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Objective: To assess whether narrow band imaging (NBI) detects fields of cancerisation around suspicious lesions in the upper aerodigestive tract, which were undetected by white light imaging (WLI). Methods: In 96 patients with laryngeal and pharyngeal lesions suspicious for malignancy, 206 biopsies were taken during laryngoscopy: 96 biopsies of suspicious lesions detected by both WLI and NBI (WLI+/NBI+), 60 biopsies adjacent mucosa only suspicious with NBI (WLI‐/NBI+), and 46 biopsies of NBI and WLI unsuspicious mucosa (WLI‐/NBI‐) as negative controls. Optical diagnosis according to the Ni‐classification was compared with histopathology. Results: Signs of (pre)malignancy were found in 88% of WLI+/NBI+ biopsies, 32% of WLI‐/NBI+ biopsies and 0% in WLI‐/NBI‐ (p <.001). In 58% of the WLI‐/NBI+ mucosa any form of dysplasia or carcinoma was detected. Conclusion: The use of additional NBI led to the detection of (pre)malignancy in 32% of the cases, that would have otherwise remained undetected with WLI alone. This highlights the potential of NBI as a valuable adjunct to WLI in the identification of suspicious lesions in the upper aerodigestive tract. [ABSTRACT FROM AUTHOR]

Background: Fibre-optic laryngoscopy is still widely used in daily clinical practice; however, high-definition laryngoscopy using narrow band imaging could be more reliable in characterising pharyngeal and laryngeal lesions. Methods: Endoscopic videos were assessed in a tertiary referral hospital by 12 observers with different levels of clinical experience. Thirty pairs of high-definition laryngoscopy with narrow band imaging and fibre-optic laryngoscopy videos were judged twice, with an interval of two to four weeks, in a random order. Inter- and intra-observer reliability, sensitivity and specificity were calculated in terms of detecting a malignant lesion and a specific histological entity, for beginners, trained observers and experts. Results: Using high-definition laryngoscopy with narrow band imaging, inter-observer reliability for detecting malignant lesions increased from moderate to substantial in trained observers and experts (high-definition laryngoscopy with narrow band imaging κ = 0.66 and κ = 0.77 vs fibre-optic laryngoscopy κ = 0.51 and κ = 0.56, for trained observers and experts respectively) and sensitivity increased by 16 per cent. Conclusion: Inter-observer reliability increased with the level of clinical experience, especially when using high-definition laryngoscopy with narrow band imaging. [ABSTRACT FROM AUTHOR]

Guidelines for cutaneous squamous cell carcinoma of the head and neck do not take the age of the patient into account, but instead assume equal tumour characteristics and prognostic factors for poor outcome in younger and elderly patients. The aim of this study was to compare tumour characteristics of younger (< 75 years) and elderly (≥ 75 years) patients and identify age-specific risk factors for progression of disease, comprising local recurrence, nodal metastasis and distant metastasis. Patient and tumour characteristics were compared using χ² or Fisher's exact tests. Multivariable competing risk analyses were performed to compare risk factors for progression of disease, incorporating the risk of dying before developing progression of disease. A total of 672 patients with primary cutaneous squamous cell carcinoma of the head and neck were retrospectively included. Larger tumour diameter, worse differentiation grade and deeper invasion were observed in older patients. In elderly patients, but not in younger patients, tumour diameter ≥ 40 mm, moderate differentiation grade and an invasion depth ≥ 2 mm were independent risk factors for progression of disease. [ABSTRACT FROM AUTHOR]

