Search

Head and neck squamous cell carcinomas (HNSCCs) arising in the mucosal linings of the upper aerodigestive tract are highly heterogeneous, aggressive, and multifactorial tumors affecting more than half a million patients worldwide each year. Classical etiological factors for HNSCC include alcohol, tobacco, and human papillomavirus (HPV) infection. Current treatment options for HNSCCs encompass surgery, radiotherapy, chemotherapy, or combinatorial remedies. Comprehensive integrative genomic analysis of HNSCC has identified mutations in TP53 gene as the most frequent of all somatic genomic alterations. TP53 mutations are associated with either loss of wild-type p53 function or gain of functions that promote invasion, metastasis, genomic instability, and cancer cell proliferation. Interestingly, disruptive TP53 mutations in tumor DNA are associated with aggressiveness and reduced survival after surgical treatment of HNSCC. This review summarizes the current evidence and impact of TP53 mutations in HNSCC.

Most cases of thyroid carcinoma are classified as low risk. These lesions have been treated with open surgery, remote access thyroidectomy, active surveillance, and percutaneous ablation. However, there is lack of consensus and clear indications for a specific treatment selection. The objective of this study is to review the literature regarding the indications for management selection for low-risk carcinomas. Systematic review exploring inclusion and exclusion criteria used to select patients with low-risk carcinomas for treatment approaches. The search found 69 studies. The inclusion criteria most reported were nodule diameter and histopathological confirmation of the tumor type. The most common exclusions were lymph node metastasis and extra-thyroidal extension. There was significant heterogeneity among inclusion and exclusion criteria according to the analyzed therapeutic approach. Alternative therapeutic approaches in low-risk carcinomas can be cautiously considered. Open thyroidectomy remains the standard treatment against which all other approaches must be compared.

Genetic, symptomatic, and biochemical heterogeneity of patients with primary hyperparathyroidism (PHPT) has become apparent in recent years. An in-depth, evidence-based review of the phenotypes of PHPT was conducted. This review was intended to provide the resulting information to surgeons who operate on patients with hyperparathyroidism. This review revealed that the once relatively clear distinction between familial and sporadic PHPT has become more challenging by the finding of various germline mutations in patients with seemingly sporadic PHPT. On the one hand, the genetic and clinical characteristics of some syndromes in which PHPT is an important component are now better understood. On the other hand, knowledge is emerging about novel syndromes, such as the rare multiple endocrine neoplasia type IV (MEN4), in which PHPT occurs frequently. It also revealed that, currently, the classical array of symptoms of PHPT is seen rarely upon initial presentation for evaluation. More common are nonspecific, nonclassical symptoms and signs of PHPT. In areas of the world where serum calcium levels are checked routinely, most patients today are "asymptomatic" and they are diagnosed after an incidental finding of hypercalcemia; however, some of them have subclinical involvement of bones and kidneys, which is demonstrated on radiographs, ultrasound, and modern imaging techniques. Last, the review points out that there are three distinct biochemical phenotypes of PHPT. The classical phenotype in which calcium and parathyroid hormone levels are both elevated, and other disease presentations in which the serum levels of calcium or intact parathyroid hormone are normal. Today several, distinct phenotypes of the disease can be identified, and they have implications in the diagnostic evaluation and treatment of patients, as well as possible screening of relatives.

Background Data about the results of transoral laser microsurgery (TLM) in elderly patients are limited. Methods A retrospective study of 72 consecutive cases of glottic carcinoma (63 pT1 and 9 pT2 cases) in elderly patients (≥70 years old, mean 76 years) treated with TLM was made. A systematic review of the literature was performed. Results Six patients (8%) had postoperative complications, but no treatment-related deaths were observed. Local recurrences occurred in 12 patients (16.5%): nine with pT1 (14%) and three with pT2 (33%) tumors. Five-year disease-specific survival (DSS), overall survival, and laryngectomy-free survival were 95%, 68%, and 88%, respectively. The literature review indicated that TLM is safe and effective treatment for these patients, with few complications and good local control (>85%) and DSS (>90%) rates. Conclusions Our results and the information from the literature show that TLM for glottic cancer in elderly patients can lead to satisfactory treatment results.

Item does not contain fulltext The objective of the review was to compare molecular and health effects of tobacco smoking using cigars, cigarillos, pipe and water pipe in relation to the effects of cigarette smoking. In this review we will focus on the upper respiratory tract. Mechanisms of interaction of tobacco smoke constituents after products other than cigarettes are similar to these associated with cigarette smoking. Carcinogenic activity was demonstrated for any type of tobacco smoking, although the risk of developing head and neck squamous cell carcinoma (HNSCC) remains lower in users of cigars, traditional pipe and water pipe as compared to cigarette smoking. Nevertheless, there is no way of safe tobacco smoking.

