Merkel cell carcinoma of the head and neck in the south-east of England.

Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine malignancy of the skin. Its incidence is increasing with half of cases involving the head and neck. To the best of our knowledge, few large studies have been published in the UK, and to date this is the largest reported series of head and neck MCC. We retrospectively reviewed the outcomes of patients with MCC in three hospitals in the south-east of England over a 12-year period (2008-2019). Diagnosis was based on histological data following biopsy. Overall survival and disease-specific survival were calculated using Kaplan-Meier and log-rank tests. Fifty-eight patients met the inclusion criteria (24 stage I, 22 stage II, 9 stage III, and 3 unclassified). Median disease-free survival was 36 months (95% CI 0 to 77.2) and median overall survival 50 months (95% CI 29.9 to 70). Overall five-year survival was 34.4% (95% CI 17% to 52%) with two-year survival at 62% (95% CI 48% to 76%). Five-year disease-free survival was 26.7% (95% CI 17 to 52%) with two-year disease-free survival at 54% (95% CI 40% to 68%). To date, this is the largest UK based study reporting overall and disease-free survival associated with MCC of the head and neck. Half the patients presented late, and surgery was the mainstay of treatment, augmented by adjuvant radiotherapy. There is a need to better stratify patients at risk of developing metastatic disease, with the use of sentinel lymph node biopsy and positron-emission tomography-computed tomography (PET-CT), as immunotherapy and targeted agents are now available to treat advanced disease.

Lateral segmental mandibulectomy reconstruction with bridging reconstruction plate and anterolateral thigh free flap: a case series of 30 consecutive patients.

Lateral posterior segmental mandibular defects present a reconstructive challenge and an osseous flap would be the gold standard to reconstruct such a defect. However, combining a mandibular reconstruction plate (MRP) with a soft-tissue free flap (to restore mucosal integrity and provide durable coverage of the plate itself) offers an alternative option for posterior segmental mandibular defects in patients who are not suitable for osseous reconstruction, or do not choose it. We retrospectively reviewed 30 consecutive patients (19 male and 11 female) who underwent reconstruction of a segmental mandibulectomy defect using a bridging MRP and anterolateral thigh (ALT) free flap. The mean (range) age was 67 (31-87) years. The American Society of Anesthesiologists' (ASA) status of the study population comprised Grade 1 (n = 10), Grade 2 (n = 18), and Grade 3 (n = 2). The majority of patients had oral cavity squamous cell carcinoma (n = 26) involving the mandible, two had osteoradionecrosis, and two mucoepidermoid carcinoma. Four patients had complications specific to the reconstruction, and flap loss occurred in one (96.7% success rate). Metalwork infection occurred in three, including one plate extrusion and one plate fracture. The median length of stay was 10 days, and mean (range) duration of follow up 23.3 (1-96) months. This technique is an alternative reconstructive option for the non-tooth-bearing mandible. Reconstructing a posterolateral segmental mandibulectomy defect with a bridging MRP and ALT free flap offers a robust reconstructive alternative with a favourable complication profile.

Current perspectives on the surgical management of mandibular third molars in the United Kingdom: the need for further research.

This survey of expert opinion regarding the management of mandibular third molar (M3M) impaction and its clinical sequelae was circulated to all members of the British Association of Oral and Maxillofacial Surgeons (BAOMS). It was completed by 289 clinicians who reported treating 60003 patients annually. Respondents included 199 (69%) specialists and 58 (20%) primary care clinicians. Most (99%) of the clinicians treated at least one M3M with complete surgical removal (CSR) annually. Only 69% performed one or more coronectomies (COR). Advocates of coronectomy reported lower rates of inferior alveolar nerve (IAN) injury, but IAN, lingual nerve, and adjacent second molar damage were rare, occurring in less than 0.5% of cases, with small differences between the COR and CSR groups. Although these differences are not statistically significant, they are likely to be clinically important. Also, the COR group would have comprised mainly high-risk teeth, while the CSR group would include many teeth at low risk of complications. This might have skewed the results. Those clinicians performing no coronectomies cited three main reasons for being low adopters of COR: the lack of irrefutable evidence to support its benefit, the increased need for a second operation, and more non-IAN complications. Although COR may prevent permanent IAN damage in high-risk cases, this paper highlights clinicians' views that there is a gap in evidence and knowledge to support COR. As a result, 47% of the clinicians surveyed recommended, and were prepared to participate in, further studies to determine the effectiveness and safety of COR.

