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In the Western world, more than 90% of head and neck cancers are head and neck squamous cell carcinomas (HNSCCs). The most appropriate treatment approach for HNSCC varies with the disease stage and disease site in the head and neck. Concurrent chemoradiotherapy has become a widely used means for the definitive treatment of locoregionally advanced HNSCC. Although this multimodality treatment provides higher response rates than radiotherapy alone, the detection of residual viable tumor after the end of therapy remains an important issue and is one of the major applications of (18)F-FDG PET. Studies have shown that negative (18)F-FDG PET or PET/CT results after concurrent chemoradiotherapy have a high negative predictive value (>95%), whereas the positive predictive value is only about 50%. However, when applied properly, FDG PET/CT can exclude residual disease in most patients, particularly patients with residual enlarged lymph nodes who would otherwise undergo neck dissection. In contrast to other malignancies, data are limited on the utility of (18)F-FDG PET for monitoring the response to induction chemotherapy in HNSCC or for assessing treatment response early during the course of definitive chemoradiotherapy. The proliferation marker (18)F-3'-deoxy-3'fluorothymidine is currently under study for this purpose. Beyond standard chemotherapy, newer treatment regimens in HNSCC take advantage of our improved understanding of tumor biology. Two molecules important in the progression of HNSCC are the epidermal growth factor receptor and the vascular endothelial growth factor (VEGF) and its receptor VEGF-R. Drugs attacking these molecules are now under study for HNSCC. PET probes have been developed for imaging the presence of these molecules in HNSCC and their inhibition by specific drug interaction; the relevance of these probes for response assessment in HNSCC will be discussed. Hypoxia is a common phenomenon in HNSCC and renders cancers resistant to chemo- and radiotherapy. Imaging and quantification of hypoxia with PET probes is under study and may become a prerequisite for overcoming chemo- and radioresistance using radiosensitizing drugs or hypoxia-directed irradiation techniques and for monitoring the response to these techniques in selected groups of patients. Although (18)F-FDG PET/CT will remain the major clinical tool for monitoring treatment in HNSCC, other PET probes may have a role in identifying patients who are likely to benefit from treatment strategies that include biologic agents such as epidermal growth factor receptor inhibitors or VEGF inhibitors.

Background The present study is aimed at identifying potential candidate genes as prognostic markers in human oral tongue squamous cell carcinoma (SCC) by large scale gene expression profiling. Methods The gene expression profile of patients (n=37) with oral tongue SCC were analyzed using Affymetrix HG_U95Av2 high-density oligonucleotide arrays. Patients (n=20) from which there were available tumor and matched normal mucosa were grouped into stage (early vs. late) and nodal disease (node positive vs. node negative) subgroups and genes differentially expressed in tumor vs. normal and between the subgroups were identified. Three genes, GLUT3 , HSAL2 , and PACE4 , were selected for their potential biological significance in a larger cohort of 49 patients via quantitative real-time RT-PCR. Results Hierarchical clustering analyses failed to show significant segregation of patients. In patients (n=20) with available tumor and matched normal mucosa, 77 genes were found to be differentially expressed (P< 0.05) in the tongue tumor samples compared to their matched normal controls. Among the 45 over-expressed genes, MMP-1 encoding interstitial collagenase showed the highest level of increase (average: 34.18 folds). Using the criterion of two-fold or greater as overexpression, 30.6%, 24.5% and 26.5% of patients showed high levels of GLUT3 , HSAL2 and PACE4 , respectively. Univariate analyses demonstrated that GLUT3 over-expression correlated with depth of invasion (P<0.0001), tumor size (P=0.024), pathological stage (P=0.009) and recurrence (P=0.038). HSAL2 was positively associated with depth of invasion (P=0.015) and advanced T stage (P=0.047). In survival studies, only GLUT3 showed a prognostic value with disease-free (P=0.049), relapse-free (P=0.002) and overall survival (P=0.003). PACE4 mRNA expression failed to show correlation with any of the relevant parameters. Conclusion The characterization of genes identified to be significant predictors of prognosis by oligonucleotide microarray and further validation by real-time RT-PCR offers a powerful strategy for identification of novel targets for prognostication and treatment of oral tongue carcinoma.

