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Background There is considerable evidence that platelets contribute to cancer growth and metastatic dissemination. In recent studies, altered mean platelet volume (MPV) has been associated with prognosis in different types of cancer. However, the prognostic role of the MPV in head and neck squamous cell cancer (HNSCC) is currently discussed controversially. The present study was performed to analyze and further elucidate the prognostic significance of the MPV in HNSCC. Methods A total of 319 oropharyngeal squamous cell cancer (OPSCC) patients treated with radiotherapy at a tertiary academic center were enrolled in the present study. Kaplan–Meier method as well as uni- and multivariate Cox proportional hazards were used to evaluate the impact of MPV on cancer-specific survival (CSS), locoregional control (LC) and recurrence-free survival (RFS). Results The median MPV was 10.30 fL (mean 10.26 ± 1.17fL). Univariate analyses showed a significant association of the MPV with CSS (HR 0.85, 95% CI 0.74–0.98, p = 0.025), LC (HR 0.86, 95% CI 0.74–0.99, p = 0.034) and RFS (HR 0.87, 95% CI 0.76–0.996; p = 0.043). In multivariate analysis, the MPV remained an independent prognostic factor for CSS (HR 0.77, 95% CI 0.63–0.93, p = 0.008), LC (HR 0.80, 95% CI 0.65–0.98, p = 0.030), and RFS (HR 0.83, 95% CI 0.685–0.999, p = 0.049). Conclusions Our findings indicate that the MPV is a prognostic marker in OPSCC patients and may contribute to future individual risk assessment.

Objectives/Hypothesis Preservation of the submandibular gland (SMG) during a neck dissection is gaining popularity and is showing an increasing tendency. The potential benefit, if the SMG is preserved, can be manifold. The aim of this study was to assess the benefit of the preservation of the SMG and the associated risk of recurrent disease in patients with oropharyngeal or oral cavity squamous cell carcinoma. Study Design Retrospective data analysis of 168 patients, with a follow-up of at least 3 years. Methods Log-rank test, univariate, and multivariate data analyses and P values for prediction of the excision of SMG on overall-, recurrence free-, and lymph node recurrence free survival. Results In patients with cancer of the floor of the mouth or tongue, lymph node recurrence-free survival was highly influenced by excision of the SMG (P

Purpose To determine the efficacy and feasibility of induction chemotherapy (ICT) with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy and cetuximab (C) in patients with locally advanced head and neck cancer. Patients and methods Forty-nine previously untreated patients with local advanced stage III and IV squamous cell carcinoma of the head and neck (SCCHN) received three courses of ICT consisting of docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1 and infusional 5-fluorouracil 750 mg/m2/day on days 1–5 followed by radiotherapy plus C at 250 mg/m2/week (after an initial loading dose of 400 mg/m2). Results After completion of ICT 44 of 49 patients received radiotherapy plus C. Three months after therapy completion tumour response was observed in 33 patients and after two years, 25 patients were in complete remission (CR). The most common grade 4 toxicity during the whole treatment period was dermatitis (30%), followed by mucositis (27%) and neutropenia (17%) without fever. One toxic related death was observed during ICT. Two-year progression-free survival (PFS) rate was 59% and two-year overall survival (OS) rate was 63%, respectively. Conclusion Concurrent radiotherapy plus C after three courses of ICT was feasible and was associated with promising CR, PFS and OS rates. Further optimisation of dose and sequence is warranted.

Purpose Oral mucositis (OM) is a debilitating toxicity of chemoradiotherapy for head and neck cancer (HNC). This randomized, placebo-controlled, double-blind study evaluated the efficacy and safety of palifermin to reduce OM associated with definitive chemoradiotherapy for locally advanced HNC. Patients and Methods Patients receiving conventionally fractionated radiotherapy (2.0 Gy/d, 5 days/wk to 70 Gy) with cisplatin (100 mg/m2 on days 1, 22, and 43) received palifermin (180 μg/kg) or placebo before starting chemoradiotherapy and then once weekly for 7 weeks. The primary end point was the incidence of severe, observable, and functional OM (WHO grade 3 to 4). Results The palifermin (n = 94) and placebo (n = 94) arms were well balanced. The incidence of severe OM was significantly lower for palifermin than for placebo (54% v 69%; P = .041). In the palifermin arm, median time to severe OM was delayed (47 v 35 days), median duration of severe OM was shortened (5 v 26 days), and the incidence of xerostomia grade ≥ 2 was lower (67% v 80%), favoring palifermin; however, the differences were not significant after multiplicity adjustment. Opioid analgesic use, average mouth and throat soreness scores, and chemoradiotherapy compliance were not significantly different between treatment arms. Adverse events were similar between arms (98%, palifermin; 93%, placebo). The most common study drug–related adverse events were rash, flushing, and dysgeusia. After median follow-up of 25.8 months, overall survival and progression-free survival were similar between treatment arms. Conclusion Although palifermin reduced severe functional OM, its role in the management of locally advanced HNC during chemoradiotherapy remains to be elucidated.

