Impact of the anterior commissure involvement on the survival of early glottic cancer treated with cricohyoidoepiglottopexy: a retrospective study.

BACKGROUND: Laryngeal early glottic tumors can benefit from different treatment modalities, including transoral laser microsurgery, open partial horizontal laryngectomy (OPHL), and radiotherapy. However, the treatment of early glottic tumors with the involvement of the anterior commissure remains controversial. The studies about the role of anterior commissure involvement in oncologic outcomes in patients with early glottic cancer treated with supracricoid laryngectomy (SCL) are very few. For this reason, we conducted a retrospective study to evaluate local recurrence-free survival and specific survival in patients with and without involvement of the anterior commissure who underwent SCL with cricohyoidoepiglottopexy. METHODS: This retrospective study has been carried out on patients with T1b-T2 glottic squamous cell carcinoma submitted to SCL with cricohyoidoepiglottopexy. The patients' demographic and clinical data were collected, and the histological findings of the surgical specimens were reviewed to identify patients who had involvement of the anterior commissure. RESULTS: A total of 72 patients were included in the study; two of them were female and 70 were male. The mean age at diagnosis was 61.5±8.0 SD years. In 26 of the 72 (36.2%) patients, anterior commissure was not pathologically involved (group A), while in 46 (63.8%) patients, it was involved (group B). The 5-year local recurrence-free survival rate was 96.1% and 93.48% in groups A and B, respectively, P=0.09. The 5-year disease-specific survival rate was 92.31% and 95.65% in groups A and B, respectively, P=0.057. CONCLUSION: SCL with cricohyoidoepiglottopexy seems to be an adequate treatment modality, even for T1b-T2 glottic tumors with anterior commissure involvement.

Early glottic cancer: role of MRI in the preoperative staging.

INTRODUCTION: Clinical staging is the most important time in management of glottic cancer in early stage (I-II). We have conducted a prospective study to evaluate if magnetic resonance imaging (MRI) is more accurate than computed tomography (CT) about tumoral extension, to exactly choose the most appropriate surgical approach, from organ preservation surgery to demolitive surgery. MATERIALS and METHODS: This prospective study was conducted on 26 male patients, with suspected laryngeal neoplasia of glottic region. The images of MRI and CT were analyzed to define the expansion of glottic lesion to anterior commissure, laryngeal cartilages, subglottic and/or supraglottic site, and paraglottic space. The results of MRI and CT were compared with each other and with the pathology report. RESULTS: CT accuracy was 70% with low sensitivity but with high specific value. MRI showed a diagnostic accuracy in 80% of cases, with a sensitivity of 100% and high specificity. Statistical analysis showed that MRI has higher correlation than CT with the pathology report. CONCLUSION: Our study showed that MRI is more sensitive than CT in the preoperative staging of early glottic cancer, to select exactly the eligible patients in conservative surgery of the larynx, as supracricoid laryngectomy and cordectomy by CO2 laser.

Prognostic role of salivary CD44sol levels in the follow-up of laryngeal carcinomas.

BACKGROUND: The purpose of this study was to verify CD44sol levels in the saliva of patients during follow-up after surgery for laryngeal cancer, to compare them with those registered at the time of diagnosis (pre-intervention) in the same patients, and to assess the reliability of the test as a prognostic indicator. METHODS: This prospective study was performed on 21 patients having laryngeal cancer who underwent surgery at the Division of Otolaryngology, University of Catanzaro; twelve adults with head and neck benign disease were recruited to form a control group. For each patient, the clinical­anamnestic data were collected and entered into a database. The sampling of undiluted saliva was performed the day before surgery and during the follow-up, every 3 months. Salivary CD44sol levels were determined using the ELISA method. RESULTS: Mean salivary CD44sol levels in the patients group before surgery (pre-intervention) were significantly higher than those in the control group (70.75 ± 33.8 vs. 12.4 ± 8.7 ng/ml). At follow-up performed 3 months after surgery, 18 of 21 (85.71%) patients had a reduction in salivary CD44sol levels, with a mean value of 50.1 ng/ml; the difference between these and pre-intervention CD44sol levels was statistically significant (P < 0.04). Mean CD44sol levels of 31.1 ng/ml at 6 months post-intervention have been determined in 19 of 21 enrolled patients; none of the 19 patients have actual signs of recurrence. CONCLUSIONS: These data seem to show that the determination of salivary CD44sol levels can represent a promising prognostic test in laryngeal carcinomas.