Background Merkel cell carcinoma (MCC) is a cutaneous neuroendocrine neoplasm with propensity for lymphatic spread. The rarity of MCC has limited analysis of factors associated with a positive sentinel lymph node biopsy (SLNB) and survival. Methods Review of a prospective MCC database was performed. Factors associated with SLNB positivity were analyzed. Univariate and multivariate analyses of factors associated with recurrence and survival were performed using the cumulative incidence (CI) function, treating death from other causes as a competing risk. Results From 1996 to 2010, a total of 153 patients with localized MCC underwent SLNB, of whom 45 (29%) were positive. Factors associated with SLNB positivity were primary tumor size (25% ≤2 cm vs. 45% >2 cm; P  = 0.02) and presence of lymphovascular invasion (LVI) (55% LVI positive vs. 4% LVI negative; P  < 0.01). SLNB-positive patients were more likely to receive radiation or chemotherapy (60% vs. 7%, P  < 0.01). With median follow-up of 41 months, there were 16 nodal/distant recurrences (10%), 11 deaths from MCC (7%), and 27 death from other causes (18%). The 2-year CIs of recurrence or death from MCC were 12% and 6%, respectively. There was no difference in recurrence or death from MCC between SLNB-positive and -negative patients. The 2-year CIs of recurrence or death from MCC for LVI-positive patients were 30% and 15%, respectively. No LVI-negative patient experienced recurrence of disease or died of MCC. Discussion SLNB identifies occult nodal metastases in 29% of patients with localized MCC. Predictors of SLNB positivity are tumor size and presence of lymphovascular invasion (LVI). Patients with SLNB-positive disease are more likely to receive further treatment; however, sentinel lymph node (SLN) status is not associated with recurrence or survival. In contrast, LVI is strongly associated with both recurrence and survival.

Electronic search strategy (with a full description of at least one electronic search strategy sufficient to allow replication of the search), process for article selection, data variables sought, assumptions and simplifications, methods for assessing bias risk of each individual study (such as selective reporting in individual studies) and utilization of this information in data synthesis, principal summary measures (risk ratio, hazard ratio, difference in means, etc.), methods of data management and combining study results, outcome level assessment, and other information should be reported. If the systematic review involves studies with paired samples and quantitative data, a summary of data should be provided for each intervention group along with effect estimates and confidence intervals for all outcomes of each study. If a meta-analysis is performed, then synthesized effect size should be reported with confidence intervals and measures of consistency (i.e. – data heterogeneity such as I2) for each meta-analysis, and assessment of bias risk across studies. Studies that lack a control group may over-estimate the effect size of the experimental intervention or condition being studied and are not ideal for meta-analyses [8].

Background Sentinel lymph node biopsy (SLNB) for primary cutaneous head and neck melanoma (CHNM) has been shown to be successful and is the current standard of care for intermediate-thickness melanoma. We evaluated our experience with CHNM associated with SLNB mapping to the region of the parotid gland. Methods Retrospective review of a prospectively collected melanoma database identified 1014 CHNMs. Two-hundred twenty-three patients underwent SLNB, and 72 (32%) had mapping in the region of the parotid gland between May 1995 and June 2003. Results The mean number of SLNs per patient was 2.5. A sentinel lymph node (SLN) was successfully identified in 94% of patients, and in 12%, the SLN was positive for metastatic disease. Biopsy of intraparotid SLNs was performed in 51.4% and of periparotid SLNs in 26.4%, and a superficial parotidectomy was performed in 22.2%. Ten patients were found to have lymph nodes in the parotid region with metastatic disease (eight identified by SLNB), and two (20%) patients developed intraparotid lymph node recurrence in the setting of a negative SLNB. Same-basin recurrence in SLN-negative patients was 3.3% with a median follow-up of 26 months. Facial nerve dysfunction was identified in seven (10%) patients. Facial nerve function returned to preoperative status in all patients. Conclusions SLNB for patients with primary CHNM mapping to the parotid gland can be performed with a high degree of accuracy and a low morbidity consisting of temporary facial nerve paresis.

