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•Macrophages are frequently reported in the microenvironment of head and neck cancers.•Macrophages may harbor two phenotypes: antitumoral M1 or protumoral M2.•Macrophages in head and ...neck cancers have been associated with a poor prognosis.•Different strategies are developed toward macrophages as a therapeutic target.•Macrophages modulators are investigated alone or in combination with standard Therapies.
The microenvironment of solid tumors has become a promising target for future therapies modulating immune cells. Patients with advanced head and neck cancer, which still portends a poor outcome, are particularly in need of innovative approaches. In oral squamous cell carcinoma, high density of tumor-associated macrophages (TAMs) appears consistently associated with poor prognosis, whereas data are currently limited for other head and neck sites. Several approaches to block TAMs have been investigated, including TAMs inactivation by means of the colony stimulating factor 1 (CSF-1)/CSF-1 receptor (CSF-1R) inhibitors or strategies to reprogram TAMs from M2 protumoral phenotype toward M1 antitumoral phenotype. This review focuses on both prognostic and therapeutic aspects related to TAMs in head and neck carcinomas.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Tracheostomy has been proposed as an option to help organize the healthcare system to face the unprecedented number of patients hospitalized for a COVID-19-related acute respiratory distress syndrome ...(ARDS) in intensive care units (ICU). It is, however, considered a particularly high-risk procedure for contamination. This paper aims to provide our experience in performing tracheostomies on COVID-19 critically ill patients during the pandemic and its long-term local complications.
We performed a retrospective analysis of prospectively collected data of patients tracheostomized for a COVID-19-related ARDS in two university hospitals in the Paris region between January 27th (date of first COVID-19 admission) and May 18th, 2020 (date of last tracheostomy performed). We focused on tracheostomy technique (percutaneous versus surgical), timing (early versus late) and late complications.
Forty-eight tracheostomies were performed with an equal division between surgical and percutaneous techniques. There was no difference in patients' characteristics between surgical and percutaneous groups. Tracheostomy was performed after a median of 17 12-22 days of mechanical ventilation (MV), with 10 patients in the "early" group (≤ day 10) and 38 patients in the "late" group (> day 10). Survivors required MV for a median of 32 22-41 days and were ultimately decannulated with a median of 21 15-34 days spent on cannula. Patients in the early group had shorter ICU and hospital stays (respectively 15 12-19 versus 35 25-47 days; p = 0.002, and 21 16-28 versus 54 35-72 days; p = 0.002) and spent less time on MV (respectively 17 14-20 and 35 27-43 days; p<0.001). Interestingly, patients in the percutaneous group had shorter hospital and rehabilitation center stays (respectively 44 34-81 versus 92 61-118 days; p = 0.012, and 24 11-38 versus 45 22-71 days; p = 0.045). Of the 30 (67%) patients examined by a head and neck surgeon, 17 (57%) had complications with unilateral laryngeal palsy (n = 5) being the most prevalent.
Tracheostomy seems to be a safe procedure that could help ICU organization by delegating work to a separate team and favoring patient turnover by allowing faster transfer to step-down units. Following guidelines alone was found sufficient to prevent the risk of aerosolization and contamination of healthcare professionals.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Mammalian target of rapamycin (mTOR) regulates cellular functions by integrating intracellular signals and signals from the tumor microenvironment (TME). The PI3K-AKT-mTOR pathway is activated in 70% ...of head and neck squamous cell carcinoma (HNSCC) and associated with poor prognosis. This phase I-II study investigated the effect of mTOR inhibition using weekly everolimus (30 mg for dose level 1, 50 mg for dose level 2) combined with weekly induction chemotherapy (AUC2 carboplatin and 60 mg/m2 paclitaxel) in treatment-naïve patients with locally advanced T3-4/N0-3 HNSCC. Patients received 9 weekly cycles before chemoradiotherapy. Objectives were safety and antitumor activity along with tissue and blood molecular biomarkers. A total of 50 patients were enrolled. Among 41 evaluable patients treated at the recommended dose of 50 mg everolimus weekly, tolerance was good and overall response rate was 75.6%, including 20 major responses (≥50% reduction in tumor size). A significant decrease in expression of p-S6K (p-value: 0.007) and Ki67 (p-value: 0.01) was observed in post-treatment tumor tissue. Pro-immunogenic cytokine release (Th1 cytokines IFN-γ, IL-2, and TNF-β) was observed in the peripheral blood. The combination of everolimus and chemotherapy in HNSCC was safe and achieved major tumor responses. This strategy favorably impacts the TME and might be combined with immunotherapeutic agents.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Previous studies have demonstrated that human papillomaviruses (HPVs) of the beta genus can contribute to the onset of cutaneous carcinomas in organ transplant recipients. In contrast, there are ...limited data related to the oncogenicity of alpha (α)-HPVs in the skin. Herein, we explore the characteristics of three cutaneous squamous cell carcinomas presenting α-HPV infection occurring in patients with HIV, in order to determine the role of α-HPV in these skin cancers.