Effectiveness of therapeutic selective neck dissection in laryngeal cancer.

BACKGROUND: The aim of this study was to evaluate the effectiveness of selective neck dissection (SND) in patients with laryngeal cancer and clinically positive cervical nodes. SUBJECTS AND METHODS: A retrospective review of the clinical records of 58 consecutive untreated patients affected by laryngeal carcinoma and submitted to surgical treatment was performed. RESULTS: Twenty-six (44.8%) patients received monolateral neck dissection and 32 (55.2%) bilateral neck dissection. A total of 90 hemineck dissections were performed. Histopathological examination revealed that 25 of the 58 patients had negative nodes (pN0) and 33 had positive nodes (pN+). Extracapsular spread was found in 12 of the 33 pN+ patients. Twenty-eight of the 58 (48.2%) patients were submitted to adjuvant radiotherapy. Six of the 58 patients submitted to neck dissection had neck recurrence (rate of 10.3%). The only independent prognostic factor for neck recurrence was extracapsular spread. For the 58 patients, the 5-year overall survival was 50% and the disease-specific survival 68.9%. The 5-year disease-specific survival was 76% for pN0 patients and 63.6% for pN+ patients. CONCLUSIONS: SND can represent a therapeutic procedure because it has shown oncological results comparable to those of comprehensive neck dissection, especially when SND is combined with adjuvant radiotherapy.

Effects of guidelines on adeno-tonsillar surgery on the clinical behaviour of otorhinolaryngologists in Italy.

BACKGROUND: Several guidelines on adeno-tonsillar disease have been proposed in recent years and some discrepancies in relation both to clinical manifestations and indications for surgical treatment have emerged. The aim of the study was to verify what influence (adeno)-tonsillectomy guidelines have had on the clinical behaviour of ENT specialists in Italy. Our study is a retrospective and multi-centre case series with chart review. METHODS: The survey involved 14,770 children, aged between the ages of 2 and 11, who had undergone adeno-tonsillar surgery between 2002 and 2008 in fourteen Italian tertiary and secondary referral centres. Anova test was used for the statistical analysis, assuming p < 0.05 as the minimum statistical significance value. RESULTS: The frequency of adeno-tonsillar surgeries did not change significantly (p>0.05) during the study period and following the Italian policy document publication. Overall, adeno-tonsillectomy was the most frequent intervention (64.1%), followed by adenoidectomy (31.1%) and tonsillectomy (4.8%). The indications for surgery did not change significantly for each of the operations (p>0.05), with the exception of adeno-tonsillectomy in case of feverish episodes due to acute recurrent tonsillitis ≥ 5 without nasal obstruction (decreased p= 0.010) , even when the feverish episodes due to acute recurrent tonsillitis were < 5 over the last year. Nasal obstruction was associated with feverish episodes due to acute recurrent tonsillitis in 65.2% of operated cases, while otitis media had been diagnosed in 43.3% of the patients studied. CONCLUSIONS: The recommendations first developed in Italy in a 2003 policy document and then resumed in guidelines in 2008, were not implemented by ENT units involved in the survey. The study highlights the fact that the indications for adeno-tonsillar operations are based on the overall clinical presentation (comorbidity) rather than on a single symptom. Guidelines are necessary to give coherent recommendations based on both the findings obtained through randomized controlled trials and the data collected from observational studies.

Expression of BMI1 and p16 in laryngeal squamous cell carcinoma.