Background Recurrent head and neck malignancies remain a therapeutic challenge. Tissue transfer, in addition to defect coverage and prevention of wound complications, may potentially decrease radiotoxicity. We evaluated radiation toxicity and survival outcomes of patients who underwent salvage surgery with reirradiation, comparing primary closure to flap reconstruction. Methods Retrospective outcomes analysis of recurrent head and neck squamous cell carcinoma (HNSCC) patients treated with curative intent by salvage surgery (± flap reconstruction) and reirradiation from 1996 to 2011. Recurrent stage, reirradiation modality, chemotherapy use, and toxicities were evaluated. Results Of 96 patients, 59 had primary closure, whereas 37 underwent flap reconstruction (26 free, 11 pedicled). Median radiation and reirradiation doses were 66 Gy and 60 Gy, respectively. Comparing nonflap and flap patients, there was no significant difference in acute mild toxicities (100 vs. 100 %, p  = 1.0) or acute severe toxicities (33.9 vs. 37.8 %, p  = 0.83). Nonflap patients experienced significantly greater incidence of both late mild toxicities (81.4 vs. 54.1 %, p  = 0.006) and late severe toxicities (47.5 vs. 21.6 %, p  = 0.02). Overall survival at 5 years was equivalent (33.1 vs. 34.7 %, p  = 0.88). Free flap patients had greater delays to postoperative reirradiation and treatment package times compared with pedicled flap patients but no meaningful difference in survival outcomes. Conclusions Vascularized tissue potentially helps offset late toxicities associated with a second radiation course in recurrent head and neck cancer patients. In these selected patients, flap coverage may confer functional benefits and improve the long-term radiotoxicity profile.

Review articles do not require institutional review board approval if the data reviewed are public (including private and government databases) and if the articles reviewed have received institutional review board approval previously. The type of systematic review, according to the Cochrane Collaboration, is based on the research question being asked, and may assess diagnostic test accuracy, review prognostic studies evidence, evaluate intervention effects, scrutinise research methodology or summarise qualitative evidence.6 In the methods section, the participants, interventions, comparisons, outcomes and study design (‘PICOS’) must be put forward. Details regarding the following aspects also should be reported: electronic search strategy (with a full description of at least one electronic search strategy sufficient to allow replication of the search), process for article selection, data variables sought, assumptions and simplifications, methods for assessing bias risk of each individual study (such as selective reporting in individual studies) and utilisation of this information in data synthesis, principal summary measures (e.g. risk ratio, hazard ratio, difference in means), methods of data management and combining study results, outcome level assessment, and any other information. Studies that lack a control group may over-estimate the effect size of the experimental intervention or condition being studied, and are not ideal for meta-analyses.8 It also should be remembered that the conclusions of a meta-analysis are only as valid as the data on which the analysis is based.

Metastasis to the regional lymph node is the most important prognostic indicator for the outcomes of patients with sold cancer. In general, it is well recognized that cancer development is genetically determined with progression from the microenvironment of the primary tumor site, oftentimes via the SLN gateway, to the distant sites. In about 20 % of the time, the cancer cells may spread directly through the blood vascular system to the distant sites. Thus, in general, cancer progression is consistent with Hellman’s spectrum theory in that development of nodal and systemic metastasis from a localized cancer growth is a progressive process. Cancer proliferation within the tumor microenvironment may give rise to increased tumor heterogeneity, which is further complicated by its continuous change through its evolution within the host in a Darwinian sense. It is crucial to understand the molecular process of lymphangiogenesis and hemangiogenesis in the tumor microenvironment with respect to the initial steps of cancer cells entering into the lymphatic and vascular systems so that rational therapy can be developed to curb the process of specific routes of metastasis. This chapter elucidates the role of lymphatics, nodal metastasis and antitumor immunity. We present novel immune targets in nodal metastases, the importance of the lymph node as a pre-metastatic niche, and immune-related proteins as biomarkers of metastasis.