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BFBNIB, FZAB, GIS, IJS, KILJ, OILJ, SBCE, SBMB, UPUK
The most common malignancies metastasizing to the heart are cancers of the lung, breast, mesothelioma, melanoma, leukemia, and lymphoma. Cardiac metastasis from a tongue cancer is a rare finding and ...only a few cases have been reported previously in the literature. In this case report and literature review, we discuss the main clinical features of patients with cardiac metastases secondary to a tongue cancer and imaging modalities performed, especially the 18F-Fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT).
This is a case of a 39-year-old woman who in April 2018 was diagnosed with an invasive well differentiated squamous cell carcinoma of the movable tongue. She underwent a left hemiglossectomy followed by a revision of hemiglossectomy and ipsilateral selective neck lymph nodes dissection levels II to III because of pathological margins. An early inoperable clinical recurrence was diagnosed and she received radiochemotherapy with good clinical and metabolic response. She remained asymptomatic thereafter.
In January 2020, a pre-scheduled 18F-FDG PET/CT showed a diffuse cardiac involvement. In February 2020, a biopsy of the lesion revealed a metastatic squamous cell carcinoma.
She was deemed to not be a cardiac surgical candidate and treated by palliative chemotherapy: taxol-carboplatin associated with cetuximab then cetuximab alone because of adverse effects. A re-evaluation imaging performed in April 2020 evidenced a progression of the cardiac involvement, which led to switch chemotherapy by immunotherapy with nivolumab.
This patient had a very poor prognosis and succumbed to major heart failure 4 months after the diagnosis of cardiac metastasis.
In this case report, 18F-FDG PET/CT proved to be useful in detecting cardiac metastasis and changed the therapeutic management of the patient. It suggests that patients with tongue malignancies in a context of poor initial prognosis should be followed-up early by 18F-FDG PET/CT with HFLC diet to facilitate detection of recurrence.
Abstract
Background. Head and neck carcinoma (H&N) is one of the leading causes of cancer deaths worldwide. Despite advances in diagnosis and treatment, the survival rates remain low mainly due to ...locoregional relapse, possibly triggered by the activation of epithelial-to-mesenchymal transition (EMT). Recently, several studies have demonstrated a positive link between macrophages, EMT and invasion in H&N cancer. The aim of this study is to analyze the interactions between human antitumoral M1/protumoral M2 macrophages and H&N human cancer cells with different EMT status, with the aim of developing new therapeutic approaches for H&N cancer patients.
Materials and Methods. M1 and M2 macrophages were obtained from THP-1 cell line (human monocyte) after 48h exposure to 25nM of PMA followed by 48h of recovery culture medium, and 72h exposure to 1ng/ml LPS + 20ng/ml IFNγ to obtain M1 phenotype or 20ng/ml IL4 + 20ng/ml IL13 to obtain M2 phenotype. Differentiation status was validated by immunofluorescence (IF) using CD14 for monocyte, CD68 for macrophage, CD80 for M1, and CD163 for M2. Eight H&N cell lines were characterized for their EMT status (E-cadherin/vimentin expression) by western blot. SQ20B (epithelial) and Hep2 (mesenchymal) cell lines were selected to study the effect of M1 and M2 conditioned medium (CM) on cell proliferation. In addition, we also analyzed the effects of CM from SQ20B and Hep2 on macrophages differentiation using IF.
Results. We confirmed the differentiation of monocytes into macrophages by a decrease of CD14 expression and an increase of CD68 expression, and the differentiation of macrophages into M1 and M2 by an increase of CD80 and CD163 expression, respectively. Among the 8 H&N cell lines, 3 cell lines showed an epithelial status (high E-cadherin expression), one a mesenchymal status (high vimentin expression), and 4 a mixed status. Based on these results, we exposed SQ20B (epithelial) and Hep2 (mesenchymal) to M1 or M2 CM. M1 CM strongly inhibited the proliferation of SQ20B cells, with moderate effect on Hep2 cells, whereas M2 CM displayed no effect on SQ20B cells and slightly increased the proliferation of Hep2 cells. Moreover, macrophages exposed to SQ20B CM displayed a M1 phenotype with an increased expression of CD80, whereas Hep2 CM induced a M2 phenotype with an increased expression of CD163.
Conclusions. In vitro, we showed that M1 and M2 macrophages displayed opposite effects on H&N cancer cells proliferation via their conditioned medium, M1 being anti-proliferative and M2 pro-proliferative. These effects were dependent on epithelial/mesenchymal status of cancer cells. In addition, we showed that factors secreted by epithelial vs mesenchymal cancer cells induced macrophages differentiation into M1 and M2, respectively. These results open up new perspectives on the role of M1/M2 macrophages in EMT-dependent H&N cancers and other tumor types such as colon, lung, and liver carcinoma.
