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Staphylococcus aureus is a common human pathogen, which is regularly part of the normal microflora found in the nose and skin. It represents a significant threat to human health, not in the least because of its capability to produce exotoxins, which have superantigenic properties. These exotoxins, in particular the staphylococcal enterotoxins (SEs), are known to be involved in the modulation and aggravation of airway inflammation. Indeed, recent studies show an important impact of SEs on the natural course of allergic rhinitis, nasal polyposis, asthma and COPD. This review outlines the current knowledge on the influence of SEs on airway inflammation. We highlight, in particular, the recent evidence on their role in asthma. Copyright © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Background: Cigarette smoke (CS) is a major risk factor for the development of COPD. CS exposure is associated with an increased risk of bacterial colonization and respiratory tract infection, because of suppressed antibacterial activities of the immune system and delayed clearance of microbial agents from the lungs. Colonization with Staphylococcus aureus results in release of virulent enterotoxins, with superantigen activity which causes T cell activation.Objective: To study the effect of Staphylococcus aureus enterotoxin B (SEB) on CS-induced inflammation, in a mouse model of COPD.Methods: C57/Bl6 mice were exposed to CS or air for 4 weeks (5 cigarettes/exposure, 4x/day, 5 days/week). Endonasal SEB (10 μg/ml) or saline was concomitantly applied starting from week 3, on alternate days. 24 h after the last CS and SEB exposure, mice were sacrificed and bronchoalveolar lavage (BAL) fluid and lung tissue were collected.Results: Combined exposure to CS and SEB resulted in a raised number of lymphocytes and neutrophils in BAL, as well as increased numbers of CD8+ T lymphocytes and granulocytes in lung tissue, compared to sole CS or SEB exposure. Moreover, concomitant CS/SEB exposure induced both IL-13 mRNA expression in lungs and goblet cell hyperplasia in the airway wall. In addition, combined CS/SEB exposure stimulated the formation of dense, organized aggregates of B- and T- lymphocytes in lungs, as well as significant higher CXCL-13 (protein, mRNA) and CCL19 (mRNA) levels in lungs.Conclusions: Combined CS and SEB exposure aggravates CS-induced inflammation in mice, suggesting that Staphylococcus aureus could influence the pathogenesis of COPD. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. We investigated and compared the effects of CS on upper and lower airways, in a mouse model of subacute and chronic CS exposure. Methods: C57BL/6 mice were whole-body exposed to mainstream CS or air, for 2, 4 and 24 weeks. Bronchoalveolar lavage fluid (BAL) was obtained and tissue cryosections from nasal turbinates were stained for neutrophils and T cells. Furthermore, we evaluated GCP-2, KC, MCP-1, MIP-3α, RORc, IL-17, FoxP3, and TGF-β1 in nasal turbinates and lungs by RT-PCR. Results: In both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3α and resulted in a neutrophilic influx. However, after chronic CS-exposure, there was a significant downregulation of inflammation in the upper airways, while on the contrary, lower airway inflammation remained present. Whereas nasal FoxP3 mRNA levels already increased after 2 weeks, lung FoxP3 mRNA increased only after 4 weeks, suggesting that mechanisms to suppress inflammation occur earlier and are more efficient in nose than in lungs. Conclusions: Altogether, these data demonstrate that CS induced inflammation may be differently regulated in the upper versus lower airways in mice. Furthermore, these data may help to identify new therapeutic targets in this disease model. [ABSTRACT FROM AUTHOR]

