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.

Predictors of distress associated with altered appearance and function in people treated surgically for oral cancers: a cross-sectional study.

This cross-sectional study was performed to examine sources of variation in distress associated with altered appearance and fundamental functions in oral cancer patients at 2 months, 12-15 months, 24-36 months, and ≥ 5 years post-definitive treatment. Eligible patients completed six scales from the FACE-Q Head and Neck Cancer Module. Pre-specified regression models were used to examine sources of variation in study outcomes for 145 patients. Patient self-reports indicated that distress associated with altered appearance and fundamental functions was highly variable, and distress was present beyond 5 years post-definitive treatment in some patients. Associations between distress scores and time post-definitive treatment, reconstructive surgery, and adjuvant therapy were not statistically significant. There was, however, moderate to strong evidence against the null hypothesis of no association between eating distress scores and sex, primary cancer site, and T-stage; smiling distress scores and age and primary cancer site; appearance distress scores and geographical remoteness and primary cancer site; and speaking distress scores and primary cancer site. Primary cancer site was the only significant independent predictor of multiple distress scores. These findings suggest that predicting the psychological impact of oral cancer treatment remains a challenge for the multidisciplinary team. Screening and interventions for psychological distress are essential beyond the preoperative and acute care settings.

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.

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.

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.

The impact of delayed diagnosis on the outcomes of oral cancer patients: a retrospective cohort study.

The contemporary literature is discordant regarding the role of delayed diagnosis in the prognosis of patients with oral cancer. This study examined data on a previously reported cohort of 101 patients with oral squamous cell carcinoma diagnosed at a single institution between 2008 and 2010. The time interval between symptom onset and initial histological diagnosis (diagnostic delay) was recorded for each patient, as were demographic data and cancer features such as T stage, nodal status, and smoking status. The mean follow-up period was 4 years 10 months. The mean diagnostic delay was 4 months, mean overall survival was 5years 6 months, and mean disease-specific survival was 4 years 9 months. No significant correlation was found between diagnostic delay and overall survival, disease-specific survival, or recurrence rates. Patients with node-positive disease were more likely to be diagnosed earlier, whereas women and non-smokers were more likely to have a delayed diagnosis. Inherent tumour biology is likely an important prognostic factor separate to diagnostic delay. Public education efforts should focus on symptom recognition and encourage early presentation for investigation of oral lesions, particularly for females and non-smokers, so that more aggressive tumours can be treated sooner to give the best chance at survival.

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.

Oral Cancer.

The management of oral cancer is a multidisciplinary endeavour, as each patient presents the treating clinicians with a unique set of challenges the management of which impacts on both survival and quality of life. This article focuses on the management of oral cancer. We highlight the epidemiology and risk factors for oral cancer in Australia, the various clinical presentations that occur and the staging of oral cancer. In the vast majority of cases surgery remains the mainstay of treatment. Radiation and medical oncology is usually used in an adjuvant context. Dental professionals play a critical role in many stages of management from the initial detection, to optimising pre treatment dental health and managing the short and long term sequelae of treatment. Monitouring for recurrence and the development of second primary tumours is a key role.

Long-term outcomes of craniofacial implants for the restoration of facial defects.

The aim of this study was to evaluate the long-term survival of craniofacial implants and prostheses and to identify factors associated with failure in a cohort of patients. A 25-year retrospective analysis was conducted at Royal Melbourne Hospital. Data included demographic characteristics, age, site and cause of the deformity, and number and survival of implants. Odds ratios were calculated and event-to-time Kaplan-Meier analyses performed. One hundred and ten patients were included (341 implants); their mean age was 46.2 years. The overall implant survival rate was 79.5% (mean follow-up 10.6 years). Temporal implants had the highest success rate (97.0%), followed by nasal implants (87.5%) and orbital implants (63.3%); differences were statistically significant (P<0.0001 and P=0.033, respectively). Kaplan-Meier analyses to determine long-term implant and prosthesis survival found temporal implants had the highest prosthetic (P<0.0001) and implant survival (P<0.0001). Patients with congenital deformities demonstrated the highest success rate. Radiotherapy was found to increase the risk of implant failure (P=0.02). Craniofacial implant-retained prostheses are a reliable and effective option for the restoration of facial defects, with good long-term success rates. Orbital implants and those placed post oncological surgery have a higher failure rate.

Candida virulence and ethanol-derived acetaldehyde production in oral cancer and non-cancer subjects.

OBJECTIVES: To compare biofilm-forming ability, hydrolytic enzymes and ethanol-derived acetaldehyde production of oral Candida isolated from the patients with oral cancer and matched non-oral cancer. MATERIAL AND METHODS: Fungal biofilms were grown in RPMI-1640 medium, and biofilm mass and biofilm activity were assessed using crystal violet staining and XTT salt reduction assays, respectively. Phospholipase, proteinase, and esterase production were measured using agar plate method, while fungal acetaldehyde production was assessed via gas chromatography. RESULTS: Candida isolated from patients with oral cancer demonstrated significantly higher biofilm mass (P = 0.031), biofilm metabolic activity (P < 0.001), phospholipase (P = 0.002), and proteinase (P = 0.0159) activity than isolates from patients with non-oral cancer. High ethanol-derived acetaldehyde-producing Candida were more prevalent in patients with oral cancer than non-oral cancer (P = 0.01). In univariate regression analysis, high biofilm mass (P = 0.03) and biofilm metabolic activity (P < 0.001), high phospholipase (P = 0.003), and acetaldehyde production ability (0.01) were significant risk factors for oral cancer; while in the multivariate regression analysis, high biofilm activity (0.01) and phospholipase (P = 0.01) were significantly positive influencing factors on oral cancer. CONCLUSION: These data suggest a significant positive association between the ability of Candida isolates to form biofilms, to produce hydrolytic enzymes, and to metabolize alcohol to acetaldehyde with their ability to promote oral cancer development.