Contains fulltext : 193448.pdf (Publisher’s version ) (Closed access) BACKGROUND: Lymph node ratio (LNR) is increasingly reported as a potential prognostic tool. The purpose of this review was to analyze the available literature on the prognostic significance of LNR in head and neck squamous cell carcinoma (HNSCC). METHODS: A PubMed internet search was performed and articles meeting selection criteria were reviewed. RESULTS: Twenty-eight studies were identified in the literature dealing with the prognostic value of LNR. The published results are variable with a range of cutoff values of LNR associated with prognosis (overall survival [OS] and/or disease-specific survival [DSS]) between 0.02 and 0.20, with an average of 0.09. CONCLUSION: The LNR is reported to be of value in assessing prognosis in the patients with HNSCC. Although it is easy to calculate and could be considered in the staging of these patients, the currently available evidence in the literature does not yet provide a solid base for implementation.

Background The purpose of this study was to investigate the clinical relevance of phosphorylated ribosomal protein S6 (p-S6), a surrogate marker of mammalian target of rapamycin (mTOR) activation, and p21 in a series of 125 patients with oral squamous cell carcinomas (OSCCs). Methods Immunohistochemical analysis was performed to ascertain the phosphorylation status of p-S6 at Ser235/236 and Ser240/244, p21, and p53 protein expression. Results Expression of phosphorylated S6 protein on either serine 235/236 or serine 240/244 was detected in 83% and 88% tumors, respectively, and both of them were inversely and significantly correlated with the tumor size and local infiltration. Positive p21 expression was found in 91.5% of the cases, and was inversely correlated with tumor size. In OSCC, p21 expression correlates with p-S6 levels, a surrogate marker of mTOR activation, independently of p53 status. Conclusion Expression of both p21 and p-S6 was found to inversely associate with tumor size but not survival outcomes in patients with OSCC.

Background HERG1 potassium channel plays a critical role in the cell proliferation. Methods HERG1 protein expression was analyzed by immunohistochemistry (IHC) in 62 patients with oral leukoplakias and 100 patients with oral squamous cell carcinomas (OSCC). HERG1 mRNA levels were assessed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in 22 patients with primary head and neck squamous cell carcinoma (HNSCC). Results Statistically significant associations were found between HERG1 expression and tobacco consumption, disease stage, tumor differentiation, tumor recurrence, and reduced survival. There was no association between HERG1 expression and the risk of progression from oral leukoplakia to OSCC. In addition, a high proportion of tumors (80%) showed increased HERG1 mRNA levels compared to normal mucosa from nononcologic patients. Conclusion Aberrant HERG1 expression increases as oral tumorigenesis progresses from oral hyperplasia to OSCC. Increased HERG1 mRNA levels were also frequently detected in OSCC and other HNSCC subsites. HERG1 expression emerges as a clinically relevant feature during tumor progression and a potential poor prognostic biomarker for OSCC. © 2016 Wiley Periodicals, Inc. Head Neck, 2016

Although most malignant lymphadenopathy in the neck represent lymphomas or metastases from head and neck primary tumors, occasionally, metastatic disease from remote, usually infraclavicular, sites presents as cervical lymphadenopathy with or without an obvious primary tumor. In general, these tumors metastasize to supraclavicular lymph nodes, but occasionally may present at an isolated higher neck level. A search for the primary tumor includes information gained by histology, immunohistochemistry, and evaluation of molecular markers that may be unique to the primary tumor site. In addition, 18F-fluoro-2-deoxyglocose positron emission tomography combined with CT (FDG-PET/CT) has greatly improved the ability to detect the location of an unknown primary tumor, particularly when in a remote location. Although cervical metastatic disease from a remote primary site is often incurable, there are situations in which meaningful survival can be achieved with appropriate local treatment. Management is quite complex and requires a truly multidisciplinary approach. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2374-E2385, 2016.

Neuroendocrine neoplasms of the sinonasal region, which are relatively uncommon but clinically very important, are reviewed here in the light of current knowledge. Using a definition for neuroendocrine based on phenotypic, histologic, immunohistochemical, and electron microscopic features rather than histogenetic criteria, sinonasal neuroendocrine carcinomas are examined with a particular emphasis on the small-cell and large-cell subtypes. This is followed by revisiting olfactory neuroblastoma because it is also a tumor that shows a neuroendocrine phenotype. Kadish clinical and Hyams histologic grading systems as prognosticators of olfactory neuroblastoma are also considered in detail. Finally, controversies regarding sinonasal undifferentiated carcinoma as a neuroendocrine tumor are discussed and a possible relationship with high-grade olfactory neuroblastoma is explored. Genetic events and current management of these tumors are also outlined. © 2015 Wiley Periodicals, Inc. Head Neck 38: E2259-E2266, 2016.

