Neck lymph node metastases from unknown primary.

Metastatic cervical carcinoma from unknown primary is a metastatic disease in the lymph nodes of the neck without any evidence of a primary tumour after appropriate investigation. The condition is rare and definite evidence is lacking for both diagnosis and treatment. In this review of the literature, we tried to draw some clinical indications based on the few available studies. We ultimately came to the following conclusions: (1) a thorough and accurate diagnostic work-up should be systematically offered. It includes accurate inspection with fibroscopy, CT or MRI, fine needle aspiration, panendoscopy and positron emission tomography, (2) Patients with low-volume neck disease, N1 and N2a stage and without extracapsular extension on histopathological examination should receive single modality treatment. Radiotherapy and surgery may be similarly effective but, if possible, surgery (excisional biopsy, neck dissection and tonsillectomy) should be favoured because it consents a more precise staging, (3) patients with more advanced conditions require combined treatment in the form of either resection followed by adjuvant radiation (±chemotherapy) or primary chemoradiation (±post-therapy neck dissection).

Development of an algorithm for the management of cervical lymphadenopathy in children: consensus of the Italian Society of Preventive and Social Pediatrics, jointly with the Italian Society of Pediatric Infectious Diseases and the Italian Society of Pediatric Otorhinolaryngology.

UNLABELLED: Cervical lymphadenopathy is a common disorder in children due to a wide spectrum of disorders. On the basis of a complete history and physical examination, paediatricians have to select, among the vast majority of children with a benign self-limiting condition, those at risk for other, more complex, diseases requiring laboratory tests, imaging and, finally, tissue sampling. At the same time, they should avoid expensive and invasive examinations when unnecessary. The Italian Society of Preventive and Social Pediatrics, jointly with the Italian Society of Pediatric Infectious Diseases, the Italian Society of Pediatric Otorhinolaryngology, and other Scientific Societies, issued a National Consensus document, based on the most recent literature findings, including an algorithm for the management of cervical lymphadenopathy in children. METHODS: The Consensus Conference method was used, following the Italian National Plan Guidelines. Relevant publications in English were identified through a systematic review of MEDLINE and the Cochrane Database of Systematic Reviews from their inception through March 21, 2014. RESULTS: Basing on literature results, an algorithm was developed, including several possible clinical scenarios. Situations requiring a watchful waiting strategy, those requiring an empiric antibiotic therapy, and those necessitating a prompt diagnostic workup, considering the risk for a severe underling disease, have been identified. CONCLUSION: The present algorithm is a practice tool for the management of pediatric cervical lymphadenopathy in the hospital and the ambulatory settings. A multidisciplinary approach is paramount. Further studies are required for its validation in the clinical field.

The assessment of children with suspected laryngopharyngeal reflux: An Otorhinolaringological perspective.

The assessment of pediatric laryngopharyngeal reflux (LPR) is controversial. Otorhinolaryngologists may play a role in the evaluation of children with suspected LPR detecting typical airway endoscopic findings and/or associated diseases and may help in the selection of children to be subjected to further instrumental tests. In this perspective the present review aims at examining the available evidence in the literature regarding the assessment of LPR in children. After careful literature search there are no current validated symptoms assessment questionnaires for LPR evaluation in children; flexible fiberoptic nasopharyngolaryngoscopy remains controversial as a diagnostic tool in suspect LPR cases; even though the multichannel intraluminal impedance with pH monitoring has been proposed as the instrumental gold standard, further evidence need to be found for validation in children with typical features of LPR.

Drug induced sleep endoscopy in the decision-making process of children with obstructive sleep apnea.

