Novel double injection technique for sentinel lymph node biopsy in oral cancer.

The development of new lymphatic tracers and the advancement of hybrid tracers, such as indocyanine green (ICG)-Nanocoll (GE Healthcare), represent an exciting step in the future of sentinel lymph node biopsy (SLNB). These tracers aim to improve our ability to detect sentinel lymph nodes by enhancing their localisation. The aim of this study was to assess the performance of a novel dual tracer, double injection technique of ICG-'cold'-Nanocoll and radiolabelled Nanocoll, in SLNB for early-stage oral cancer. A double injection technique was performed first using 99mTc-Nancoll prior to sentinel node imaging followed by ICG-'cold'-Nanocoll injection in theatre. Analysis involved examination of the number, labelling, and location of the nodes harvested, sentinel node status, survival analysis, false negative rate, and complications associated with use of the technique. ICG 'cold' Nanocoll results showed concordance of fluorescence and radioactivity detection in 74 nodes in 24 patients. Most importantly, all nodes found positive for metastasis (6 nodes) were discovered to be both 'hot' and fluorescent; 74 nodes removed were both 'hot' and fluorescent, eight fluorescent only and six 'hot' only. Our results indicate that two sets of tracer injections given at two different time points will flow to the same sentinel nodes. This double labelling increased our confidence that the retrieved node was a sentinel node.

Neck failure following pathologically node-negative neck dissection (pN0) in oral squamous cell carcinoma: a systematic review and meta-analysis.

Due to the risk of occult cervical metastasis, elective neck dissection (END) is recommended in the management of patients with early oral cavity squamous cell carcinoma (OSCC) and a clinically node-negative (cN0) neck. This paper presents a systematic review and meta-analysis of studies that recorded isolated regional recurrence (RR) in the pathologically node-negative neck dissection (pN0) neck following END in order to quantify the failure rate. Pubmed and Ovid databases were systematically searched for relevant articles published between January 2009 and January 2019. Studies reporting RR following END in patients with OSCC who had no pathological evidence of lymph node metastasis were eligible for inclusion in this meta-analysis. In addition, a selection of large head and neck units were invited to submit unpublished data. Search criteria produced a list of 5448 papers, of which 18 studies met the inclusion criteria. Three institutions contributed unpublished data. This included a total of 4824 patients with median follow-up of 34 months (2.8 years). Eight datasets included patients staged T1-T4 with RR 17.3% (469/2711), 13 datasets included patients staged T1-T2 with RR 7.5% (158/2113). Overall across all 21 studies, isolated neck recurrence was identified in 627 cases giving a RR of 13.0% (627/4824) on meta-analysis. Understanding the therapeutic effectiveness of END provides context for evaluation of clinical management of the cN0 in these patients. A pathologically negative neck does not guarantee against future recurrence.

The impact of complex facial surgery provided on a short-term surgical mission.

The long-term consequences of performing facial surgery on patients living in rural Ethiopia are largely unknown. A review of 36 patients who had been treated on a short-term surgical mission (STSM) in the previous 2 years was conducted to evaluate the outcomes of the surgical interventions performed. There was a significant reduction in social isolation following a surgical intervention. Improvements in postoperative self-reported changes were found for facial appearance, facial function, and quality of life. Positive outcomes can be achieved when surgical treatment is performed on a STSM.

Long-term outcomes associated with short-term surgical missions treating complex head and neck disfigurement in Ethiopia: A retrospective cohort study.

BACKGROUND: Long-term follow-up after short-term reconstructive missions is challenging, often due to financial constraints, remote geography and lack of post-operative communication with patients. The aim of this study was to conduct long-term follow-up of patients who have undergone surgery for complex facial disfigurement in Ethiopia. METHODS: A retrospective cohort study was conducted in Ethiopia over a 2-week period between February and March 2017. All patients who were previously operated on by the charity Project Harar were eligible. Data were collected from semi-structured interviews and clinical examinations. RESULTS: Seventy patients (41 males: 29 females) were included in this study. This equates to a follow-up rate of 20% (70/350) of all patients operated on by the charity since 2008. Mean patient age was 26.8 years (range, 3-61 years). The most common pathologies were noma (24%), ameloblastoma (16%) and trauma (11%). The mean follow-up time after final surgery was 47 months (range, 12-180) with an average of 1.3 (range, 1-6) operations per patient. Long-term complications were reported by 30% of patients, with chronic fistula (n = 6) and chronic infection (n = 3) the most common. Following surgery, stigma experienced by patients decreased from 92% to 3%. CONCLUSIONS: This study demonstrates that complex head and neck reconstruction can be safely undertaken in resource-limited settings with improvements in stigma experienced and quality of life for patients. However, despite a decade of experience and refinements, early and late complications do occur, and this should be factored into pre-mission planning and careful follow-up. New, cost-neutral follow-up protocols are being developed.