Primary mucosal melanomas (PMMs) of the head and neck are uncommon malignancies that arise mainly in the nasal cavity and paranasal sinuses, followed by the oral cavity. The mainstay of treatment is radical surgical resection followed by adjuvant radiotherapy in selected patients with high-risk features. Multimodality therapy has not been well studied and is not standardized. Adjuvant radiotherapy seems to improve locoregional control but does not improve overall survival (OS). Elective neck dissection is advocated in patients with oral PMM. Systemic therapy should be considered only for patients with metastatic or unresectable locoregional disease. Despite improvements in the field of surgery, radiotherapy, and systemic therapy, patients with PMM still face a very unfavorable prognosis (5-year disease-free survival [DFS]

Regional metastasis is a prominent feature of head and neck squamous cell carcinoma (HNSCC) and is an important prognostic factor. The currently available imaging techniques for assessment of the neck have limitations in accuracy; thus, elective neck dissection has remained the usual choice of management of the clinically N0 neck (cN0) for tumors with significant (≥20%) incidence of occult regional metastasis. As a consequence, the majority of patients without regional metastasis will undergo unnecessary treatment. The purpose of this review was to discuss new developments in techniques that potentially improve the accuracy of the assessment of the neck in patients with HNSCC. Although imaging has improved in the last decades, a limitation common to all imaging techniques is a lack of sensitivity for small tumor deposits. Therefore, complementary to improvements in imaging techniques, developments in more invasive diagnostic procedures, such as sentinel node biopsy (SNB) will add to the accuracy of diagnostic algorithms for the staging of the neck.

Neck dissection is an important treatment for metastases from upper aerodigestive carcinoma; an event that markedly reduces survival. Since its inception, the philosophy of the procedure has undergone significant change from one of radicalism to the current conservative approach. Furthermore, nonsurgical modalities have been introduced, and, in many situations, have supplanted neck surgery. The refinements of imaging the neck based on the concept of neck level involvement has encouraged new philosophies to evolve that seem to benefit patient outcomes particularly as this relates to diminished morbidity. The purpose of this review was to highlight the new paradigms for surgical removal of neck metastases using an evidence-based approach.

BACKGROUND: The purpose of this study was to give an overview on hereditary syndromes associated with head and neck paragangliomas (HNPGs). METHODS: Our methods were the review and discussion of the pertinent literature. RESULTS: About one third of all patients with HNPGs are carriers of germline mutations. Hereditary HNPGs have been described in association with mutations of 10 different genes. Mutations of the genes succinate dehydrogenase subunit D (SDHD), succinate dehydrogenase complex assembly factor 2 gene (SDHAF2), succinate dehydrogenase subunit C (SDHC), and succinate dehydrogenase subunit B (SDHB) are the cause of paraganglioma syndromes (PGLs) 1, 2, 3, and 4. Succinate dehydrogenase subunit A (SDHA), von Hippel-Lindau (VHL), and transmembrane protein 127 (TMEM127) gene mutations also harbor the risk for HNPG development. HNPGs in patients with rearranged during transfection (RET), neurofibromatosis type 1 (NF1), and MYC-associated factor X (MAX) gene mutations have been described very infrequently. CONCLUSION: All patients with HNPGs should be offered a molecular genetic screening. This screening may usually be restricted to mutations of the genes SDHD, SDHB, and SDHC. Certain clinical parameters can help to set up the order in which those genes should be tested. (c) 2013 Wiley Periodicals, Inc. Head Neck 36: 907-916, 2014.

Recent studies support an important role for human papillomavirus (HPV) in oropharyngeal squamous cell carcinomas (OPSCC), although the incidence varies widely depending on the geographic location and time period studied. The aim of this study was to determine the proportion of HPV in a large cohort of OPSCC in northern Spain in the years 1990–2009. Clinical records and paraffin embedded tumor specimens of 248 consecutive patients surgically treated for OPSCC (140 tonsillar and 108 base of tongue) between 1990 and 2009 were retrieved. OPSCC cases were histomorphologically evaluated, and protein expression of p16 and p53 was analyzed by immunohistochemistry. Detection of high-risk HPV DNA was performed by GP5+/6+-PCR and in situ hybridization (ISH). Thirty cases (12%) were positive for p16 immunostaining, of which eight (3.2% of the total series) were found positive for HPV type 16 by genotyping of GP5+6+-PCR products. All HPV GP5+/6+-PCR-positive tumors were p53-immunonegative, seven had a basaloid morphology and seven were also positive by HPV ISH. Presence of HPV correlated inversely with tobacco and alcohol consumption (p < 0.001), but not with age of onset of OPSCC. Overall survival was better in the HPV-positive group, although not statistically significant (p = 0.175). OPSCC patients in northern Spain demonstrated a low involvement of HPV, increasing (although not significantly, p = 0.120) from 1.8% in 1990–1999 to 6.1% of cases in 2000–2009.

