DOI) ≥ 3 mm and T2-4 tumours was 22% and 25%, respectively. END in these groups was associated with a lower rate of loco-regional recurrence (DOI ≥3 mm subgroup: 5% vs 38%, P = 0.029; T2-4 subgroup: 6% vs 50%, P = 0.028) and longer time to recurrence (DOI ≥3 mm subgroup: 119 months vs 96 months, P = 0.042; T2-4 subgroup: 117 months vs 56 months, P = 0.031) than observation of the neck. On multivariate analysis, close/involved margins were associated with an increased risk of overall mortality (hazard ratio 3.4, 95% confidence interval 1.0-11.3, P = 0.043) and disease recurrence (hazard ratio 2.8, 95% confidence interval 1.1-7.1, P = 0.031). In maxillary OSCC, a ≥ 5 mm histological margin should remain the goal of ablative surgery. END should be considered in tumours with DOI ≥ 3 mm.

A change in surgical margin: do wider surgical margins lead to decreased rates of local recurrence in T1 and T2 oral tongue cancer?

The purpose of this study was to assess the impact of a change in macroscopic/surgical margin width upon histological margins and loco-regional failure in early oral tongue squamous cell carcinoma (OTSCC). In 2009, the surgical margin protocol was increased from 10 mm to 15 mm. A retrospective review was performed of all patients who underwent treatment for early OTSCC between 2009 and 2016 with a 15-mm surgical margin (n = 142), and these patients were compared to those treated between 1999 and 2008 with a 10-mm surgical margin (n = 78). There was a significant increase in the rate of clear histological margins (P < 0.001). The rates of close (P = 0.002) and involved (P < 0.001) histological margins decreased significantly. There were significant reductions in local (P < 0.001) and regional (P < 0.001) recurrence rates. This study demonstrated that a surgical margin of 15 mm delivered significantly lower rates of close/involved histological margins and improved local and regional disease recurrence in early OTSCC when compared with a surgical margin of 10 mm.

The impact of travel distance to treatment centre on oral tongue squamous cell carcinoma survival and recurrence.

There have been no prior studies examining the effect of distance to the treatment centre on oral squamous cell carcinoma outcomes in Australia. The purpose of this study was to analyse the impact of travel distance on oral tongue squamous cell carcinoma (OTSCC) outcomes. This was a retrospective analysis of 243 patients who received surgical treatment ± adjuvant therapy between 2007 and 2016. The overall survival (OS), disease-specific survival (DSS), and freedom from loco-regional failure (FFLRF) survival analyses were conducted using Kaplan-Meier curves and a multivariate Cox proportional hazards model. A competing risk (CR) analysis was conducted. Patients living ≥200 km from the treatment centre, when compared with those living within 40 km, had worse OS (hazard ratio (HR) 3.11, 95% confidence interval (CI) 1.74-5.54), DSS (HR 2.58, 95% CI 1.30-5.12), and FFLRF (HR 2.47, 95% CI 1.22-5.01). These discrepancies were significant when adjusted for socioeconomic status (OS P < 0.001, DSS P 0.004, FFLRF P = 0.005) and in the presence of CR (OTSCC-specific death with CR 'non-disease-related death' P =0.030, FFLRF with CR 'any cause death' P = 0.013, FFLRF with CR 'OTSCC-specific death' P = 0.004). Patients with OTSCC living ≥200 km from the treatment centre were found to have worse outcomes than those living within 40 km.

Postoperative pulmonary complications following major head and neck cancer surgery.

The primary aim of this observational study was to describe the incidence of postoperative pulmonary complications (PPCs) in 60 consecutive, surgically treated head and neck cancer patients requiring free flap reconstruction and tracheostomy, using both a prospective and a retrospective outcome measure. Secondary aims were to identify risk factors for PPC development, explore the effects of PPC on outcomes, and describe the provision of postoperative physiotherapy in this population. Postoperative pulmonary complications occurred in nine (15%) patients based on the Melbourne Group Scale and 27 (45%) patients based on Health Information Service coding data. The occurrence of a PPC was not statistically correlated with age, smoking history, comorbidities, operative time, or type of resection or free flap. Patients who developed a PPC, compared to those who did not, had a higher preoperative body mass index (P=0.022) and were more likely to be sat out of bed earlier post-surgery (P=0.038). Overall, patients required a median of 9.0 (interquartile range 7.0-11.0) physiotherapy sessions. Patients developing a PPC required significantly more physiotherapy sessions (P=0.007) and additional days of supplemental oxygen (P=0.022) as compared to those without a PPC, despite a similar hospital length of stay. In future, targeted physiotherapy interventions may reduce PPCs in this population.

Can radiological examination of mandibular bone invasion accurately predict the need for mandibular resection in oral squamous cell carcinoma?

