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.

Challenges and outcomes in establishing a sentinel lymph node biopsy service for oral squamous cell carcinoma in a regional district specialist hospital.

UK national guidelines in 2016 recommended that sentinel lymph node biopsy (SLNB) should be offered to patients with early oral squamous cell carcinoma (OSCC). We review the establishment of an OSCC SLNB service with specific consideration to resources, service implications and patient outcomes. A review of processes was performed to identify key stages in establishing the service, and subsequently a retrospective cohort study consisting of 46 consecutive patients with T1/T2 N0 OSCC was undertaken. The key stages identified were: coordinating a nuclear medicine pathway and reliable cost-appropriate pathology service, constructing a Trust business case, and gaining approval of a new interventional service policy. A median (range) of 3.3 (1-8) sentinel nodes (SLN) were removed, with 17 patients having a positive SLN. The negative predictive value of SLNB was 100%, with 12 having a SLN outside the field if elective neck dissection (END) was planned. There was a significantly increased risk of a positive SLN with increasing depth of invasion (DOI) (p=0.007) and increased diameter (p=0.036). We also identified a longer-than-ideal time to completion neck dissection and inadequate ultrasound follow up of negative SLNB patients. Establishment of a service requires careful planning. Our results were in keeping with those reported in the literature, and showed that SLNB for OSCC has a high negative predictive value and can identify at-risk SLN outside the traditional END levels, even in well-lateralised tumours. Our findings show that DOI and size of SLN were significantly associated with a positive SLN, and also identified areas requiring improvement.

Vismodegib for periocular basal cell carcinoma: an international multicentre case series.

INTRODUCTION: Vismodegib (Erivedge, Genentech) is a first-in-class inhibitor of the hedgehog (Hh) pathway, which is licensed for use in locally advanced basal cell carcinoma (BCC) and metastatic BCC. The National Institute for Health and Care Excellence withdrew recommendation for use of vismodegib secondary to a lack of data comparing vismodegib to standard supportive care. The purpose of this multicentre, international case series is to report outcomes of patients with locally advanced periocular BCC who have been treated with vismodegib. METHODS: The medical records of all patients treated with vismodegib were retrospectively reviewed across seven institutions in the United Kingdom, Australia, and New Zealand. RESULTS: Thirteen patients were identified. Seven (54%) patients were male. All BCCs were ill-defined, with seven (58%) having orbital involvement at presentation. Median treatment time was 7 months (range 2-36 months). Eleven out of 13 patients developed side effects, the most common being fatigue in six patients (46%). Median follow-up was 24 months (range 12-48 months). Complete response was found in 5/13 patients (38%) and a partial response in 8/13 patients (62%). Six patients had further surgery after vismodegib, with three classed as globe-sparing operations. Three patients developed recurrence (23%). Three patients (23%) ultimately underwent exenteration. DISCUSSION: This study demonstrates vismodegib to be a well-tolerated treatment which may, in some cases, facilitate globe-sparing surgery and hence avoid disfiguring operations such as exenteration. Uncertainty does remain regarding the long-term outcomes of patients treated with vismodegib.

Immediate compared with late repair of extracranial branches of the facial nerve: a comparative study.

The best outcomes after injury to the facial nerve are seen after immediate direct coaptation, but in practice, this happens infrequently. We ask whether late repair (between 3 weeks and 18 months) is comparable to immediate repair. In this prospective observational study over a two-year period (2016-18), we identified 18 patients (11 male and 7 female, mean (range) age 58 (23-94) years), who had sustained extracranial injuries to the facial nerve. Eight were identified in the acute phase (within 72hours of injury) and repaired (immediate repair group). Ten presented in the late phase beyond six months (late repair group), and had direct coaptation, neurolysis, nerve transfer, or non-vascularised or vascularised nerve grafts. Patients were followed up clinically with photographic or video analysis every three months using the Sunnybrook facial grading scale and Terzis scores as quantitative tools. In the immediate repair group six patients had direct nerve coaptations, one had a free vascularised nerve graft, and one a fascicular nerve flap. In the late repair group six patients had coaptations, two had nerve transfers, one had neurolysis, and one nerve transfer and a free vascularised nerve graft. The null hypothesis that there was no difference between immediate and late repair of the facial nerve in terms of clinical improvement was accepted. The overall facial grading scale between the two groups showed no significant difference (mean 97 compared with 87; 95% CI: -25.61 to 5.32; p=0.18). However, the individual volitional facial grading score for the affected division showed that immediate repair fared significantly better than late repair (mean 4.55 compared with 3.14; 95% CI: -2.5 to -0.3; p=0.027). Supermicrosurgical techniques, together with advanced systems for nerve identification allow for coaptation of the maximum number of injured nerve branches. These factors accounted for a 97% mean return of function after immediate repair and an 87% recovery in the late repair group. While quantitatively, immediate repair is best, the re-establishment of nerve-muscle continuity before degeneration of the motor endplate confers the best possible physiological outcome, and is far superior to any of the techniques used to treat chronic facial paralysis.

