Does Induction Chemotherapy Still Have a Role in Larynx Preservation Strategies? The Experience of Institut Catala d'Oncologia in Stage III Larynx Carcinoma

BACKGROUND: Radiotherapy with concurrent cisplatin is the standard alternative to total laryngectomy for patients with locally advanced laryngeal cancer. The value of induction chemotherapy in larynx-preservation therapies remains unknown. Hyperfractionation radiotherapy might improve disease-free survival. METHODS: From August 1993 to August 2004, 71 patients with T3N0-1 larynx tumors and eligible for total laryngectomy received induction chemotherapy with three cycles of cisplatin plus fluorouracil. Clinical tumor response was assessed by indirect laryngoscopy and computed tomography scan. Patients with complete response received hyperfractionation radiotherapy, whereas those without complete response were proposed for total laryngectomy. RESULTS: A total of 71 consecutive patients were included. Thirty-three patients achieved complete response to induction chemotherapy (46.5%), four of them presented a tumor relapse, and all underwent salvage surgery. Seventy-six percent of surviving patients preserved a functional larynx. Despite not achieving complete response, 15 patients refused total laryngectomy and received hyperfractionation radiotherapy. Seven patients presented a tumor relapse and salvage surgery was performed in three of them. Fifty percent of surviving patients preserved a functional larynx. Twenty-two patients without complete response underwent total laryngectomy; three of them presented a tumor relapse but none could be rescued. With a median follow up of 68 months, 5 five-year overall survival, 5-year disease-free survival, and 5-year larynx function preservation survival rates were 68% (confidence interval [CI], 57-80), 75% (CI, 64-87), and 42% (CI, 29-54), respectively. No differences in overall survival were observed between groups. Five-year disease-free survival of patients without complete response who received hyperfractionation radiotherapy was significantly lower than that of the other two groups (P < .02). Ten patients with larynx preservation and no tumor relapse had chronic toxicity that caused the loss of larynx function: seven patients required permanent tracheotomy, two died from pneumonia, and one patient died as a result of a laryngeal necrosis. CONCLUSIONS: Patients with complete response to induction chemotherapy in laryngeal carcinoma have a high probability of cure after hyperfractionation radiotherapy. However, hyperfractionation radiotherapy induces a high degree of toxicity that reduces the laryngeal function preservation rate and may jeopardize overall survival.     

Does Acid Suppressive Therapy Reduce the Risk of Laryngeal Cancer Recurrence?

OBJECTIVE/HYPOTHESIS: Gastroesophageal reflux disease (GERD) is implicated in laryngeal cancer pathogenesis and recurrence posttherapy. There are currently limited data on the effect of acid suppressive therapy in decreasing the recurrence of laryngeal cancer. Therefore, we conducted this study to identify potential effect of GERD and acid suppressive therapy on recurrences after larynx-preserving therapies. STUDY DESIGN: Case control study. METHODS: Cases and controls, derived from a single tertiary care center, were patients who had newly diagnosed localized laryngeal cancer (T3 or less and absence of nodes) and having undergone larynx-preserving surgery or radiotherapy/chemotherapy were followed between January 1, 2000 and December 31, 2003. Univariable associations were performed for demographics, smoking and alcohol patterns, stage of tumor, initial treatment, surgeon of record, presence of GERD, and the use of acid suppressive medications. Multivariable associations were performed for clinically significant variables. RESULTS: Of 258 patients with laryngeal cancer, 61 satisfied the selection criteria. Twenty-two of 61 (36%) developed recurrence and constituted cases, whereas 39/61 (64%) did not have recurrence and constituted controls. On univariable analysis, significant factors for decreased recurrences were GERD, hazard ratio 0.24 (95% confidence interval [CI] 0.08-0.71), and acid suppressive therapy, hazards 0.22 (95% CI 0.07-0.66). On multivariable analysis, laryngeal cancer recurrence was significantly less in those on acid suppressive therapy, hazard 0.31 (95% CI 0.13-0.75). CONCLUSIONS: Acid suppression postlaryngeal cancer therapies may have protective effect on laryngeal cancer recurrences. A prospective study is needed to better define this perceived beneficial effect.     

Does it make sense to preserve the stapedial muscle during surgical treatment for otosclerosis?

Our study aimed to show whether it is useful to preserve the stapedial muscle during the surgical treatment of otosclerosis. The study was carried out on 67 patients with tympanoscopic evidence of otosclerosis. In group A (34 patients) the stapedial muscle was intra-operatively preserved as follows: the stapedial suprastructure with preserved muscle tendon was transpositioned onto the longer arm of the incus and secured with a wire loop. The mean uncomfortable level for sounds was measured after surgery and the results of group A patients were compared with those obtained in group B (33 patients, who underwent standard surgery). One month after surgery, in group A patients, the cochleostapedial reflex was evoked in 21 patients (61.8 per cent) and two months later in 32 patients (94.1 per cent). One month after operation, in group A patients the mean uncomfortable level was 108.8 dB, while three months later it increased to 114.1 dB. In group B, the relevant values were 97.8 dB one month after surgery, and 98.0 dB three months later. Our presumption that stapedial muscle preservation is necessary has been proved by the fact that the patients with the preserved muscle had a higher noise discomfort threshold.     