Results of flap reconstruction: categorisation to reflect outcomes and process in the management of head and neck defects.

The reporting of the outcomes of flap reconstruction is often based on numerical success rates. Whilst this remains a useful variable with which to measure success, it is limited in its ability to reflect the complex processes involved. The lack of consistency in the categorisation of outcomes of flap reconstruction in the head and neck could potentially lead us to lose the opportunity to fully capture the implications of its success or failure, or both. We propose a classification that moves away from primarily reporting the results of its binary nature, and focuses more on the process of reconstruction, particularly in the head and neck.

Current trends in the medical management of osteoradionecrosis using triple therapy.

Recent guidelines from the National Institute for Health and Care Excellence (NICE) have suggested that the medical management of osteoradionecrosis (ORN) of the jaws should be used in clinical trials only, and some drugs and therapeutics committees have withdrawn funds for such prescriptions. With increased scrutiny on the use of these agents, the aims of this study were to ascertain current trends in the presentation and management of ORN, with particular focus on which agents are being used.

Current Concepts in Osteoradionecrosis after Head and Neck Radiotherapy.

Osteoradionecrosis (ORN) of the jaws is a feared complication of head and neck radiotherapy. ORN causes significant morbidity for patients and controversy among clinicians. This overview considers the variations in definition and classification of the condition that affect estimates of incidence and also the interpretation of evidence. The influence of newer radiotherapy techniques in reducing ORN through reduced dose and xerostomia is balanced against a probable increase in a vulnerable population through a rising head and neck cancer incidence. Theories of pathophysiology of ORN include radiation-induced osteomyelitis, hypoxic and hypovascular theory and fibroatrophic theory. Prevention strategies include restorative dentistry and radiation planning techniques. Treatments range from conservative 'watch and wait' through to more radical surgical strategies. Newer medical management strategies are available with a limited evidence base. The use of hyperbaric oxygen therapy remains controversial and the background and need for newer hyperbaric oxygen trials is discussed.

SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma.

BACKGROUND: Extracapsular spread (ECS) in cervical lymph nodes is the single-most prognostic clinical variable in oral squamous cell carcinoma (OSCC), but diagnosis is possible only after histopathological examination. A promising biomarker in the primary tumour, alpha smooth muscle actin (SMA) has been shown to be highly prognostic, however, validated biomarkers to predict ECS prior to primary treatment are not yet available. METHODS: In 102 OSCC cases, conventional imaging was compared with pTNM staging. SERPINE1, identified from expression microarray of primary tumours as a potential biomarker for ECS, was validated through mRNA expression, and by immunohistochemistry (IHC) on a tissue microarray from the same cohort. Similarly, expression of SMA was also compared with its association with ECS and survival. Expression was analysed separately in the tumour centre and advancing front; and prognostic capability determined using Kaplan-Meier survival analysis. RESULTS: Immunohistochemistry indicated that both SERPINE1 and SMA expression at the tumour-advancing front were significantly associated with ECS (P<0.001). ECS was associated with expression of either or both proteins in all cases. SMA+/SERPINE1+ expression in combination was highly significantly associated with poor survival (P<0.001). MRI showed poor sensitivity for detection of nodal metastasis (56%) and ECS (7%). Both separately, and in combination, SERPINE1 and SMA were superior to MRI for the detection of ECS (sensitivity: SERPINE1: 95%; SMA: 82%; combination: 81%). CONCLUSION: A combination of SMA and SERPINE1 IHC offer potential as prognostic biomarkers in OSCC. Our findings suggest that biomarkers at the invasive front are likely to be necessary in prediction of ECS or in therapeutic stratification.

The epigenetic landscape of oral squamous cell carcinoma.

