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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.

​INTRODUCTION: Large periocular defects have always been a reconstructive challenge in terms of viability, cosmesis and functionality. Their vicinity with important anatomical structures makes reconstruction difficult to plan and the surgeon should take into account several alternatives. AIM: Our aim is the presentation of techniques performed on our department patients. Four intendedly different cases treated with respective flaps are documented preoperatively, postoperatively and in the follow-up period. MATERIAL – METHODS: 4 Patients (2 male and 2 female) with cutaneous malignancies concerning: the inner canthal ligament area (1), the nasal flank and lower eyelid (1) and the lower tarsal plate (2). 1 inferiorly based advancement nasolabial flap, 2 Mustardé flaps and 1 Tenzel flap were performed. The mean age of the patients was 85,75 y.o. (range from 77 to 96). RESULTS: All four patients had disease-free margins of excision and no recurrence at all. We avoided composite approaches with concern to their age and general condition. No complications were mentioned (including necrosis of the flap, wound dehiscence or infection). The esthetic result is judged fair (1 patient), good (1 patient), very good (2 patients). In the follow-up period, one patient presented mild epiphora and another mild corneal exposure. One patient being planned to undergo a differed correction postponed his treatment. CONCLUSION: Meticulously designed traditional flaps such as V-Y advancement flap, Mustardé flap and Tenzel flap can offer an acceptable outcome balanced between functionality and cosmetic result on the one hand and lessening complications on the other.

INTRODUCTION: Elderly patients with advanced head and neck cancer undergoing major surgery are at high risk due to their co-morbidities and prolonged procedures. Thus, they often require admission in the ICU. PURPOSE: We herein describe the perioperative management of elderly patients, with significant comorbidities, surgically treated for stage II-IV head and neck cancer with a specialized anesthesia protocol in the COVID-19 era. MATERIAL - METHOD: In total, 11 consecutive patients (4 female, 7 male, mean age 74 years, ASA III-IV), with advanced cancer involving oral mucosa, salivary glands and metastatic skin cancer were treated in UHL between 3/2021 and 3/2022. Operation duration varied from 5 to 13 hours, as the extent of disease necessitated extirpation and reconstruction with free or regional flaps in most cases. Hence, an individualized and patient-centered approach was implemented, with the preanesthetic evaluation, the utilization of both an enhanced recovery (ERAS), specialized anesthesia protocol and the prompt postoperative care delivered by the anesthesia team. . RESULT: No intraoperative adverse events were reported. Admissions in ICU were obviated. One patient underwent neck exploration for bleeding control being treated with therapeutic doses of LMWH (grade IIIb Clavien-Dindo). One more patient required blood transfusion (grade II Clavien-Dindo). Donor site wound breakdown was recorded in 4 patients (grade IIIa Clavien-Dindo). Hospital length ranged from 5 to 14 days. 30-day mortality was 0%. CONCLUSION: Good rapport between involved teams along with the implementation of an individualized perioperative approach of this patient cohort resulted in an uneventful outcome amid the COVID-19 pandemic.

Keypoints: • The presence of a pharyngeal mucosal space abscesses (PMA), being confined between the pharyngeal mucosa and the pharyngeal constrictor muscle, is considered rare. However, in our series represented 14,3% of deep neck infections (DNIs), suggesting that they may not be so rare as they are considered to be. • PMAs’ symptoms and clinical findings are similar to those of other DNIs, but trismus and neck swelling seem to be significant lower in PMAs. • Imaging studies will set PMA diagnosis, while CT with contrast is the modality of choice. • PMAs seems to be less dangerous than their deep-seated counterparts, since its superficial location renders them amenable to spontaneous drainage, aspiration, incision and drainage intraorally obviating spread to deeper structures.