Tonsillectomy and adenoidectomy (T&A) is currently recommended in children with Obstructive Sleep Apnea (OSA). However, the condition persists after surgery in about one third of cases. It has been suggested that Drug Induced Sleep Endoscopy (DISE) may be of help for planning a more targeted and effective surgical treatment but evidence is yet weak. The aim of this review is to draw recommendation on the use of DISE in children with OSA. More specifically, we aimed at determine the proportion of cases whose treatment may be influenced by DISE findings. A comprehensive search of articles published from February 1983 to January 2014 listed in the PubMed/MEDLINE databases was performed. The search terms used were: "endoscopy" or "nasoendoscopy" or "DISE" and "obstructive sleep apnea" and "children" or "child" or "pediatric." The main outcome was the rate of naive children with hypertrophic tonsils and/or adenoids. The assumptions are that clinical diagnosis of hypertrophic tonsils and/or adenoids is reliable and does not require DISE, and that exclusive T&A may solve OSA in the vast majority of cases even in the presence of other concomitant sites of obstruction. Five studies were ultimately selected and all were case series. The median (range) number of studied children was 39 (15-82). Mean age varied from 3.2 to 7.8 years. The combined estimate rate of OSA consequent to hypertrophic tonsils and/or adenoids was 71% (95%CI: 64-77%). In children with Down Syndrome, the combined estimated rate of hypertrophic tonsils and/or adenoids was 62% (95%CI: 44-79%). Our findings show that DISE may be of benefit in a minority of children with OSA since up to two thirds of naive cases presents with hypertrophic tonsils and/or adenoids. Its use should be limited to those whose clinical evaluation is unremarkable or when OSA persists after T&A.

Nasopharyngeal tonsils (adenoids) contain extrathymic corticothymocytes.

Adenoidal tissue (also known as nasopharyngeal tonsils) of 58% of humans in the pediatric age group contains immature T-lymphoid cells with the phenotype of thymocytes (TdT+, CD1abc+, cytoplasmic CD3+, coexpressing CD4 and CD8, lacking an Intraepithelial Lymphocyte-associated phenotype). The notable difference in comparison to palatine tonsils is the clustering in groups and sheets, comprising hundreds or thousands of cells (1.7%±0.2 of total T cells). The thymic epithelium is morphologically and phenotypically absent. Adenoids share with tonsils and lymph nodes the presence of immature B cell precursors (TdT+, CD1a-, Pax5+, Surrogate light chain±), however in these latter the presence of TdT+, CD1a+, Pax5- precursors is absent or limited to individual cells. Human adenoids are distinct among the Waldeyer's ring lymphoid tissue because of the known embryogenic derivation from the third pharyngeal pouch, from which the thymus develops; in addition, they may display phenotypic incomplete features of a vestigial thymus.

Risk of recurrence in children operated for thyroglossal duct cysts: A systematic review.

PURPOSE: To determine the rate of recurrence following surgical treatment of thyroglossal duct cysts (TDGCs) in children. METHODS: A search of electronic databases (Pubmed and MEDLINE) was performed in order to identify studies concerning surgical treatment of TGDCs in children published between 1980 and 2012. The following terms were used: "thyroglossal duct cysts", "recurrent", "recurrence", "children", "pediatric". RESULTS: Sixteen articles were selected with the majority published during the last decade. The total number of included subjects was 1233. The mean (95% confidence interval (CI)) rate of recurrences was 10.7% (9.1%-12.6%). Eleven studies involving 751 subjects reported the frequency of recurrences separately for primary cases. The mean (95% CI) rate of recurrences was 10.8% (8.7%-13.3%). Five studies reported separately results of surgery for secondary cases. The mean (95% CI) rate of recurrences was 20.0% (12.2%-30.8%). Eight of the sixteen studies reported data on risk factors for recurrence. The use of the Sistrunk technique is a protective factor, whereas children who experienced repeated episodes of infection prior to surgery are exposed to a higher risk of recurrence. CONCLUSION: Recurrences after surgery for TDGCs remain a clinically relevant issue. One of ten operated children experiences a recurrence. Available data support the use of the Sistrunk technique but further studies aimed at improving the clinical management of TDGCs are required.

Intratympanic steroid treatment for sudden deafness: a meta-analysis of randomized controlled trials.

