Clinical outcomes in relapsed oropharyngeal cancer after definitive (chemo) radiotherapy.

OBJECTIVES: To report clinical outcomes of relapsed oropharyngeal squamous cell carcinoma (OPSCC) after definitive intensity-modulated (chemo)radiotherapy [(C)RT]. MATERIALS AND METHODS: Data for all relapsed patients treated for OPSCC with definitive (C)RT between 2010 and 2016 were collected. Primary end-point was post-failure survival (PFS). RESULTS: Overall, 273 OPSCC patients completed definitive (C)RT. Of these, 42 cases (n = 26 human papilloma virus (HPV)-negative; n = 16 HPV-positive) had relapsed (n = 23 persistent disease; n = 19 recurrent disease) and were included in the final analysis. Two-year PFS for the entire population was 30.6%; 20.5% for HPV-negative and 43.8% for HPV-positive patients. Salvage curative surgery was associated with a significantly higher 2 years PFS rate (56.2%) compared with palliative treatment (22.9%) and best supportive care (0%) (p < 0.001). A positive trend in 2 years PFS was recorded in the early complete response cases (49.5%) versus patients who did not achieve a complete response within 3 months of the end of (C)RT (23.0%) (p = 0.11). CONCLUSION: A higher PFS rate is achieved when relapsed OPSCC cases are treated with salvage curative intent. HPV-positive disease and early complete response within 3 months from the end of (C)RT may be related to better PFS.

(18)F-FDG PET/CT to assess response and guide risk-stratified follow-up after chemoradiotherapy for oropharyngeal squamous cell carcinoma.

PURPOSE: To evaluate the use of (18)F-FDG PET/CT as the principal investigation to assess tumour response, to determine the need for further surgery and to guide follow-up following radical chemoradiotherapy for stage III/IV oropharyngeal squamous cell carcinoma (OPSCC). METHODS: A retrospective analysis was undertaken in 146 patients treated at our centre with radical chemoradiotherapy for OPSCC and who had a PET/CT scan to assess response. According to the PET/CT findings, patients were divided into four groups and recommendations: (1) complete metabolic response (enter clinical follow-up); (2) low-level uptake only (follow-up PET/CT scan in 12 weeks); (3) residual uptake suspicious for residual disease (further investigation with or without neck dissection); and (4) new diagnosis of distant metastatic disease (palliative treatment options). RESULTS: The initial PET/CT scan was performed at a median of 12.4 weeks (range 4.3 - 21.7 weeks) following treatment. Overall sensitivity and specificity rates were 92.0 % (74.0 - 99.0 %) and 85 % (77.5 - 90.9 %). Of the 146 patients, 90 (62 %) had a complete response and had estimated 3-year overall and disease-free survival rates of 91.9 % (85.6 - 98.2 %) and 85.6 % (78.0 - 93.2 %), respectively, 17 (12 %) had residual low-level uptake only (with two having confirmed residual disease on subsequent PET/CT, both surgically salvaged), 30 (21 %) had suspicious residual uptake (12 proceeded to neck dissection; true positive rate at surgery 33 %). HPV-positive patients with reassuring PET/CT findings had an estimated 3-year progression-free survival rate of 91.7 % (85.2 - 98.2 %), compared with 66.2 % (41.5 - 90.9 %) of HPV-negative patients. CONCLUSION: A strategy of using PET/CT results alongside clinical examination to help select patients for salvage surgery appears successful. Despite a complete response on the 12-week PET/CT scan, HPV-negative patients have a significant risk of disease relapse in the following 2 years and further studies to assess whether surveillance imaging in this group could improve outcomes are warranted.

Insights into the nuclear and mitochondrial genome of the Lemon shark Negaprion brevirostris using low-coverage sequencing: Genome size, repetitive elements, mitochondrial genome, and phylogenetic placement.