Introduction Skin grafting onto the ear has its challenges, loss of the skin results in inadequate vascular bed for the graft leading to decreased uptake 1,2. As a result, advancement flaps or sacrifice of the underlying cartilage allows primary closure with compromised aesthetics. A two staged procedure however leads to acceptable scarring, can be performed under local anaesthetic, is quick and easy enabling transfer of skin to acutely exposed cartilage. The authors demonstrate a two staged reconstruction technique of the superior helix after traumatic degloving of the dermal tissues. Method Under local anaesthetic an incision in line with the most inferior extent of the skin loss is made. A subdermal plane is expanded superiorly, and the exposed auricular cartilage inserted, healing of the adjacent margins occurs and enables later skin transfer. The patient was discharged on oral antibiotics and returns at two weeks to have the pedicle divided in an outpatient setting. A further skin incision superior to the extent of the tip of the helix is performed. This skin flap is then thinned and folded to reconstruct the posterior aspect of the ear. The skin is sutured in place and the patient is sent home on oral antibiotics. A further reviewed in two weeks to check healing is advised and the patient was subsequently discharged. Conclusions In conclusion, this is demonstrated to be a useful technique to add to the Oral and Maxillofacial Surgeons armament for reconstruction of the superior helix when iatrogenic or traumatic loss of skin coverage occurs.

Many studies have evaluated the clinical implications of lymph node ratio (LNR) as a prognostic factor in patients with oral squamous cell carcinoma (OSCC). The main purpose of this systematic review and meta-analysis was to address LNR as a prognosticator in patients with OSCC. A systematic search was conducted in the following databases: PubMed, EMBASE, Google Scholar, OpenGrey, Cochrane library, and ClinicalTrials.gov, and studies between 2009 and 2020 were sought. The pooled relative risk was calculated along with 95% confidence intervals for the following endpoints: overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), distant metastasis-free survival (DMFS), locoregional disease-free survival (LRDFS), local recurrence-free survival (LRFS), and recurrence-free survival (RFS) according to the random-effects model (Der Simonian–Laird approach). Subgroup and meta-regression analyses were performed as well. Finally, 32 cohort studies were eligible, which included 20,994 patients with OSCC. Patients were subdivided into two categories, group YES (studies that included in their analysis only patients with positive lymph nodes) and group NO (studies that did not exclude LNR = 0 patients). In the group YES, patients with high LNR had shorter OS (RR = 1.68, 95% CI: 1.47–1.91), DFS (RR = 1.68, 95% CI: 1.42–1.99), DSS (RR = 1.94, 95% CI: 1.56–2.42), DMFS (RR = 1.83, 95% CI: 1.13–2.96), LRDFS (RR = 1.55, 95% CI: 1.10–2.20), and LRFS (RR = 1.73, 95% CI: 1.41–2.13) compared to patients with low LNR. In the group NO, patients with high LNR in comparison had shorter OS (RR = 2.38, 95% CI: 1.99–2.85), DFS (RR = 2.04, 95% CI: 1.48–2.81), and DSS (RR = 2.90, 95% CI: 2.35–3.57) compared to patients with low LNR. Based on those findings, LNR might be an independent prognostic factor for OS in patients with OSCC and could be incorporated into future classification systems for better risk stratification.