BACKGROUND: The clinical evolution of laryngeal squamous cell carcinoma (SCC) is undetectable with the current staging criteria. To more completely understand the biology of laryngeal SCC, we assessed the expression of the proteins B-cell-specific Moloney murine leukemia virus integration site 1 (BMI1) and p16. METHODS: We assessed immunohistochemically the expression of BMI1 and p16 in 25 laryngeal SCCs at different stages. RESULTS: High BMI1 expression was detected in 11.7% of glottic tumors and in 50% of supraglottic tumors. No significant differences were observed in the patients' clinical data after they were stratified by the tumor expression of p16. The expression of nuclear BMI1 in the absence of p16 immunoreactivity correlated significantly with the pN status of the primary tumors. CONCLUSION: Nuclear BMI1 expression in the absence of p16 expression seems to characterize a subset of patients with a high risk of developing lymph node metastasis.

Modified supracricoid laryngectomy: oncological and functional outcomes in the elderly.

BACKGROUND: Supracricoid laryngectomy is an organ preservation surgical technique for early-stage glottic tumors. Modified supracricoid laryngectomy using sternohyoid muscles for neoglottis reconstruction is a new surgical technique. This report evaluates oncological and functional outcomes of this new technique and its feasibility in elderly patients. METHODS: Clinical records from 21 consecutive patients affected by glottic cancer and treated by modified SCL between 2004 and 2009 were retrospectively reviewed. Postoperative parameters and quality of voice after modified SCL were retrospectively reviewed. Actuarial overall survival, disease-specific survival rates, and recurrence-free survival rates were assessed. The functional and oncological outcomes of patients over 65 years were compared with those of patients younger than 65 years of age. RESULTS: There were no postoperative complications and all of the patients had complete swallowing rehabilitation. Twenty of the 21 patients had decannulation. Two patients received total laryngectomy for locoregional relapse. Overall survival and disease-specific survival rates were 100%. Recurrence-free survival rates were 90.1% and 90% in patients younger and older than 65 years of age, respectively. The larynx preservation index was lower in patients who were older than 65 years of age. The postoperative courses with regard to functional outcome and voice quality in elderly patients were similar to those of patients younger than 65 years of age. CONCLUSION: Modified SCL is a new open organ preservation surgical technique that is oncologically safe. The positive functional and oncological outcomes of this surgical procedure allow it to be performed in elderly patients.

Nuclear BMI-1 expression in laryngeal carcinoma correlates with lymph node pathological status.

BACKGROUND: The main cause of treatment failure and death in laryngeal squamous cell carcinoma is metastasis to the regional lymph nodes. The current clinical staging criteria fail to differentiate patients with occult metastasis from patients without metastasis. Identifying molecular markers of the disease might improve our understanding of the molecular mechanisms underlying the pathogenesis and development of laryngeal carcinoma and may help improve clinical staging and treatment. METHODS: Sixty-four previously untreated patients who underwent surgical excision of laryngeal squamous cell carcinoma with neck dissection were included in this study. The expression of B cell-specific Moloney murine leukemia virus integration site 1 (BMI-1) was examined immunohistochemically on formalin-fixed paraffin-embedded primary tissue specimens. RESULTS: Nuclear expression of BMI-1 (nBMI-1) was detected in 32 of the 64 tumors (50%), cytoplasmic expression of BMI-1 (cBMI-1) was detected in 22 (34.4%), and 10 tumors (15.6%) showed no BMI-1 immunoreactivity. High nBMI-1 expression levels (≥ 10) were detected in 28 of the 32 (87.5%) nBMI-1-positive patients. Multivariate analysis including age at diagnosis, grade, tumor location, TNM status, and nBMI-1 expression showed that a high nBMI-1 expression level was an independent prognostic factor for lymph node metastasis. CONCLUSION: The expression of BMI-1 in patients with laryngeal carcinoma seems to correlate with lymph node metastasis.

Quality of voice evaluation in patients treated by supracricoid laryngectomy and modified supracricoid laryngectomy.

