The progression of epithelial cancer is associated with an intense immunological interaction between the tumor cells and immune cells of the host. However, little is known about the interaction between tumor cells and polymorphonuclear granulocytes (PMNs) in patients with head and neck squamous cell carcinoma (HNSCC). In our study, we investigated systemic PMN-related alterations in HNSCC, the role of tumor-infiltrating PMNs and their modulation by the tumor microenvironment.We assessed the infiltration of HNSCC tissue by PMNs (retrospectively) and systemic PMN-related alterations in blood values (prospectively) in HNSCC patients (n 5 99 and 114, respectively) and control subjects (n 5 41). PMN recruitment, apoptosis and inflammatory activity were investigated in an in vitro system of peripheral blood PMNs and a human HNSCC cell line (FaDu). HNSCC tissue exhibited considerable infiltration by PMNs, and strong infiltration was associated with poorer survival in advanced disease. PMN count, neutrophil-to-lymphocyte ratio and serum concentrations of CXCL8 (interleukin-8), CCL4 (MIP-1b) and CCL5 (RANTES) were significantly higher in the peripheral blood of HNSCC patients than in that of controls. In vitro, HNSCC-conditioned medium inhibited apoptosis of PMNs, increased chemokinesis and chemotaxis of PMNs, induced release of lactoferrin and matrix metalloproteinase 9 by PMNs and enhanced the secretion of CCL4 by PMN. Our findings demonstrate alterations in PMN biology in HNSCC patients. In vitro, tumor-derived factors modulate cellular functions of PMNs and increase their inflammatory activity. Thus, the interaction between HNSCC and PMNs may contribute to host-mediated changes in the tumor microenvironment.Worldwide, head and neck cancer is one of the six most common cancers. More than 90% of head and neck cancers are squamous cell carcinomas (HNSCCs) that primarily originate in the oral cavity, the pharynx and the larynx. [1][2][3] HNSCCs display an inflammatory microenvironment with frequent infiltration by large numbers of immune cells. This infiltration results in a reciprocal interaction between the malignant tissue and the immune cells that causes local and systemic alterations, often resulting in the downregulation of immune functions and the tumor escape from immune control. [4][5][6] Accumulating evidence suggests that polymorphonuclear granulocytes (PMNs) and other myeloid cells play an important tumor-promoting role during tumor progression. 7-9 High numbers of PMNs before treatment, as determined in the peripheral blood of patients with malignant melanoma, 10 and an increased neutrophil-to-lymphocyte ratio (NLR), as demonstrated in ovarian cancer, 11 have been proposed as independent prognostic factors for short overall survival. Tumor-infiltrating PMNs have been linked to a poorer prognosis for patients with lung adenocarcinoma of the bronchioloalveolar subtype, 12 but they seem to be associated with a reduced mortality for patients with gastric carcinoma. 13 PMN functions are modulated by a variety of ...

Neurology. 2002;59:1450‐1453. Trigeminal pain processing was studied in 14 patients with unilateral migraine attacks and 14 age‐ and sex‐matched patients with comparable unilateral headache from frontal sinusitis. Using a nociception‐specific blink reflex method (nBR), a facilitation of nBR responses predominantly on the headache side was observed in migraine, but not in sinusitis. The facilitation of trigeminal nociception may be specific for migraine rather than a consequence of peripheral pain such as frontal sinusitis. Comment: Here we have evidence for the central hyperexcitability of migraine, not found in the previously cited article by Boska et al. SJT

BackgroundSince image based diagnostic tools fail to detect early metastasis in head and neck squamous cell carcinoma (HNSCC) it is crucial to develop minimal invasive diagnostic methods. A promising approach is to identify and characterize circulating tumor cells (CTC) in the peripheral blood of HNSCC patients. In this pilot study, we assessed which non-hematopoietic cell types are identifiable and whether their numbers differ in pre- and postoperative blood samples.Methods20 ml citrated peripheral blood was taken from 10 HNSCC patients before and after curative resection. CTC were enriched using density gradient centrifugation. CTC presence was verified by multi-immunofluorescence staining against cytokeratin (CK; epithelial), N-cadherin (mesenchymal); CD133 (stem-cell), CD45 (hematopoietic) and DAPI (nucleus). Individual cell type profiles were analyzed.ResultsWe were able to detect cells with epithelial properties like CK+/N-cadherin−/CD45− and CK+/CD133−/CD45− as well as cells with mesenchymal features such as N-cadherin+/CK−/CD45− and cells with both characteristics like N-cadherin+/CK+/CD45−. We also observed cells showing stem cell-like features like CD133+/CK−/CD45− and cells with both epithelial and stem cell-like features such as CD133+/CK+/CD45−. The number of CK positive cells (p = 0.002), N-cadherin positive cells (p = 0.002) and CD133 positive cells (p = 0.01) decreased significantly after resection. Kaplan-Meier test showed that the survival was significantly shorter when N-cadherin+ cells were present after resection (p = 0.04; 474 vs. 235 days; [HR] = 3.1).ConclusionsThis is - to the best of our knowledge- the first pilot study identifying different CTC populations in peripheral blood of HNSCC patients and showing that these individual cell type profiles may have distinct clinical implications.

Vascular erosion following primary or adjuvant R(C)T represents a rare and potentially life-threatening complication requiring immediate emergency treatment involving head and neck surgeons, anesthesiologists and neuroradiologists. For patients with oropharyngeal neoplasms treated by R(C)T and showing recurrent bleeding episodes and mucosal ulceration particularly after the acute treatment phase, hospitalization with prophylactic surgical ligature or embolization of affected arteries is recommended.

The (-938C>A) SNP represents a potential novel prognostic marker in patients with OSCC that could help to identify a group of patients at high risk for relapse and death.