Background: Tipifarnib is a highly selective farnesyltransferase inhibitor that has shown promising activity in HRAS mutant recurrent/metastatic HNSCC. The incidence of HRAS mutations in HNSCC is 4-10%. Since HRAS mutated HNSCC can be successfully targeted with Tipifarnib, we sought to analyze the immune and genomic landscape of these tumors to guide combinatorial strategies. Methods: We identified thirteen patients with HRAS mutant tumors. We included in the analysis 50 patients with HRAS wild-type tumors. Genomic DNA from baseline biopsies of tumors was purified and subjected to targeted sequencing (TruSightTM Oncology 500 panel). PD-L1 expression in formalin-fixed tumor samples was assessed using the PD-L1 IHC 22C3 pharmDx assay (Agilent Technologies, Carpinteria, CA, USA) and characterized by the combined positive score (CPS). Assessment of PD-L1+ cells inside and at the periphery of the tumor was performed. HRAS mutational status was correlated with PD-L1 status. The genomic data derived from the targeted gene panel of HRAS mutant tumors were compared to those with wild-type HRAS. Results: Thirty-seven patients had both genomic and PD-L1 expression data available. The presence of HRAS mutations was associated with higher TPS PD-L1 scores (26% vs 40% vs 100% in TPS 50% respectively, p=0.043). Similar results were obtained for CPS (28% vs 80% in CPS 10%, p=0.047). HRAS mutations were more commonly found with TP53 mutations (16% in WT TP53 and 55.6% in mutated TP53, p=0.073). Higher PD-L1 TPS showed increased survival without reaching significance when measuring either in the margins (64.1 vs 35.8, p=0.066) or the center of the tumor (p=0.097) due to the small sample size. Conclusions: HRAS mutant HNSCC are associated with high PD-L1 expression and co-occurrence of p53 mutations. Combinations of tipifarnib with an anti-PD1 antibody, an anti-PDL1 antibody, or an anti-CTLA-4 antibody warrant clinical investigation in this rare subset of HNSCC. Citation Format: Amanda Psyrri, Miriam Anastasiou, Aris Spathis, Stergios Doumas, Panagiota Economopoulou, Ioannis Kotsantis, Anastasios Pantazopoulos, Anastasios Kyriazoglou, George Kavourakis, Theodoros Rampias, Periklis Foukas. Translating genotype to immunophenotype in HRAS mutated head and neck squamous cell carcinoma (HNSCC) to identify effective Tipifarnib partners for optimal patient outcomes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3882.

Objectives We aimed to audit current United Kingdom (UK) practice of Head and Neck Cancer (HNC) post-treatment surveillance against national guidelines, and determine the outcomes of these practices in detecting recurrence. Design National cross-sectional study of current HNC surveillance practice. Setting UK HNC outpatient departments. Participants HNC patients reviewed for post-treatment surveillance. Main outcome measures Compliance with UK multidisciplinary guidelines, and rates of cancer recurrence detection by time, clinic type and symptoms. Results Data were analysed from 5,123 consultations across 89 UK centres. 30% of consultations were in dedicated multidisciplinary clinics, with input from Allied Health Professionals (AHPs) available on the day in 23% of all consultations. Recurrence was suspected in 344 consultations and investigated with MRI in 29.6% (n=102) and PET-CT in 14.2% (n=49). Patient education regarding recurrence symptoms, and smoking and alcohol advice, was provided in 20.4%, 6.2%, and 5.3% of cases, respectively. Rates of recurrence detected were 35% in expedited appointments and 5.2% in planned follow-ups (p=0.0001). Of the expedited appointments, 63% were initiated by patients and 37% by clinicians. Recurrence was higher in those with new symptoms (7.1% versus 2.2%). The strongest predictors of recurrence were dyspnoea (positive predictive value (PPV)=16.2%), neck pain (PPV=10.4%) and mouth/throat pain (PPV=9.2%). Conclusions Dedicated multidisciplinary clinics comprise a minority of consultations for HNC surveillance in the UK, with low availability of AHPs. PET-CT and MRI were underutilised for the investigation of suspected recurrence. There may be scope for greater emphasis on patient education and consequent patient-initiated symptom driven follow-up.

