The Minor's test in Frey syndrome treated with botulinum toxin: Methodology and efficacy.

In this paper, we aimed at methodologically presenting a video-case of Frey Syndrome occurred after parotidectomy, assessed by means of Minor's Test and treated with intradermic botulinum toxin A (BoNT-A) injection. Although largely described in the literature, a detailed explanation of both the procedures has not been previously elucidated. In a more original approach, we also highlighted the role of the Minor's test in identifying the most affected skin areas and new insight on the patient-tailored approach provided by multiple injections of botulinum toxin. Six months after the procedure, the patient's symptoms were resolved, and no evident signs of Frey syndrome were detectable through the Minor's test.

IFN-γ and other serum cytokines in head and neck squamous cell carcinomas.

SUMMARY: Altered immune responses have been reported in head and neck cancer, and some of these responses have been associated with poor clinical outcomes. A multiple-array technology platform was used to simultaneously evaluate the levels of 25 cytokines. Pre-treatment serum levels were evaluated in 31 HNSCC patients and 6 healthy controls. The levels of 8 cytokines, specifically IL-1ra, IL-2, IL-5, IL-6, IL-8, IL-17, IFN-γ and IP-10, were significantly higher in patients than in controls. Among cancer patients we observed lower levels of IFN-γ and IL-7 in cases with nodal metastases compared to those with cN0 disease. We observed increases in the levels of some serum cytokines in HNSCC patients, as well as reductions in selected cytokines associated with regional progression. These findings provide an intriguing perspective on the development and validation of novel markers for follow-up evaluations and predictions of regional spreading in HNSCC patients.

Prognostic factors in head and neck cancer: a 10-year retrospective analysis in a single-institution in Italy.

This study was undertaken to evaluate the association between demographics, lifestyle habits, and clinical data and overall survival (OS), recurrence and second primary cancer (SPC) in patients with first primary head and neck cancer (HNC). We retrospectively reviewed data from 482 patients treated at the "Agostino Gemelli" Teaching Hospital, Rome, between 2002-2012 for primary HNC. Individual parameters were evaluated for association with specific outcomes such as OS, cancer recurrence and second primary cancer (SPC) appearance using hazard ratios (HR) and 95% confidence intervals (CIs). Five-year OS was 60.6% for all HNC cases, 49.0% for oral cavity, 54.8% for oropharynx, 50.0% for hypopharynx and 63.4% for larynx. Predictors of OS were older age (HR = 1.04; 95% CI: 1.02-1.05) and advanced tumour stage (HR = 2.00; 95% CI: 1.41-2.84). The risk of recurrence was associated with drinking 8-14 drinks per week (HR = 1.73; 95% CI: 1.00-2.97). The risk of developing SPC increased with advanced tumour stage (HR = 2.75; 95% CI: 1.39-5.44) and with smoking for more than 40 years (HR = 3.68; 95% CI: 1.10-12.30). OS differed among HNC sites. Increasing age was an unfavourable predictor of HNC OS. Tumour stage was a prognostic factor both for OS and for risk of developing SPC. Alcohol and tobacco consumption were prognostic factors for recurrence and SPC, respectively.

Sensory dysfunction and quality of life after great auricular nerve sacrifice during parotidectomy: our experience.

OBJECTIVE: This study aimed to investigate the impact on patients' quality of life of great auricular nerve sacrifice during parotidectomy. METHODS: A retrospective review was conducted of 191 consecutive patients who underwent parotidectomy with great auricular nerve sacrifice between 2006 and 2011. Residual sensory dysfunction and its impact on quality of life was analysed using an eight-item quality of life survey. RESULTS: In all, 139 out of 191 patients (72.8 per cent) experienced one or more abnormal sensations in the ear or neck region after surgery. There was a moderate inverse correlation between the number of abnormal sensations and time elapsed since surgery. Moreover, the degree of discomfort correlated significantly with the frequency of symptom occurrence (p < 0.001), duration of the abnormal sensation (p < 0.001) and size of the affected area (p < 0.001). CONCLUSION: Sacrifice of the great auricular nerve has only a small impact on patient quality of life; their daily activities are not significantly affected.