Eosinophilic granulocytes (Eos) are found in great numbers both in the tissue and in the mucus of patients suffering from chronic rhinosinusitis with polyposis (ECRS). Interleukin-16 (IL-16) is known as a highly potent chemotactic and chemoattractant molecule (ED 10-11) for Eos. In an open, explorative, controlled study we examined the presence of IL-16 in mucosa tissue, mucus and serum in patients suffering from ECRS and its association to Eos activation. Tissue and nasal mucus specimen from 10 previously untreated, non allergic ECRS-patients undergoing paranasal sinus surgery and from 10 healthy non sinusitis subjects, undergoing nasal surgery because of anatomic nasal obstruction were investigated by real-time (RT-) PCR targeting human IL-16 mRNA. Haematoxylin-eosin (HE) staining and immunohistochemistry of formalin embedded tissue and mucus were applied for detection and determination of the proportion of activated Eos (aEos) and IL-16. Serum IL-16 was analyzed by enzyme-linked-immunosorbent assay (ELISA). IL-16 mRNA and IL-16 protein levels were elevated in nasal mucus, polyp tissue and in the serum of ECRS patients compared to healthy controls. There was a high proportion of aEos in ECRS patients compared to healthy subjects. Serum IL-16, IL-16 mRNA expression and IL-16 protein in mucus and tissue specimens were significantly associated with the presence of aEos in polyps of ECRS patients. Immunohistochemically IL-16 protein was mainly expressed in aEos, mast cells, lymphocytes and epithelial cells. In conclusion our data indicate that IL-16 may stimulate the migration and persistence of activated Eos in ECRS. IL-16 production in ECRS patients is not mediated by Immunglobuline-E (IgE).

Background A diagnosis of squamous cell carcinoma of an unknown primary (CUP) is a major burden for patients. Because the location of the primary tumor is unclear, patients remain fearful of recurrence, which aggravates the uncertain prognosis of the disease. This study evaluates factors associated with long-term recurrence-free and overall survival of patients with CUP of the head and neck. Additionally, patient survival rates are compared with those of patients with head and neck squamous cell carcinoma (HNSCC). Methods A total of 293 consecutive patients operated on between January 1999 and December 2009 with at least a 5-year follow-up (survival permitting), were evaluated retrospectively. Results Twenty-six patients with a CUP of the head and neck were identified. Patients with CUP had a low overall survival rate, comparable with that of patients with pN + HNSCC, and recurrent disease occurred with a similar likelihood as in patients with pN + HNSCC. The median recurrence-free survival in the CUP group was 28.5 months compared with 48 months in the whole of the HNSCC group. The median overall survival of the CUP group was 56 months versus 65 months for the HNSCC group. Extracapsular spread was the only independent prognostic factor for overall survival for CUP patients. Conclusion Patients diagnosed with CUP syndrome have a poorer prognosis for overall survival compared with other HNSCC patients. Postoperative radiotherapy diminished disease recurrence and improved overall survival. Omission of postoperative radiotherapy resulted in a very high recurrence rate (75%) for CUP patients. Based on these results we suggest postoperative radiotherapy including the oral mucosa for all patients, regardless of histopathological results, possible favorable nodal disease, or favorable lymph node ratios.

Objectives: To describe the course of total and ionized magnesium and total calcium levels in maternal serum during low-risk pregnancies and to compare women who developed preterm labor and delivery with those who delivered at term. Methods: 209 women with low-risk pregnancies were enrolled in a prospective trial before the 18th week of gestation. No woman received oral magnesium supplementation. The ionized and total magnesium and total calcium levels in maternal serum were measured every 4–6 weeks. The data were grouped into 3 gestational periods (≤18, 19–27 and ≥28 weeks of gestation) for overall comparison and analyzed with the general linear model for repeated measurements and ANOVA. p values of < 0.05 were considered statistically significant. Results: 145 gestations were available for analysis. 27 women were hospitalized for preterm labor and in 16 of these preterm delivery occurred. Ionized and total magnesium and calcium levels were significantly lower after the 18th week of gestation than before. The cation levels in women with preterm labor and delivery did not differ from those with term delivery. Conclusion: Ionized and total magnesium and calcium levels decrease with increasing gestational age. Preterm labor and delivery do not seem to be related to changes in serum cation levels.