Poor postoperative healing after sinus surgery is associated with high concentrations of matrix metalloproteinase-9 (MMP-9). The frontal recess is especially vulnerable to restenosis, and frontal sinus stents have been used to overcome this problem. However, the long-term success rate is still controversial and may be poor. In this perspective, we developed doxycycline (DC)-releasing stents, delivering the MMP-9 synthesis-suppressing agent locally to the frontal recess area. We evaluated postoperative MMP-9 levels, bacterial colonization, healing quality, and symptom scores in patients suffering from chronic rhinosinusitis with (CRSwNP) and without nasal polyposis (CRSsNP) ( n=10) who underwent functional endoscopic sinus surgery during which the DC-releasing and placebo stents were placed. We found that MMP-9 concentrations were significantly lower at the side of the DC-releasing stent (3,414±582 ng/mL) compared with the contralateral placebo stent (9,172±2,564 ng/mL) ( p<0.05) at month 3 postsurgery. DC stents adequately suppressed bacterial growth compared with placebo stents. Furthermore, the visual analog scale (VAS) for the frontal region was significantly better (mean value 75.1 vs. 52.8, p<0.001) compared with its placebo counterpart. We conclude that compared with placebo stents, DC-releasing stents significantly lowered MMP-9 concentrations and bacterial colonization locally, and improved postoperative healing quality after functional endoscopic sinus surgery, as demonstrated by visual analog scale and ostial closure. [ABSTRACT FROM AUTHOR]

• A prospective longitudinal study design was used to investigate the evolution of vocal function in thyroidectomy patients. • Thyroidectomy without laryngeal nerve injury does not cause a permanent voice change. • Progressive amelioration of voice quality was found in patients who underwent thyroidectomy. This study investigates the long-term voice outcome of thyroidectomy up to 10 years after the surgery using a longitudinal prospective study design. Eighteen participants (6 men and 12 women, mean age: 54 years) who underwent a thyroidectomy between September 2006 and May 2007 were included in this study. A voice assessment protocol consisting of subjective (videolaryngostroboscopic evaluation, auditory- perceptual evaluation, patients' self-report) and objective voice assessments (maximum performance task, acoustic analysis, voice range profile and Dysphonia Severity Index) was used to evaluate the participants' pre- and postoperative voice. Voice measurements were compared before and one week, six weeks, three months and 10 years after the surgery. No significant differences over time in auditory-perceptual and objective voice parameters were found, except for shimmer. Only in the first postoperative condition, significantly more patients reported vocal complaints. A progressive amelioration of the vocal folds' movement patterns was observed in the postoperative conditions. The findings of this small longitudinal prospective study suggest that thyroidectomy without laryngeal nerve injury does not cause a permanent deterioration of the laryngeal aspect or function, vocal fold behavior and the self-perceived, perceptual and objective vocal quality. The increase of the shimmer 10 years post-thyroidectomy may be related to vocal aging. [ABSTRACT FROM AUTHOR]

Purpose: Intestinal-type adenocarcinoma (ITAC) is a rare sinonasal malignancy. Curative treatment requires multidisciplinary approach, with surgical options consist of the endonasal endoscopic approach (EEA) and external surgery (EXTS). Here, we provide the post-operative and survival results from a single-center long-term follow-up. Methods: We report long-term follow-up of 92 ITAC cases treated between 1998 and 2018, treated with EEA (n = 40) or EXTS (n = 52). Survival estimates, post-operative complications and duration of hospitalization were compared between surgical modalities. Results: Baseline characteristics were similar. A higher number of T4b tumors (16%), and subsequently more tumoral invasion (39%), was present in patients undergoing EXTS compared to EEA (3% and 18%, respectively). No difference in Barnes histology subtypes was noticed. Patients undergoing EEA had a shorter post-operative hospitalization stay versus EXTS (4 versus 7 days). Use of EEA was associated to improved disease-specific survival (DSS; 11.4 versus 4.4 years; HREEA = 0.53), especially for patients with T3–4a tumors (11.4 versus 3.0 years; HREEA = 0.41). Patients with T3–4 stage, tumoral invasion, positive surgical margins, mucinous or mixed histology, and prolonged post-operative hospital stay showed poor local relapse-free, disease-free, overall, and DSS. Conclusions: Long-term follow-up in locally advanced ITAC demonstrates that resection by EEA is correlated with improved DSS compared to EXTS, especially for T3–4 tumors. No significant differences between both treatment modalities was observed regarding per- and post-operative complications, although hospitalization in patients undergoing EEA was shorter than for patients treated with EXTS. These results confirm that EEA should remain the preferred surgical procedure in operable cases of sinonasal ITAC. [ABSTRACT FROM AUTHOR]