Gastroesophageal reflux disease (GERD), or its variation known as laryngopharyngeal reflux (LPR), has been recognized as a potential cause of several laryngeal disorders. Patients with laryngeal cancer have lifestyle risk factors, especially tobacco and alcohol consumption, that play an etiological role in the development of their cancer but also places them at risk for reflux. The question then arises whether there is merely an association or a causal relationship between laryngeal cancer and reflux. However, despite a number of studies, a causal relationship with laryngeal cancer is uncertain. In this article, we address the current literature in a critical manner to evaluate the relationship between reflux and laryngeal cancer. From the review of the literature, we conclude that there is insufficient evidence to support a causal role of reflux in laryngeal cancer, mainly because of the confounding effect of tobacco and alcohol consumption and the inaccuracies in the diagnosis of reflux.

Background The recognition of patients at high risk for the development of distant metastasis (DM) is required to recognize a subset of patients who may benefit from systemic therapy. Methods In a retrospective analysis of patients treated between 1995 and 2006, 443 patients with surgically treated primary head and neck squamous cell carcinoma were included. The frequency and clinicopathologic risk factors for DM were evaluated. Results A total of 60 patients (13.5%) developed DM. In a univariate analysis, tumor site (pharynx), pN classification (pN2–N3), differentiation grade (poorly differentiated), disease stage (stage IV), number (3 or more nodes), and site (bilateral nodes) of nodal metastasis were found to be significantly associated with the risk of DM. In a multivariate analysis, the only significant risk factors were the differentiation grade and the number and site of nodal metastasis. Conclusions Patients with pharyngeal poorly differentiated tumors, with multiple or bilateral nodal metastases, are at greater risk of DM and should be considered for systemic therapy. © 2011 Wiley Periodicals, Inc. Head Neck, 2011

Objectives: The gold standard of treatment of cancer of the lateral wall of the oropharynx continues to be unclear, especially in advanced stages. In this study, we report our experience with surgical treatment of these cancers and describe the functional and oncological results of the procedures. Study Design: Retrospective review. Methods: A total of 155 previously untreated patients with squamous cell carcinoma of the lateral wall of the oropharynx who underwent a surgical resection of the lesion at our department from January 1990 to January 2008 were included. Sixty-seven percent of these patients received postoperative radiotherapy. The records of these patients were reviewed to obtain measures such as local and regional control, disease-specific survival, and speech and swallowing function. Results: Six patients had a stage I disease, 15 had a stage II disease, 31 had a stage III disease, 86 had a stage IVA, and 17 had stage IVB disease. The overall recurrence rate was 60%, and the local recurrence rate was 40%. The 5-year overall survival and disease-specific survival rates were 33% and 43%, respectively. Five-year disease-specific survival rates by stage were as follows: 100%, 59%, 57%, 31%, and 33% for stages I to IVB, respectively. Multivariate analysis showed two parameters that were independent predictors of a reduced disease-specific survival: cervical lymph node metastases pN2–3 (P = .027) and primary tumor classified as pT3–4 (P = .029). In 122 patients, a tracheotomy was performed, and it couldn't be sealed in 23% of them. Oral alimentation was successfully recovered in 93% of the patients. Conclusions: Surgical treatment of cancer of the lateral wall of the oropharynx provides acceptable oncological and functional results, especially in early and moderately advanced stages (stages I–III). In advanced stages (stage IV), we obtained good functional preservation rates but poor oncological outcomes. Consequently, these groups of patients could be considered for another treatment modality, such as radiochemotherapy.

Item does not contain fulltext Adenocarcinomas of various types account for 10% to 20% of all primary malignant neoplasms of the nasal cavity and paranasal sinuses. There is a general consensus that the optimal treatment of adenocarcinoma is surgery and postoperative radiotherapy. The purpose of this report was to review the results of this combined treatment as well as other treatment strategies and their outcome. Most series present outcome data from a heterogeneous group of patients, with a wide variety of tumor subtypes presenting at differing stages, who received a variety of treatment strategies. Surgical excision remains the treatment of choice. The choice of approach is determined by what will best allow complete excision of the disease. Endoscopic techniques, if feasible for complete removal of the tumor, offer results comparable to those of external approaches with lower morbidity. Although clear evidence to support the use of radiotherapy in sinonasal adenocarcinoma is difficult to obtain, local control rates of combined treatment strategies for advanced cases are comparable to less advanced cases with surgery alone, suggesting a positive role for postoperative radiotherapy. However, the importance of thorough surgical resection should be stressed. (c) 2011 Wiley Periodicals, Inc. Head Neck, 2012. 01 augustus 2012

Item does not contain fulltext The decision regarding treatment of the clinically negative neck has been debated extensively. This is particularly true with early-stage tumors for which surgery is the treatment of choice, and the tumor has been resected transorally without a cervical incision. Elective neck dissection in this situation is an additional procedure with potential associated morbidity. The alternative strategy for the clinically negative neck is to "wait and watch." Both an elective neck dissection policy and a "watchful waiting" policy have their proponents. The purpose of this article was for us to review the literature about this subject to try to answer the following question: if the tumor has been resected transorally, should an elective treatment of the neck be performed or is a "watchful waiting" policy safe and adequate? We conclude that, currently, the best available evidence suggests that elective neck dissection does not seem to be superior to the policy of observation without neck surgery, with regard to survival and control of neck disease. This review highlights the need for further well-designed prospective studies that will provide more reliable answers to the debatable issue of the management of the clinically negative neck in such cases.