Bone invasion by oral squamous cell carcinoma necessitates jaw resection, with preoperative imaging ideally able to guide the resection. A retrospective review of 109 patients with oral squamous cell carcinoma who underwent mandibular resection was performed. Eighty-three had preoperative computed tomography (CT) imaging and 72 underwent magnetic resonance imaging (MRI). The presence of bone invasion on imaging was compared to histopathology. Bone invasion was detected in 44 of 109 resection specimens (40.4%) and was identified on CT in 31 of 83 cases (37.4%) and on MRI in 35 of 72 cases (48.6%). The sensitivity and specificity of CT for detecting bone invasion was 69.0% and 79.6%, respectively, while for MRI was 87.1% and 80.5%, respectively. Histological detection of bone invasion was associated with greater disease-specific mortality (P=0.002), as was MRI detection of bone invasion (P=0.027). CT detection was not significant (P=0.240). Negative prediction of bone invasion was 95% accurate for both modalities in clinically non-invaded mandibles. Survival was reduced in patients who underwent marginal mandibular resection when bone invasion was detected histologically (33.3% vs. 70.5%, P=0.277) and with CT, although this was not statistically significant. More data are required to determine whether more aggressive resection is warranted when bone invasion is detected preoperatively.

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.

Frequency and prognostic significance of p16(INK4A) protein overexpression and transcriptionally active human papillomavirus infection in laryngeal squamous cell carcinoma.

BACKGROUND: Human papillomavirus (HPV) infection is a powerful prognostic biomarker in a subset of head and neck squamous cell carcinomas, specifically oropharyngeal cancers. However, the role of HPV in non-oropharyngeal sites, such as the larynx, remains unconfirmed. METHODS: We evaluated a cohort of 324 laryngeal squamous cell carcinoma (LSCC) patients for the expression of p16(INK4A) (p16) protein by immunohistochemistry (IHC) and for high-risk HPV E6 and E7 mRNA transcripts by RNA in situ hybridisation (ISH). p16 expression and HPV status were correlated with clinicopathological features and outcomes. RESULTS: Of 307 patients assessable for p16 IHC, 20 (6.5%) were p16 positive. Females and node-positive patients were more likely to be p16 positive (P<0.05). There were no other significant clinical or demographic differences between p16-positive and -negative cases. There was no difference in overall survival (OS) between p16-positive and -negative patients with 2-year survival of 79% in each group (HR=0.83, 95% CI 0.36-1.89, P=0.65). There was no statistically significant difference in failure-free survival (FFS) with 2-year FFS of 79% and 66% for p16-positive and -negative patients, respectively (HR=0.60, 95% CI 0.26-1.36, P=0.22). Only seven cases were found to be HPV RNA ISH positive, all of which were p16 IHC positive. There was no statistically significant difference in OS between patients with HPV RNA ISH-positive tumours compared with -negative tumours with 2-year survival of 86% and 71%, respectively (HR=0.76, 95% CI 0.23-2.5, P=0.65). The 2-year FFS was 86% and 59%, respectively (HR=0.62, 95% CI 0.19-2.03, P=0.43). CONCLUSIONS: p16 overexpression is infrequent in LSCC and the proportion of cases with high-risk HPV transcripts is even lower. There are no statistically significant correlations between p16 IHC or HPV RNA ISH status and OS or disease outcomes.

Preoperative evaluation of oral tongue squamous cell carcinoma with intraoral ultrasound and magnetic resonance imaging-comparison with histopathological tumour thickness and accuracy in guiding patient management.

The aim of this study was to investigate the correlation between tumour thickness (TT) on intraoral ultrasound (US) and magnetic resonance imaging (MRI) with the histologically determined TT of tongue cancers. Secondary objectives included evaluation of potential confounders that affect this association and the predictive value for simultaneous neck dissection. Eighty-eight consecutive patients referred to the study institution between January 2007 and August 2012 with the presumptive diagnosis of invasive squamous cell carcinoma (SCC) of the tongue were analyzed. Seventy-nine patients had preoperative US and 81 had MRI. Correlation between image-determined TT and histological TT was assessed by Bland-Altman plot and Pearson's correlation coefficient. Potential confounders were assessed by subgroup analysis. Preoperative TT as determined by US demonstrated high correlation and MRI moderate correlation with histological TT. With subgroup analysis, negative associations were biopsy prior to imaging and resection diagnosis other than invasive SCC. Our experience suggests that US could be considered the initial modality of choice for preoperative assessment of TT.

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.

Impaired Akt phosphorylation in insulin-resistant human muscle is accompanied by selective and heterogeneous downstream defects.