Hematological diseases, due to their complex nature and diverse manifestations, pose significant diagnostic challenges in healthcare. The pressing need for early and accurate diagnosis has driven the exploration of novel diagnostic techniques. Infrared (IR) spectroscopy, renowned for its noninvasive, rapid, and cost-effective characteristics, has emerged as a promising adjunct in hematological diagnostics. This review delves into the transformative role of IR spectroscopy and highlights its applications in detecting and diagnosing various blood-related ailments. We discuss groundbreaking research findings and real-world applications while providing a balanced view of the potential and limitations of the technique. By integrating advanced technology with clinical needs, we offer insights into how IR spectroscopy may herald a new era of hematological disease diagnosis. [ABSTRACT FROM AUTHOR]

Purpose: Recent technical advancements in PET imaging have improved sensitivity and spatial resolution. Consequently, clinical nuclear medicine will be confronted with PET images on a previously unfamiliar resolution. To better understand [18F]FDG distribution at submillimetric scale, a direct correlation of radionuclide-imaging and histopathology is required. Methods: A total of five patients diagnosed with a malignancy of the head and neck were injected with a clinical activity of [18F]FDG before undergoing surgical resection. The resected specimen was imaged using a preclinical high-resolution PET/CT, followed by slicing of the specimen. Multiple slices were rescanned using a micro-PET/CT device, and one of the slices was snap-frozen for frozen sections. Frozen sections were placed on an autoradiographic film, followed by haematoxylin and eosin staining to prepare them for histopathological assessment. The results from both autoradiography and histopathology were co-registered using an iterative co-registration algorithm, and regions of interest were identified to study radiotracer uptake. Results: The co-registration between the autoradiographs and their corresponding histopathology was successful in all specimens. The use of this novel methodology allowed direct comparison of autoradiography and histopathology and enabled the visualisation of uncharted heterogeneity in [18F]FDG uptake in both benign and malignant tissue. Conclusion: We here describe a novel methodology enabling the direct co-registration of [18F]FDG autoradiography with the gold standard of histopathology in human malignant tissue. The future use of the current methodology could further increase our understanding of the distribution of radionuclides in surgically excised malignancies and hence, improve the integration of pathology and molecular imaging in a multiscale perspective. Trial registration: ClinicalTrials.gov Identifier: NCT05068687 [ABSTRACT FROM AUTHOR]

Simple Summary: In patients with relapsed or metastasized squamous cell cancer of the head and neck (R/M SCCHN), the PD-L1 Combined Positive Score (CPS) is currently the only predictive biomarker for treatment with anti-PD-1 agents. However, ambiguous results have been determined regarding the overall response rates of immunotherapeutic agents based on PD-L1 status, which may be partially attributed to spatiotemporal heterogeneity. Furthermore, tumor-infiltrating lymphocytes (TILs) have proven to be of significant prognostic value, yet lack of a standardized method for quantification impedes their integration into the current armamentarium of biomarkers in SCCHN. In this paper, concordance of PD-L1 CPS and stromal TILs was investigated in different paired samples of SCCHN subtypes. The results were then linked to well-known clinicopathological variables and prognosis. Background: The clinical significance of tumor-infiltrating lymphocytes (TILs) and programmed cell death-ligand 1 (PD-L1) expression has been thoroughly researched in squamous cell carcinoma of the head and neck (SCCHN). To address the impact of intra- and intertumoral heterogeneity in these biomarkers, we explored the concordance of PD-L1 combined positive score (CPS) and stromal TILs in different paired tissue sample types, while evaluating their internal relationship and prognostic impact. Methods: A total of 165 tissue blocks from 80 SCCHN patients were reviewed for TILs and PD-L1 CPS. Concordance between paired tissue samples was evaluated, and their association with several clinicopathological variables, overall survival (OS), and disease-free survival (DFS) was determined. Results: Biopsies and paired resection material were severely discordant in 39% and 34% of samples for CPS and TIL count, respectively, of which CPS was underscored in 27% of biopsies. In paired primary tumor–metastatic lesions, the disagreement was lower for CPS (19%) but not for TIL count (44%). PD-L1 CPS was correlated with prolonged OS when calculated from tissue acquirement, while extended OS and DFS were observed for high TIL density. Conclusion: Intertumoral and, especially, intratumoral heterogeneity were confounding factors when determining PD-L1 CPS and TIL count on paired tissue samples, indicating the increasing necessity of assessing both biomarkers on representative tissue material. Although TILs hold valuable prognostic information in SCCHN, the robustness of PD-L1 as a biomarker in SCCHN remains ambiguous. [ABSTRACT FROM AUTHOR]