The Lemon shark Negaprion brevirostris is an important species experiencing conservation issues that is in need of genomic resources. Herein, we conducted a genome survey sequencing in N. brevirostris and determined genome size, explored repetitive elements, assembled and annotated the 45S rRNA DNA operon, and assembled and described in detail the mitochondrial genome. Lastly, the phylogenetic position of N. brevirostris in the family Carcharhinidae was examined using translated protein coding genes. The estimated haploid genome size ranged between 2.29 and 2.58 Gbp using a k-mer analysis, which is slightly below the genome size estimated for other sharks belonging to the family Carcharhinidae. Using a k-mer analysis, approx. 64-71 % of the genome of N. brevirostris was composed of repetitive elements. A relatively large proportion of the 'repeatome' could not be annotated. Taking into account only annotated repetitive elements, Class I - Long Interspersed Nuclear Element (LINE) were the most abundant repetitive elements followed by Class I - Penelope and Satellite DNA. The nuclear ribosomal operon was fully assembled. The AT-rich complete mitochondrial genome was 16,703 bp long and encoded 13 protein coding genes, 2 ribosomal RNA genes, and 22 transfer RNA genes. Negaprion brevirostris is closely related to the genera Carcharhinus, Glyphis and Lamiopsis in the family Carcharinidae. This new genomic resources will aid with the development of conservation plans for this large coastal shark.

Expansion of Typical Values for Paediatric Patients in Ireland and Comparison with Published DRLs - Experiences of a Single Institution.

INTRODUCTION: To reduce the risks involved with ionising radiation exposure, typical values (TVs) and diagnostic reference levels (DRLs) have been established to help keep radiation doses 'as low as reasonably practicable. TVs/DRLs provide standardised radiation dose metrics that can be used for comparative purposes. However, for paediatrics, such values should consider the size of the child instead of their age. This study aimed to establish and compare paediatric TVs for chest, abdomen and pelvis radiography. METHODS: Study methods followed processes for establishing paediatric DRLs as outlined by the Health Information and Quality Authority (HIQA). Kerma-area product (KAP) values, excluding rejected images, were retrospectively acquired from the study institution's Picture Archiving and Communications System (PACS). Paediatric patients were categorised into the following weight-based groupings (5 to <15 kg, 15 to <30 kg, 30 to <50 kg, 50 to 80 kg) and stratified based on the examination that was performed (chest, abdomen, and pelvis), and where it was performed (the different X-ray rooms). Anonymised data were inputted into Microsoft Excel for analysis. Median and 3rd quartile KAP values were reported together with graphical illustrations. RESULTS: Data from 407 X-ray examinations were analysed. For the previously identified weight categories (5 to <15 kg, 15 to <30 kg, 30 to <50 kg, 50 to 80 kg), TVs for the chest were 0.10, 0.19, 0.37 and 0.53 dGy.cm2, respectively. For the abdomen 0.39, 1.04, 3.51 and 4.05 dGy.cm2 and for the pelvis 0.43, 0.87, 3.50 and 7.58 dGy.cm2. Between X-ray rooms TVs varied against the institutional TVs by -60 to 119 % (chest), -50 to 103 % (abdomen) and -14 and 24 %% (pelvis). CONCLUSION: TVs in this study follow established trends with patient weight and examination type and are comparable with published literature. Variations do exist between individual examination rooms and reasons are multifactorial. Given that age and size do not perfectly correlate further work should be undertaken around weight-based TVs/DRLs in the paediatric setting.

The rise and fall of a second-generation CBNRM project in Zambia: insights from a project perspective.