Item does not contain fulltext Cutaneous squamous cell carcinoma (SCC) of the head and neck may metastasize in up to 5% of patients, with the parotid lymph nodes the most frequent site for spread. Metastases frequently show delayed presentation after the primary cancer had been treated. The optimum treatment should be surgery followed by adjuvant radiotherapy, with an appropriate parotidectomy, and preservation of the facial nerve if not involved by tumor and treatment to the neck. In a clinically N0 neck, levels I to III should be cleared for facial primaries, levels II to III for anterior scalp and external ear primaries, and levels II to V for posterior scalp primaries. Approximate 5-year disease-specific survival (DSS) after treatment was 70% to 75%. Patients with immunosuppression, in particular transplant recipients, are at high risk of developing aggressive metastatic cutaneous SCC. Modifications of the staging systems have demonstrated the prognostic benefits of accurately staging parotid and/or neck nodal disease. (c) 2010 Wiley Periodicals, Inc. Head Neck, 2010.

Item does not contain fulltext Adenoid cystic carcinoma (ACC) is an uncommon tumor usually arising in the head and neck region, mainly in the salivary glands. It demonstrates an indolent prolonged course and is characterized by perineural invasion. Primary treatment of local and locoregional disease consists mainly of surgery and/or irradiation. During follow-up these patients frequently develop local recurrences and distant metastases, especially in the lung, although long-term survival is possible. The role of chemotherapy in ACC is limited, and studies with only a limited number of patients are performed. In this article we review the literature on chemotherapy regimens, including monotherapy and combination chemotherapy schedules, as well as the new targeted therapies.

Objective The purpose of this study was to examine whether a relationship exists between HIF-1α expression and the pro-apoptotic protein p53 in supraglottic laryngeal squamous cell carcinomas (SCCs), which could provide information concerning patient prognosis. Methods The study population was composed of 106 previously untreated men with SCC of the supraglottic larynx. All the patients underwent surgical resection of the tumor and bilateral neck dissection. Immunohistochemical analysis of HIF-1α and p53 protein expression was performed in relation with clinicopathological parameters and prognosis. Results HIF-1α nuclear expression was detected in 71% of primary carcinomas and 55% of the paired lymph node metastases. There was a significant positive correlation between HIF-1α and T-classification but no associations were observed with other clinicopathological variables and with prognosis. There was no correlation between the expression of HIF-1α and p53. HIF-1α overexpression in combination with p53 immunostaining was not associated with disease recurrence or survival. Conclusion The data suggest that HIF-1α expression does not have a prognostic value in surgically treated supraglottic laryngeal SCC, and that immunohistochemical determination of p53 does not allow improving the clinical significance of HIF-1α. J. Surg. Oncol. 2009;99:373–378. © 2009 Wiley-Liss, Inc.

Objective Paragangliomas (PGLs) of the head and neck are benign neoplasms derived from the autonomic nervous system. Familial PGLs have been associated with germline mutations in succinate dehydrogenase (SDH) genes, and occasionally in Von Hippel–Lindau (VHL) and RET. The aim of this study was to compare somatic DNA copy number changes in tumors of familial and sporadic origin. Material and Methods Eight familial and 16 sporadic patients were analyzed for germline mutations and exon deletions in SDHB, SDHC, SDHD, VHL, and RET by direct sequencing and MLPA. Microarray CGH analysis was applied to map genome-wide somatic copy number changes. Results Fifteen cases carried a germline mutation in SDHB or SDHD, four of which not described before. Microarray CGH detected abnormalities in 10 of 18 cases, most frequently concerning deletions at 1p, 1q, and 11q, the sites where SDH are located. However, these deletions occurred in both SDH mutation–positive and SDH mutation–negative cases. Conclusions These data suggest that inactivating germline SDH mutations and somatic deletions of SDH genes as a “second hit” are involved in a subset, but not in all PGLs. Additional genes and mechanisms may need to be studied, especially in the group of sporadic PGL showing no chromosomal aberrations.