Impact of microvascular free flap reconstruction in oral cavity cancer: our experience in 130 cases.

The aim of this study was to investigate the oncological outcomes in patients affected by oral carcinoma treated with radical compartmental surgery followed by microvascular flap reconstruction. We conducted a retrospective analysis on a cohort of 130 patients. All patients underwent ablative tumour resection (compartmental surgery) followed by immediate reconstruction with free flaps and adjuvant chemoradiotherapy, when necessary according to our tumour board and international guidelines. Disease-specific survival (DSS) curves were obtained using the Kaplan-Meier method. Log-rank test and generalised Wilcoxon test were used to investigate the most important prognostic factors on 5-year DSS. A Cox proportional hazards model was constructed to provide hazard ratios or relative risks for individual variables. 88.5% of patients were affected by SCC. There were 46 (35.4%) women and 84 (64.6%) men in the sample with a mean age of 58.5 years. At the end of the follow-up period, 36 (27.7%) patients died, only 3 of which for other causes. The 5-year DSS rate was 67.8% (S.E. 4.9%). In univariate Kaplan-Meier analysis and in multivariate Cox regression model, seven variables were found to have a significant relationship with DSS: T (p = 0.026) and N (p = 0.0001) status, clinical stage (according to the UICC TNM Sixth Edition) (p = 0.007), margins of resection (p = 0.001), extracapsular spread (p = 0.005), recurrence of disease (p = 0.00002) and treatment modality (evaluated as surgery alone or surgery + RT/CHT) (p = 0.004). Our results confirmed findings already reported in the literature, and allowed us to conclude that compartmental surgery combined with free flap reconstruction can increase survival in oral cancer patients.

Effects of the administration of epidermal growth factor receptor specific inhibitor cetuximab, alone and in combination with cisplatin, on proliferation and apoptosis of Hep-2 laryngeal cancer cells.

BACKGROUND: Epidermal growth factor receptor (EGFR) overexpression and prognostic value in head and neck squamous cell cancer is the basis for targeting by anti-EGFR antibodies, which increase the efficacy of radiotherapy. In order to evaluate the best therapeutic schedule, the effects of cetuximab (C225) on Hep-2 cell proliferation, alone and in combination with cisplatin, were studied. METHODS: Hep-2 cells were treated with cetuximab alone or in combination with cisplatin. After determining cell viability with trypan blue, morphological features of apoptotic degeneration were analysed by fluorescence microscopy with Hoechst 33258 stain. RESULTS: Cetuximab alone mildly inhibited Hep-2 proliferation and showed no pro-apoptotic effects. When administered concomitantly with cisplatin, cetuximab synergistically increased inhibition of proliferation and apoptosis. CONCLUSION: The antiproliferative activity of cetuximab is consistent with its hypothesised role in inhibiting repopulation. However, the increase in the effects of pro-apoptotic agents induced by cetuximab may be even more relevant to its clinical effectiveness than the inhibition of repopulation.

Contemporary role of pectoralis major regional flaps in head and neck surgery.

Countless disadvantages of the "old" pectoralis major have been listed while the amazing versatility of the free flap armamentarium gives the opportunity to suit the defect deriving from virtually every ablative head and neck surgery with a tailored reconstruction. Nevertheless, pectoralis major is still the "workhorse" for head and neck reconstruction in developing countries thanks to its ease of harvest, and minimal requirements in term of instrumentation. Furthermore, even in facilities with a high volume of reconstructions by free flaps, a certain number of pectoralis major flaps is still raised every year. The history, present role and current indications of the most widely head and neck reconstructive procedure ever has been reviewed.

New insights into human papillomavirus-associated head and neck squamous cell carcinoma.