Since the advent of community-based natural resource management (CBNRM) in the mid-1980s, scholars and practitioners have sought to explain the uneven performance of CBNRM programs. Most CBNRM assessments examine the underlying principles of community-based conservation, the local social and ecological contexts, and connections with larger political and historical patterns. In this article, I argue that analysis of the potential and pitfalls of CBNRM also requires an understanding of the institutional history and internal dynamics of projects that implement CBNRM reforms. Drawing upon theory and methods from development ethnography and public policy, I examine the rise and fall of CONASA, a second-generation CBNRM project in Zambia that operated from 2001 to 2004. CONASA was constituted from a merger of organizations and discourses to provide continuity with previous projects. Its ambitious suite of activities included support for household livelihoods, community-based resource management, policy analysis, advocacy, and conservation enterprises at local, national, and transboundary levels. While individual activities were largely successful, CONASA's hybrid origins and logframe-centric management created fissures between its holistic design and operational logics, and hindered its ability to develop a broader narrative and maintain key alliances. This case study illustrates the importance of understanding the interplay between project design and operational context to fully appreciate the possibilities and limitations of project-mode conservation.

Sentinel lymph node biopsy for T1/T2 oral cavity squamous cell carcinoma--a prospective case series.

BACKGROUND: Sentinel lymph node biopsy (SLNB) is an established technique in breast and melanoma surgery and is gaining acceptance in the management of oral cavity squamous cell carcinoma. We report a single institution's experience of SLNB between 2006 and 2010. METHODS: Prospective consecutive cohort study of 59 patients recruited between 2006 and 2010. All patients underwent SLNB with preoperative lymphoscintigraphy, intraoperative blue dye, and handheld gamma probe. Sentinel nodes were evaluated with step-serial sectioning and immunohistochemistry. Endpoints included: overall survival (OS), disease-specific survival (DSS), local recurrence-free survival (LRFS), and regional recurrence-free survival (RRFS). RESULTS: A total of 59 patients (36 male and 23 female) were operated on. Of these, 42 patients (71%) were pT1 and 17 patients (29%) were pT2. In two patients the sentinel node was not identified and proceeded to elective neck dissection. A total of 150 nodes were harvested from the remaining 57 patients of which 21 nodes were positive in 17 patients; three patients had positive contralateral nodes. The 2-year OS, DSS, LRFS, and RRFS for the SLNB negative patients were 97.5, 100, 95.8, and 95.8% and for the SLNB positive patients 68.2, 81.8, 83.9, and 100% respectively. Only OS and DSS approached statistical significance with P values of 0.07 and 0.06. CONCLUSIONS: SLNB is a safe and accurate diagnostic technique for staging the neck with a negative predictive value in our series of 97.5%. Furthermore, in our series three patients (5%) had positive contralateral neck drainage that would have been missed by conventional ipsilateral neck dissection.

Using Lean tools to improve the efficiency of awake fibreoptic intubation setup.

BACKGROUND: Awake fibreoptic intubation is a complex advanced airway technique used by anaesthesiologists in the management of a difficult airway. The time to setup this important procedure can be significant which may dissuade its use by some providers. In our institution, the awake intubation setup process was highly variable and error prone. METHODS: We deployed Lean methods to improve the efficiency and accuracy of the awake fibreoptic intubation setup process. A 2-day improvement event with a multidisciplinary team addressed the setup process, tested solutions and created standard work documents. Twenty awake fibreoptic intubation simulations were conducted before and after the intervention to quantify gains in setup efficiency and error reduction. RESULTS: Variability in the setup process, including clinical locations visited, was reduced through creating a standardised process. The average time to for an awake fibreoptic intubation setup was reduced by approximately 50%, from 23 min to 11 min (p<0.001). In addition, awake fibreoptic intubation equipment set out without error increased in the postintervention simulations from 59% to 85% (p=0.003). CONCLUSION: Using Lean tools, we were able to make the setup of awake fibreoptic intubation not only more efficient, but also more accurate. A similar methodological approach may have value for other complex anaesthesia procedures.

Treating the N0 neck in early stage oral cancer: a pause for re-assessment?