The potential for the misinterpretation of positron-emission tomography (PET) scans in the context of a possible malignancy has been confirmed in a case report showing increased 18F-fluorodeoxyglucose (FDG) uptake after unilateral vocal fold augmentation medialization. We sought to expand these findings by investigating FDG uptake in a larger cohort of patients via a retrospective chart review. We examined the records of 15 adults—8 men and 7 women—who had undergone vocal fold augmentation for unilateral vocal fold paralysis and at least one subsequent PET scan. The differences in PET standard uptake value (SUV) between the injected and noninjected vocal folds were assessed via the Wilcoxon signed-rank test. A Spearman rank correlation coef-ficient was then used to estimate the relationship between differences in PET uptake and the length of time between the injection and the follow-up PET scan. The mean SUV of the injected vocal folds was 3.70, and the mean in the noninjected folds was 2.97. The difference did not achieve statistical significance (p = 0.34). In addition, the rank correlation coefficient with regard to the association between the difference in PET uptake and the duration between injection and PET was −0.24, suggesting an inverse relationship. However, the correlation coefficient did not differ significantly from zero (p = 0.34). We conclude that PET uptake after vocal fold augmentation medialization is variable and that it can increase substantially. This information should be considered in the context of the diagnostic accuracy of malignancy on PET.

Hallmarks of legitimate journals include: A well‐known editorial board of recognized experts in the field; An International Standard Serial Number (ISSN); Listing in the Directory of Open Access Journals at https://doaj.org; Publisher membership in the Open Access Scholarly Publishers Association; Affiliation with recognized societies. [...]authors who may have been rejected by legitimate peer‐reviewed journals may find that some open access journals offer an avenue for publication without editorial oversight. [...]we suggest the following guidelines when evaluating whether a journal is predatory. Rakesh Chandra, MDCo‐Editor‐in‐Chief, American Journal of Rhinology & AllergyEdward W. Fisher, MA, DM (Oxon), FRCSSenior Editor, Journal of Laryngology and OtologyTerry M. Jones, BSc(Hons), MBBS, FRCSEd, FRCS(ORL‐HNS), MDEditor‐in‐Chief, Clinical OtolaryngologyDavid W. Kennedy, MDEditor‐in‐Chief, International Forum of Allergy & RhinologyDennis H. Kraus, MD, FACSCo‐Editor‐in‐Chief, Journal of Neurological Surgery ‐part BJohn H. Krouse, MD, PhD, MBAEditor‐in‐Chief, Otolaryngology—Head and Neck SurgeryEditor‐in‐Chief, OTO‐OpenMichael Link, MDCo‐Editor‐in‐Chief, Journal of Neurological Surgery ‐part BLawrence R. Lustig, MDEditor‐in‐Chief, Otology & NeurotologyBert W. O'Malley, Jr., MDEditor‐in‐Chief, Journal for Oto‐Rhino‐Laryngology, Head and Neck SurgeryJay F. Piccirillo, MD, FACSEditor‐in‐Chief, JAMA Otolaryngology—Head & Neck SurgeryRobert Ruben, MD, FAAP, FACSEditor‐in‐Chief, International Journal of Pediatric OtorhinolaryngologyRobert T. Sataloff, MD, DMA, FACSEditor‐in‐Chief, Journal of Voice;Editor‐in‐Chief, Ear, Nose and Throat JournalRaj Sindwani, MDCo‐Editor‐in‐Chief, American Journal of Rhinology & AllergyRichard J. Smith, MDEditor‐in‐Chief, Annals of Otology, Rhinology & LaryngologyMichael G. Stewart, MD, MPH, FACSEditor‐in‐Chief, The LaryngoscopePeter C. Weber, MDEditor‐in‐Chief, American Journal of OtolaryngologyD.