Fragments of drains retained during operations on the temporomandibular joint.

Drains are robust and reports of breakages and retained fragments are rare. There is no consensus about the management of such cases and we know of no reported cases. We present the case of an 18-year-old man with a retained drain fragment after repair of an open condyle.

Verruciform Xanthoma of the Oral Mucosa: A Series of Eight Typical and Three Anomalous Cases.

In this series, there are 8 typical verruciform xanthomas of the oral mucosa and 3 anomalies, 1 polypoid, 1 florid, and 1 carcinomatous. All were characterized by infiltrates of CD68-positive xanthomatous histiocytes in the lamina propria. The 11 patients comprised 6 men and 5 women (mean age = 54.5 years, range = 40-69). Both keratinized and nonkeratinized sites were affected. A history of lichenoid inflammation was recorded in 5 patients. The polypoid xanthoma presented in a woman aged 54 years as a polyp of the labial commissure. The florid lesion affected the dorsum of the tongue of a man aged 54 years and at 20 mm was the largest of the 11 lesions, but the only one with candidal infection. The squamous cell carcinoma manifested as a papilloverrucous hyperkeratosis of the palatal gingiva in a man aged 69 years. The latter 2 (and 1 "typical" verruciform xanthoma) required re-excision, but none has since recurred.

Implications of changing trekker demographics on travel health in the Annapurna region.

OBJECTIVE: The objective is to investigate trekkers' changing demographics, travel patterns and experience of illness in the Annapurna region. STUDY DESIGN: A mixed method study comprising a cross-sectional survey was carried out with trekkers who had completed trekking in the Annapurna region. METHODS: Interviews were carried out with trekkers using a standardised questionnaire from September to December (main trekking season) 2014 and 2016. The interview format included trekkers' demographic characteristics, travel patterns, preparation and logistics and experiences of illness and treatment. RESULTS: The demographic composition of trekkers had changed. Chinese and Nepalese trekkers were the most dominant groups along with other international trekkers from 16 different countries. In terms of the trekking pattern, the Chinese and the Nepalese trekkers spent a median of 7 days each in the trek and trekked to a median altitude of 3500 m, while other international trekkers spent a median of 10 days and trekked to a median altitude of 4000 m. In general, trekkers' food habits and travel patterns were good. They undertook some health preparation by using the Internet, consulting friends and travel guidebooks and consulting a doctor, pharmacist and other healthcare providers and brought medicines accordingly. However, 25% of trekkers, most commonly Chinese, Korean and Nepalese, came without any health preparation and with no medicines. Thirty percent of the trekkers became sick during the trek with common illnesses such as diarrhoea, vomiting, the common cold, headache, fever and altitude-related symptoms. CONCLUSIONS: Trekkers' demographic composition has changed from that found in previous studies, and this was reflected in their trekking pattern. Trekkers' health preparations for high-altitude trekking were still inadequate, especially among the newer groups such as the Nepalese, Chinese and Korean trekkers. Issues such as trekkers' health preparation and practice, eating patterns, the length of trek and altitude and health and safety provision need further improvement, especially in the context of these changing trekker demographics.

A new method for the recovery and evidential comparison of footwear impressions using 3D structured light scanning.