Case presentation: We report for the first time a synchronous papillary and follicular thyroid carcinoma in a 12-year-old girl presenting with a large (5 cm diameter) left thyroid nodule, an increased left and right upper pole technetium tracer uptake at scintigraphy and hyperthyroidism. The uptake at the right lobe was explained by the crossing of the left nodule to the right site of the neck at Computed Tomography (CT) scanning. Background: Although thyroid nodules are less common in children than in adults, there is more vigilance required in children because of the higher risk of malignancy. According to literature, about 5% of the thyroid nodules in adults are malignant versus 20–26% in children. The characteristics of 9 other pediatric cases with a differentiated thyroid carcinoma presenting with a toxic nodule, which have been reported during the last 20 years, are summarized. A nodular size of more than 3.5 cm and female predominance was a common finding. Conclusions: The presence of hyperthyroidism in association with a hyperfunctioning thyroid nodule does not rule out thyroid cancer and warrants careful evaluation, even in the absence of cervical lymph node invasion. [ABSTRACT FROM AUTHOR]

View large Download slide View large Download slide OBJECTIVES After oesophagectomy, stomach grafts are most frequently used to restore intestinal continuity. Less frequently, a colonic graft is used. There is quite a large body of literature addressing the functional outcome after gastric pull-up, but little is known about the functional results of colonic interposition (CI). The aim of this study was to assess the short-term outcomes and the long-term quality of life and function of the CI postoesophagectomy. METHODS Between 2002 and 2016, we retrospectively collected data on 80 patients with CI from personal health records at the Ghent University hospital. We prospectively compared the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30, EORTC QLQ-OG25 and Swallowing Quality of Life (SWAL-QOL) questionnaire scores to the healthy reference group and the gastric tube (GT) group. RESULTS The 30-day mortality rate was 5%. Anastomotic leakage occurred in 37.5% and stenosis in 20% of the patients. The median overall survival of all patients was 33.9 months (95% confidence interval 8.3–59.4). The mean general health score of the CI patients was less than the healthy reference group but comparable to the GT group (CI = 62.1 vs healthy reference group = 71.2 vs GT = 60). Fifty percent of the patients reported their health as good and 15% as very good. The mean functional results with a CI were better than with a GT. Compared to GT patients, CI patients had less dyspnoea, reflux and dysphagia, but they reported more food selection, diarrhoea and weight loss. CONCLUSIONS Despite the high complication rate, the severity of the disease and the demanding operation, patients perceived themselves as being in good health and reported very good long-term functionality after CI. Clinical trial registration number B670201630635. [ABSTRACT FROM AUTHOR]

Background: To identify predictive factors for the development of late grade 4 mucosal ulcers in adaptive dose-escalated treatments for head-and-neck cancer. Material and methods: Patient data of four dose-escalated three-phase adaptive dose-painting by numbers (DPBN) clinical trials were analyzed in this study. Correlations between the development of late grade 4 ulcers and factors related with the treatment, disease characteristics and the patient were investigated. Dosimetrical thresholds were searched among the highest doses received by 1.75 cm3 (D1.75cc) of the primary gross tumor volume (GTVT) and the corresponding normalized isoeffective dose (NID21.75cc, with a reference dose of 2Gy/fraction and α/β of 3 Gy). Results: From 39 studied patients, nine developed late grade 4 mucosal ulcers. The continuation to either smoke or drink alcohol after therapy was the factor that showed a strong (eight out of nine patients) association with the occurrence of grade 4 ulcers. Six of the patients who continued to smoke or/and drink had D1.75cc and NID21.75cc above 84 Gy and 95.5 Gy, respectively. Seven of the patients with grade 4 had the dose levels above these thresholds, but even if the D1.75cc threshold was significant in the prediction of late grade 4 ulcers, it could not be considered as the only contributing factor. Conclusions: The search for patterns provided strong reasons to apply a dosimetrical threshold for the peak-dose volume of 1.75 cm3 as a preventive measure for late grade 4 mucosal ulcers. Also, patients that continue to smoke or drink alcohol after therapy have increased risk to develop late mucosal ulcers. [ABSTRACT FROM AUTHOR]