OBJECTIVE: To compare quality of voice in patients treated by supracricoid laryngectomy and patients treated by modified supracricoid laryngectomy using the sternohyoid muscle for neoglottis reconstruction. STUDY DESIGN: Case series. Setting. Teaching hospital. SUBJECTS AND METHODS: This study was performed between 2004 and 2008 on 28 consecutive patients affected by T1b-T2 laryngeal carcinoma. Eleven patients were treated by supracricoid laryngectomy, and 17 patients were treated by modified supracricoid laryngectomy. For each patient, postoperative parameters such as decannulation time, nasogastric feeding tube, and length of hospitalization were noted. Vocal function, Voice Handicap Index scores, and perceptual voice analysis scores on intelligibility, noise, fluency, and voice scale were evaluated. RESULTS: The postoperative course of the patients treated by modified supracricoid laryngectomy was similar to patients treated by supracricoid laryngectomy. No delay in the length of hospitalization was detected in patients undergoing surgery with the new technique. A significant difference was detected in the nasogastric tube removal time and decannulation time. The data from intelligibility, noise, fluency, and voice scale analyses revealed a better quality of voice in patients treated by modified supracricoid partial laryngectomy with a significant difference in intelligibility, fluency, and voicing. The Voice Handicap Index mean value of physical, functional, and emotional subscales confirmed patients' perceptions of a minor voice handicap in patients treated by modified supracricoid laryngectomy, with a significant difference on the physical subscale. CONCLUSION: Modified supracricoid laryngectomy seems to be a good way to improve quality of voice and quality of life in patients with early laryngeal cancer.

Gestural automatisms during syncope related to cervical malignancy.

Cervical malignancies are a rare but well-known cause of syncope. Gestural automatisms during syncope have only rarely been reported. We describe a patient presenting with bimanual automatisms during syncopal episodes caused by parapharyngeal carcinoma involving the right laterocervical region. Ictal phenomenology was strongly suggestive of focal seizures and only video-polygraphic recording including EEG and ECG allowed the correct diagnosis to be established. Syncopal episodes ceased after partial removal of the mass. Although gestural automatisms in the context of a sudden spell with loss of consciousness are strongly suggestive of focal (mainly frontal or temporal) seizures, the diagnosis of syncope must be taken in account and confirmed or excluded by appropriate neurophysiological investigations.

Insulin receptor isoforms and insulin-like growth factor receptor in human follicular cell precursors from papillary thyroid cancer and normal thyroid.

CONTEXT: Factors involved in the biology of normal and cancer stem/precursor cells from the thyroid are unknown. Thyroid cancer cells are responsive to insulin and IGF-I and IGF-II and often overexpress the insulin receptor (IR) and the IGF-I receptor (IGF-IR). OBJECTIVE: We investigated the role of IR isoforms (IR-A and IR-B), IGF-IR, and their ligands in thyroid follicular cell precursors both normal and malignant. DESIGN: We established cultures of follicular cell precursors as thyrospheres from three papillary thyroid cancers and the corresponding nonaffected tissues. The expression of IR, IGF-IR, and their ligands was evaluated by quantitative RT-PCR and, in one case, also by Western blot. The effects of insulin and IGFs on thyrosphere growth and self-renewal were evaluated. RESULTS: Thyrospheres were characterized by the expression of stem cell markers and low/absent thyroid specific markers. Thyrospheres from normal tissue, but not from cancer tissue, could be induced to differentiate. Both IR isoforms, IGF-IR, IGF-I and IGF-II, were expressed at high levels in thyrospheres and markedly decreased in differentiating cells. IR-A was the predominant isoform in thyrospheres, especially from cancer, while IR-B was predominant in differentiating cells. Cancer thyrosphere growth was stimulated by insulin and IGFs. CONCLUSIONS: Our data suggest that IR isoforms and IGF-IR play a role in the biology of follicular thyroid precursors. Cell differentiation is associated with marked changes in the expression of these receptors and cognate ligands. These data may provide insight for future differentiation therapies in thyroid cancer.

13-cis retinoic acid in head and neck cancer chemoprevention: results of a randomized trial from the Italian Head and Neck Chemoprevention Study Group.

