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Circular pharyngolaryngectomy for oncologic resection requires a tubular reconstruction. Different options can be proposed to the patient: digestive free flap, fasciocutaneous flap, or musculocutaneous flap. The jejunum free flap is a tubular flap commonly used in esophageal and pharyngeal reconstruction with good functional outcomes and an acceptable rate of complications. Reconstruction with a jejunum free flap is an ideal choice. Patients at Gustave Roussy Institute (Villejuif, France) were offered a jejunum flap free flap for all circular pharyngolaryngectomies. The surgical technique is explained with a step-by-step video. The jejunum flap free flap has many advantages in circular pharyngolaryngectomy. This video article explains surgical steps for other teams., (© 2024 The Author(s). Head & Neck published by Wiley Periodicals LLC.)

Background: One of the challenges after total pharyngolaryngectomy (TPL) is to restore the swallowing function. The aim of this study was to compare swallowing outcomes between patients who underwent reconstruction with jejunum free flap (JFF) and other free flaps (OFFs)., Methods: This retrospective study included patients who underwent TPL and free flap reconstruction. The endpoints were the evolution of swallowing outcomes during the first five years after treatment assessed by the Functional Oral Intake Scale (FOIS), and outcomes associated with complications., Results: One hundred and eleven patients were included, 84 patients in the JFF group and 27 in the OFF group. The patients in the OFF group experienced more chronic pharyngostoma (p = 0.001) and pharyngoesophageal stricture (p = 0.008). During the first year, a lower FOIS score tended to be associated with OFF (p = 0.137), and this result remained stable over time., Conclusions: This study suggests that JFF reconstruction provides better swallowing outcomes than OFF reconstruction, stable over time., Competing Interests: Declaration of Competing Interest No conflict of interest statements., (Copyright © 2023 British Association of Plastic, Reconstructive and Aesthetic Surgeons. Published by Elsevier Ltd. All rights reserved.)

Background: Many classifications exist to select patients with "high-risk" head and neck cutaneous squamous cell carcinoma (HNCSCC)., Objective: To compare the performance of the Brigham and Women's Hospital (BWH) classification with the performance of the American Joint Committee on Cancer 8th Edition (AJCC8), the Union for International Cancer Control 8th Edition (UICC8), and the National Comprehensive Cancer Network (NCCN) classifications., Methods: In this single-center retrospective study, HNCSCC resected in a tertiary care center were classified as "low-risk" or "high-risk" tumors according to the four classifications. Rates of local recurrence (LR), lymph node recurrence (NR), and disease-specific death (DSD) were collected. The performance of each classification was then calculated in terms of homogeneity, monotonicity, and discrimination and compared., Results: Two hundred and seventeen HNCSCC from 160 patients, with a mean age of 80 years, were included. For predicting the risk of any poor outcome and risk of NR, the BWH classification had the best specificity and positive predictive value. However, its concordance index was not significantly higher than that of the AJCC8 and UICC8 classifications. The NCCN classification was the least discriminant., Conclusions and Relevance: This study suggests that the BWH classification is the most appropriate for predicting the risk of poor outcomes in patients with HNCSCC when compared with the NCCN, UICC8, and AJCC8 classifications.

Objective: Indeterminate thyroid nodules (ITN) are common and often lead to (sometimes unnecessary) diagnostic surgery. We aimed to evaluate the performance of two machine learning methods (ML), based on routinely available features to predict the risk of malignancy (RM) of ITN., Design: Multi-centric diagnostic retrospective cohort study conducted between 2010 and 2020., Methods: Adult patients who underwent surgery for at least one Bethesda III-V thyroid nodule (TN) with fully available medical records were included. Of the 7917 records reviewed, eligibility criteria were met in 1288 patients with 1335 TN. Patients were divided into training (940 TN) and validation cohort (395 TN). The diagnostic performance of a multivariate logistic regression model (LR) and its nomogram, and a random forest model (RF) in predicting the nature and RM of a TN were evaluated. All available clinical, biological, ultrasound, and cytological data of the patients were collected and used to construct the two algorithms., Results: There were 253 (19%), 693 (52%), and 389 (29%) TN classified as Bethesda III, IV, and V, respectively, with an overall RM of 35%. Both cohorts were well-balanced for baseline characteristics. Both models were validated on the validation cohort, with performances in terms of specificity, sensitivity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve of 90%, 57.3%, 73.4%, 81.4%, 84% (CI95%: 78.5%-89.5%) for the LR model, and 87.6%, 54.7%, 68.1%, 80%, 82.6% (CI95%: 77.4%-87.9%) for the RF model, respectively., Conclusions: Our ML models performed well in predicting the nature of Bethesda III-V TN. In addition, our freely available online nomogram helped to refine the RM, identifying low-risk TN that may benefit from surveillance in up to a third of ITN, and thus may reduce the number of unnecessary surgeries., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of (ESE) European Society of Endocrinology.)