Background To determine, from October 2010 to October 2018, the epidemiology of Deep Neck Infections (DNIs), regarding the detection, the identification and the susceptibility to antimicrobials of causative microorganisms, in Thessaly-Central Greece. Methods An analysis of data from a prospective database was conducted on 610 consecutive patients with DNIs treated in the Otolaryngology / Head & Neck Surgery Department of University Hospital of Larissa. Demographics, clinical features and microbiological data were analyzed. Results Among the 610 patients (1,9/1 male to female ratio, mean age: 39,24 ± 17,25) with DNIs, 579 had a single space (94,9%), while the remaining 31 had a multi-space (5,1%) DNI. The most common areas affected were the peritonsillar space (84,6%) followed by the submandibular space (6,5%). Clinical samples were obtained from 462 patients, and were tested by culture and by the application of 16S rRNA PCR. Two hundred fifty-five samples (55,2%) gave positive cultures, in which Streptococcus pyogenes and Staphylococcus aureus were predominant. The application of the 16S rRNA PCR revealed that 183 samples (39,6%) were positive for bacterial DNA; 22 of them, culture negative, were found to be positive for anaerobic (Fusobacterium necrophorum, Actinomyces israellii etc) and for fastidious microorganisms (Brucella mellitensis, Mycobacterium avium). Conclusion DNIs represent a medical and surgical emergency and evidence-guided empirical treatment with intravenous infusion of antibiotics at the time of diagnosis is mandatory, highlighting the importance of epidemiological studies regarding the causative microorganisms. Although, in our study, the predominant pathogens were S. pyogenes and S. aureus, the combination of culture and molecular assay revealed that anaerobic bacteria play also a significant role in the pathogenesis of DNIs. Based on the local epidemiology, we propose as empirical therapy the intravenous use of a beta-lactam /beta-lactamase inhibitor; metronidazole or clindamycin can be added only in specific cases such as in immunocompromised patients.

Preclinical data suggest that head and neck squamous cell carcinoma (HNSCC) is a profoundly immunosuppressive disease, characterized by abnormal secretion of proinflammatory cytokines and dysfunction of immune effector cells. Based on landmark phase III trials, two anti-Programmed Cell Death-1 (PD-1) antibodies, pembrolizumab and nivolumab have been approved for HNSCC by FDA and EMEA in the recurrent/metastatic setting; in addition, pembrolizumab has recently received FDA and EMEA approval as first line treatment. In clinical practice, only a minority of patients with HNSCC derive benefit from immunotherapy and the need for the discovery of novel biomarkers to optimize treatment strategies is becoming increasingly more relevant. Although currently only PD-L1 is widely used as a predictive biomarker for response to immune checkpoint inhibitors in HNSCC, there are many ongoing trials focusing on the identification of new biomarkers. This review will summarize current data on emerging biomarkers for response to immunotherapy in HNSCC.

The discovery and implementation into everyday clinical practice of immune checkpoint inhibitors (ICIs) has marked a therapeutic renaissance in the treatment of advanced solid tumors. In head and neck cancer, nivolumab and pembrolizumab have both been approved for recurrent/metastatic disease based on robust clinical activity observed in landmark phase III clinical trials. Despite tremendous improvements in overall survival, patterns of response and progression to ICIs may be distinct from those traditionally described with classical chemotherapy or molecularly targeted therapies. In this context, pseudoprogression is observed in patients treated with ICIs that show response after a transient increase in tumor burden and hyperprogression is described as rapid radiological or clinical progression after immunotherapy. Most importantly, the assessment of radiological response in patients receiving ICIs needs to be differentiated. In this review, we aim to describe radiologic criteria for immune response evaluation and illustrate the newly reported concepts of atypical patterns of response to ICIs.

The management of enlarged retropharyngeal lymph nodes (RLN) in patients with confirmed oral, oropharyngeal, or nasopharyngeal squamous cell carcinoma (SCC) has prognostic relevance and is a challenge for the clinical teams. There is, however, no consensus regarding their clinical management or radiographic evaluation. The aim of this review therefore was to present the current thinking on management to help improve outcomes. We searched several online databases using the key terms "retropharyngeal node", "oral cancer", "head and neck cancer", "oropharyngeal cancer", "nasopharyngeal cancer", "nasopharynx", "oral cavity", "oropharynx", "TORS", and "radiotherapy". A total of 1024 papers were screened, of which 32 were eligible. There was no consensus about the management of RLN. There is a lack of randomised studies and a lack of consistency in the presentation of results. Management should be tailored in patients with nasopharyngeal carcinoma (NPC), and prophylactic irradiation is warranted as these nodes are at high risk of metastasis. In patients with non-NPC tumours, we prefer to resect them during primary operations when there is radiological uncertainty or evidence that they are affected, as the combination of radiological and histological outcomes will further our understanding. In both NPC and non-NPC tumours, sampling may also help to standardise the radiological criteria for the diagnosis of RLN by contrast-enhanced computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET) CT.