Footwear impressions are one of the most common forms of evidence to be found at a crime scene, and can potentially offer the investigator a wealth of intelligence. Our aim is to highlight a new and improved technique for the recovery of footwear impressions, using three-dimensional structured light scanning. Results from this preliminary study demonstrate that this new approach is non-destructive, safe to use and is fast, reliable and accurate. Further, since this is a digital method, there is also the option of digital comparison between items of footwear and footwear impressions, and an increased ability to share recovered footwear impressions between forensic staff thus speeding up the investigation.

Staging of squamous cell carcinoma of the tongue: extrinsic lingual muscles and the 8th editions of the American Joint Committee on Cancer/Union for International Cancer Control staging manuals.

Our aim was to find out first whether the extrinsic muscles of the tongue are histologically identifiable, and secondly to what degree the use of the new criteria in the 8th editions of the American Joint Committee on Cancer(AJCC)/Union for International Cancer Control (UICC) manuals (which have recognised the importance of depth of invasion of tumour, rather than invasion of the extrinsic muscles of the tongue and extranodal extension), will alter staging of lingual squamous cell carcinoma (SCC). The histological sections from 165 patients who had had primary resection of lingual SCC were reviewed, and one or more extrinsic muscles of the tongue was identified in 100 patients (61%), with the genioglossus seen the most often (in 96). By contrast, the hyoglossus was identified in only eight patients, the styloglossus in two, and the palatoglossus in none. Identification was straightforward only in extensive resections. Applying the criteria from the 8th edition increased the number of pT3 SCC with a simultaneous reduction in pT4a tumours. The number of pN2b SCC was also reduced, but the new category of pN3b meant that overall 53% of tumours were upstaged. The kappa scores for agreement between the two sets of criteria were 0.221 (weighted 0.410) for the pT values, 0.508 (0.713) for pN values (but 0.227, weighted 0.386, if the pN0 values were removed before calculation), and 0.243 (0.514) for overall stage, indicating poor to fair agreement. We conclude that the removal of invasion of extrinsic muscles of the tongue as a criterion for a pT4a SCC is justified, and that many SCC of the tongue will be upstaged as a result of implementation of the 8th editions.

Inflammatory pseudotumour of the maxilla.

Inflammatory pseudotumour (IP), also known as inflammatory myofibroblastic tumour (IMT), is a rare lesion of the maxillofacial skeleton and a diagnosis by exclusion. We describe three cases which affected the maxilla, two women and one man of ages 67, 56 and 70 years at presentation. All showed the typical, rather non-specific histopathological features. IgG4-positive plasma cells varied greatly in prominence, and none of the three lesions expressed ALK-1. Both women responded to steroids and radiotherapy, though one also required azathioprine. Despite maxillectomy, radiotherapy, steroids and cyclophosphamide, the man suffered intracranial spread and succumbed to persistent disease. The cases described here demonstrate the clinicopathological difficulties presented by this entity and its aggressive, unpredictable behaviour.

Manufacturing method affects mitochondrial DNA release and extracellular vesicle composition in stored red blood cells.

BACKGROUND AND OBJECTIVES: Damage-associated molecular patterns (DAMPs) are found in transfusion products, but their potential impacts are not fully understood. We examined the influence of manufacturing method on levels of mitochondrial (mt) DNA and extracellular vesicle (EV) DAMPs in red cell concentrates (RCCs). MATERIALS AND METHODS: Eighty-seven RCCs were prepared using nine different methods (6-15 units/method), including three apheresis, five whole blood (WB)-derived leucoreduced (LR) and one WB-derived non-LR method. On storage days 5 and 42, levels of mtDNA (by PCR) and number and cell of origin of EVs (by flow cytometry) were assessed in RCC supernatants. RESULTS: There was a 100-fold difference in mtDNA levels among methods, with highest levels in non-LR, followed by MCS+ and Trima apheresis RCCs. There was a 10-fold difference in EV levels among methods. RBC-derived CD235a+ EVs were found in fresh RCCs and increased in most during storage. Platelet-derived CD41a+ EVs were highest in non-LR and Trima RCCs and did not change during storage. WBC-derived EVs were low in most RCCs; CD14+ EVs increased in several RCCs during storage. CONCLUSION: DAMPs in RCCs vary by manufacturing method. MtDNA and EV could be informative quality markers that may be relevant to RCC immunomodulatory potential.

The effect of processing method on the in vitro characteristics of red blood cell products.