Human papillomavirus (HPV)-associated head and neck squamous cell carcinoma (HNSCC) is an entity with peculiar clinical and molecular characteristics, which mainly arises from the reticulated epithelium lining the crypts of the palatine tonsils and the base of the tongue. The only head and neck site with a definite etiological association between persistent high-risk (HR) HPV infection and development of SCC is the oropharynx. HPV-positive malignancies represent 5-20% of all HNSCCs and 40-90% of those arising from the oropharynx, with widely variable rates depending on the geographic area, population, relative prevalence of environment-related SCC and detection assay. HPV-16 is by far the most common HR HPV genotype detected in oropharyngeal SCC (OPSCC), and the only definitely carcinogenic genotype for the head and neck region. Patients with HPV-induced OPSCC are more likely to be middle-aged white men, non-smokers, non-drinkers or mild to moderate drinkers, with higher socioeconomic status and better performance status than subjects with HPV-unrelated SCC. HPV-induced HNSCCs are often described as non-keratinizing, poorly differentiated or basaloid carcinomas, and are diagnosed in earlier T-category with a trend for a more advanced N-category, with cystic degeneration, than the HPV-unrelated carcinomas. HPV positivity is associated with better response to treatment and modality-independent survival benefit. Treatment selection in HPV-related oropharyngeal carcinoma is becoming a critical issue, and although there is no evidence from randomized, controlled trials to support a treatment de-escalation in HPV-positive SCC, some investigators argue that intensive combined modality strategies may represent an overtreatment.

HPV infection in squamous cell carcinomas arising from different mucosal sites of the head and neck region. Is p16 immunohistochemistry a reliable surrogate marker?

BACKGROUND: Human papillomavirus 16 infection has been proven to be associated with oropharyngeal squamous cell carcinomas (SCCs) and is probably the main reason of the reported increase in the incidence. The role of high-risk (HR) HPV for carcinogenesis of other sites in the head and neck awaits confirmation. With the aim to evaluate the prevalence of HPV infection and the reliability of different diagnostic tools in SCCs of different sites, 109 consecutive untreated head and neck SCCs were enrolled, and fresh tumour samples collected. METHODS: Human papillomavirus DNA was detected by Digene Hybrid Capture 2 (HC2). Human papillomavirus E6 and E7 mRNA were detected by NucliSENS EasyQ HPVv1. P16 expression was evaluated by immunohistochemistry. RESULTS: In all, 12.84% of cases were infected by HR genotypes and 1.84% by low-risk genotypes. Human papillomavirus 16 accounted for 87% of HR infections. The overall agreement between DNA and RNA detection is 99.1%. Although p16 expression clearly correlates with HPV infection (P=0.0051), the inter-rater agreement is poor (k=0.27). The oropharynx showed the highest HR HPV infection rate (47.6%) and was also the only site in which p16 immunohistochemistry revealed to be a fair, but not excellent, diagnostic assay (κ=0.61). CONCLUSION: The prognostic role of HR HPV infection in oropharyngeal oncology, with its potential clinical applications, underscores the need for a consensus on the most appropriate detection methods. The present results suggest that viral mRNA detection could be the standard for fresh samples, whereas DNA detection could be routinely used in formalin-fixed, paraffin-embedded samples.

Clinical approach and treatment of benign and malignant parotid masses, personal experience.

Parotid gland tumours account for 80% of all salivary gland neoplasms, 20% of these are malignant, but in daily clinical practice most parotid masses are operated on before obtaining the final histological diagnosis. This clinical setting further complicates the critical point of parotid surgery, which is the management of the facial nerve. In the present study, data were evaluated referring to 540 patients who underwent parotidectomy for a mass which was discovered to be a benign (470 cases) or a malignant (70 cases) neoplasm, between November 1994 and December 2007, at our Institution. The most significant single parameter in this series of malignancies regarding disease specific survival was the clinical involvement of the facial nerve at diagnosis (p = 0.006). Also for this reason, as there is no evidence that liberal VIIth nerve sacrifice improves prognosis, when it is not clinically involved, every attempt is made to dissect and preserve it. At present, the most complicated situation concerning nerve preservation may be, on the other hand, recurrence of a benign tumour, in particular pleomorphic adenoma, which, in our series, has a higher incidence (8.3%) of permanent facial dysfunction, than surgery with nerve preservation for malignancy (3.7%).

Oral cavity defect reconstruction using anterolateral thigh free flaps.