Preservation of the submandibular gland (SMG) during a neck dissection is gaining popularity and is showing an increasing tendency. The potential benefit, if the SMG is preserved, can be manifold. The aim of this study was to assess the benefit of the preservation of the SMG and the associated risk of recurrent disease in patients with oropharyngeal or oral cavity squamous cell carcinoma.Retrospective data analysis of 168 patients, with a follow-up of at least 3 years.Log-rank test, univariate, and multivariate data analyses and P values for prediction of the excision of SMG on overall-, recurrence free-, and lymph node recurrence free survival.In patients with cancer of the floor of the mouth or tongue, lymph node recurrence-free survival was highly influenced by excision of the SMG (P0.001) and occurred in 28.5% of patients in whom the SMG was preserved. In all other tumor sites of the oral cavity and oropharyngeal region, excision of the SMG did not influence lymph node recurrence-free survival (P = 0.455).Patients with squamous cell carcinoma (SCC) of the oral cavity or oropharyngeal region will benefit from preservation of the ipsilateral SMG. This is not true for patients with SCC of the surrounding tissue nearest the SMG (i.e., floor of the mouth or the tongue). In such patients, the SMG must be excised.

Introduction: TNM status is questioned as an exact predictor of survival in different tumour entities. Recently, lymph node ratio (LNR) has been described as a predictor of survival in patients with HNSCC. The purpose of this study was to evaluate to which degree LNR could be used as a more accurate predictor than TNM staging? Methods: A total of 291 patients, with a follow-up of at least 3years, were analyzed using log-rank statistic, univariate and multivariate data analyzes, and p values, for prediction of lymph node ratio on overall and recurrence-free survival. Results: Survival differed significantly if patients were stratified for LNR. Impact of LNR on survival was significantly different even in patients with extracapsular spread. Patients with pN0 had no survival benefit compared with patients with pN1 or higher with a LNR lower than 6%. Conclusions: LNR is a prognostic tool in patients with a lymph node status pN0-pN2b. LNR remained significant even in patients with extracapsular spread, contrary to TNM status. With LNR, stratification for high-risk patients (higher than 6% LNR) can be evaluated easily. We would suggest using LNR in the clinical routine.

OBJECTIVES/HYPOTHESIS: Knowledge of histopathological factors, such as perineural invasion (PNI), extracapsular spread (ECS), angiolymphatic vessel invasion, and conglomerate lymph nodes, in patients with head and neck squamous cell carcinoma is important for appropriate treatment decisions. Given the availability of aggressive therapeutic options with known side effects and burdens for the patient, choosing the correct treatment option is vital. STUDY DESIGN: Retrospective patient database. METHODS: Using a retrospective database of patients treated over a 10-year period, independent prognostic factors for disease-free survival and overall survival were assessed. Univariate analysis was used to identify significant variables, and multivariate Cox regression analysis was used to determine independent prognostic factors. RESULTS: Between January 1, 1999 and December 31, 2009, 291 patients with head and neck squamous cell carcinoma were analyzed to identify influence of histopathological factors on pattern of metastasis. PNI tends to set metastasis locoregional, both in ipsilateral and contralateral lymph nodes. Lymphangiosis eases the way toward ipsilateral lymph node metastasis. ECS spread and hemangiosis demonstrated a significantly higher risk of distant metastasis. With the occurrence of conglomerate lymph nodes, patient data demonstrated a highly significant accumulation of distant metastasis. CONCLUSIONS: Patients with PNI and lymph vessel invasion tend toward locoregional lymph node metastasis on the ipsilateral side of the neck. In cases of PNI, the patient is at risk for a contralateral neck recurrence of the tumor. In patients with ECS, blood vessel invasion, or conglomerate disease, disseminated spread of the disease to distant locations is more likely and has a high negative impact on survival of the patient. LEVEL OF EVIDENCE: 4 Laryngoscope, 2013.