The incidence of metastases following neck dissection in the apparent lymph node negative neck in oral cancer is between 7% and 33%; early resection of cervical metastases may well increase survival. Modern imaging techniques can reduce the yield of previously undiagnosed metastatic nodes in elective neck dissection (END). An audit of 112 consecutive cases was conducted to determine the proportion of undiagnosed nodal metastases, after END. There were neck metastases in 10 cases (9%), which were mainly (but not all) micrometastic. The 20% likelihood of nodal metastases was only apparent in primary tumours greater than 6 mm thick. The length of inpatient stay was increased from 3.7 to 16.5 days with free vascularised transfer. There were complications including cranial nerve damage. There were two peri-operative deaths. No ipsilateral neck failures occurred, median follow up was 937 days. To reduce unnecessary END, resection can be undertaken as a prior procedure, subsequently only carrying out END on tumours greater than 6 mm, or with unfavourable tumour characteristics.

Risk stratified follow up for head and neck cancer patients - An evidence based proposal.

Head and neck squamous cell carcinoma (HNSCC) has a significant impact on patients' quality of life and treatment can be associated with severe morbidity. Following completion of treatment, patients are followed up in order to detect potentially salvageable recurrences and to manage long-term toxicities. In recent years, a growing interest has been given to risk stratified follow-up interventions to prevent and detect recurrences and manage treatment toxicities in other tumour sites as well as to transfer some of that care to community services. We review the literature for HNSCC and propose a risk stratified follow up protocol to address these issues and assist clinicians in decision making. A shift in patterns of care is suggested in order to provide a basis to improve care for HNSCC patients after complete response to primary treatment.

TNM 8 staging is a better prognosticator than TNM 7 for patients with locally advanced oral cavity squamous cell carcinoma treated with surgery and post-operative radiotherapy.

PURPOSE: To assess TNM 8 staging in discriminating overall survival (OS) amongst patients with locally advanced oral cavity squamous cell carcinoma (OCSCC) treated with surgery and post-operative radiotherapy (PORT), compared to TNM 7. MATERIAL AND METHODS: Data from OCSCC patients treated with surgery and PORT between January 2010 and December 2018 were reviewed. Demographics, tumour characteristics and treatment response data were collected, and patients staged according to both TNM 7 and TNM 8. OS and disease free survival (DFS) were estimated using the Kaplan Meier method. Univariate and multivariable analyses were conducted for factors affecting OS, DFS and early disease recurrence within 12 months. RESULTS: Overall 172 patients were analyzed. Median follow up was 32 months for all patients and 48 months for surviving patients. TNM 8 staging demonstrated significant stratification of OS and DFS amongst the entire cohort, whereas TNM 7 staging did not. On multivariable analysis, TNM 8 stage, performance status (PS) and a positive surgical margin were prognostic for OS. Looking at disease recurrence within 12 months, TNM 8 stage IVB, presence of lymphovascular invasion (LVSI), younger age and lesser smoking history were predictive factors on multivariable analysis. CONCLUSION: TNM 8 is a good development of its predecessor in terms of predicting survival for patients with locally advanced OCSCC. We have also identified younger age (<60 years) and a smoking history of <10 pack years as risk factors for early disease recurrence, potentially representing a separate biological cohort within OCSCC patients.

Integrated media presentation in multidisciplinary head and neck oncology meetings.

Multidisciplinary meetings (MDMs) are an essential part of the management of head and neck cancer. Practice care guidance set up by the British Association of Head and Neck Oncologists has recommended that MDMs should have appropriate projection equipment for computer-generated images so that all members of group have access to the same information. The aim of this paper is to review our experience with the integrated visual presentation of head and neck oncology patients and to demonstrate its advantages over conventional approaches. Digital photographs are taken of patients and of their index tumour at presentation or at the time of diagnostic endoscopy. All relevant pre-treatment digitised images from tumour sites and radiological images and histological slides are incorporated into a single presentation using Microsoft PowerPoint software. During the past 2 years, on-line radiological scans have also become accessible for the meeting to aid treatment planning. Subsequently, all peri-operative pictures and post-surgical macroscopic and microscopic histopathological images are added to each patient's presentation, which is then hyperlinked into the agenda. The Guy's and St Thomas' Head and Neck Cancer Centre treats over 400 patients a year, and since 2002, all new cancer diagnoses have been discussed in the weekly MDM as described above. A total of 1,638 presentations have been incorporated in a centralized database that is updated in the event of recurrence, further primary tumours or other clinical developments. Satisfactory documentation and staging of head and neck tumours must include a verbal description, accurate measurement, diagrammatic representation, photographic recording and appropriate radiological imaging. Integrated presentation at MDM collates all relevant findings for clinical management decisions on patients with head and neck cancer. This approach is also an extremely valuable adjunct to long-term clinical monitoring.