Citation Format: Lucile Astorgues-Xerri, Diane Evrard, Matthieu Martinet, Eric Raymond, Sandrine Faivre, Annemilaï Tijeras-Raballand. Link between M1/M2 human macrophages and epithelial-mesenchymal status in head and neck cancer cell lines abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 1080.
Background Video-assisted thoracic surgery (VATS) is usually performed using three ports. Uniportal VATS has not yet been widely developed. We report our single institution experience in uniportal ...VATS for the surgical management of 351 patients with pneumothorax. Methods Between November 2009 and February 2016, we conducted a study in 351 patients treated for pneumothorax using uniportal VATS. Resection of apical bullae associated with partial pleurectomy, pleural abrasion, or talc effusion was performed. Results The mean age was 29.6 ± 10.1 years. Surgical indications were mainly persistence or recurrence of pneumothorax. Sixty-seven patients (19%) presented with complications. At the 30-day control, 60.1% of patients were asymptomatic; 85% of patients were satisfied with the single small scar. The recurrence rate was 3.6% at 24 ± 13 months. Conclusions Uniportal VATS is feasible, safe, and reproducible in the treatment of pneumothorax. Morbidity is similar to multiport VATS. The recurrence rate is comparable with best results after multiport VATS or thoracotomy. Patients were satisfied with the single small scar.
Patterns of nodal involvement in adenoid cystic carcinoma (ACC) of the head and neck have not been sufficiently assessed to guide a decision of prophylactic neck dissection (ND). The objective of ...this study is to analyse the influence of ND on event-free survival (EFS) for patients with cN0 ACC.
A multicentre prospective study was conducted between 2009 and 2018. Patients presenting cN0 non-metastatic ACC on any site, and who received surgery on the tumour, were included. EFS was the main judgement criterion. A comparative survival analysis between the groups that received a ND versus those that did not was performed, using a propensity score. Analyses were carried out using the R software.
Between 2009 and 2018, 322 patients with cN0 ACC were included, out of which 58% were female. The average age was 53 years. Tumours were in minor salivary glands in 58% of cases, and 52% had T3/T4 stages.
ND was performed on 46% of patients. Out of them, seven had histological lymph node invasion, out of which six had tumour infiltration in the mucosa of oral cavity.
After propensity score, the median EFS for N0 patients with ND was 72 months (95% Confidence Interval (CI) 48–81), compared to 73 months (95% CI 52–85) for patients without ND (HR = 1.33; 95% CI 0.82–2.16; p = 0.2).
ND of cN0 patients does not provide any benefit on EFS, which suggests that its application on such patients is not necessary.
•The incidence of occult lymph node metastases is low in head and neck adenoid cystic carcinoma (5%).•They are mainly found when tumours infiltrate of the oral cavity mucosa (6/7 cases).•Given a close preoperative assessment, prophylactic neck dissection should not be performed in cN0 patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Laryngeal chondrosarcoma (LCS) is a rare tumor of slow evolution whose treatment is poorly codified. For a long time, a radical treatment by total laryngectomy (TL) was proposed. More recent studies ...tend to propose a conservative surgical approach of the larynx. The objective of this study was to compare the overall survival (OS) of total laryngectomized patients (TL+) versus non-laryngectomized patients (TL-). The secondary objectives were to analyse the reoperation free survival (RFS), the total laryngectomy free survival (TLFS) and to identify the preoperative factors leading surgeons to propose TL.
A retrospective analysis of prospectively collected incident cases from the REFCOR and NetSarc-ResOs multicenter databases between March 1997 and June 2021 was conducted. A propensity score matching analysis was performed to compare the OS of TL+ and TL-patients.
74 patients were included. After propensity score, the 5-year OS of TL+ and TL-patients was comparable (100 %, p = 1). The 5-year RFS rate was 69.2 % (95 % CI 57.5–83.4) and the 5-year TLFS was 61.7 % (95 % CI 50.4–75.5). Cricoid involvement greater than 50 % (HR 3.58; IC 95 % 1.61–7.92 p < 0.001), an ASA score of 3 or 4 (HR 5.07; IC 95 % 1.64–15.67 p = 0.009) and involvement of several cartilages (HR 5.26; IC 95 % 1.17–23.6 p = 0.04) are prognostic factors for TL. Dyspnea caused by the tumour is a prognostic factor for reoperation (HR 2.59; IC 95 % 1.04–6.45 p = 0.03).
These results demonstrate that conservative treatment should be considered as first-line treatment for laryngeal chondrosarcoma.
•For a long time, total laryngectomy was proposed to treat laryngeal chondrosarcoma•A propensity score analysis was performed to compare patient laryngectomized or not•The 5-year overall survival was comparable•Cricoid invasion over 50 % is the main prognostic factor for total laryngectomy•Conservative treatment must be considered as first-line treatment
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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