BACKGROUND: The efficacy of intratympanic steroid (ITS) treatment in sudden deafness (SD) remains controversial. To shed light on this issue, we performed a systematic review of randomized controlled trials to assess the overall efficacy of ITS therapy and to clarify whether it is more suitable as a first-line approach (primary treatment) or as a salvage treatment when traditional systemic agents have failed. METHODS: An electronic database search (MEDLINE and PubMed) was performed with the objective of identifying all studies published in the English language between January 1980 and November 2011 on the efficacy of ITS in the treatment of SD. All relevant articles were retrieved, and the related reference lists were reviewed systematically to identify other reports that could be included. Data were synthesized using the Mantel-Haenszel model. Results are expressed as odds ratio (OR) with 95% confidence interval (CI). RESULTS: A total of 11 randomized studies including 472 subjects allocated to ITS and 453 controls were selected. Intratympanic steroid regimens used and treatments administered to controls varied widely across studies. When considering together trials investigating ITS therapy as a primary (n = 4) or salvage (n = 7) treatment, the common OR for recovery was 1.7 (95% CI, 1.3-2.3). When considering them separately, the common ORs for recovery were 0.9 (95% CI, 0.7-1.6) for primary and 2.9 (95% CI, 1.9-4.5) for salvage therapy. CONCLUSION: Intratympanic steroid therapy seems to confer a certain degree of benefit as a salvage but not as a primary treatment of SD. However, further evidence is needed to clarify some yet uncertain aspects, such as the optimal protocol of therapy.

Nasal lavage in pregnant women with seasonal allergic rhinitis: a randomized study.

BACKGROUND: Nasal rinsing appears particularly suitable in the management of pregnant women with seasonal allergic rhinitis since no deleterious effects on the fetus are to be expected. However, to date, no studies have specifically investigated this option. METHODS: Pregnant women with seasonal allergic rhinitis were randomized to intranasal lavage with hypertonic saline solution 3 times daily (n = 22) versus no local therapy (n = 23) during a 6-week period corresponding to the pollen season. Patients were invited to keep a daily record of rhinitis symptoms (rhinorrea, obstruction, nasal itching and sneezing), to record consumption of oral antihistamine and to undergo rhinomanometry. RESULTS: The rhinitis score was similar at study entry but a statistically significant improvement in this score was observed in the study group during all subsequent weeks (p < 0.001 for weeks 2-6). The mean number of daily antihistamines use per patient per week was significantly reduced at weeks 2, 3 and 6 (p < 0.001, p < 0.001 and p = 0.001, respectively). Baseline rhinomanometry performed at week 1 showed similar nasal resistance in the study and control groups. In contrast, a statistically significant difference emerged in the 2 following evaluations. At week 3, nasal resistance in the study and control groups was 0.96 +/- 0.44 and 1.38 +/- 0.52 Pa/ml/s, respectively (p = 0.006). At week 6, it was 0.94 +/- 0.38 and 1.35 +/- 0.60 Pa/ml/s, respectively (p = 0.006). No adverse effect was reported in the active group. CONCLUSIONS: Nasal rinsing is a safe and effective treatment option in pregnant women with seasonal allergic rhinitis.

Effectiveness of adenotonsillectomy in PFAPA syndrome: a randomized study.

OBJECTIVE: To evaluate whether adenotonsillectomy leads to complete resolution in children with PFAPA (periodic fever, aphthous stomatitis, pharyngitis, and cervical adenitis) syndrome. STUDY DESIGN: Thirty-nine children with PFAPA syndrome were randomized to either adenotonsillectomy (surgery group; n = 19) or expectant management (control group; n = 20). All patients were then invited prospectively to record all PFAPA episodes, and were evaluated clinically every 3 months for 18 months after randomization. RESULTS: The proportion of patients experiencing complete resolution was 63% in the surgery group and 5% in the control group (P < .001). The mean (+/- standard deviation) number of episodes recorded during the study period was 0.7 +/- 1.2 in the surgery group and 8.1 +/- 3.9 in the control group (P < .001). The episodes were less severe in the surgery group. CONCLUSIONS: Adenotonsillectomy is an effective treatment strategy for children with PFAPA syndrome.

MAP kinase modulation in squamous cell carcinoma of the oral cavity.