Audit of minimally-invasive surgery for submandibular sialolithiasis.

Sialolithiasis is one of most common diseases to affect major salivary glands, with a symptomatic incidence of 27 cases per million per annum. The majority form within the submandibular gland where minimally-invasive treatments have all but eliminated adenectomy. All records of patients presenting with submandibular stones between 1997 and 2015 were reviewed. Stones <5mm were retrieved through endoscopic or radiographic techniques, 5-7mm stones were initially considered for extra-corporeal shock wave lithotripsy, but after poor results were treated through intraoral surgical removal with those >7mm. Follow up was performed at 1 week and 3 months with current status performed with postal and telephone questionnaires. 378 patients had 424 stones removed, successful retrieval in 94% (n=356), with 50 having had previous failures. Median number of stones per patient was 1 (range 1-4), with a mean size of 8.6mm (SD 4.5mm) mainly located at the hilum (50.5%), anterior duct (30%) and Genu (17%). 256 patients (65%) treated through intraoral surgical extraction, 92 (24%) endoscopic alone. Inpatient stay was 1.4 days in first third and 0.5 days in final third. Adenectomy occurred in 14 patients, due to failure to retrieve the sialolith or unresolved symptoms. Complications involved 11 patients with permanent paraesthesia, 7 ranulas and 14 strictures. Patients with preoperative strictures were more likely to develop complications (p=0.002) with paraesthesia being most common. Intraoral minimally-invasive surgery is aesthetic, curative and spares the risk to marginal mandibular nerve and submandibular gland. Length of inpatient stay improved and ranula risk reduced throughout the study.

Biopsy of the sentinel lymph node in oral squamous cell carcinoma: analysis of error in 100 consecutive cases.

UK national guidelines in 2016 recommended that sentinel lymph node biopsy should be offered to patients with early oral cancer (T1-T2 N0) in which the primary site can be reconstructed directly. This study describes the pitfalls that can be avoided in the technique of biopsy to improve outcomes. We retrospectively analysed the data from 100 consecutive patients and recorded any adverse events. Lymphatic drainage of tracer failed in two patients as a result of procedural errors. Two patients with invaded nodes developed recurrence after total neck dissection, one after micrometastases had been diagnosed, and the other as a result of extranodal spread that had led to understaging and therefore undertreatment. Two results would not have been mistakenly classified as clear if all the harvested nodes had been analysed histologically according to the protocol. The disease-specific (96%) and disease-free (92%) survival were better than expected for a group of whom a third had stage 3 disease. If all harvested nodes had been analysed by the correct protocol then two of the three nodes wrongly designated clear would have been detected, two deaths potentially avoided, and the false-negative rate would have fallen from 8.3% to 2.7%. We conclude that minor deviations from protocol can result in a detrimental outcome for the patient.

Sentinel lymph node biopsy for oral squamous cell carcinoma. Where are we now?

Recent data have confirmed that elective surgical management of the cN0 neck improves survival in patients with early (T1-T2) oral squamous cell carcinoma (SCC), and is better than watchful waiting. However, elective neck dissection (END) may not always be necessary. Sentinel node biopsy (SNB), which is a reliable staging test for patients with early disease and a radiologically N0 neck, can detect occult metastases with a sensitivity of 86%-94%. Patients with no sign of metastases on SNB could avoid neck dissection, and individual treatment should reduce both morbidity and cost. Currently, SNB for oral SCC is available at a limited number of centres in the UK, but this is likely to change as national guidelines have recommended that it is incorporated into the standard treatment pathway. It is therefore important to understand the current evidence that supports its use, its limitations and related controversies, and to plan for a validated training programme.

An exploratory, open-label, randomized, multicenter study to investigate the pharmacodynamics of a glycoengineered antibody (imgatuzumab) and cetuximab in patients with operable head and neck squamous cell carcinoma.