Macrophages from human and mouse skin share phenotypic and functional features, but remain to be characterized in pathological skin conditions. Skin-resident macrophages are known to derive from embryonic precursors or from adult hematopoiesis. In this report, we investigated the origins, phenotypes and functions of macrophage subsets in mouse and human skin and in cutaneous squamous cell carcinoma (cSCC) using the spectral flow cytometry technology that enables cell autofluorescence to be considered as a full-fledged parameter. Autofluorescence identifies macrophage subsets expressing the CD206 mannose receptor in human peri-tumoral skin and cSCC. In mouse, all AF + macrophages express the CD206 marker, a subset of which also displaying the TIM-4 marker. While TIM-4 - CD206 + AF + macrophages can differentiate from bone-marrow monocytes and infiltrate skin and tumor, TIM-4 identifies exclusively a skin-resident AF + macrophage subset that can derive from prenatal hematopoiesis which is absent in tumor core. In mouse and human, AF + macrophages from perilesional skin and cSCC are highly phagocytic cells contrary to their AF - counterpart, thus identifying autofluorescence as a bona fide marker for phagocytosis. Our data bring to light autofluorescence as a functional marker characterizing subsets of phagocytic macrophages in skin and cSCC. Autofluorescence can thus be considered as an attractive marker of function of macrophage subsets in pathological context., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bourdely, Petti, Khou, Meghraoui-Kheddar, Elaldi, Cazareth, Mossadegh-Keller, Boyer, Sieweke, Poissonnet, Sudaka, Braud and Anjuère.)

Introduction: Hypopharyngeal cancer (HC) is an aggressive and life-threatening malignancy that requires a complex multimodal treatment. The aims of the present study were to analyze, in locally advanced HC patients, the oncologic and swallowing outcomes and their predictive factors according to the therapeutic strategy., Methods: All patients with locally advanced HC (T3/T4, N0-3, M0) treated at our institution between 2000 and 2020 were included in this retrospective study. Patients were classified in 3 groups according to the therapeutic strategy: primary radical surgery (RS), induction chemotherapy (ICT) or definitive (chemo)-radiation therapy ((C)RT). Predictive factors of oncologic outcomes (overall, cause-specific and recurrence-free survival: OS, CSS and RFS) and swallowing outcome (dysphagia outcome and severity scale: DOSS) were investigated in univariate and multivariate analysis., Results: A total of 217 patients were included in this study (RS: 40; ICT: 106; (C)RT: 71). 5-year OS, CSS and RFS rates were 36, 38 and 32%, respectively. ICT was associated with improved oncologic and swallowing outcomes in univariate analysis. After multivariate analysis, patient age ≥ 70 years (p = 0.0002) was the only factor significantly associated with a worse OS, whereas patient age ≥ 70 years (p = 0.002) and N stage ≥ 2 (p = 0.01) were significantly associated with a worse CSS. Comorbidity level (KFI ≥ 2; p = 0.01) and N stage (≥ 2; p = 0.02) were significantly associated with worse swallowing outcomes., Conclusion: In selected locally advanced HC patients, an ICT-based therapeutic strategy offers acceptable oncologic and functional outcomes. Patient age, N stage and comorbidity level are the main determinants of oncologic and functional outcomes., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

The success of immune checkpoint therapy in cancer has changed our way of thinking, promoting the design of future cancer treatments that places the immune system at the center stage. The knowledge gained on immune regulation and tolerance helped the identification of promising new clinical immune targets. Among them, the lectin-like transcript 1 (LLT1) is the ligand of CD161 (NKR-P1A) receptor expressed on natural killer cells and T cells. LLT1/CD161 interaction modulates immune responses but the exact nature of the signals delivered is still partially resolved. Investigation on the role of LLT1/CD161 interaction has been hampered by the lack of functional homologues in animal models. Also, some studies have been misled by the use of non-specific reagents. Recent studies and meta-analyses of single cell data are bringing new insights into the function of LLT1 and CD161 in human pathology and notably in cancer. The advances made on the characterization of the tumor microenvironment prompt us to integrate LLT1/CD161 interaction into the equation. This review recapitulates the key findings on the expression profile of LLT1 and CD161, their regulation, the role of their interaction in cancer development, and the relevance of targeting LLT1/CD161 interaction., Competing Interests: CG is full-time employee of Biomunex Pharmaceuticals. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Braud, Meghraoui-Kheddar, Elaldi, Petti, Germain and Anjuère.)