AIMS/HYPOTHESIS: Muscle insulin resistance, one of the earliest defects associated with type 2 diabetes, involves changes in the phosphoinositide 3-kinase/Akt network. The relative contribution of obesity vs insulin resistance to perturbations in this pathway is poorly understood. METHODS: We used phosphospecific antibodies against targets in the Akt signalling network to study insulin action in muscle from lean, overweight/obese and type 2 diabetic individuals before and during a hyperinsulinaemic-euglycaemic clamp. RESULTS: Insulin-stimulated Akt phosphorylation at Thr309 and Ser474 was highly correlated with whole-body insulin sensitivity. In contrast, impaired phosphorylation of Akt substrate of 160 kDa (AS160; also known as TBC1D4) was associated with adiposity, but not insulin sensitivity. Neither insulin sensitivity nor obesity was associated with defective insulin-dependent phosphorylation of forkhead box O (FOXO) transcription factor. In view of the resultant basal hyperinsulinaemia, we predicted that this selective response within the Akt pathway might lead to hyperactivation of those processes that were spared. Indeed, the expression of genes targeted by FOXO was downregulated in insulin-resistant individuals. CONCLUSIONS/INTERPRETATION: These results highlight non-linearity in Akt signalling and suggest that: (1) the pathway from Akt to glucose transport is complex; and (2) pathways, particularly FOXO, that are not insulin-resistant, are likely to be hyperactivated in response to hyperinsulinaemia. This facet of Akt signalling may contribute to multiple features of the metabolic syndrome.

Are wider surgical margins needed for early oral tongue cancer?

BACKGROUND: Traditionally, a 1-cm surgical resection margin is used for early oral tongue tumours. METHODS: All tumour stage one (n = 65) and stage two (n = 13) oral tongue cancers treated between January 1999 and January 2009 were followed for a median of 38 months (minimum 12 months). The sites of close and involved margins were histologically reviewed. RESULTS: Involved and close margins occurred in 14 and 55 per cent of cases, respectively. The number of involved vs clear or close margins was equivalent in tumour stage one (90 vs 82 per cent), node-negative (100 vs 84 per cent) and perineural or lymphovascular invasion (20 vs 21 per cent) cases. Close or involved margins were similarly likely to be posterior (59 per cent) as anterior (41 per cent, p = 0.22), lateral (57 per cent) as medial (43 per cent, p = 0.34), and mucosal (59 per cent) as deep (41 per cent, p = 0.22). Local recurrence occurred in 28 per cent of cases at a median of 12 months, and was more likely in cases with involved (50 per cent) than clear or close margins (25 per cent, p = 0.10). Disease-free survival was worse in involved margins cases (p = 0.002). CONCLUSION: Involved margins are common in early tongue tumours, and are associated with increased local recurrence and worse survival. Close or involved margins occur in all directions and all tumour types. A wider margin may be justified.

Role of radiotherapy in adenoid cystic carcinoma of the head and neck.

This study retrospectively reviewed 183 cases of adenoid cystic carcinoma treated over 40 years. The local recurrence free survival rate was 68.2 per cent at five years and 40.8 per cent at 10 years. At 10 years, local recurrence free survival was significantly worse following radiotherapy alone (0 per cent), compared with surgery alone (41.8 per cent, p = 0.004) or combined with post-operative radiotherapy (43.5 per cent, p = 0.001). Neither tumour stage three or four, perineural invasion, solid subtype nor involved margins predicted local recurrence. Treatment with radiotherapy alone resulted in worse survival than surgery alone (p = 0.002) or combined with post-operative radiotherapy (p = 0.001). Survival rates following local recurrence (n = 34) were higher following surgery (p = 0.006) but not significantly improved following radiotherapy (p = 0.139). Chemotherapy for distant metastases did not prolong survival (p = 0.747) but did result in improved eating and aesthetics scores, while decreasing overall physical health. These results indicate that surgery is preferable for primary and recurrent adenoid cystic carcinoma of the head and neck. The incidence of local recurrence following surgery and postoperative radiotherapy was similar to surgery alone cases although the latter had less adverse prognostic features. Contemporary chemotherapy may benefit quality of life but not survival in patients with distant metastases due to adenoid cystic carcinoma of the head and neck.

Extraosseous osteoblastoma of larynx presenting with acute airway obstruction.

OBJECTIVE: We report the case of an osteoblastoma of the larynx arising from the vocal fold, which presented with acute airway obstruction and cardiopulmonary arrest. METHOD: The histopathological findings, differential diagnoses and a novel method of treating laryngeal osteoblastoma, using transoral laser therapy, are discussed. RESULTS: Benign osteoblastoma is a rare primary bone tumour usually presenting in young patients in the spine and sacrum. Its occurrence in the larynx is very rare, with only three similar case reports in the literature, none involving tumour arising from the vocal fold. Differential diagnoses must be considered and excluded using both histopathological and clinical features. Once the diagnosis is confirmed, successful treatment is achieved with surgical excision. CONCLUSION: Osteoblastoma of the larynx is rare, and the clinical features can vary with the anatomical site of the lesion. The recommended treatment is surgical excision which, if available, may be achieved by transoral laser microsurgery. Due to its potential rapid growth, careful follow up is essential in order to detect recurrence.