Purpose/objective The benefit of upfront neck dissection (ND) in locally advanced head and neck squamous cell carcinoma (HNSCC) treated with primary (chemo-) radiotherapy (R(C)T) is debated. Therefore, we retrospectively compared disease control and toxicity between patients who were treated with and without upfront ND followed by R(C)T. Material/methods Two-hundred sixty-four consecutive patients with HNSCC without distant metastases at diagnosis and with lymph node stage N2–N3 were included in 2 centers. Patients were all treated between January 2002 and December 2012, and received definitive R(C)T in center 1 and upfront ND followed by R(C)T in center 2. Clinical data and outcome were assessed retrospectively. Toxicity was scored using the LENT-SOMA scale at 6, 12, 18 and 24 months following the end of treatment. Results We included 150 patients in the group without ND (center 1) and 114 patients in the group with upfront ND (center 2). Mean follow up was 5.68 years in the group without ND and 5.83 years in the group with upfront ND. Local, regional and distant control after 2 years were 91.07% and 85.96% ( p = 0.09), 89.22% and 83.27% ( p = 0.12) and 76.74% and 75.13% ( p = 0.92) in the group with and without upfront ND, respectively. We did not find a significant difference between both groups regarding edema and atrophy at 6, 12, 18 and 24 months. We found a trend at all time-points toward worse outcome in the ND group at all time-points ( p = 0.06). A significantly higher proportion of moderate to severe fibrosis (grade ≥2) was present in the ND group ( p = 0.01) at all time points. Conclusion There was no significant difference in local, regional or distant control and disease-free survival between both patient populations. Fibrosis, specifically fibrosis grade ≥2 is more prominent following upfront ND and R(C)T when compared to R(C)T alone. [ABSTRACT FROM AUTHOR]

The use of cytotoxic and/or targeted agents is the gold standard in first- and second-line treatment of metastatic head and neck cancer. Currently the focus of oncologic research is shifting to the implementation of immune checkpoint inhibitor regimens. Many trials are being performed evaluating the survival benefit of various PD-1/PD-L1 blocking antibodies in both solid and haematological malignancies. Also, evaluation of the predictive value of PD-L1 expression on tumour cells and immune cells is being explored. We first review the current knowledge and possible pitfalls for PD-L1 expression in squamous cell carcinoma of the head and neck. Next, we provide an update on the therapeutic use of PD-1/PD-L1 blocking antibodies as treatment modality for patients with squamous cell carcinoma of the head and neck and we assess the predictive value of tumour PD-L1 positivity. Finally, we elaborate on other promising predictive biomarkers of interest in this patient population. [ABSTRACT FROM AUTHOR]

BACKGROUND: Postoperative scarring is a common cause of patient dissatisfaction. Several strategies have been developed to improve its clinical aspects. OBJECTIVE: To assess efficacy and safety of the 10,600 nm ablative fractional carbon dioxide (CO2) laser in the treatment of recent surgical scars in the head and neck region. METHODS AND MATERIALS: A prospective, randomized, single-blind intrapatient controlled study was conducted on 9 postoperative scars in the head and neck region. On half of the scar, 3 treatment sessions were performed. Physician/Patient Global Assessment (PhGA/PGA) and Patient and Observer Scar Assessment Scales (POSAS) were used to evaluate treatment efficacy. Safety was evaluated by registration of pain and adverse events. RESULTS: No statistically significant differences were noted in terms of PhGA or POSAS (observer). Patient Global Assessment (p = 0.058) and POSAS (patient) (p = 0.091) showed a trend toward better improvement of the treated half. Itch score (p = 0.046) and global end evaluation (patient) (p = 0.026) demonstrated a statistically significant difference in favor of the treated part. Adverse events were minor, and no long-term side effects were noted. CONCLUSION: The use of CO2 fractional laser is safe and is associated with high patient satisfaction. However, objective measurements could not confirm its efficacy in the treatment of recent surgical scars. [ABSTRACT FROM AUTHOR]