Cryoglobulins are immunoglobulins that precipitate in vitro at temperatures

Non-Hodgkin lymphoma (NHL) accounts for less than 1% of all head and neck malignancies, although this anatomic location is the second most common extranodal site for NHL, lagging behind only the GI tract. Specifically, in the sinonasal tract, NHL is a common neoplasm, while its overall incidence ranges from 0.2% to 2% of all lymphoma cases in the Western world. Among paranasal sinuses, the maxillary sinus is the most common site of involvement, followed by the ethmoid, sphenoid and the frontal sinus. Men are predominantly affected and there is a prevalence of middle to older ages. The most common subtype is diffuse large B-cell lymphoma (DLBCL), comprising approximately two thirds of cases [1].

Impetigo is the most common skin infection in children. The face, especially the perioral region, is one of the most frequently involved areas. Impetigo is a disease that interests the pediatric dentist, as it poses significant problems in its differential diagnosis from other conditions. Sixteen otherwise healthy children were examined suffering from facial and perioral impetigo. The typical clinical appearance was scattered, painless, slightly pruritic erosions covered by "honey-colored" crusts. In 4 children impetigo was localized in the facial and perioral area, whereas in all other cases lesions were diffused in perioral area and several regions throughout the body. Four children exhibited neck lymphadenopathy and one had mild fever. The treatment of impetigo included the application of topical measures with the systemic antibiotic chemotherapy.

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.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.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.Neither fractalkine nor fractalkine receptor is a reliable surrogate marker of PNI in lingual SCC.

The coexistence of different types of malignancy in cervical lymph nodes has been reported previously. We report the first case, to the best of our knowledge, of concurrent metastatic adenoid cystic carcinoma and squamous cell carcinoma (SCC) in cervical lymph nodes. A primary SCC developed three decades after treatment for adenoid cystic carcinoma of the palate, and the synchronous metastases became clinically apparent the following year. The aetiology of the SCC may have been related to radiotherapy or smoking. Whether the adenoid cystic carcinoma would have remained dormant, or was reactivated after perturbation of host defence mechanisms, is not known.

Ampullary carcinoma is the second most common cancer of the peri-ampullary area after pancreatic carcinoma and metastasizes mostly intra-abdominally and to the liver. Extra-abdominal metastases are less frequent. In this report we describe the case of a patient with resected adenocarcinoma of the ampulla of Vater who developed skeletal metastases in the lower extremity and brain metastases. We briefly discuss aspects of this comparatively rare gastrointestinal malignancy.

Human cytomegalovirus is a ubiquitous pathogen with protean clinical manifestations. After initial infection, the virus remains in a persistent state in the host. Immunity plays a pivotal role in counteracting its virulence, albeit intermittent virus shedding occurs in immunocompetent individuals. Should deficiencies in immunity occur, e.g., as a consequence of AIDS or iatrogenic immunosuppression, then virus replication and subsequent pathogenic manifestations ensue. In the oral and maxillo-facial region, the virus causes a wide variety of diseases, mainly atypical chronic ulcerations and sialadenitis. These morbidities are rarely reported and sometimes cause significant problems for clinicians.

Human secretory leukocyte protease inhibitor (SLPI) is an 11.7-kDa cationic protein and a member of the innate immunity-associated proteins. It is a nonglycosylated, highly basic, acid-stable, cysteine-rich, 107-amino acid, single-chain polypeptide ([50][1]). The SLPI gene, along with the elafin