BACKGROUND AND OBJECTIVES: While the clinical impact of differences in red blood cell (RBC) component processing methods is unknown, there are concerns they may be confounding variables in studies such as the ongoing 'age of blood' investigations. Here, we compare the in vitro characteristics of red cell concentrates (RCCs) produced by several different processing methods. MATERIALS AND METHODS: Nine processing methods were examined: three apheresis methods (Alyx, MCS+ and Trima), as well as leucoreduced whole blood-derived RCCs produced by buffy coat and whole blood filtration and non-leucoreduced RCCs. RCCs were stored in saline-adenine-glucose-mannitol or additive solutions (AS) 1 or 3 for 42 days, with quality tested on day 5 and day 42. RESULTS: Many significant product differences were observed both early in and at the end of storage. Mean haemoglobin (Hb) ranged from 52 to 71 g/unit and mean Hct from 59·5 to 64·8%. Most RCC passed regulated quality control criteria according to Canadian Standards Association guidelines, although there were some failures relating to Hb content and residual WBC counts. CONCLUSION: Processing method impacts RCC characteristics throughout storage; better understanding of these differences and reporting of processing method details is critical.

Fractalkine (CX3CL1) and fractalkine receptor (CX3CR1) in squamous cell carcinoma of the tongue: markers of nerve invasion?

PURPOSE: Perineural invasion (PNI) in oral squamous cell carcinoma (SCC) is an independent predictor of poor prognosis. As PNI is not always identified with routine histology, a surrogate marker of PNI would improve detection and better inform treatment planning. The chemokines fractalkine (CX3CL1) and its receptor (CX3CR1) have shown such potential in other cancers, but have yet to be investigated with respect to PNI in oral SCC. METHODS: Thirty SCCs of the tongue in which PNI was identified histologically, and 30 in which it was not, were stained for fractalkine and fractalkine receptor using polyclonal antibodies and an immunoperoxidase technique. Tumours were assessed as either positive or negative; no attempt was made to subjectively assess staining intensity or extent. RESULTS: Both markers labelled myofibroblasts in the stroma surrounding the tumour, various neural components, leucocytes, endothelium and salivary myoepithelial cells. Fractalkine also labelled salivary ductal epithelium, vascular smooth muscle and 12/30 SCC which showed PNI. Eight of 30 positive SCCs in which PNI was not identified were also positive for this marker. There was no statistically significant association between fractalkine staining and PNI (p = 0.273). No SCC was positive for fractalkine receptor, but immune dendritic cells within tumour islands were strongly positive, as was striated muscle. CONCLUSIONS: Neither fractalkine nor fractalkine receptor is a reliable surrogate marker of PNI in lingual SCC.

Isolation of bacterial strains able to metabolize lignin from screening of environmental samples.

AIMS: To develop a method to detect bacteria from environmental samples that are able to metabolize lignin. METHODS AND RESULTS: A previously developed UV-vis assay method for lignin degradation activity has been developed for use as a spray assay on agar plates. Nine mesophilic strains were isolated using this method from woodland soil incubated in enrichment cultures containing wheat straw lignocellulose: four Microbacterium isolates, two Micrococcus isolates, Rhodococcus erythropolis (all Actinobacteria) and two Ochrobactrum isolates (Alphaproteobacteria). Three thermotolerant isolates were isolated from the same screening method applied at 45°C to samples of composted wheat straw from solid-state fermentation: Thermobifida fusca and two isolates related to uncharacterized species of Rhizobiales and Sphingobacterium (Bacteroidetes), the latter strain showing tenfold higher lignin degradation activity than other isolates. The isolated strains were able to depolymerize samples of size-fractionated high molecular weight and low molecular weight Kraft lignin, and produced low molecular weight metabolites oxalic acid and protocatechuic acid from incubations containing wheat straw lignocellulose. CONCLUSIONS: A new method for the isolation of bacteria able to metabolize lignin has been developed, which has been used to identify 12 bacterial isolates from environmental sources. The majority of isolates cluster into the Actinobacteria and the Alphaproteobacteria. SIGNIFICANCE AND IMPACT OF THE STUDY: Lignin-degrading bacterial strains could be used to convert lignin-containing feedstocks into renewable chemicals and to identify new bacterial lignin-degrading enzymes.