BACKGROUND: In addition to inhibiting epidermal growth factor receptor (EGFR) signaling, anti-EGFR antibodies of the IgG1 'subtype' can induce a complementary therapeutic effect through the induction of antibody-dependent cell-mediated cytotoxicity (ADCC). Glycoengineering of therapeutic antibodies increases the affinity for the Fc-gamma receptor, thereby enhancing ADCC. PATIENTS AND METHODS: We investigated the changes in immune effector cells and EGFR pathway biomarkers in 44 patients with operable, advanced stage head and neck squamous cell carcinoma treated with two preoperative doses of either glycoengineered imgatuzumab (GA201; 700 or 1400 mg) or cetuximab (standard dosing) in a neoadjuvant setting with paired pre- and post-treatment tumor biopsies. RESULTS: Significant antitumor activity was observed with both antibodies after just two infusions. Metabolic responses were seen in 23 (59.0%) patients overall. One imgatuzumab-treated patient (700 mg) achieved a 'pathological' complete response. An immediate and sustained decrease in peripheral natural killer cells was consistently observed with the first imgatuzumab infusion but not with cetuximab. The functionality of the remaining peripheral natural killer cells was maintained. Similarly, a pronounced increase in circulating cytokines was seen following the first infusion of imgatuzumab but not cetuximab. Overall, tumor-infiltrating CD3+ cell counts increased following treatment with both antibodies. A significant increase from baseline in CD3+/perforin+ cytotoxic T cells occurred only in the 700-mg imgatuzumab group (median 95% increase, P < 0.05). The most prominent decrease of EGFR-expressing cells was recorded after treatment with imgatuzumab (700 mg, -34.6%; 1400 mg, -41.8%). The post-treatment inflammatory tumor microenvironment was strongly related to baseline tumor-infiltrating immune cell density, and baseline levels of EGFR and pERK in tumor cells most strongly predicted therapeutic response. CONCLUSIONS: These pharmacodynamic observations and relationship with efficacy are consistent with the proposed mode of action of imgatuzumab combining efficient EGFR pathway inhibition with ADCC-related immune antitumor effects. CLINICAL TRIAL REGISTRATION NUMBER: NCT01046266 (ClinicalTrials.gov).

Sialendoscopy-assisted transfacial removal of parotid calculi.

Superficial parotidectomy has significant morbidity, and minimally invasive techniques have therefore been developed, including those involving sialendoscopy, to remove sialoliths and preserve the gland along with its function. The size, mobility and location of the sialolith, alongside the presence of strictures, all dictate management. We outline basic treatment paradigms and describe two sialoendoscopyassisted surgical procedures developed for treating stones, one intraoral and one extraoral.

The financial burden for the surgical management of osteoradionecrosis.

Osteoradionecrosis (ORN) remains a difficult clinical problem. In large refractory cases surgery appears to be the only option but it does not guarantee a cure and is expensive. Cost analysis of 31 patients who had resection with or without reconstruction of their mandible was £892,357. The largest cost was in-patient stay, which accounted for 62% of the total. This article explores in detail the expenditure associated with major ORN surgery and its subsequent implications.

Validating a benchmarking tool for audit of early outcomes after operations for head and neck cancer.

INTRODUCTION In 2013 all UK surgical specialties, with the exception of head and neck surgery, published outcome data adjusted for case mix for indicator operations. This paper reports a pilot study to validate a previously published risk adjustment score on patients from separate UK cancer centres. METHODS A case note audit was performed of 1,075 patients undergoing 1,218 operations for head and neck squamous cell carcinoma under general anaesthesia in 4 surgical centres. A logistic regression equation predicting for all complications, previously validated internally at sites A-C, was tested on a fourth external validation sample (site D, 172 operations) using receiver operating characteristic curves, Hosmer-Lemeshow goodness of fit analysis and Brier scores. RESULTS Thirty-day complication rates varied widely (34-51%) between the centres. The predictive score allowed imperfect risk adjustment (area under the curve: 0.70), with Hosmer-Lemeshow analysis suggesting good calibration. The Brier score changed from 0.19 for sites A-C to 0.23 when site D was also included, suggesting poor accuracy overall. CONCLUSIONS Marked differences in operative risk and patient case mix captured by the risk adjustment score do not explain all the differences in observed outcomes. Further investigation with different methods is recommended to improve modelling of risk. Morbidity is common, and usually has a major impact on patient recovery, ward occupancy, hospital finances and patient perception of quality of care. We hope comparative audit will highlight good performance and challenge underperformance where it exists.

Use of pentoxifylline and tocopherol in radiation-induced fibrosis and fibroatrophy.

Radiation-induced fibrosis in the head and neck is a well-established pathophysiological process after radiotherapy. Recently pentoxifylline and tocopherol have been proposed as treatments to combat the late complications of radiation-induced fibrosis and a way of dealing with osteoradionecrosis. They both have a long history in the management of radiation-induced fibrosis at other anatomical sites. In this paper we review their use in sites other than the head and neck to illustrate the potential benefit that they offer to our patients.

Management of Salivary Gland Tumours: United Kingdom National Multidisciplinary Guidelines.