Purpose To evaluate disease control, survival and severe late toxicity after high-dose fractionated reirradiation using intensity-modulated radiotherapy (IMRT) for recurrent head-and-neck cancer. Materials and methods Sixty consecutive patients were reirradiated with IMRT between 1997 and 2011. The median prescribed dose was 70 Gy in 35 daily fractions until 2004 and 69.12 Gy in 32 daily fractions thereafter. The median cumulative dose was 132 Gy. Sixty-seven percent of patients had non-metastatic stage IV disease. Surgery prior to reirradiation and concomitant systemic therapy was performed in 13 (22%) and 20 (33%) patients, respectively. Results Median follow-up in living patients was 18.5 months. Actuarial 1-, 2- and 5-year locoregional control was 64%, 48% and 32%, respectively. Median overall (OS) and disease-free survival was 9.6 and 6.7 months, respectively. Actuarial 1-, 2- and 5-year OS was 44%, 32% and 22%, respectively. Seventeen (27%) and 2 (3%) patients had grade 3 and 4 acute toxicity, respectively. Cumulative incidence of late grade ≥ 3 toxicity was 23%, 27% and 66% at 1, 2 and 5 years, respectively. In 4 patients, death was attributed to toxicity: fatal bleeding (n = 2), aspiration pneumonia (n = 1) and skin necrosis (n = 1). Conclusions High-dose fractionated reirradiation with IMRT offers 5-year disease control and OS in recurrent head-and-neck cancer for 1/3 and 1/4 patients, respectively. Severe late toxicity after 1-2 and 5 years occurs in 1/4 and 2/3 patients, respectively. [ABSTRACT FROM AUTHOR]

Background: Allergic rhinitis (AR) is the most common allergic disorder and its prevalence has significantly increased worldwide, nowadays affecting up to 40% of the population in young adults. The objective of the present survey was to evaluate the prevalence of allergic sensitization and the prevalence of clinically diagnosed AR in a sample of the Belgian population, and to estimate the effect of age and gender. Methods: We performed a cross-sectional population-based study at an annual public fair in Ghent. Participants underwent a skin prick test (SPT) to 3 aeroallergens: a mix of trees (hazel, alder, and birch), grass pollen, and house dust mite (HDM). The clinical relevance of sensitization was assessed by relating relevant symptoms of AR to the corresponding SPT. Results: A total of 2,320 participants (1,475 females, median age 44.7 years, range 3-86) were included in this study. The standardized prevalence rates of sensitization were 13.2% for tree mix, 25.9% for grass pollen, and 25.9% for HDM. Sensitization to at least one of the allergens was present in 40.3% of the subjects. Symptomatic sensitization related to trees was reported in 9.7% of cases, grass-related AR was 17.6%, and HDM-related AR was 17.1%. The overall prevalence of AR was 30.9%. Conclusion: In this study we demonstrated a 40.3% prevalence of a positive SPT to one or more common aeroallergens. A clinical diagnosis of AR was present in 30.9% of cases, peaking in the third and fourth decades of life. It is to be expected that in the next decades, when this generation grows older, the general AR prevalence will further increase. Copyright © 2012 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

The surgical treatment of head and neck malignancies relies on the complete removal of tumoral tissue, while inadequate margins necessitate the use of adjuvant therapy. However, most positive margins are identified postoperatively as deep margins, and intraoperative identification of the deep positive margins could help achieve adequate surgical margins and decrease adjuvant therapies. To improve deep-margin identification, we investigated whether the use of high-resolution preclinical PET and CT could increase certainty about the surgical margins in three dimensions. Patients with a malignancy of the head and neck planned for surgical resection were administered a clinical activity of 4MBq/kg 18F-FDG approximately one hour prior to surgical initiation. Subsequently, the resected specimen was scanned with a micro-PET-CT imaging device, followed by histopathological assessment. Eight patients were included in the study and intraoperative PET/CT-imaging of 11 tumoral specimens and lymph nodes of three patients was performed. As a result of the increased resolution, differentiation between inflamed and dysplastic tissue versus malignant tissue was complicated in malignancies with increased peritumoral inflammation. The current technique allowed the three-dimensional delineation of 18F-FDG using submillimetric PET/CT imaging. While further optimization and patient stratification is required, clinical implementation could enable deep margin assessment in head and neck resection specimens. [ABSTRACT FROM AUTHOR]