Health-seeking behaviour in Pakistan: a narrative review of the existing literature.

INTRODUCTION: This narrative review was carried out to collate the work of researchers on health-seeking behaviour in Pakistan, to discuss the methods used, highlight the emerging themes and identify areas that have yet to be studied. STUDY DESIGN: Review. METHODS: An overview of studies on health-seeking behaviour in Pakistan, found via searches on scholarly databases intended to locate material of medical and anthropological relevance. RESULTS: In total, 29 articles were reviewed with a range of different methodologies. A retrospective approach was the most common. A variety of medical conditions have been studied in terms of health-seeking behaviour of people experiencing such conditions. However, a wide range of chronic illnesses have yet to be studied. Nevertheless, some studies highlighting unusual issues such as snake bites and health-seeking behaviour of street children were also found. In terms of geographical area, the majority of studies reviewed were performed in the provinces of Sind and Punjab, with little research targeting the people from the two other provinces (Balochistan and Khyber Pakhtunkhwa) of Pakistan. Predominant utilization of private healthcare facilities, self-medication, involvement of traditional healers in the healthcare system, women's autonomy, and superstitions and fallacies associated with health-seeking behaviour were found to be the themes that repeatedly emerged in the literature reviewed. CONCLUSIONS: The sociocultural and religious background of Pakistan means that health-seeking behaviour resembles a mosaic. There is a need to improve the quality of service provided by the public healthcare sector and the recruitment of female staff. Traditional healers should be trained and integrated into the mainstream to provide adequate healthcare. Serious efforts are required to increase the awareness and educational level of the public, especially women in rural areas, in order to fight against myths and superstitions associated with health-seeking behaviour.

Formation of compartments in the neck to facilitate suction drainage during transfer of free flaps.

A method of surgical compartmentalisation of the neck is reported. This technique can be used in order to maintain suction drainage without compromising the flow of the anastomoses when an end-to-side technique in the internal jugular vein is used.

Photopatch testing of 1155 patients: results of the U.K. multicentre photopatch study group.

BACKGROUND: Photoallergic contact dermatitis can be difficult to diagnose if not appropriately investigated. Currently, the most common U.K. photoallergens appear to be sunscreen chemicals. The investigation of choice is photopatch testing (PPT), which is probably underused. In part, this is due to differences in methodology and results interpretation. OBJECTIVES: To conduct PPT using a group of sunscreen chemicals, defined indications and a standardized methodology including interpretation and relevance of reactions in patients attending for investigation at 17 centres across the U.K., Ireland and the Netherlands. METHODS: Patients (n = 1155) who fulfilled the inclusion criteria were investigated with PPT using sunscreen chemicals in addition to suspected topical products. Readings were taken at 24, 48 and 72 h following standardized ultraviolet A irradiation (5 J cm(-2)). The clinical relevance of any reaction was recorded. RESULTS: Of the 1155, 130 had allergic reactions (11.3%). Of these, 51 had photoallergy (PA) (4.4%), 64 had contact allergy (CA) (5.5%), and 15 patients had combined PA and CA (1.3%). Multiple PA was seen in some. The most common photoallergen was benzophenone-3 (27 reactions; 21%). Most reactions (60%) were clinically relevant. The most common indication for testing in patients found to have PA was a history of reacting to a sunscreen (41%). The other 59% had an exposed-site dermatitis/skin problem or a photodermatosis. Some centres (n = 8) performed readings after the standard 48-h reading, and an extra 32 PA and 22 CA reactions were detected, which were not evident at 48 h. A new photoallergen (octyl triazone) was detected in two patients. CONCLUSIONS: Sunscreen PA and CA are probably equally uncommon. Most reactions, of both reaction types, were relevant clinically. A large proportion of patients (59%) found to have PA was unaware of reacting to a sunscreen chemical, suggesting that PA should be considered as an explanation in any exposed-site dermatitis. Although this study focused on reactions at 48 h postirradiation, readings performed up to 96 h, while inconvenient, add value by detecting additional relevant responses. A previously unknown photoallergen was found, highlighting the need for awareness of novel photoallergens in the marketplace. A standardized PPT method not only encourages more use of this investigation, but also facilitates comparison of results between centres and so will improve our understanding of PA.