NK cells and tissue-resident innate lymphoid cells (ILCs) are innate effectors found in the skin. To investigate their temporal dynamics and specific functions throughout the development of cutaneous squamous cell carcinoma (cSCC), we combined transcriptomic and immunophenotyping analyses in mouse and human cSCCs. We identified an infiltration of NK cells and ILC1s as well as the presence of a few ILC3s. Adoptive transfer of NK cells in NK cell‒ and ILC-deficient Nfil3 -/- mice revealed a role for NK cells in early control of cSCC. During tumor progression, we identified a population skewing with the infiltration of atypical ILC1 secreting inflammatory cytokines but reduced levels of IFN-γ at the papilloma stage. NK cells and ILC1s were functionally impaired, with reduced cytotoxicity and IFN-γ secretion associated with the downregulation of activating receptors. They also showed a high degree of heterogeneity in mouse and human cSCCs with the expression of several markers of exhaustion, including TIGIT on NK cells and PD-1 and TIM-3 on ILC1s. Our data show an enrichment in inflammatory ILC1 at the precancerous stage together with impaired antitumor functions in NK cells and ILC1 that could contribute to the development of cSCC and thus suggest that future immunotherapies should take both ILC populations into account., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: To assess patient needs and concerns after head and neck squamous cell carcinoma (HNSCC) treatment and their possible correlations with long-term quality of life (QoL) and to examine the potential impact of psychological distress on these results., Methods: Alive and disease-free HNSCC patients at least 1 year after treatment were enrolled in this cross-sectional multicentric study and completed the EORTC QLQ-C30 and H&N35 QoL questionnaires, the head and neck cancer-specific patient concerns inventory (PCI-HN) questionnaire and the hospital anxiety and depression scale (HADS). Correlations between QoL outcomes and patient needs and concerns were investigated using Spearman's correlation tests., Results: Seventy-two patients were enrolled in the study. Fear of cancer recurrence was the main patient concern followed by dental, salivary, fatigue, speech, and eating problems. The leading patient needs in terms of consultation were to be referred to the surgeon, the speech, and swallow therapist and the oral rehabilitation team. The number of patient concerns correlated negatively (r < .40) with functioning scales score and positively (r > .40) with general and head and neck symptoms. Psychological distress was the main determinant of QoL outcomes (p < .0001). We found a significant impact of gender (p = .002) on the number of patient concerns, and of patient age (p = .003) on the number of staff members selected by patients., Conclusion: Identification of patient needs and concerns along with multidisciplinary management of persistent symptoms and psychological distress seem essential steps towards improving QoL of HNSCC patients.

The integrative analysis of tumor immune microenvironment (TiME) components, their interactions and their microanatomical distribution is mandatory to better understand tumor progression. Imaging Mass Cytometry (IMC) is a high dimensional tissue imaging system which allows the comprehensive and multiparametric in situ exploration of tumor microenvironments at a single cell level. We describe here the design of a 39-antibody IMC panel for the staining of formalin-fixed paraffin-embedded human tumor sections. We also provide an optimized staining procedure and details of the experimental workflow. This panel deciphers the nature of immune cells, their functions and their interactions with tumor cells and cancer-associated fibroblasts as well as with other TiME structural components known to be associated with tumor progression like nerve fibers and tumor extracellular matrix proteins. This panel represents a valuable innovative and powerful tool for fundamental and clinical studies that could be used for the identification of prognostic biomarkers and mechanisms of resistance to current immunotherapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Elaldi, Hemon, Petti, Cosson, Desrues, Sudaka, Poissonnet, Van Obberghen-Schilling, Pers, Braud, Anjuère and Meghraoui-Kheddar.)

Introduction: The proportion of elderly patients with head and neck cancer is increasing. However, predictive factors of postoperative outcomes are insufficiently explored in this population. In this study, we aimed to determine predictive factors of postoperative outcomes in elderly patients undergoing head and neck free-flap reconstructive surgery in order to determine criteria on which patient selection could be based., Methods: All patients aged 65 years or over who underwent head and neck free-flap reconstructive surgery at our institution, between 2000 and 2016, were included in this retrospective study. Predictive factors of postoperative outcomes were investigated in uni- and multivariate analysis., Results: Two-hundred patients were included in the study. Older age (>70, >75 or > 80 yrs) had no significant impact on postoperative outcomes. Free flap failure local and general complications rates were 11%, 34% and 43%, respectively. Oromandibular reconstruction (p = 0.04) was significantly associated with free flap failure and salvage surgery (p = 0.04) with local complications. A high comorbidity level (Charlson Comorbidity Index score ≥ 4; p = 0.02) was associated with a higher risk of general complications. A G8 (Geriatric 8 questionnaire) score < 15 (p = 0.004), a high comorbidity level (Kaplan-Feinstein Index score ≥ 2; p = 0.04) and oromandibular reconstruction (p = 0.04) were associated with poor swallowing function at 6 months., Conclusion: Head and neck free flap reconstruction should be offered to fit (G8 score ≥ 15) elderly patients without severe comorbidities (KFI < 2 or CCI < 4), particularly when oral/pharyngeal soft-tissue reconstruction is planned., (Copyright © 2020 Elsevier Ltd. All rights reserved.)