Objectives/Hypothesis: Topical antifungal treatment is a subject of discussion in the treatment of chronic rhinosinusitis. The aim of this research was to study the effects of antifungal drugs on ciliary beat frequency (CBF) of human nasal mucosa under in vitro conditions. Study Design: Case series of in vitro experiments and in vitro study of cultured ciliated cells of human nasal mucosa. Methods: Human nasal mucosa was acquired during routine endoscopic sinus surgery. Cells were cultivated on object slides and exposed to different antifungal drugs in a newly developed test system. This system allowed continuous and reproducible exposure to different drugs at constant temperature, pH value, and osmolarity. The drugs were amphotericin B in two different concentrations and itraconazole. Results: Rinsing with higher concentrations of amphotericin B led to an immediate decrease of CBF, with a total stop after 15 minutes. A different result was seen in the group with lower concentrations; CBF decreased again quickly after rinsing with the test drug, but all of them recovered after rinsing with neutral solution. When using itraconazole a decline in CBF was observed again; one half of the samples returned to activity. Conclusions: Our in vitro results demonstrate a dose-dependent effect of the antifungal drugs amphotericin B and itraconazole on ciliary beat frequency of human nose epithelium. Laryngoscope, 2010

Purpose To determine the efficacy and feasibility of induction chemotherapy with docetaxel, cisplatin and 5-fluorouracil followed by radiotherapy and cetuximab in patients with locally advanced head and neck cancer. Patients and methods Forty-nine previously untreated patients (median age: 53 years) with local advanced stage III and IV squamous cell carcinoma of the head and neck received three courses of induction chemotherapy consisting of docetaxel 75 mg/m2 day 1, cisplatin 75 mg/m2 day 1, and infusional 5-Fluorouracil 750 mg/m2/day on days 1-5 followed by radiotherapy plus cetuximab at 250mg/m2/week (after an initial loading dose of 400mg/m2). Patients with an ECOG performance score of 0 or 1 without severe co-morbidities adequate hematopoietic, hepatic, and renal functions were eligible. Results After completion of induction chemotherapy 44 of 49 patients received radiotherapy plus cetuximab. In 45 patients ICT was delivered without delay or dose reduction and 38 patients received RT at the full dose. Three months after therapy completion tumor response was observed in 33 patients and after 2 years, 25 patients were in complete remission. Although treatment was accompanied with a rate of grate 3 and 4 toxicity of 30% during induction chemotherapy and up to 68% during radiotherapy with cetuximab, our treatment seems feasible. Toxicities resolved within 3 months after end of treatment and only two patients became dependent on gastric feeding tubes after two years, compared to 21 patients during treatment. We lost one patient because of treatment related toxicity and 73% of the 49 included patients finished treatment without dose reduction or delay of treatment. 2-year progression-free survival rate was 59% and 2-year overall survival rate was 63%, respectively. Conclusion Concurrent radiotherapy plus cetuximab after three courses of induction chemotherapy was feasible and associated with promising complete remission, progression-free and overall survival rates. Further optimization of dose and sequence is warranted. Disclosure All authors have declared no conflicts of interest.

6016^ Background: The DeLOS-II trial is a German multicenter randomized phase II trial (IIT) investigating IC with or without cetuximab for patients with LHSCC, followed by R assessing FOP. Methods...

Objective. The aim of this study was to evaluate the rate of transtubal dissemination of endometrial carcinoma cells by hysteroscopy and the functional viability of disseminated tumor cells by assessing cell adhesion in an in vitro model. Methods. We studied 24 uteri obtained at TAH+BSO in patients with endometrial carcinoma. Further inclusion criteria were negative peritoneal cytology, no involvement of the uterine serosa or extrauterine disease, and endometrial surface involvement >1 cm in diameter. In vitro fluid hysteroscopy was performed with a 5-mm single-flow rigid hysteroscope. A maximum of 150 ml saline was infused at a maximum pressure of 100 mm Hg for a maximum of 3 min. Fluid running off through the tubes was collected. The cell suspension was enriched by a density gradient centrifugation. The isolated cells had a mean viability of 90% as judged by trypan blue exclusion. Viable cells (5 × 10 4 per 2-cm 2 polyvinyl chloride well plate) were cultured with equal parts of Dulbecco's modified Eagle's minimal essential medium and Ham's F-12 for 24 h. The endpoint of the analysis was the adherence of tumor cells to the polyvinyl chloride well plate, which was taken as a proxy for functional cell viability. Cytological evaluation was performed separately by two cytologists blinded to the source and date of the smears. Results. Transtubal fluid dissemination was seen in 20 of 24 (83%) uteri. Tumor cells were found in 17 specimens (71%). In 10 (42%) specimens the disseminated tumor cells were functionally viable. Conclusions. Our model suggests that hysteroscopy can cause dissemination of malignant cells into the abdominal cavity from uteri containing endometrial carcinoma and that these cells can be functionally viable and adhere to a matrix.