BACKGROUND: Oral squamous cell carcinoma (OSCC) represents the sixth most diffused cancer in developed countries. Mitogen-activated protein kinases (MAPKs) are proteins which transduce a vast array of extracellular signals into intracellular responses. The role of MAPK signalling pathway in cancer is not completely understood. MATERIALS AND METHODS: In this study, we attempted to specifically evaluate the activation state of MAPK in OSCC. MAPK expression and activation were analyzed by immunoblotting in thirty tissue samples of OSCC and their paired nonneoplastic perilesional tissues. On the same tissues, the activation and expression of MAPK JNK/SAPK were also evaluated by ELISA assay. RESULTS: Analyzing the levels of phospho-ERK1/2(p44/p42), a statistically significant reduction was observed in tumors compared to normal tissues. No statistically significant difference between tumor and control tissue was found for p38MAPK or JNK/SAPK. CONCLUSION: These results suggest that a reduction in ERK1/2(p44/p42) phosphorylation is correlated with tumor growth in OSCC.

Lymphomas of head and neck in pediatric patients.

Cancer among children is relatively uncommon, with approximately 1 in 7,000 children 0 to 14 years of age being newly diagnosed each year in the United States, and Hodgkin and non-Hodgkin's lymphomas constitute 10-15% of all childhood cancers in the more developed countries, after acute leukemias and brain tumors. The diagnosis of lymphoma frequently involves otolaryngologists that play also an important role in the its management. A high index of suspicion for lymphoma as a cause of complaints in the head and neck region can lead an early diagnosis and improved outcome for lymphomas. This article reviews the epidemiology, presentation, diagnosis, staging, treatment and prognosis of Hodgkin and non-Hodgkin's lymphomas in children.

Prognostic influence of gender in patients with oral tongue cancer.

OBJECTIVES: The purpose of this study was to evaluate the independent role of gender in affecting prognosis in patients with anterior tongue cancer. DESIGN: Patients recorded in the head and neck cancer registry of Milano-Bicocca School of Medicine between January 1981 and December 1998 were reviewed. Female patients with squamous cell carcinoma of the tongue were identified and matched to men for year of diagnosis, age, TNM classification, histologic grading, and treatment modalities. For each woman, two men were matched. RESULTS: Seventy-one women and 142 men satisfied our selection criteria. The frequency of recurrences was similar in the two study groups. This event occurred in 33 (46%) women and in 78 (55%) men (Fisher exact test, P = 0.25). The survival analysis confirmed that the rate of recurrences did not differ (log-rank test, P = 0.31). The number of cancer-related deaths in women and men was 23 (32%) and 55 (39%), respectively (Fisher exact test, P = 0.45). The survival analysis confirmed that gender did not affect survival (log-rank test, P = 0.34). CONCLUSION: In this study, gender does not influence prognosis in patients with oral tongue cancer.

Oral tongue cancer in young patients: a matched analysis.

Previous studies on squamous cell carcinoma of the tongue have reported conflicting results with respect to age and prognosis. The aim of this study is to elucidate if any differences in outcome exist between patients younger and older than 40 years. A case-control study was performed. Patients recorded in the head and neck cancer registry of Milano-Bicocca School of Medicine between January 1981 and December 1998 were reviewed. Cases were patients with squamous cell carcinoma of the tongue aged 40 years or less. Controls were patients older than 40 who were matched to cases for diagnosis, sex and TNM classification. Two controls were matched for each case, thus forty-six cases and 92 controls were selected. The frequency of recurrences was found to be significantly higher in younger patients. The survival analysis further supports this conclusion (log-rank test, p=0.002). The number of cancer-related deaths in patients younger and older than 40 years were 23 (50%) and 31 (34%), respectively (p=0.10). A statistical significant difference emerged when the number of deaths was compared using survival curves (log-rank test, p=0.05). In conclusion, in patients with squamous cell carcinoma of the tongue, young age is an independent predictor of worse survival.

Risk factors for distant metastases in head and neck squamous cell carcinoma.