p53 mutations in deep tissues are more strongly associated with recurrence than mutation-positive mucosal margins.

PURPOSE: Application of ultrasensitive diagnostics has shown that small numbers of p53 mutation-positive cells may signify the presence of residual tumor in histologically normal tissues after resection of squamous cell carcinomas arising in the head and neck area. To date, most studies in this area have focused on analysis of tissues at the mucosal aspect of the resection and highlighted the importance of molecular changes in the field with respect to the risk of recurrence. EXPERIMENTAL DESIGN: In the present investigation, we analyzed normal tissues from mucosal and deep surgical margins, referred to as "molecular margins," for the presence of the signature p53 mutation identified for each tumor. RESULTS: The p53 mutation status of these carcinomas did not correlate with clinical or histopathologic variables, but these mutations provided an excellent target for ultrasensitive analysis of margin status. We found that 11 of 16 (68%) of cases with histologically tumor-free (including 9 without dysplasia), but with p53 mutation-positive molecular margins, developed recurrence. The probability of developing local recurrence was significantly higher for the group with p53 mutation-positive margins when compared with the group with clear margins (P = 0.048) and more strongly associated with p53 mutation-positive deep molecular margins than mutation-positive mucosal molecular margins or positivity at both sites (P = 0.009). CONCLUSIONS: This shows that although persistent mucosal fields may contribute to recurrence, clonal p53 mutations in deep tissues are an important cause of treatment failure, and molecular margins from both sites should be analyzed in future prospective series.

Microneurolysis and decompression of long thoracic nerve injury are effective in reversing scapular winging: long-term results in 50 cases.

BACKGROUND: Long thoracic nerve injury leading to scapular winging is common, often caused by closed trauma through compression, stretching, traction, direct extrinsic force, penetrating injury, or neuritides such as Parsonage-Turner syndrome. We undertook the largest series of long thoracic nerve decompression and neurolysis yet reported to demonstrate the usefulness of long thoracic nerve decompression. METHODS: Winging was bilateral in 3 of the 47 patients (26 male, 21 female), yielding a total of 50 procedures. The mean age of the patients was 33.4 years, ranging from 24-57. Causation included heavy weight-lifting (31 patients), repetitive throwing (5 patients), deep massage (2 patients), repetitive overhead movement (1 patient), direct trauma (1 patient), motor bike accident (1 patient), and idiopathic causes (9 patients). Decompression and microneurolysis of the long thoracic nerve were performed in the supraclavicular space. Follow-up (average of 25.7 months) consisted of physical examination and phone conversations. The degree of winging was measured by the operating surgeon (RKN). Patients also answered questions covering 11 quality-of-life facets spanning four domains of the World Health Organization Quality of Life questionnaire. RESULTS: Thoracic nerve decompression and neurolysis improved scapular winging in 49 (98%) of the 50 cases, producing "good" or "excellent" results in 46 cases (92%). At least some improvement occurred in 98% of cases that were less than 10 years old. Pain reduction through surgery was good or excellent in 43 (86%) cases. Shoulder instability affected 21 patients preoperatively and persisted in 5 of these patients after surgery, even in the 5 patients with persistent instability who experienced some relief from the winging itself. CONCLUSION: Surgical decompression and neurolysis of the long thoracic nerve significantly improve scapular winging in appropriate patients, for whom these techniques should be considered a primary modality of functional restoration.

Physiological and clinical advantages of median nerve fascicle transfer to the musculocutaneous nerve following brachial plexus root avulsion injury.