Amplification of the 11q13 region is a prevalent genetic alteration in head and neck squamous cell carcinoma (HNSCC). We investigated the clinical significance of cortactin (CTTN) and cyclin D1 (CCND1) amplification in both malignant transformation and tumour progression. CTTN and CCND1 amplification was analysed by differential and real-time PCR in a prospective series of laryngeal/pharyngeal carcinomas and archival premalignant tissues. CTTN mRNA and protein expression were respectively determined by real-time RT-PCR and immunohistochemistry, and correlated with gene status. Molecular alterations were associated with clinicopathological parameters and disease outcome. CTTN and CCND1 amplifications were respectively found in 75 (37%) and 90 (45%) tumours. Both correlated with advanced disease; however, only CTTN amplification was associated with recurrence and reduced disease-specific survival (p = 0.0022). Strikingly, CTTN amplification differentially influenced survival depending on tumour site (p = 0.0001 larynx versus p = 0.68 pharynx) and was an independent predictor of reduced survival in the larynx (p = 0.04). CCND1 amplification was detected in early tumourigenesis and increased with the severity of dysplasia. Importantly, CTTN amplification was only found in high-grade dysplasias that progressed to invasive carcinoma. CTTN gene status strongly correlated with mRNA and protein expression. Furthermore, CTTN overexpression correlated significantly with reduced disease-specific survival (p = 0.018). Taken together, these data indicate that CTTN may serve as a valuable biomarker to identify patients with laryngeal tumours at high risk of recurrence and poor outcome.

Malignant ethmoid and maxillary sinus tumors frequently involve the orbit. Orbital involvement is an important prognostic predictor of recurrence-free, disease-specific, and overall survival. Most authors agree that orbital preservation as opposed to orbital exenteration or clearance does not result in significant differences in local recurrence or actuarial survival. The eye can be safely preserved in most patients with ethmoid or maxillary sinus cancer invading the orbital wall, including malignancies that invade the orbital soft tissues with penetration through the periorbita provided that they can be completely dissected away from the orbital fat. Malposition of the globe and nonfunctional eyes frequently result when patients have not had adequate rigid reconstruction of the orbital floor, particularly if they have received postoperative radiotherapy. This underscores the importance of such reconstruction. Isolated defects following orbital exenteration may be reconstructed with a temporalis muscle flap. Microvascular free-tissue transfer is the best option for repair of defects following orbital exenteration and total maxillectomy, although an obturator still has a role in selected patients.

OBJECTIVE: Assess the amplification of CCND1, EMS1, PIK3CA, ERBB1, and ERBB2 oncogenes in ethmoid sinus adenocarcinomas.STUDY DESIGN AND SETTING: Tissue samples from 13 primary ethmoid adenocarcinomas and 2 recurrences were studied at Hospital Central de Asturias, Oviedo, Spain, between July 1998 and February 2002. A semiquantitative evaluation of CCND1, EMS1, PIK3CA, ERBB1, and ERBB2 amplification was performed by multiplex polymerase chain reaction.RESULTS: Three (23%) cases presented CCND1 amplification, one of them with a concurrent PIK3CA amplification. EMS1 was amplified in the 2 studied recurrences. ERBB1 was amplified in 1 case (8%), whereas none presented ERBB2 amplification. Oncogenic amplifications were only detected in advanced (stage III) tumors; however, no prognostic value could be shown for them.CONCLUSIONS: CCND1, EMS1, PIK3CA, and ERBB1 amplifications are uncommon and appear to be late events in the development of ethmoid sinus adenocarcinoma.SIGNIFICANCE: New information on the carcinog...

Background. The treatment of the clinically negative (N0) neck in supraglottic laryngeal cancer continues to be an area of controversy. The aim of this study was to analyze the long-term efficacy of routine bilateral neck dissection compared with ipsilateral neck dissection in T1–T2 N0 lateral supraglottic carcinomas. Methods. A retrospective review of 108 patients who underwent surgery for T1-T2 supraglottic squamous cell carcinoma was performed. Forty-eight had undergone ipsilateral functional neck dissection, and 60 had undergone bilateral functional neck dissections. None of these patients received adjuvant radiotherapy. Results. No significant differences (p = .78) in regional recurrence were observed between the patients treated with bilateral neck dissection (13%) and those treated with ipsilateral neck dissection (17%). The 5-year survival rates were 73% and 80% for the patients who received a bilateral and ipsilateral neck dissection, respectively (p = .51). Conclusions. This study suggests that routine bilateral neck dissection may not be necessary in the surgical treatment of all supraglottic cancers.© 2006 Wiley Periodicals, Inc. Head Neck 28:534–539, 2006