Does xanthine oxidase contribute to the hydroxyl radical generation in ischemia and reperfusion of the cochlea?

We investigated the effect of a hydroxyl radical scavenger, 1,3-dimethyl-2-thiourea (dimethylthiourea), and two xanthine oxidase inhibitors, oxypurinol and allopurinol, on the threshold shift of the compound action potential (CAP) after transient ischemia of the cochlea. Transient ischemia of 30 min duration was induced in albino guinea pigs via a skull base approach. The animals were treated with perilymphatic perfusion of dimethylthiourea, oxypurinol or allopurinol from 10 min before the onset of ischemia to 4 h after the termination of ischemia. Dimethylthiourea ameliorated the CAP threshold shifts at 4 h after the onset of reperfusion in a dose-dependent manner. However, oxypurinol and allopurinol did not affect the post-ischemic cochlear dysfunction. These results imply that the hydroxyl radical plays an important role in generation of cochlear dysfunction induced by ischemia-reperfusion and that xanthine oxidase may not be the primary source of this radical.     

Does otosclerosis occur only in the temporal bone?

HYPOTHESIS: Otosclerosis does not occur outside the temporal bone. BACKGROUND: The widely accepted assumption that otosclerosis is confined to the temporal bone has never been tested. It is important to investigate this issue, particularly because of evidence that otosclerosis may be a systemic (genetic) disease that could affect other bones. METHODS: Biopsies from 9 to 11 skeletal sites were obtained from 2 patients with clinical otosclerosis. Two hundred forty-one nontemporal bone sections were examined by light microscopy. RESULTS: No nontemporal skeletal bone section showed histologic evidence of otosclerosis. The data indicate, with 95% confidence, that the true prevalence of otosclerosis in the extratemporal skeleton of the 2 patients examined was < 3%. CONCLUSIONS: These findings suggest that otosclerosis is unlikely to occur outside the temporal bone. Factors unique to the otic capsule that may predispose it to otosclerosis are lack of bone remodeling and the presence of globuli interossei.     

Does the serological study for viral infection in autoimmune inner ear disease make sense?

Viral infections of the labyrinth have been considered a major source of auditory and vestibular system pathology. However, the involvement of virus in the development of immune reactions responsible for immunomediated inner ear disease has not been studied enough. Following viral infection, an effector immune response, humoral (B cell) and/or cytotoxic (T cell) is directed against a virus and it might cross-react with self-protein or autoantigen, evoking an autoimmune response. Since clinically it can be very difficult to establish a viral etiology for such disorders, serologic studies can be used to confirm the suspected diagnosis. Patients affected by immunomediated inner ear disease that had presented an upper respiratory tract infection underwent an immunologic workup study including microbiological study. After the application of this diagnostic protocol, only one patient, that was subsequently diagnosed with Cogan's syndrome, showed a positive serological test for viral infection. On the basis of the low efficacy of serological testing and due to the lack of evidence, we do not recommend to carry out serologic studies for viral infection.     

Does nicotine add to the carcinogenic strain of tobacco smoke?

BACKGROUND: It is accepted that nicotine in tobacco smoke causes addiction via nicotinic acetylcholine receptors in the central nervous system. For a long time, the tumorigenic potential of smoking was attributed to compounds other than nicotine. However, more recently data have accumulated which suggest that nicotine may add to the cancer risk by stimulating cellular growth via non-neuronal acetylcholine receptors, by suppressing apoptosis, and by inducing angiogenesis not only in atheromatous plaques but also in tumors. In the present study the possible direct genotoxic effects of nicotine on DNA were investigated in human target cells of carcinogenesis in the upper aerodigestive tract. PATIENTS AND METHODS: Human nasal mucosa, lymphatic tissue of the palatine tonsils, supraglottic epithelium of the larynx, and peripheral lymphocytes were exposed to rising concentrations of nicotine. DNA damage was investigated by alkaline single-cell microgel electrophoresis (Comet) assay. Cytotoxicity was assessed by trypan blue exclusion.RESULTS: Nicotine induced dose-dependent DNA damage in all cell types at low cytotoxic concentrations that allowed viabilities well above 80%. The lowest nicotine concentrations eliciting a significant increase in DNA migration were 1 mM for tonsillar cells and 0.25 mM for all other cell types. CONCLUSION: Nicotine induces genotoxic effects in human target cells of carcinogenesis in the upper aerodigestive tract at relevant concentrations. Thus, nicotine may contribute directly to tumor initiation resulting from smoking.     

Does radiation dose to the vestibule predict change in balance function and patient perceived dizziness following stereotactic radiotherapy for vestibular schwannoma?