There are straightforward guidelines for treatment of keratinocyte carcinoma (formerly known as non-melanoma skin cancer); however, there are no clear recommendations specifically for elderly patients. The aim of this review was to provide an overview of the current literature about the effect of patient characteristics, specifically life expectancy, frailty and comorbidity, on treatment decisions in elderly patients with keratinocyte carcinoma, by searching PubMed database. It was found that the literature is limited and based mostly on small retrospective studies. Therefore, it is difficult to give firm recommendations about how to treat elderly people who have keratinocyte carcinoma. A "one-size-fits-all" approach to this population is not sufficient: life expectancy and frailty need to be considered in the decision-making process regarding treatment for elderly people with keratinocyte carcinoma. Among the comorbidity scores, Adult-Comorbidity-Evaluation-27-index seems to have the best prognostic value. Prospective studies are needed to generate more individualized recommendations for this increasing and often vulnerable group. [ABSTRACT FROM AUTHOR]

Background: The purpose of this study was to determine the additional diagnostic value of squamous cell carcinoma antigen (SCC‐Ag) in cervical lymph node fine needle aspiration (FNA) samples for the detection of regional metastases of head and neck squamous cell carcinoma (HNSCC). Methods: In 149 FNA samples of 114 patients, SCC‐Ag concentration was retrospectively analyzed and associated with diagnosis to establish a cutoff concentration in relation to sensitivity and specificity of HNSCC detection. Results: SCC‐Ag was elevated in lymph nodes from patients with HNSCC compared to lymph nodes from other patients (P < 0.01). With 0.3 μg/L as the cutoff concentration, SCC‐Ag has 96% sensitivity for detecting HNSCC. Conclusions: SCC‐Ag in FNA is a reliable test for detecting HNSCC in cervical lymph nodes. [ABSTRACT FROM AUTHOR]

Objectives: The primary goal was to study the diagnostic potential of narrow‐band imaging (NBI), and the secondary goal was to evaluate the most common mistakes when using and interpreting NBI. Design: Retrospective study. Setting: University Medical Center Groningen, tertiary referral hospital, the Netherlands. Participants: Three hundred and seventy patients who underwent rigid endoscopy of the upper aerodigestive tract. Two observers assessed all lesions. Twelve observers assessed a selection of 100 lesions. All observers were provided with both white light imaging and NBI. Main outcome measures: Sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), accuracy and reasons for insufficient photograph quality. Results: When using NBI, the sensitivity, specificity, PPV, NPV and accuracy for detecting invasive carcinoma, carcinoma in situ or high‐grade dysplasia were 92%, 68%, 61%, 94% and 77%, respectively. In multiple‐observer analysis, values were 76%, 58%, 53%, 83% and 65% with the evaluation strictly based on type V patterns of Ni's classification, vs 83%, 68%, 64%, 85% and 74% when evaluation was also based on lesion‐specific clinical characteristics. Lesions that caused misinterpretations were leukoplakia, papillomas and mucosal lesions after irradiation. In total, 185 photographs were assessed to be of suboptimal quality due to blurring (36%), bleeding (6%), insufficient zooming (15%) and/or insufficient lighting (17%). Conclusion: NBI is a relatively reliable screening method for detecting malignancy. Evaluation based on Ni's classification alone is not sufficient. To optimise NBI photograph quality, we recommend sufficient zooming and prevention of bleeding, blurring and inadequate lighting. [ABSTRACT FROM AUTHOR]

The cover image is based on the Original Article Detection of high‐grade dysplasia, carcinoma in situ and squamous cell carcinoma in the upper aerodigestive tract: Recommendations for optimal use and interpretation of narrow‐band imaging, by Manon A. Zwakenberg et al., https://doi.org/10.1111/coa.13229. [ABSTRACT FROM AUTHOR]

Purpose: Diagnostic endoscopy with biopsy under general anesthesia (DE-GA) is still considered as the established standard to assess laryngopharyngeal cancer patients. Office-based flexible laryngoscopic biopsy (FLB) offers an alternative, but the effect on oncological outcome remains uncertain. Therefore, the diagnostic process and survival of patients undergoing FLB, compared to those undergoing DE-GA were evaluated., Methods: Patients suspected of laryngopharyngeal cancer who underwent FLB were evaluated. Patients with FLB-confirmed squamous cell carcinoma (SCC) were matched with DE-GA patients based on tumor site, T-classification, N-classification, age, and