Thyroid cancers are the most common endocrine malignancies and are being diagnosed with increased frequency in modern clinical practice. Among other diagnostic modalities, fine-needle aspiration (FNA) biopsy of clinically suspicious thyroid nodules is becoming increasingly popular. Preliminary investigations have suggested that molecular diagnostic assays using tumor-specific markers may improve the sensitivity and accuracy of FNA and so may be expected to reduce the frequency of open surgical procedures by identifying those patients with demonstrably benign lesions who do not require definitive surgical excision of their lesions for diagnosis. At the same time, thyroid-specific mRNA assays (especially thyroglobulin mRNA testing) have been used by investigators in the postoperative follow-up of patients with thyroid cancer as a potential means of detecting tumor recurrence in the peripheral blood. Although these studies have not all reported unqualified successes—indeed, some problems based on both technical and biologic limitations have been identified—these assays still hold out the possibility that potentially important new advances in the management of patients with well-differentiated thyroid cancer may be offered by these and other molecular diagnostic methods. © 2006 Wiley Periodicals, Inc. Head Neck, 2006

Although perioperative antibiotic prophylaxis has significantly reduced surgical wound infection rates, this complication is still a frequent complication of head and neck cancer surgery. Because these infections are typically polymicrobial, our study evaluated the safety and efficacy of piperacillin-tazobactam in the treatment of surgical wound infection after clean-contaminated head and neck oncologic surgery.In this multicenter, prospective clinical trial, 70 patients with surgical wound infection received piperacillin-tazobactam.Of patients who were evaluable, 92.4% were also clinically cured or improved, and the bacteriologic eradication rate was 80.3%. Of the 70 patients enrolled in the study, six (8.5%) experienced six adverse events: two cases of moderate diarrhea, one allergic skin reaction, and three cases of phlebitis. No deaths were attributable to the study drug.Piperacillin-tazobactam is a good choice of treatment as monotherapy for surgical wound infection after clean-contaminated head and neck oncologic surgery.

OBJECTIVE: Complement C4d-containing fragments have been proposed as diagnostic markers for lung cancer. The purpose of this study was to evaluate the presence of C4d in oropharyngeal (OPSCC) and oral (OSCC) squamous cell carcinomas. SUBJECTS AND METHODS: C4d staining was analyzed by immunohistochemistry in 244 OPSCC surgical specimens. C4d levels were quantified by ELISA in resting saliva samples from 48 patients with oral leukoplakia and 62 with OSCC. Plasma samples from 21 patients with leukoplakia and 30 with oral carcinoma were also studied. RESULTS: C4d staining in OPSCC specimens was associated with nodal invasion (P = 0.001), histopathologic grade (P = 0.014), disease stage (P = 0.040), and focal-adhesion kinase expression (P < 0.001). No association was found between C4d and prognosis. Saliva C4d levels were higher in patients with oral cancer than in subjects with leukoplakia (0.07 +/- 0.07 vs 0.04 +/- 0.03 mu g ml(-1), P = 0.003). The area under the ROC curve was 0.63 (95%CI: 0.55-0.71). Salivary C4d levels in stage IV patients were higher than in patients with earlier stages (P = 0.028) and correlated with tumor size (P = 0.045). Plasma C4d levels also correlated with salivary C4d levels (P = 0.041), but differences between patients with oral cancer and subjects with leukoplakia were not significant (1.26 +/- 0.59 vs 1.09 +/- 0.39 mu g ml(-1), P = 0.232). CONCLUSION: C4d-containing fragments are detected in oral primary tumors and are increased in saliva from patients with OSCC., We thank Amaya Lavin for technical assistance. This work was supported by Foundation for Applied Medical Research (FIMA), Red Tematica de Investigacion Cooperativa en Cancer (RD12/0036/0015, RD12/0036/0025, and RD12/0036/0040), and Fondo de Investigacion Sanitaria-Fondo Europeo de Desarrollo Regional (FEDER, PI11/00618, PI13/00806, PI11/00929, and PI14/01686).

Desmoid tumor, or aggressive fibromatosis, is a rare, histologically benign, fibroblastic lesion that infrequently presents in the head and neck. Desmoid tumors often grow locally, invasively, and may, in rare instances, be fatal secondary to invasion into critical structures, such as airway or major vessels. The most common treatment is surgery, but desmoid tumors are characteristically associated with a high local recurrence rate after resection. Although the margin status seems to be of importance, operations that avoid function loss and esthetic disfigurement should be the primary goal. The efficacy of postoperative radiotherapy is controversial. Its potential benefit should be carefully balanced against possible radiation-induced adverse effects. Alternative treatment modalities, such as primary radiotherapy and medical treatment or a wait-and-see policy, may be preferable to mutilating surgery. Considering all the aforementioned, it seems obvious that desmoid tumors of the head and neck present a therapeutic challenge and require an individualized approach.