Objective

To date, the majority of the vestibular schwannoma (VS) literature has focused on tumor control rates, facial nerve function and hearing preservation. Other factors that have been shown to significantly affect quality-of-life (QOL), such as dizziness, remain understudied. The primary objective of the current study is to investigate the association between radiation dose to the vestibule and post-treatment changes in vestibular function and patient reported dizziness handicap.

Materials and methods

This is a prospective observational pilot study at a tertiary academic referral center including all subjects that underwent linear accelerator-based stereotactic radiotherapy (SRS) for sporadic VS and completed pre-treatment and post-treatment vestibular testing and Dizziness Handicap Inventory (DHI) questionnaires. Associations between objective vestibular test results, patient-reported DHI scores and radiation dose parameters were investigated.

Results

Ten patients met inclusion criteria. Tumor control was achieved in all individuals. There were no statistically significant associations or identifiable trends between radiation dose and change in vestibular function or DHI scores. Notably, the four ears receiving the highest vestibular dose had minimal changes in vestibular function tests and DHI scores.

Conclusions

To the best of our knowledge, no previous reports have described the association between radiation dose to the vestibule and post-treatment changes in vestibular function and patient reported DHI. Based on these preliminary data, radiation dose to the vestibule does not reliably predict change in objective or subjective vestibular outcome measures.     

Does septoplasty enhance the quality of life in patients?

Evaluation of the severity of disease and the effectiveness of operative treatment is commonly done by registering pre- and postoperative symptoms. During the preceding decade, greater awareness has focused not only on the symptoms but also on patients’ quality of life (QoL). The aim of the study was to determine the effect of septoplasty, as measured by generic and disease-specific QoL questionnaires. The generic 15D and disease-specific SNOT-22 questionnaires were given to patients before the operation and 6?months after the operation. Data analysis consisted originally of 188 septoplasty patients. One-hundred and twenty-six patients (67%) answered the SNOT-22 questions, and in the 15D, the response rate was 76%. In the post-operative SNOT-22, the need to blow the nose, sneezing, runny nose, nasal obstruction, loss of smell or taste, post-nasal discharge, facial pain/pressure, difficulty in falling asleep and waking up at night improved significantly. However in the 15D the mean QoL, i.e., general well-being, became significantly poorer. The QoL became increasingly poor especially in the older age groups and among the patients in which the improvement achieved in nasal symptoms postoperatively was minor. The more nasal symptoms the patients had pre- or postoperatively, the poorer the QoL was in general. Based on our results, critical evaluation of the symptoms and findings in the patients is essential in deciding whether surgery or other treatment should be given to individual patients having nasal blockage symptoms. Especially in patients with mild symptoms or among older patients, adequate medical treatment has to be tried before even considering surgery. The results also encourage the use of a systematic questionnaire to estimate the severity of symptoms in daily clinical practice.     

Does septoplasty improve the quality of life in children?

Objectives

The aim of this study is to evaluate the outcomes of septoplasty and the effects of septoplasty on the quality of life and to determine postoperative patient satisfaction in children using nose obstruction symptom evaluation (NOSE) and visual analog scale (VAS).

Methods

Only pediatric patients who underwent septoplasty were included in the study. Patients who underwent adenoidectomy, endoscopic sinus surgery, or turbinate surgery in addition to septoplasty and total septal reconstruction with open technique septorhinoplasty were excluded from the study. Patients and their parents were inquired about their nasal obstruction symptoms using the NOSE scale before and 3 and 12 months following the surgery. VAS was used to analyze overall satisfaction of the patients and their parents on the outcomes of surgery, at the last follow-up examination 12 months after the surgery.

Results

Thirty-five patients with a mean age of 13.4 ± 2.8 (8–16) were included in the study. There was a very significant improvement in NOSE score at 3 months after septoplasty. The mean subjective satisfaction score measured with VAS at the 12th month postoperatively was 7.9 ± 2.1. Improvement in NOSE score was correlated with patient satisfaction.

Conclusion

Septoplasty is a very effective and satisfactory treatment for nasal obstruction caused by nasal septal deviation in children. The NOSE scale can be used for the evaluation of nasal obstruction symptoms.     

Does rhinitis lead to asthma?

Rhinitis and asthma are commonly linked even if the precise pathological mechanisms explaining the relationship are not fully understood. Although there is increasing evidence that rhinitis may influence the development of asthma, there remain many gaps in our understanding of the processes involved. The complexity of this relationship is mainly due to the multiple interactions between genetic background, environmental factors and the specific host reaction. Epidemiological surveys have highlighted significant clinical associations and identified some factors that favour the progression from rhinitis to asthma. Basic research has demonstrated numerous similarities in inflammatory and immunological mechanisms.     

Does the use of recombinant TSH in preparation for I-131 scintigraphy scan affect hearing function?

Objective

The objective of this study was to examine the effect of hypothyroidism on hearing function in patients surgically treated for differentiated thyroid cancer and subsequently experienced hypothyroidism during preparation for follow up I-131 scintigraphy scan by either recombinant human thyroid stimulating hormone (rhTSH) treatment or thyroid hormone withdrawal (THW).