OBJECT: Loss of biceps muscle function is a significant disability after brachial plexus root avulsion injuries. Nerve grafting techniques to reestablish anatomical and functional continuity between the spinal cord and the avulsed root have not proven successful. Using nerve transfers for functional restoration of root avulsion injuries appears to be effective and has physiological advantages for reducing regeneration distances. Since the early 1990s, the Oberlin technique of transferring ulnar nerve fascicles to the motor branch of the musculocutaneous nerve has been the preferred operative technique for reinnervation and restoration of biceps muscle function. In the current study the authors examine the efficacy of an alternative technique using median nerve fascicles transferred to the musculocutaneous nerve to reinnervate the biceps muscle. METHODS: Forty consecutive patients with combined C5-6 brachial plexus root avulsions were evaluated pre- and postoperatively according to the British Medical Research Council Motor Grading Scale. Personal interviews concerning quality of life (QOL) after surgery were conducted and scored based on standards set by the World Health Organization. All patients showed some degree of improvement in biceps muscle function. Thirty-six (90%) of the 40 patients regained movement against gravity. The patients had a 77% improvement in overall QOL after the surgery; most notably, 92% of the patients reported their lack of need for medication and 75% a significant lessening of postoperative pain. Redirection of part of the healthy median nerve resulted in no measurable functional deficits, and only 28 patients reported minor sensory disturbances in the first web space for an average of 3 months after surgery. CONCLUSIONS: Median nerve fascicle transfer resulted in a significant improvement in biceps muscle function with an acceptable level of morbidity and should be considered an effective, and in many cases preferable, alternative to ulnar nerve fascicle transfer.

Current concepts in the management of oral cancer.

For patients diagnosed with oral cancer, treatment may involve surgery or radiotherapy alone, or a combination of the two. Where radiotherapy is the sole modality, the addition of chemotherapy may be beneficial, particularly with advanced tumours. If the treatment is surgery, this may involve extensive microsurgical reconstruction. Follow up of treated patients should be rigorous and, ideally, quality of life should be measured.

Osteoradionecrosis following treatment for head and neck cancer and the effect of radiotherapy dosimetry: the Guy's and St Thomas' Head and Neck Cancer Unit experience.

OBJECTIVES: To analyze clinical features, dosimetric parameters, and outcomes of osteoradionecrosis (ORN). STUDY DESIGN: Thirty-six patients with ORN who had been previously treated with radiotherapy (RT) were retrospectively identified between January 2009 and April 2014. ORN volumes were contoured on planning computed tomography (CT) scans. Near maximum dose (D2%), minimum dose (Dmin), mean dose (Dmean), and percentage of bone volume receiving 50 Gy (V50) were examined. Clinical and dosimetric variables were considered to compare ORN resolution versus ORN persistence. RESULTS: Median interval time from end of RT to development of ORN was 6 months. Of the ORN cases, 61% were located in the mandible. Dmean to affected bone was 57.6 Gy, and 44% had a D2% 65 Gy or greater. Smoking was associated with ORN persistence on univariate analysis, but no factors were found to impact ORN resolution or progression on logistic regression. CONCLUSIONS: Prevention strategies for ORN development should be prioritized. Dose-volume parameters could have a role in preventing ORN.

Free vascularised iliac crest graft: an audit of 26 consecutive cases.

Over an 18 month period 26 vascularised myo-osseus, and one myo-osseus-cutaneous iliac crest flaps were used to reconstruct 18 mandibular and eight maxillary defects. During the operation one flap failed to reperfuse and was removed. Postoperatively three patients were returned to theatre for appraisal and reanastomoses, which in two cases involved thrombolysis. In all three salvage was deemed successful but in all there was partial muscle necrosis. There were 10 cases of anaesthesia of the skin supplied by the lateral cutaneous nerve of the thigh, three incisional hernias, one wound dehiscence in the thigh, two oronasal fistulas, one wound dehiscence in the neck, one infection by methicillin resistant Staphylococcus aureus in the thigh, and two long-term and one medium-term disturbances of gait. Complications were graded as severe (4%), intermediate (27%), and minor (46%).