Background Although appropriate perioperative antibiotic prophylaxis has significantly reduced wound infection rates in clean-contaminated head and neck surgical procedures, controversy still remains regarding the optimal antibiotic regimen. Methods In this prospective, double-blind clinical trial, 159 patients were randomized to receive amoxicillin-clavulanate, clindamycin plus gentamicin, or cefazolin intravenously up to ½ hour before surgery and at 8-hour intervals for an additional three doses. Results An overall wound infection rate of 23% was observed. Thirteen (22.8%) infections occurred in the amoxicillin-clavulanate-treated group, 11 (21.2%) in the clindamycin plus gentamicin-treated group, and 13 (26%) in the cefazolin-treated group, which was not statistically significant. Only prior medical illnesses, such as chronic obstructive pulmonary disease and diabetes mellitus, correlated with an increased wound infection rate (p = 0.018). Conclusions Amoxicillin-clavulanate, clindamycin plus gentamicin, and cefazolin seem to have similar efficacy when administered prophylactically in clean-contaminated head and neck surgical procedures. © 1997 John Wiley & Sons, Inc. Head Neck 19: 188–193, 1997.

Problem: Hypoxia, a hallmark of solid tumors, functions as a driving force in cancer progression. The hypoxia-inducible factor-1alpha (HIF-1alpha) is a transcription factor that is overexpressed in many human cancers and up-regulates genes that promote lethal tumor progression. Although significant associations between HIF-1alpha overexpression and patient mortality have been shown in most cancers, the function of HIF-1alpha in HNSCC tumor progression is controversial. Methods: Expression of HIF-1alpha was investigated by immunohistochemistry on paraffin-embedded sections from 34 patients with HNSCC and 9 patients with premalignant lesions. Results: HIF-1alpha was expressed in 85% of tumor sections with a nuclear expression pattern. The distribution of immunoreactive cells was independent of blood vessel and necrosis proximity, which indicates that factors other than hypoxia contribute to HIF-1alpha expression in HNSCC. Areas of hyperplasia adjacent to the tumor also showed nuclear reactivity; whereas none of the preinvasive isolated lesions show any HIF-1alpha expression. HIF-1alpha expression was significantly higher in advanced T-stage tumors (T4) compared with T1 tumors (P = 0.014). There was no significant difference in HIF-1alpha expression between categories of age, N-stage, histological grade, or localization. As primary tumors, paired lymph node metastases showed nuclear immunoreactivity to HIF-1alpha. There was a significant correlation between the percentage of HIF-1alpha positive cells in the primary tumor and the percentage in the corresponding metastasis (P = 0.006), suggesting a role of HIF-1alpha on cancer expansion. Conclusion: Our results suggest that HIF-1alpha expression in HNSCC is driven by an oxygen-independent mechanism, and that HIF-1alpha could contribute to the progression of these tumors. Significance: Overexpression of HIF-1alpha is a frequent event in HNSCC, suggesting that HIF-1alpha could be a therapeutic target in these carcinomas. Support: None reported.

7. Weiss D, Koopmann M, Rudack C. Prevalence and impact on clinicopa-thological characteristics of human papillomavirus-16 DNA in cervicallymph node metastases of head and neck squamous cell carcinoma.Head Neck 2011;33:856–862.8. Armas GL, Su CY, Huang CC, Fang FM, Chen CM, Chien CY. Theimpact of virus in N3 node dissection for head and neck cancer. EurArch Otorhinolaryngol 2008;265:1379–1384.9. Barwad A, Sood S, Gupta N, Rajwanshi A, Panda N, Srinivasan R.Human papilloma virus associated head and neck cancer: a PCR basedstudy. Diagn Cytopathol 2011;Epub ahead of print.10. Hoffmann M, Gottschlich S, G€or €ogh T, et al. Human papillomaviruses inlymph node neck metastases of head and neck cancers. Acta Otolaryngol2005;125:415–421.11. Desai PC, Jaglal MV, Gopal P, et al. Human papillomavirus in metastaticsquamous carcinoma from unknown primaries in the head and neck: a ret-rospective 7 year study. Exp Mol Pathol 2009;87:94–98.12. Compton AM, Moore-Medlin T, Herman-Ferdinandez L, et al. Humanpapillomavirus in metastatic lymph nodes from unknown primary headand neck squamous cell carcinoma. Otolaryngol Head Neck Surg 2011;145:51–57.

The activation of ERBB oncogenes has been described in various human tumours, including squamous cell carcinomas of the head and neck (SCCHN), and, in some of them, it has been correlated with a poor prognosis. Tissue samples from 59 patients with SCCHN were studied. After DNA extraction, the ERBBZ, ZXBB2 and EMU33 copy number in tumour samples was estimated with the polymerase chain reaction (PCR) meti, od. The PCR products were analysed by agarose gel electrophoresis and quantified by image analysis techniques. 9 (15%) cases presented with EMU32 amplification, which was correlated with lymph node involvement (P = 0.04), poorly differentiated tumours (P = 0.03) and a hypopharyngeal primary site (P = 0.035). No correlation among amplification status, recurrence, metastases and survival was observed, although this may be due to the small number of patients in the amplified group. None of the 59 cases presented amplification of ERBB2 and ERBB3 oncogenes. Copyright