BACKGROUND: There is relatively little methylation array data available specifically for oral squamous cell carcinoma (OSCC). This study aims to compare the DNA methylome across a large cohort of tumour/normal pairs. METHODS: DNA was extracted from 44 OSCCs and paired normal mucosa. DNA methylation analysis employed the Illumina GoldenGate high-throughput array comprising 1505 CpG loci selected from 807 epigenetically regulated genes. This data was correlated with extracapsular spread (ECS), human papilloma virus (HPV) status, recurrence and 5-year survival. RESULTS: Differential methylation levels of a number of genes distinguished the tumour tissue sample from the matched normal. Putative methylation signatures for ECS and recurrence were identified. The concept of concordant methylation or CpG island methylator phenotype (CIMP) in OSCC is supported by our data, with an association between 'CIMP-high' and worse prognosis. Epigenetic deregulation of NOTCH4 signalling in OSCC was also observed, as part of a possible methylation signature for recurrence, with parallels to recently discovered NOTCH mutations in HNSCC. Differences in methylation in HPV-driven cases were seen, but are less significant than that has been recently proposed in other series. CONCLUSION: Although OSCC seems as much an 'epigenetic' as a genetic disease, the translational potential of cancer epigenetics has yet to be fully exploited. This data points to the application of epigenetic biomarkers and targets available to further the development of therapy in OSCC.

Patterns of treatment of osteoradionecrosis with hyperbaric oxygen therapy in the United Kingdom.

We aimed to find out the number of patients with osteoradionecrosis (ORN) being treated by hyperbaric chambers in the UK during 2006-07, and the protocols that were being used. We did a telephone survey of 76 chambers to find out whether they treated patients with ORN, how many patients they treated in 2006-07, what chamber pressure they used, the duration of each session, and the total number of sessions/patient. A total of 25 chambers treated 273 patients with ORN in 2006-07; 10 were listed by the British Hyperbaric Association (BHA) and 15 were at multiple sclerosis (MS) centres. MS centres treated 23 (8%) of patients with ORN with a variable number of sessions of shorter duration and lower pressures than the chambers listed by the BHA. Most BHA chambers treated patients at 2.2 ATA for 90 min/session with 30 preoperative and 10 postoperative sessions/patient.

Palatability of bison semimembranosus and effects of marination.

The present study was conducted to investigate the palatability of bison semimembranosus muscle (SM) and the effects of injection with sodium chloride and sodium tripolyphosphate on cooking yield, colour, shear force and consumer acceptability. Twenty paired SM were obtained from 10 intact male bison (aged 24-30 months); each of these muscles was divided longitudinally into two sections. One section was injected to 110% of its original weight to contain 0.5% sodium chloride and 0.3% sodium tripolyphosphate, while the other was kept as a non-injected control. HunterLab a* (redness) and b* (yellowness) values did not differ (P>0.05) between injection treatments; however, injected steaks had lower L* values (darker) compared to controls. Control samples from bison SM were very lean and high in protein but not very tender. Marination by injection was able to significantly reduce shear force values of SM; that is, injected steaks/roasts had significantly (P<0.001) lower shear force values (63.9 N) compared to control samples (102.3 N). Cooking yields for the steaks/roasts from the injected sections were significantly (P<0.001) higher compared to those from control non-injected sections when cooked to either 71 or 77 °C. Bison samples cooked by moist-heat had significantly (P<0.001) lower cooking losses and shear force values compared to those cooked by dry-heat. As expected, steaks/roasts were more tender and had higher cooking yields when cooked to a medium level of doneness (71 °C) compared to an internal temperature of 77 °C (well done). A panel of 80 consumers preferred injected steaks cooked to 77 °C endpoint over other combinations, followed by non-injected steaks cooked to 71 °C, whereas injected steaks cooked to 71 °C and non-injected steaks cooked to 77 °C were equally but least preferred. Hence, injection seems to be protecting against moisture loss at high end-point cooking temperatures.

The influence of goat genotype on the production of Capretto and Chevon carcasses. 2. Meat quality.

The effect of five goat genotypes, Boer×Angora (BA), Boer×Saanen (BS), Feral×Feral (FF), Saanen x Angora (SA) and Saanen x Feral (SF) on the meat quality of Capretto and Chevon carcasses obtained from 50 buck kids, was assessed. Genotype had an influence on cooking loss and longissimus thoracis muscle colour coordinates (CIE L(*), a(*), b(*) values). BS kids from the Capretto group had paler muscle colour compared to other genotypes; pale muscle colour being required for Capretto carcasses. Total pigment concentration, fat colour, shear force values and sensory scores for flavour, tenderness, juiciness and overall acceptability did not differ significantly between genotypes. Muscle colour became darker and fat colour became more yellow with increasing animal age. Tenderness decreased with animal age as indicated by higher shear force values. Age had no significant influence on cooking loss and sensory scores.