p16 overexpression. Time from first visit to diagnosis (FVD), time to treatment interval (TTI), disease-specific survival (DSS) and overall survival (OS) were analyzed., Results: FLB yielded a definitive diagnosis in 155/164 (95 %) patients. No complications were observed. Ninety-eight of the 124 patients in which FLB revealed a SCC received curative treatment and were compared with 98 matched patients who underwent DE-GA. Median FVD interval was 6 days after FLB and 15 days after DE-GA (p < 0.001). Median TTI interval (FLB: 28 days, DE-GA: 28 days) was equal (p = 0.91). Oncological outcomes were comparable (p > 0.05) between FLB (OS: 2-yr: 76 %, 5-yr: 42 %; DSS: 2-yr: 86 %, 5-yr: 85 %) and DE-GA groups (OS: 2-yr: 76 %, 5-yr: 50 %; DSS: 2-yr: 81 %, 5-yr: 79 %)., Conclusion: FLB in the outpatient setting demonstrates a high diagnostic accuracy, is safe, accelerates the diagnostic process and has no negative effects on clinical outcome compared to DE-GA. Therefore, FLB should be considered as the standard diagnostic procedure in patients suspected of laryngopharyngeal cancer., Competing Interests: Declaration of competing interest Boudewijn E. C. Plaat had a consultancy role for Olympus Medical Systems EU. Boudewijn E.C. Plaat and Jeroen M. Westra report an unrestricted grant from Olympus EU (Research funding including contracted research where the institution receives and manages the funds) and part of this Olympus EU grant was used for this study. Bert van der Vegt reports honoraria received by UMCG for expertise or scientific advisory board/consultancy (on request): Visiopharm, Philips, MSD/Merck, Daiichi-Sankyo/AstraZeneca; Speaker's fee from Visiopharm, Diaceutics, MSD/Merck. All unrelated to this publication. The other authors have no other funding, financial relationships, or conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate glycoprotein nonmetastatic melanoma protein B (GPNMB) and vascular endothelial growth factor (VEGF) as potential fluorescent imaging markers by comparing their protein expression to epidermal growth factor receptor (EGFR)., Materials and Methods: Thirty-eight paired samples of untreated head and neck squamous cell carcinoma (HNSCC) primary tumours (PT) and corresponding synchronous lymph node metastases (LNM) were selected. After immunohistochemical staining, expression was assessed and compared by the percentage of positive tumour cells. Data were analysed using the Mann-Whitney test, effect sizes (ESr) and Spearman's correlation coefficient (r)., Results: GPNMB expression was observed in 100 % of PT, and median 80 % (range 5-100 %) of tumour cells, VEGF in 92 % and 60 % (0-100 %), EGFR in 87 % and 60 % (0-100 %) respectively. In corresponding LNM, GPNMB expression was observed in 100 % of LNM and median 90 % (20-100 %) of tumour cells, VEGF in 87 % and 65 % (0-100 %), and EGFR in 84 % and 35 % (0-100 %). A positive correlation was found between expression in PT and LNM for GPNMB (r = 0.548) and EGFR (r = 0.618) (p < 0.001), but not for VEGF (r = -0.020; p = 0.905). GPNMB expression was present in a higher percentage of tumour cells compared to EGFR in PT (p = 0.015, ESr = -0.320) and in LNM (p < 0.001, ESr = -0.478), while VEGF was not (p = 1.00, ESr = -0.109 and - 0.152, respectively)., Conclusion: GPNMB expression is higher than EGFR in untreated HNSCC PT and corresponding LNM, while VEGF expression is comparable to EGFR. GPNMB is a promising target for fluorescent imaging in HNSCC., Competing Interests: Declaration of competing interest Boudewijn E.C. Plaat has a consultancy role for and has received unrestricted research grants from Olympus Medical Systems EU. Bert van der Vegt reports honoraria received by UMCG for expertise or scientific advisory board/consultancy (on request): Visiopharm, Philips, MSD/Merck, Daiichi-Sankyo/AstraZeneca; Speaker's fee from Visiopharm, Diaceutics, MSD/Merck. All unrelated to this publication. Sjoukje F. Oosting reports research grants from Novartis (2009), Pfizer (2011) and Celldex Therapeutics (2015); a speakers fee from Merck, and consultancy fees from Genmab, Merck, and Bristol Myers Squibb (all paid to the institution). The other authors have no other funding, financial relationships, or conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Intraoperative fluorescence imaging (FI) of head and neck squamous cell carcinoma (HNSCC) is performed to identify tumour-positive surgical margins, currently using epidermal growth factor receptor (EGFR) as imaging target. EGFR, not exclusively present in HNSCC, may result in non-specific tracer accumulation in normal tissues. We aimed to identify new potential HNSCC FI targets., Materials and Methods: Publicly available transcriptomic data were collected, and a biostatistical method (Transcriptional Adaptation to Copy Number Alterations (TACNA)-profiling) was applied. TACNA-profiling captures downstream effects of CNAs on mRNA levels, which may translate to protein-level overexpression. Overexpressed genes were identified by comparing HNSCC versus healthy oral mucosa. Potential targets, selected based on overexpression and plasma membrane expression, were immunohistochemically stained. Expression was compared to EGFR on paired biopsies of HNSCC, adjacent macroscopically suspicious mucosa, and healthy mucosa., Results: TACNA-profiling was applied on 111 healthy oral mucosa and 410 HNSCC samples, comparing expression levels of 19,635 genes. The newly identified targets were glucose transporter-1 (GLUT-1), placental cadherin (P-cadherin), monocarboxylate transporter-1 (MCT-1), and neural/glial antigen-2 (NG2), and were evaluated by IHC on samples of 31 patients. GLUT-1 was expressed in 100 % (median; range: 60-100 %) of tumour cells, P-cadherin in 100 % (50-100 %), EGFR in 70 % (0-100 %), MCT-1 in 30 % (0-100 %), and NG2 in 10 % (0-70 %). GLUT-1 and P-cadherin showed higher expression than EGFR (p < 0.001 and p = 0.015)., Conclusions: The immunohistochemical confirmation of TACNA-profiling results showed significantly higher GLUT-1 and P-cadherin expression than EGFR, warranting further investigation as HNSCC FI targets., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Boudewijn E.C. Plaat has a consultancy role for and has received unrestricted research grants from Olympus Medical Systems EU. Bert van der Vegt reports honoraria received by UMCG for expertise or scientific advisory board/consultancy (on request): Visiopharm, Philips, MSD/Merck, Daiichi-Sankyo/AstraZeneca; Speaker’s fee from Visiopharm, Diaceutics, MSD/Merck. All unrelated to this publication. Sjoukje F. Oosting reports research grants from Novartis (2009), Pfizer (2011) and Celldex Therapeutics (2015); a speakers fee from Merck, and consultancy fees from Genmab, Merck, and Bristol Myers Squibb (all paid to the institution). The other authors have no other funding, financial relationships, or conflicts of interest to disclose., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: Assessing whether the additional use of narrow-band imaging (NBI) in transoral laser surgery (TOLS) for early laryngeal cancer improves clinical outcomes., Study Design: Randomized controlled trial, performed between September 2015 and November 2022., Setting: A tertiary referral hospital in The Netherlands., Methods: TOLS was carried out in 113 patients. The procedure was performed with white light imaging (WLI, n = 56) alone, or combined with NBI (n = 57). Patients received frequent follow-up laryngoscopy. Resection margin status, recurrence rate, and recurrence-free survival at 12 months, 18 months, and after study termination (maximum 86 months) were analyzed., Results: Thirty-one cases in the WLI group had a positive resection margin, versus 16 in the NBI group (p = .002). After 12 months, the recurrence-free survival was 92%: 87% for WLI versus 96% for NBI, p = .07. The recurrence rate was 7/56 (13%) for WLI, versus 2/57 (4%) for NBI, p = .09. After 18 months, the recurrence-free survival was 84% for WLI versus 96% for NBI, p = .02. The recurrence rate was 9/56 (16%) for WLI, versus 2/57 (4%) for NBI, p = .02. After study termination, the recurrence-free survival was 71% for WLI versus 83% for the NBI group (p = .08). The recurrence rate was 16/56 for WLI, versus 10/57 for NBI (p = .16)., Conclusion: The additional use of NBI during TOLS significantly decreased the number of positive resection margins. Although not statistically significant at all time points, patients treated with NBI-supported