Referral patterns for oral squamous cell carcinoma in Australia: 20 years progress.

BACKGROUND: The aim of this study was to identify changes in referral patterns and delays in diagnosis and treatment of oral squamous cell carcinoma (OSCC), managed at a tertiary institution in Victoria, Australia. METHODS: The hospital records of all patients with newly diagnosed OSCC, managed by The Royal Melbourne Hospital (RMH) Head and Neck Tumour Stream between January 2008 and December 2010, were retrospectively reviewed. RESULTS: Of the 101 patients, 52% first sought help from general medical practitioners (GMP) while 43% initially attended a general dental practitioner (GDP). The most common site of OSCC was oral tongue (42%). The most common presentation was ulceration (31%). Seventy per cent of patients presented with T1 (39%) or T2 (31%) tumours. The diagnostic delay ranged from 0 to 8 years with an average of 4.5 months. Patient delay ranged from 0 to 1.4 years with an average of 1.8 months. Professional delay ranged from 0 to 8 years with an average of 2 months. CONCLUSIONS: Delays in patients seeking advice have decreased compared to previous studies, while delays in professionals making a diagnosis have not improved considerably. There has been a significant shift towards initial presentation to GMP rather than GDP. Further decrease in delays is possible by improving both population awareness and clinician education.

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.

Ameloblastoma: demographic data and treatment outcomes from Melbourne, Australia.

BACKGROUND: There is a lack of published data on the demographics and treatment outcomes of ameloblastomas treated in Australia. Our objective was to collect this data and compare the findings to other international studies. METHODS: A retrospective study of 42 patients with ameloblastoma was conducted at The Royal Melbourne Hospital, Australia. Data on the demographic features, management techniques (ablative and reconstructive), and outcomes were collected and analysed. RESULTS: The majority of tumours were solid/multicystic (81%) and occurred most commonly in the mandible (80.5%). Unicystic ameloblastomas affected a younger age group, with Type 3 being the most common subtype. Overall, the recurrence rate for solid/multicystic ameloblastomas was 14.7%; however, radical surgery was found to have a significantly lower recurrence rate when compared to conservative management (p=0.015), with a mean of 51 months follow-up. Results indicated that vascularized free-flaps had fewer postoperative complications than non-vascularized bone grafts; however, the differences did not reach statistical significance. CONCLUSIONS: This is the largest clinicopathological study regarding ameloblastoma management from Australia, and our results support the current literature in recommending radical surgery for the treatment of solid/multicystic and Type 3 unicystic tumours.

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.

The development and validation of a rapid genetic method for species identification and genotyping of medically important fungal pathogens using high-resolution melting curve analysis.

Accurate, rapid and economical fungal species identification has been a major aim in mycology. In this study, our goal was to examine the feasibility of a high-resolution melting curve analysis (HRMA) of internal transcribed regions ITS1 and ITS2 in ribosomal DNA (rDNA) for a rapid, simple and inexpensive differentiation of eight clinically relevant Candida species (Candida albicans, Candida glabrata, Candida parapsilosis, Candida krusei, Candida tropicalis, Candida guilliermondii, Candida dubliniensis and Candida lusitaniae). In addition, for the first time, we tested the applicability of HRMA to classify C. albicans strains into four previously described genotypes (A, B, C and D) using a primer set that spans the transposable intron region of 25S of rDNA. Type and unknown clinical oral isolates were used in this study and the melting curve analysis was compared with both amplicons' sequencing and agarose gel electrophoresis analysis. Real-time PCR and subsequent HRMA of the two described rDNA regions generated distinct melting curve profiles that were in accord with sequencing and gel electrophoresis analysis, highly reproducible, and characteristic of each of the eight Candida species and C. albicans genotypes. Moreover, results were obtained in 4 h and without the need for any post-amplification handling, so reducing time and cost. Owing to its simplicity and speed, this technique is a good fit for genotypic analysis of hundreds of clinical strains in large epidemiological settings.

Influence of the site of origin on the outcome of squamous cell carcinoma of the maxilla-oral versus sinus.

The maxilla may be affected by squamous cell carcinoma (SCC) from both oral and sinus sites. We sought to determine whether the site of origin of the maxillary tumour, oral as compared to sinus, influences survival. Univariate Kaplan-Meier and multivariate Cox proportional hazard models analysis of 58 patients with SCC involving the maxilla, treated with curative intent, was conducted. The overall 5-year disease-free survival for the group was 41.7%. Five-year disease-free survival for oral subsite SCC was 56.8%, while for sinus subsite was only 21.6%. Univariate analysis found SCC of sinus origin to be associated with a poorer prognosis, however this was not confirmed on multivariate analysis. T-stage and positive margins were found to be the only independent risk factors. For SCC of the maxilla, sinus origin of the tumour per se does not confer a poorer prognosis; however, as a result of the complex anatomy of the midface, these tumours can present at an advanced stage, while surgical control of the disease can be more difficult, especially posteriorly. Tumour size and positive margins were the determinants of a poor prognosis in this group of patients with maxillary SCC.

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.