OBJECTIVES: To evaluate the frequency of distant metastases (DM) and to determine the ability of certain clinical and pathologic factors to predict the development of distant metastases. DESIGN: Retrospective analysis. SETTING: University hospital. PATIENTS: A total of 1972 patients with oral, oropharyngeal, hypopharyngeal, and laryngeal squamous cell carcinomas who were treated from 1981 to 1998 and who were not diagnosed as having DM at the time of initial treatment. MAIN OUTCOME MEASURES: We evaluated the frequency of DM and the influence of different variables in their appearance. RESULTS: A total of 181 patients (9.2%) (95% confidence interval, 7.9%-10.5%) developed DM. Younger age (<45 years), hypopharyngeal localization, an advanced T stage and/or N stage tumor according to the TNM staging system, high histologic grade, and locoregional control were found to be significantly associated with the risk of DM at both univariate and multivariate analyses. CONCLUSIONS: The incidence of DM in subjects with head and neck squamous cell carcinoma is relatively low. The risk of DM is influenced by age, site of primary cancer, local and/or regional extension, grading, and achievement of locoregional control.

Selective reduction of extracellular signal-regulated protein kinase (ERK) phosphorylation in squamous cell carcinoma of the larynx.

Mitogen-activated protein kinase (MAPK) cascades transmit and amplify signals involved in cell proliferation as well as in cell death. In this study, the potential derangement of MAPK pathways has been evaluated in human squamous cell carcinomas (SCC) of the larynx. The expression and activity of the MAPK p38, ERK1/2p44/p42 and JNK/SAPKp46/p54 have been investigated by immunoblot analysis of tissue homogenates in 27 samples of primary laryngeal cancer and in 27 paired non-neoplastic laryngeal mucosa. On the same tissues, the activation of MAPK JNK/SAPKp46/p54 was also analyzed by an ELISA assay. The results obtained showed that both total and phosphorylated levels of JNK/SAPKp46/p54 and p38 were not different between tumor and normal samples. Conversely, while total protein levels for both ERK1p44 and ERK2p42 were not statistically different between tumor and normal samples, the analysis of the level of the activated forms of ERK1/2 showed a statistically significant decreased phosphorylation of both isoforms in the tumor samples compared to the control tissues. The rate of reduction was similar for both isoforms. Immunohistochemical analysis of all the activated MAPK (p38, JNK/SAPKp46/p54 and ERK1/2p44/p42) in both laryngeal SCC and normal mucosa demonstrated no difference of cellular localization. Activated ERK1/2p44/p42 and activated p38 demonstrated a nucleo-cytoplasmic distribution whereas activated JNK/SAPKp46/p54 were localized into the cytoplasmic membrane. The decreased activity of ERK1/2p44/42 in laryngeal SCC might reflect alterations in tumor suppressing activity or might derive from the interplay among various transduction pathways.

Incidence of inverted papilloma in recurrent nasal polyposis.

OBJECTIVES: A diagnosis of inverted papilloma in apparently normal bilateral polyps is a possible albeit rare event. The frequency of this diagnosis varies between 0.00% and 0.92%. There are no studies evaluating whether this possibility is significantly different in patients operated for recurrence when compared with those undergoing first surgery. The aim of this study is to evaluate the frequency of inverted papilloma in a series of histologic specimens obtained from patients undergoing surgery for recurrent nasal polyposis. METHODS: The authors conducted a retrospective chart and pathologic review of data from 1887 surgical interventions for removal of unremarkable bilateral nasal polyps. Frequency of inverted papilloma was assessed. RESULTS: Five cases of inverted papilloma were identified. The incidence of this diagnosis was thus 0.26% (95% confidence interval, 0.08-0.62%). Age, gender, and number of recurrences did not influence the frequency of this diagnosis. CONCLUSIONS: The occurrence of inverted papilloma in unremarkable recurrent cases of nasal polyps is rare. This rate is similar to the one observed in patients undergoing first surgery.

Histopathology of routine nasal polypectomy specimens: a review of 2,147 cases.