Voice outcomes following transoral laser microsurgery for early glottic squamous cell carcinoma.

INTRODUCTION: Early glottic cancer may be treated with primary radiotherapy or transoral laser microsurgery with comparable survival. The choice of therapy therefore depends on patient preference after discussion of risks, benefits and alternatives. MATERIALS AND METHODS: All previously untreated patients undergoing transoral laser microsurgery for T1 or T2 glottic cancer at St Vincent's Hospital between July 1997 and December 2004 had their staging and demographics recorded. Surgery was categorised according to the European Laryngological Society. A voice recording was made pre-operatively then at 12 weeks post-operatively and scored by two independent speech therapists on the Oates Russell Voice Profile - a scale of zero (normal) to five (severe dysphonia). Follow up was for a minimum of two years. RESULTS AND ANALYSIS: Fifty-three patients with a mean age of 56 were included. The observed survival was T1 89.4 per cent and T2 85.3 per cent after a mean follow up of 47 months. Nineteen patients staged T1 underwent cordectomy. A second procedure was required in 22.2 per cent, however, none required a laryngectomy. Thirty-four patients staged T2 underwent hemilaryngectomy. A second procedure was required in 41.2 per cent including 8.8 per cent requiring salvage laryngectomy. One patient died with unresectable nodal disease. The mean Oates Russell Voice Profile for T1 disease was 2.37 and for T2 2.68 (range 1 to 4) indicating a mild (2) to moderate (3) degree of voice impairment. CONCLUSIONS: Survival outcomes following transoral laser microsurgery are comparable to treatment with radiotherapy. Voice impairment is usually mild to moderate following transoral laser microsurgery for early glottic cancer but overall may be greater than in radiotherapy patients. The repeatability of transoral laser microsurgery may result in a lower laryngectomy rate compared with published series using radiotherapy.

AMP-activated protein kinase, super metabolic regulator.

The AMP-activated protein kinase (AMPK) is a metabolic-stress-sensing protein kinase that regulates metabolism in response to energy demand and supply by directly phosphorylating rate-limiting enzymes in metabolic pathways as well as controlling gene expression.

Palliative surgery for neoplastic unilateral vocal cord paralysis.

BACKGROUND: Locally advanced, recurrent or metastatic neoplasms are the commonest causes of unilateral vocal cord paralysis (UVCP). The aim of the present study was to evaluate both survival and results of treatment of vocal cord medialization procedures in this group of patients. METHODS: Fifty-seven patients (36 male, 21 female) with UVCP considered to be due to advanced malignancy who underwent medialization (Teflon injection or type I thyroplasty) between January 1994 and July 2000 were retrospectively reviewed. RESULTS: The malignancy responsible for UVCP was non-small-cell lung carcinoma (NSCLC) in 43 patients, small-cell lung carcinoma (SCLC) in four patients, thyroid carcinoma in three patients and metastatic lower cervical lymph nodes in seven patients. All patients complained of dysphonia and 29 patients had symptoms of aspiration. Teflon injection was performed in 44 patients and thyroplasty in 13. Improvement in voice occurred in 51 patients (89%) and resolution of aspiration in 28 patients (97%) after 2 months. The median time from onset of symptoms of UVCP to death in NSCLC was 170 days; SCLC, 69 days; thyroid carcinoma, 783 days; and metastatic lower cervical lymph nodes, 304 days. CONCLUSION: Surgical treatment of neoplastic UVCP provides satisfactory palliation of symptoms, and management decisions should be based on patient survival expectations.

Eversion carotid endarterectomy.

BACKGROUND: Eversion carotid endarterectomy (ECEA) is a technique that obviates the need for traditional longitudinal arteriotomy and patch closure, with low stroke and restenosis rates. The aim of the present study was to report an Australian experience and technique of ECEA. METHODS: All patients who underwent ECEA by the investigating surgeons between October 1997 and July 2000 were followed up clinically and with duplex ultrasound. The technique of ECEA is described. RESULTS: One hundred and fifty-two ECEA were performed, 13 combined with coronary artery bypass grafting (CABG). The combined perioperative stroke and death rate was 2%; 0.65% excluding CABG combined cases. This compares with 2.9% for standard carotid endarterectomy throughout Victoria. Significant restenosis occurred in 2.6% after a mean follow up of 21.7 months. CONCLUSION: ECEA is a simple and safe alternative to standard carotid endarterectomy.