Patients with squamous cell carcinoma of the head and neck (HNSCC) after being treated radically remain at high risk for both recurrent and second primary tumours. 13-cis retinoic acid (13-cRA) was demonstrated to reverse pre-malignant lesions of the oral cavity and to reduce the incidence of second primary tumours in patients treated radically for HNSCC. Synergism between retinoids and interferon in tumoural cell lines have been demonstrated. Based on these data, the Italian Head and Neck Chemoprevention Study Group started a randomized chemoprevention study in patients radically treated for stage III and IV HNSCC. From February 1992 to January 1996, 267 patients were randomized: 126 were allocated to the control group, 126 were randomized to receive 13-cRA at a dose of 0.5 mg/kg per day per os and 15 patients have been assigned to the group of 13-cRA plus interferon alpha2a (IFN-alpha2a) at a dose of 3,000,000 UI 3 times a week (randomization in this arm interrupted due to administrative financial problems). The mean follow-up was 39 months. The 5-year actuarial survival was 58.9% for patients of the 13-cRA group and 57.2% for those of the control group (P=0.94). Among evaluable patients, disease progression was observed in 45 of 123 patients (36.6%) of the 13-cRA group and in 42 of 124 (33.9%) of the control group. The 5-year actuarial relapse-free survival was 48.9% for the 13-cRA group and 55.6% for the control group (P=0.62). Adverse effects, mostly of grade I were reported in 69.4% of treated patients (haematologic disorders, mucositis, conjunctivitis, cutaneous toxicity, hypertriglyceridemia and hypercholesterolemia). Only 5 patients (4.1%) reported grade III-IV toxicity. Low-dose of 13-cRA given for 1 year is ineffective as chemoprevention in patients with radically treated HNSCC.

beta-carotene supplementation in patients radically treated for stage I-II head and neck cancer: results of a randomized trial.

This study was aimed at evaluating the efficacy of beta-carotene in improving survival (S) and in disease-free survival (DFS) and reducing the incidence of second primary tumors (SPT) in patients with a radically treated stage I-II squamous head and neck tumors. Eligible patients were randomly allocated to receive beta-carotene (n=104) or no treatment (n=110). beta-carotene was administered at the dose of 75 mg/day for 3-month cycles within one month intercycle intervals for a 3-year period. The 3-year compliance to the beta-carotene was 68.7%. Only eight patients reported drug-related toxicity (7.8%). The median follow-up of all patients was 59 months. The median follow-up was 61 months (range 1-116 months) in the beta-carotene and 58 months (1-123 months) in the control group. The 10-year DFS was 75.7% for the patients in the beta-carotene and 74.3% for those in the control group (P=0.56). The 10-year S was 85.9% in the beta-carotene group and 80.9% in the control group (P=0.20). beta-carotene supplementation had no significant effect on the incidence of second primary tumors (RR=0.99; 95% C.I. 0.28-3.44). A statistically non-significant 40% reduction in the risk of death among subjects assigned to the beta-carotene compared to the controls was observed (RR=0.60; 95% C.I. 0.26-1.38). No increase in the death from cardiovascular diseases was observed among patients treated with beta-carotene. Our results might support the hypothesis that an adequate beta-carotene treatment could be potentially associated with a decreased risk of death in these patients.

Effects of patch or gel estrogen therapies on auditory brainstem response in surgically postmenopausal women: a prospective, randomized study.

OBJECTIVE: To study the effects of gonadal steroids on the nongenital audiological target in surgically postmenopausal women treated with patch or gel transdermal estrogen therapy (ET). DESIGN: Prospective randomized study. SETTING: Research Group for Sexology, University of Catania, Italy. PATIENT(S): One hundred twenty-two surgically postmenopausal women. INTERVENTION(S): Transdermal E(2) by patch or gel, and evaluation of auditory brainstem response by auditory-evoked potentials for waves I, III, and V latencies, and for interpeak I-III, I-V, and III-V intervals. MAIN OUTCOME MEASURE(S): Changes in auditory wave latencies and in interpeak intervals during treatment with ET with respect to baseline levels. RESULT(S): One hundred two women completed the study. Forty-eight subjects used E(2) patches and 54 E(2) gel. No significant difference was observed in plasma E(2) improvement and in auditory brainstem response values with the two estrogen (E) formulations. The wave latencies and the interpeak intervals showed lower values during the E treatment than at baseline. CONCLUSION(S): Auditory brainstem response seems to depend on the type of E given. Our data suggest that fluctuating E levels act on waves, even if the exact mechanism of the gonadal steroids is not clear. However, we believe that E could influence neuronal plasticity, the metabolic levels of neurotransmitters, and thus, the neuronal conduction time into the audiological system.