BACKGROUND: It is estimated that about 92,000 new cases of oral cavity and pharyngeal cancer occurred in Europe in 2008. During the past 30 years in the USA and Western Europe, the prognosis for oral cancer has clearly improved thanks to the possibility of reconstruction with microvascular free flaps, resulting in broader and safer resections. The anterolateral thigh flap is now being increasingly employed for this goal. The aim of the present work is to evaluate the anterolateral thigh free flap in the reconstruction of oral cavity defects. MATERIALS AND METHODS: Between July 2004 and February 2009, we harvested 73 free flaps for the reconstruction of soft tissue defects in the oral cavity of 70 patients at our institution. The oncological and functional results in these 70 patients were evaluated, particularly in those patients reconstructed with anterolateral thigh (ALT) free flap. We also evaluated the quality of life using the FACT-H&N questionnaire. RESULTS: We observed no significant differences in functional and oncological results between patients reconstructed by ALT and patients reconstructed with other flaps. Swallowing may be more difficult in patients who undergo adjuvant irradiation. CONCLUSIONS: In our opinion, the very low morbidity at the donor site, great versatility, and very long pedicle make the ALT free flap the first choice for reconstructing soft tissue defects in the oral cavity (particularly mobile tongue).

Pharyngocutaneous fistula onset after total laryngectomy: scintigraphic analysis.

Pharyngocutaneous fistula is the most common non-fatal complication following total laryngectomy. To start oral feeding and exclude the presence of a pharyngocutaneous fistula, a subjective test and instrumental assessments using videofluoroscopy, have been described. The aim of this study was to evaluate the effectiveness of oral-pharyngo-oesophageal scintigraphy as an objective and non-invasive tool to establish presence, site and dimensions of the fistula. Observations were performed on 3 male patients, mean age 65 years, who underwent total laryngectomy and mono or bilateral neck dissection after failure of radiotherapy in 2 cases and of conservative laryngeal surgery in the third case, complicated by post-operative pharyngocutaneous fistula. Oral-pharyngo-oesophageal scintigraphy dynamic study with sequential images were obtained during the swallowing phases. In case 1, the test showed a wide pharyngocutaneous fistula the internal orifice of which was at the level of the base of the tongue: on the scintigraphic images, the radiomarked water bolus, from the fistulous orifice, descended along the stoma walls and only a small part reached the oesophagus. In the other two patients, the pharyngocutaneous fistula was small and the internal fistulous orifice was detected in the lower part of T-suture line. In conclusion, scintigraphy offered the possibility to precisely identify presence of pharyngocutaneous fistula and location of its internal orifice and to monitor its spontaneous closure. Therefore, important information could be obtained regarding the suture line status and the possibility of deciding whether to remove the nasogastric tube or to leave it in place. Finally, these data showed that oral-pharyngo-oesophageal scintigraphy could be performed in the early post-operative period to optimize starting safe oral feeding.

Post-surgical role of botulinum toxin-A injection in patients with head and neck cancer: personal experience.

Personal experience is discussed in the use of botulinum neurotoxin injections into both parotids, performed in order to transiently reduce salivation in patients undergoing major ablative and ablative-reconstructive oncologic surgery for head and neck tumours. Overall, 8 adult patients (2 female, 6 male) have been treated. Six cases were affected by pharyngocutaneous fistulas, one by severe sialorrhoea and one recurrent sialocele. After the injection, patients were regularly observed at follow-up and asked to give their subjective assessment of salivary flow. Investigations concerning possible complaints, including side-effects, as well as complete examination of the head and neck area were performed. Follow-up periods ranged from 12 to 24 weeks (mean 20 weeks). Following botulinum neurotoxin injection, the fistula was dry after a mean period of 4.5 days (min 3 days, max 8 days) and was closed 6.6 days (min 5 days, max 8 days) later. The patient affected by severe hypersalivation reported subjective improvement in sialorrhoea 4 days post-treatment. The patient affected by recurrent sialocele, required only one aspiration of fluid two days after the treatment, after which there were no further problems. Post-operative saliva-related complications significantly increase patient morbidity and hospital stay after major tumour surgery. The easy, safe and effective treatment with botulinum neurotoxin injection, observed in our experience, suggest its significant role as a useful option in the post-operative saliva-related complications.

High resolution magnifying endoscopy: a new diagnostic tool also for laryngeal examination?