This is the official guideline endorsed by the specialty associations involved in the care of head and neck cancer patients in the UK. Salivary gland tumours are rare and have very wide histological heterogeneity, thus making it difficult to generate high level evidence. This paper provides recommendations on the assessment and management of patients with cancer originating from the salivary glands in the head and neck. Recommendations • Ultrasound guided fine needle aspiration cytology is recommended for all salivary tumours and cytology should be reported by an expert histopathologist. (R) • Adjuvant radiotherapy (RT) following surgery is recommended for all malignant submandibular tumours except in cases of small, low-grade tumours that have been completely excised. (R) • For benign parotid tumours complete excision of the tumour should be performed and offers good cure rates. (R) • In the event of intra-operative tumour spillage, most cases need long-term follow-up for clinical observation only. These should be raised in the multidisciplinary team to discuss the merits of adjuvant RT. (G) • As a general principle, if the facial nerve function is normal pre-operatively then every attempt to preserve facial nerve function should be made during parotidectomy and if the facial nerve is divided intra-operatively then immediate microsurgical repair (with an interposition nerve graft if required) should be considered. (G) • Neck dissection is recommended in all cases of malignant parotid tumours except for low-grade small tumours. (R) • Where malignant parotid tumours lie in close proximity to the facial nerve there should be a low threshold for adjuvant RT. (G) • Adjuvant RT should be considered in high grade or large tumours or in cases where there is incomplete or close resection margin. (R) • Adjuvant RT should be prescribed on the basis of clinical factors in addition to histology and grade, e.g. stage, pre-operative facial weakness, positive margins, peri-neural invasion and extracapsular spread. (R).

Head and neck sarcomas: clinical and histopathological presentation, treatment modalities, and outcomes.

BACKGROUND: Sarcoma of the head and neck is a rare condition that poses significant challenges in management and often requires radical multimodality treatment. OBJECTIVES: This study aimed to analyse current clinical presentation, evaluation, management dilemmas and oncological outcomes. METHODS: Computer records and case notes were analysed, and 39 patients were identified. Variables were compared using Pearson's chi-square test and the log-rank test, while survival outcomes were calculated using the Kaplan-Meier method. RESULTS: The histopathological diagnosis was Kaposi sarcoma in 20.5 per cent of cases, chondrosarcoma in 15.3 per cent and osteosarcoma in 10.2 per cent. A range of other sarcomas were diagnosed in the remaining patients. The site of disease was most commonly sinonasal, followed by the oral cavity and larynx. CONCLUSION: Wide local excision with clear resection margins is essential to achieve local control and long-term survival. There is a need for cross-specialty collaboration in order to accrue the evidence which will be necessary to improve long-term outcomes.

A change in the NICE guidelines on antibiotic prophylaxis.

Since 2008, NICE clinical guidelines have stated: 'Antibiotic prophylaxis against infective endocarditis is not recommended for people undergoing dental procedures'. This put UK guidance at odds with guidance in the rest of the world, where antibiotic prophylaxis is recommended for patients at high-risk of infective endocarditis undergoing invasive dental procedures. Many dentists also felt this wording prohibited the use of antibiotic prophylaxis, regardless of the wishes of the patient or their personal risk of infective endocarditis and made it difficult for them to use their clinical judgment to deliver individualised care in the best interests of their patients. NICE have now changed this guidance to 'Antibiotic prophylaxis against infective endocarditis is not recommended routinely for people undergoing dental procedures.' This article examines the implications of this small but important change.

Evolution of the management of ranulas: change in a single surgeon's practice 2001-14.

Excision of the sublingual gland is the traditional cure for ranulas, but is invasive with considerable morbidity. We report techniques that have been developed to minimise this by targeting their specific pathophysiology, which include an intraoral approach to plunging ranulas, and gland-preserving selective excision with a highly conservative suture technique for simple ranulas. Fifty-four ranulas in 53 (20 male and 33 female, mean age 29 (range 7-57) years) consecutive patients were treated by a single surgeon between 2001-14 and their records reviewed retrospectively. Their personal details, operations, types of ranula, and outcomes were recorded. Follow up was for a minimum of six months without recurrent disease before discharge. Of the 54 ranulas treated, 26 had standard traditional sublingual gland excision (17 simple and 9 plunging), nine simple ranulas were selectively excised, 10 were treated with the new suture technique, and nine plunging ranulas were aspirated, after which they were ligated and the sublingual gland excised. Two of the 10 treated by the new suture technique had residual ranulas. The procedure was repeated in both cases, and one had a small residual ranula for which further intervention was declined. One complication developed after excision of a plunging ranula using the traditional intraoral and extraoral approaches, and two developed after aspiration of the sac, ligation, and excision of the gland. Traditional excision of simple ranulas was followed by three complications, but none were reported after simple ranulas had been treated with selective excision or suture. Minimally invasive techniques offer cure, with a lower risk of morbidity.