The influence of goat genotype on the production of Capretto and Chevon carcasses. 1. Growth and carcass characteristics.

Fifty buck kids from five goat genotypes, Boer × Angora (BA), Boer × Saanen (BS), Feral × Feral (FF), Saanen × Angora (SA) and Saanen × Feral (SF) were compared for production of Capretto and Chevon carcasses. BS and SF kids had significantly better average daily gain compared to other genotypes and took less time to reach the required liveweight for Capretto and Chevon production. The development of visceral organs was not influenced by genotype. Kids from dairy breeds (SA in case of Capretto and SF in case of the Chevon group) deposited more internal fat in comparison to other genotypes. Dressing percentage (based on empty body weight) of kids ranged from 50-55%. At the same liveweight, dressing percentage and eye muscle dimensions did not vary between genotypes. However, BS and SF kids produced longer carcasses. Subcutaneous fat thickness was significantly greater in Chevon carcasses from BA compared to other genotypes. A high correlation was found between fat thickness measured by ultrasound on the live animal and ruler measurement on the carcass at the 12/13th rib position. Based on growth and carcass characteristics BS and SF kids performed better than kids from other genotypes used in the present study.

The influence of goat genotype on the production of Capretto and Chevon carcasses. 3. Dissected carcass composition.

The dissected composition from left sides of the carcasses obtained from 50 buck kids from five goat genotypes (10 kids/genotype), Boer x Angora (BA), Boer x Saanen (BS), Feral x Feral (FF), Saanen x Angora (SA) and Saanen x Feral (SF), was compared at two age groups. The muscle content of various primal cuts varied between 53 and 73% for Capretto and Chevon groups, with minor differences between genotypes. SA kids had significantly higher separable carcass fat compared to BS and SF for the Capretto group, while Chevon carcasses from BA and SF deposited more carcass fat than FF. The bone content (19-21%) of the carcass side did not differ significantly between genotypes for the Chevon group. The dissected carcass components (muscle, fat and bone) were significantly correlated with those components of most of the individual cuts. The percentage carcass muscle and fat increased and bone content decreased significantly with age.

The influence of goat genotype on the production of Capretto and Chevon carcasses. 4. Chemical composition of muscle and fatty acid profiles of adipose tissue.

The chemical composition of muscle and the fatty acid composition of adipose tissue from the carcasses obtained from 50 buck kids from five genotypes (10 kids/genotype), Boer x Angora (BA), Boer x Saanen (BS), Feral x Feral (FF), Saanen x Angora (SA) and Saanen x Feral (SF) reared for Capretto and Chevon production, were compared. Genotype did not influence the chemical composition of muscle except for muscle from BA carcasses, which had significantly higher extractable fat content. The proportions of individual fatty acids differed significantly between genotypes for the Capretto kids. Adipose tissue from the Capretto group had a higher concentration of palmitic acid (31-34%), while the proportion of oleic acid (37-40%) was greater in the Chevon group. With an increase in age and resultant change in diet, the saturated fatty acid concentration decreased and the unsaturated fatty acid concentration increased.

Loss of high-molecular-weight proteins in liver microsomes of rats treated with hepatocarcinogens.

Microsomal preparations from rats treated with 2-acetylaminofluorene (2-AAF) or with 4-dimethylaminoazobenzene (4-DAB), alone or followed by phenobarbital (PB), showed almost complete loss of microsomal proteins of molecular weights higher than 60,000, as shown by Sephadex G-150 gel filtration technique. Induction of a number of microsomal proteins in the lower ranges of molecular weights was also recorded due to the treatment of these two hepatocarcinogens with and without the use of PB as a promoter. These modifications in the protein patterns of microsomes might be due to altered genetic expression resulting in uncontrolled cell division/cell cycle.

Rapid detection of chemical carcinogens by measuring RNA released from microsomes in post-mitochondrial supernatant.

Incubation of carcinogens with post-mitochondrial supernatant (PMS) and NADPH releases ribosomes from microsomes resulting in increased RNA concentration in post-microsomal supernatant. However, non-carcinogens fail to do so. Enhanced concentration of RNA in test over control samples can provide a useful index for the carcinogenicity of environmental pollutants.