Aim of this report is to introduce the use of a new high resolution magnifying endoscope in the endoscopic examination of the upper aerodigestive tract and discuss the usefulness of this tool in the diagnosis of laryngeal lesions. A total of 26 patients presenting various laryngeal disorders were examined by means of an electronic videoendoscope and a high resolution magnifying endoscope. The images obtained were examined and compared. High resolution high magnification endoscopic examination allowed a better description of the laryngeal lesions (colour, extension and thickness of the lesion, irregularities in surface and borders) with easy characterisation of aspect of neighbouring laryngeal mucosa especially in pre-malignant lesions. Furthermore, the optical magnifying zoom does not require a close approach to the laryngeal mucosa, therefore, local anaesthesia is not required. In conclusion, the high resolution magnified images obtained with this new tool provide important information on the characteristics of the laryngeal structures. This new endoscopic technology, as already occurred in gastric, oesophageal and colorectal disorders, could also be improved by using chromo-endoscopy and other vital stain techniques in order to provide useful information concerning pre-neoplastic lesions of the larynx.

Predictive factors of neck metastases in laryngeal squamous cell carcinoma. Towards an integrated clinico-molecular classification.

Our group has 25 years' experience in the use of molecular predictive markers in head and neck cancer, on a large patient population, enrolled from a single institution, with a long follow-up, and, most of all, homogeneous regarding histology (squamous cell carcinoma) and site (larynx). Among the most frequent malignancies in the US, cancers of the larynx and uterine corpus are the only types not showing an increase in 5-year Survival Rates over the last 30 years. As far as concerns laryngeal squamous cell carcinoma, we can identify several potential reasons for this failure, the most relevant probably lies in the neck. For this reason, a key issue in laryngeal oncology is to assess metastatic potential of squamous cell carcinoma at diagnosis. Nevertheless, the combination of clinical and histological parameters is not sufficiently reliable in the prediction of lymph node metastases. Molecular characterization, by the study of molecular predictive factors, is a clinical approach aimed to define homogeneous subgroups for clinical metastatic behaviour. Defining invasiveness by means of studies on selected molecular markers (among which the most reliable is probably Epidermal Growth Factor Receptor (EGFR)) may be useful in the choice of the most appropriate treatment on both T and on N.

Laryngeal carcinoma and laryngo-pharyngeal reflux disease.

A correlation between laryngo-pharyngeal reflux and laryngeal carcinoma is currently debated. Chronic inflammation is a mutagen factor confirmed in the cancerogenesis of various tumours. Aim of the present study was to evaluate, in an objective and consecutive way, with 24h multi-electrode pH-metry the presence of proximal and distal oesophageal reflux in patients presenting pre-cancerosis or squamous cell laryngeal and/or pharyngeal carcinomas. From our data, a strict correlation emerged between laryngo-pharyngeal reflux and neoplasias of the upper airways, documented through multi-electrode pH-metry. Data emerging from this study would seem to support the theory that the protracted exposure (> 20 years) to biliary reflux would represent a statistically significant added risk factor in the precancerous lesions and squamous pharyngo-laryngeal carcinoma as it occurs at oesophageal level. Moreover, a significant statistical association (p < 0.0001) emerged between laryngeal carcinoma and previous gastro-resection (odds ratio 3.8).

Use of titanium mesh in comminuted fractures of frontal sinus anterior wall.

The personal experience with the surgical treatment of reduction and fixation of comminuted fractures of the anterior wall of the frontal sinus is reported. Cosmetic results were examined with regard to patients' degree of satisfaction on a 0 to 2 scale and nasal function assessed via rhinoscopy and nasal endoscopy during clinical follow-up, in the course of which the integrity and functionality of the supraorbitary and facial nerves were evaluated. All patients were satisfied, on the whole, with the aesthetic result, with 0-degree satisfaction (no deformity compared with their condition prior to the injury). The operations were performed between the 2nd and 7th post-injury day. The importance of the preoperative clinico-radiological work-up is stressed, with particular regard to the detection of simultaneous involvement of the inferior and/or posterior wall, and to the choice of surgical approach. The evolution of the surgical techniques in the treatment of frontal sinus fractures is discussed. With reference to the new means of fixation, in cases of comminuted fractures of the anterior wall, titanium mesh is preferred. In the Authors' opinion it combines excellent fixation with easy adaptability (cosmetic results are good) without requiring in the majority of cases, autologous bone grafts.