Panmictic and Clonal Evolution on a Single Patchy Resource Produces Polymorphic Foraging Guilds.

We develop a stochastic, agent-based model to study how genetic traits and experiential changes in the state of agents and available resources influence individuals' foraging and movement behaviors. These behaviors are manifest as decisions on when to stay and exploit a current resource patch or move to a particular neighboring patch, based on information of the resource qualities of the patches and the anticipated level of intraspecific competition within patches. We use a genetic algorithm approach and an individual's biomass as a fitness surrogate to explore the foraging strategy diversity of evolving guilds under clonal versus hermaphroditic sexual reproduction. We first present the resource exploitation processes, movement on cellular arrays, and genetic algorithm components of the model. We then discuss their implementation on the Nova software platform. This platform seamlessly combines the dynamical systems modeling of consumer-resource interactions with agent-based modeling of individuals moving over a landscapes, using an architecture that lays transparent the following four hierarchical simulation levels: 1.) within-patch consumer-resource dynamics, 2.) within-generation movement and competition mitigation processes, 3.) across-generation evolutionary processes, and 4.) multiple runs to generate the statistics needed for comparative analyses. The focus of our analysis is on the question of how the biomass production efficiency and the diversity of guilds of foraging strategy types, exploiting resources over a patchy landscape, evolve under clonal versus random hermaphroditic sexual reproduction. Our results indicate greater biomass production efficiency under clonal reproduction only at higher population densities, and demonstrate that polymorphisms evolve and are maintained under random mating systems. The latter result questions the notion that some type of associative mating structure is needed to maintain genetic polymorphisms among individuals exploiting a common patchy resource on an otherwise spatially homogeneous landscape.

Osteoradionecrosis--a review of current concepts in defining the extent of the disease and a new classification proposal.

Osteoradionecrosis (ORN) is potentially a debilitating and serious consequence of radiotherapy to the head and neck. Although it is often defined as an area of exposed bone that does not heal, it can also exist without breaching the mucosa or the skin. Currently, 3 classifications of ORN are in use, but they depend on the use of hyperbaric oxygen or are too complicated to be used as a simple aide-mémoire, and include features that do not necessarily influence its clinical management. We propose a new classification to cover these shortcomings and to take into account the increasingly widespread use of antifibrotic medical treatment. We classified a series of 85 patients with varying severities of ORN into 4 groups. An analysis of the outcomes of the series showed that the classification staged the severity of the condition simply and that the stage was relevant to both treatment and outcome. The new classification was therefore verified by the series presented.

Trismus following radiotherapy to the head and neck is likely to have distinct genotype dependent cause.

OBJECTIVES: Trismus frequently occurs as a consequence of radiotherapy or chemo-radiotherapy to the head and neck, with a loss of function that can reduce the overall quality of life. Radiation can trigger an intense fibrosis within the masticatory muscles and transforming growth factor beta 1 (TGF ß1) is involved in this process. As in other tissues the degree of fibrosis may be related to a single nucleotide polymorphism; C-T at position -509 in the TGF ß1 gene. MATERIALS AND METHODS: Trismus was measured in 62 patients before and after radiotherapy or chemoradiotherapy, blood was taken for DNA extraction, and genotype analysis of the TGF ß1 gene. Trismus was analysed against, patient age, sex, tumour site and stage, radiotherapy, and chemotherapy. RESULTS AND CONCLUSIONS: After radiotherapy or chemo-radiotherapy the reduction in mouth opening was shown to be significantly related to the presence of the T allele (p<0.001), with patients homozygous the most likely to be severely affected. No other patient, tumour or treatment factors were significant. Hence the TGF ß1 genotype is likely to be an important predictor of the degree of post radiotherapy or chemo-radiotherapy trismus.