Simple Summary: The role of innate immune cells in the tumor microenvironment (TME), more specifically the presence of the tumor associated macrophages (TAMs), is becoming more important in the prognosis and treatment of patients diagnosed with malignancies. The aim of this systematic review and meta-analysis was to assess the potential prognostic value of CD206-expressing TAMs, a subclass of macrophages, which were previously proposed to negatively impact the patient's prognosis. We identified 27 manuscripts describing the role of CD206 in patient prognosis for 14 different tumor types. Despite a large heterogeneity in the results, we identified a significantly worse overall and disease-free survival for patients with increased CD206-expressing TAMs in the TME. The use of CD206-expressing TAMs could therefore be used as a prognostic marker in patients diagnosed with solid malignancies. An increased presence of CD206-expressing tumor associated macrophages in solid cancers was proposed to be associated with worse outcomes in multiple types of malignancies, but contradictory results are published. We performed a reproducible systematic review and meta-analysis to provide increased evidence to confirm or reject this hypothesis following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. The Embase, Web of Science, and MEDLINE-databases were systematically searched for eligible manuscripts. A total of 27 papers studying the prognostic impact of CD206 in 14 different tumor types were identified. Meta-analyses showed a significant impact on the overall survival (OS) and disease-free survival (DFS). While no significant differences were revealed in progression-free survival (PFS) and disease-specific survival (DSS), a shift towards negative survival was correlated with increased CD206-expresion. As a result of the different tumor types, large heterogeneity was present between the different tumor types. Subgroup analysis of hepatocellular carcinoma and gastric cancers revealed no heterogeneity, associated with a significant negative impact on OS in both groups. The current systematic review displays the increased presence CD206-expressing macrophages as a significant negative prognostic biomarker for both OS and DFS in patients diagnosed with solid cancers. Because a heterogenous group of tumor types was included in the meta-analysis, the results cannot be generalized. These results can, however, be used to further lead follow-up research to validate the specific prognostic value of CD206 in individual tumor types and therapeutic approaches. [ABSTRACT FROM AUTHOR]

Background: Cigarette smoke (CS) is known to initiate a cascade of mediator release and accumulation of immune and inflammatory cells in the lower airways. We investigated and compared the effects of CS on upper and lower airways, in a mouse model of subacute and chronic CS exposure.Methods: C57BL/6 mice were whole-body exposed to mainstream CS or air, for 2, 4 and 24 weeks. Bronchoalveolar lavage fluid (BAL) was obtained and tissue cryosections from nasal turbinates were stained for neutrophils and T cells. Furthermore, we evaluated GCP-2, KC, MCP-1, MIP-3alpha, RORc, IL-17, FoxP3, and TGF-beta1 in nasal turbinates and lungs by RT-PCR.Results: In both upper and lower airways, subacute CS-exposure induced the expression of GCP-2, MCP-1, MIP-3alpha and resulted in a neutrophilic influx. However, after chronic CS-exposure, there was a significant downregulation of inflammation in the upper airways, while on the contrary, lower airway inflammation remained present. Whereas nasal FoxP3 mRNA levels already increased after 2 weeks, lung FoxP3 mRNA increased only after 4 weeks, suggesting that mechanisms to suppress inflammation occur earlier and are more efficient in nose than in lungs.Conclusions: Altogether, these data demonstrate that CS induced inflammation may be differently regulated in the upper versus lower airways in mice. Furthermore, these data may help to identify new therapeutic targets in this disease model. [ABSTRACT FROM AUTHOR]