OBJECTIVES: There is controversy about whether all nasal polyps removed at operation should be sent for histopathologic examination. The primary aim of this study was to assess the incidence of unsuspected clinically relevant diagnoses in a large series of patients undergoing nasal polypectomy. A review of the literature on the frequency of this event was also performed. STUDY DESIGN: Retrospective study and review. METHODS: Data from patients undergoing nasal polypectomy over a 14 year period were reviewed. All adult patients undergoing first surgical removal of bilateral nasal polyps were included. Monolaterality and presence of suspicious looking lesions were exclusion criteria. RESULTS: A total of 2,147 patients were recruited. Eight cases of clinically relevant unexpected diagnoses were identified, corresponding to a frequency of 0.37% (95% confidence interval 0.16-0.73%). Inverted papilloma occurred in seven cases, neoplasia in one case. Affected patients tended to be older. Four previous smaller studies on this topic were identified. The reported incidence of unsuspected clinically relevant diagnoses varied between 0.00% and 0.92%. CONCLUSIONS: Although rare, unexpected clinically relevant findings may be identified during routine histologic examination of nasal polyps specimens. Future cost effectiveness analyses are required to clarify whether routine histology is a cost effective strategy.

Nasal rinsing with hypertonic solution: an adjunctive treatment for pediatric seasonal allergic rhinoconjunctivitis.

BACKGROUND: Recent but limited evidence suggests that nasal lavage with hypertonic saline may be useful as an adjunctive treatment modality in the management of pediatric allergic rhinitis. The aim of this study was to clarify whether nasal irrigation with hypertonic solution should be routinely recommended to children with seasonal grass pollen rhinoconjunctivitis. METHODS: Fourty-four children with seasonal grass pollen rhinoconjunctivitis were recruited. Twenty-two patients were randomized to receive three-times daily nasal rinsing with hypertonic saline during the pollen season, which lasted 7 weeks. Twenty-two patients were allocated to receive no nasal irrigation and were used as controls. Twenty patients per group completed the study. A mean daily rhinoconjunctivitis score based on the presence of nasal discharge and obstruction as well as ocular symptoms as reddening and itching were calculated for each week of the pollen season. Patients were allowed to use oral antihistamines when required and the mean number of drugs taken per week was also calculated. RESULTS: The mean weekly rhinoconjunctivitis score in the active group was reduced during the whole pollen period. This difference was statistically significant in week 6 and 7 of therapy. A markedly reduced intake of oral antihistamines was also observed in patients allocated to nasal rinsing, being statistically significant in 5 of the 7 weeks. No adverse effect was reported in the active group. CONCLUSIONS: This study supports the use of nasal rinsing with hypertonic saline in the pediatric patient with seasonal allergic rhinoconjunctivitis. This treatment proved to be tolerable, inexpensive and effective.

Reversed ipsilateral acoustic reflex: a study on subjects treated with muscle relaxants.

OBJECTIVES: To rule out any possible involvement of the middle ear muscles in the genesis of the reversed ipsilateral acoustic reflex (RIAR). DESIGN: Prospective study to evaluate the effects of muscle relaxants on the RIAR of otosclerotic ears as well as on the acoustic reflex of individuals with normal middle ear function. Admittance recording during ipsilateral acoustic stimulation was performed in patients undergoing pharmacological treatment for surgical procedures. Fentanyl, propofol, and a muscle relaxant were sequentially administered intravenously. Ipsilateral acoustic reflexes were recorded before and after each drug injection. Three patients were affected from otosclerosis, whereas 14 individuals had normal middle ear function. Moreover, the ipsilateral acoustic reflex obtained in normal subjects after their treatment with muscle relaxants was compared with that of 10 otosclerotic patients who were not treated pharmacologically. RESULTS: The RIAR of three otosclerotic ears was not inhibited by muscle relaxants as well as by fentanyl and propofol. Moreover, muscle relaxants, when administered in normal subjects, always induced the block of the stapedial reflex that was replaced by a reversed reflex strictly similar to the RIAR of the 10 otosclerotic patients not treated pharmacologically. Propofol could also induce, in most of the cases, the reduction and in some occasion even the reversal of the stapedial reflex, whereas fentanyl did not affect it significantly. CONCLUSION: The RIAR does not appear to be related to the contraction of the middle ear muscles.