TOLS showed a lower recurrence rate and better recurrence-free survival. Further studies in larger patient groups are needed to confirm these results., (© 2023 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Objective: To determine the diagnostic value of measuring squamous cell carcinoma antigen (SCC-Ag) and cancer antigen 15-3 (CA15-3) concentrations in fine-needle aspiration (FNA) samples for the detection of squamous cell carcinoma (SCC) metastases in cervical lymph nodes., Study Design: A prospective study with patients consecutively included between November 2018 and May 2021., Setting: A tertiary head and neck oncologic center., Methods: Out of 138 patients, SCC-Ag concentrations were analyzed in 168 FNA cervical lymph node samples and CA15-3 in 152 samples. Results were compared with FNA cytology (FNAC) or definitive histology to establish sensitivity and specificity rates., Results: For the detection of cervical SCC lymph node metastases, SCC-Ag measurement had an 89.4% sensitivity and 79.3% specificity at a cutoff concentration of 0.1 µg/L. Measurement of CA15-3 concentration in addition to SCC-Ag concentration did not lead to improved accuracy for the detection of SCC. In histology-confirmed cases, FNAC had an 80.0% sensitivity and 100% specificity, as opposed to 93.3% and 57.1%, respectively, for SCC-Ag., Conclusion: Measurement of SCC-Ag concentration for detection of SCC lymph node metastases has a sensitivity at least comparable to FNAC and could be used as a relatively cheap screening tool in samples with nondiagnostic or indeterminate FNAC results or when multiple lymph nodes are sampled. However, SCC-Ag in FNA samples has a lower specificity than FNAC assessed by pathologists experienced in head and neck oncology. Addition of CA15-3 measurement did not lead to improved accuracy., (© 2022 The Authors. Otolaryngology-Head and Neck Surgery published by Wiley Periodicals LLC on behalf of American Academy of Otolaryngology-Head and Neck Surgery Foundation.)

Background: Cutaneous squamous cell carcinoma is the second most common malignancy of the skin, often occurring in older patients and in the head and neck area (cSCCHN). Age, life expectancy, and frailty are not taken into consideration by current guidelines., Objectives: The objective of this study was to evaluate the influence of frailty and life expectancy on guideline deviation, treatment outcomes, and quality of life (QoL) after treatment in patients with cSCCHN., Methods: Patients with cSCCHN were prospectively included. A geriatric assessment was performed, including the Geriatric 8 (G8), Groningen Frailty Indicator, and Timed Up and Go test (TUG). The Lee index was used to predict a limited life expectancy, and the Adult Comorbidity Evaluation-27 was used as a comorbidity index. QoL was assessed by the Basal and Squamous cell carcinoma Quality of Life (BaSQoL) questionnaire at three time points., Results: Seventy-seven patients with cSCCHN were included. Frail patients had significantly more high-risk tumours. Guideline deviation occurred in 7.8% and was more common in patients who were frail (G8), with high-risk tumours (≥T2), with a limited life expectancy or an increased TUG. Guideline deviation did not lead more often to progression of disease in our study. No predictors for post-operative complications were found. BaSQoL subscores were very low at each time point and did not change significantly with time in the total group. Frail patients reported more fear of recurrence or new tumours 3 months after treatment, and less concern about other people's skin 6 months after treatment, compared to non-frail patients. Complication rate, gender, or guideline deviation did not affect any subscale scores., Conclusions: Assessment of frailty and life expectancy can guide physicians and patients in treatment decisions. Deviation from guidelines towards less aggressive treatment schedules can be considered in frail patients with a limited life expectancy, since it did not negatively affect short-term outcomes or QoL in patients with cSCCHN in our study. However, these results should be confirmed by other, larger prospective studies with a longer follow-up period., (© 2022 The Author(s). Published by S. Karger AG, Basel.)