Midfacial fractures: our experience.

Authors report their experience in the treatment of midfacial fractures in 201 patients, 177 of whom underwent surgery for reduction and fixation of the fracture. Since no functional or aesthetic deficits were present, surgery was not performed in the remaining 24 cases. Of the 177 patients, the maxillary complex was involved in 70 (classified as central and centro-lateral fractures), the zygomatic-maxillary-orbital complex in another 70, isolated fractures of the orbital floor blow-out in 18, and, isolated fractures of the zygomatic arch in 19. The results obtained and the degree of satisfaction were evaluated in 90 patients with clinical visits, as well as by telephone interview. A total of 88 patients expressed complete satisfaction with the results of the surgical outcome, while the remaining 2 patients were not satisfied with the aesthetic outcome. All patients were operated within 24-48 hours post-trauma in the case of incarceration of extrinsic ocular muscles, and within 10 days in other types of trauma, even in those patients in intensive care. The importance of clinical and radiological pre-operative diagnosis is stressed as well as the choice of the most suitable therapeutic approach for the different types of fractures, considering recent tendencies towards minimally invasive procedures to achieve better cosmetic results. The latest developments in fixation techniques with reference to titanium mini- and/or micro-plates that may eventually be substituted with absorbable materials are discussed.

The role of acid and alkaline reflux in laryngeal squamous cell carcinoma.

HYPOTHESIS: At present, main factors considered responsible for the onset of squamous cell carcinoma are tobacco smoking, alcohol abuse, and exposure to viral and toxic agents. In last years, great interest has been focused on gastroesophageal reflux as independent carcinogenic factor and co-carcinogen in association with smoking and alcohol assumption. STUDY DESIGN: Initially, the aim of this study was to objectively evaluate the presence of distal and proximal esophageal reflux with multielectrode pH measurement in patients with cancer of the larynx and/or hypopharynx (group A). However, in the course of the study, pharyngolaryngeal cancer was also observed in 4 patients with achlorhydria; therefore, the hypothesis that alkaline reflux might be involved in the onset of laryngeal cancer was tested (group B). METHODS: Twenty-one consecutive patients with laryngeal or hypopharyngolaryngeal squamous cell carcinoma (group A) entered the study. Twenty-one patients without laryngo-pharyngeal diseases were used as control subjects. A validated questionnaire of the clinical history was completed by all patients who underwent 24-hour pH monitoring. Group B included 40 consecutive gastrectomized patients (28 males and 12 females) in whom biliary or alkaline reflux was directly consequent to Billroth I or Billroth II operation. The control group was composed of 40 non-gastrectomized dyspeptic patients. The clinical history was controlled and obtained; EDGS and ENT examination with videolaryngoscopy was performed in all patients. RESULTS: In group A, pH measurement showed pathological reflux in 80.9% (17 of 21) of patients with no typical symptoms in 63.7% of them. The difference was significant with respect to the control group. In group B, 6 of 40 (15%) had preneoplastic lesions or a history of laryngeal tumor. The difference was significant with respect to the control group. A total of 7.5% of group B patients had previously undergone CO2 laser cordectomy for laryngeal squamous cell carcinoma and 7.5% had leukoplakia. We found a significantly higher incidence (<.05) of neoplastic and preneoplastic disease of the larynx in patients undergoing Billroth II and total gastrectomy than in those undergoing Billroth I and Roux-en-Y resection. We also found a significant increase (<.01) in ENT lesions in the group of patients who had undergone gastrectomy more than 20 years previously. CONCLUSIONS: In agreement with literature reports, results obtained in group A confirmed that gastroesophageal reflux is often present in patients with neoplastic lesions of the pharynx and larynx. Furthermore, gastric resection is indicated for the first time as an additional risk factor or cofactor of precancerosis and squamous cell carcinoma of the pharynx or larynx. Further studies are necessary to establish the cause and effect relationship between biliary reflux and pharyngo-laryngeal tumors.