Transoral radiofrequency of the terminal branches of the recurrent nerve in the treatment of adductor spasmodic dysphonia: our experience over 11 patients.

PURPOSE: Spasmodic dysphonia (SD) or laryngeal dystonia is as a rare vocal disorder characterized by involuntary action-induced endolaryngeal contraction. In the last decade, botulin toxin injection has become the standard treatment in adductor spasmodic dysphonia necessitating repetitive injections. The purpose of this study is to analyze retrospectively data from patients treated with the minimal-invasive transoral radiofrequency-induced thermotherapy (RFITT) of the terminal branches of the recurrent nerve. METHODS: Between 2009 and 2015, 11 patients (six females and five males aged from 32 to 91 years) with adductor SD were treated with RFITT. Pre-operative and post-operative vocal assessments (VHI-30, GRBASI, and acoustic-aerodynamics measurements), number of surgical revisions, delay between procedures, and post-operative complications were recorded. Statistical analyses were carried out on the first vocal assessment performed 2-8 weeks after the first procedure. RESULTS: Based on available data from ten patients, voice handicap index (VHI) showed improvement with a mean value of -17.7 points (p-value (pval) = 0.014, adjusted p-value (adj pval) = 0.21); instability has also revealed improvement in six patients (pval = 0.05, adj pval = 0.31). Four patients underwent only one procedure including one patient showing still long-term beneficial results after 5 years of follow-up. Other patients required one to three new procedures with an average time between procedures of 15.3 months. Over 24 surgeries performed on a total of 11 patients, one definitive treatment-related severe adverse event was reported. CONCLUSION: Thanks to long-lasting effect, repetitive treatments are less frequent compared to botulin toxin therapy. In our opinion, RFITT is a promising alternative to botulin toxin as a second-step procedure in case of toxin resistance or patient's lack of compliance.

Transoral robotic surgery (TORS) with the Medrobotics Flex™ System: first surgical application on humans.

Head and neck surgery can be fraught with difficulties in accessing the pharynx and larynx. Minimally invasive surgery has developed with the recent advances in technology. Currently, we have a variety of high-definition multichannel videoendoscopes and robots in our armamentarium. We present our experience in a new robotic surgical system-'The Medrobotics Flex™ System' at our tertiary referral unit. We aimed to assess the safety, functionality and ease of use of this new device in this prospective study. Thus far, this is the first study in live human subjects who have undergone surgery for the following conditions: (1) obstructive sleep apnoea involving the base of tongue, the tonsil and the velum; (2) vocal fold polyp; (3) carcinoma of the lateral edge of the tongue. There were no complications in our series and the system provided good visualisation and access to these subsites without compromising safety or success. In summary, we found the Medrobotics Flex™ System to have certain other advantages including ease of set up and use besides being reliable and safe.

Functional outcomes after transoral robotic surgery for squamous cell carcinoma of the oropharynx.

Over the past decade, the development of transoral robotic surgery (TORS) brought a new opportunity in the treatment of early T-stage oropharyngeal squamous cell carcinoma (OPSCC). The objective of this study is to review the functional outcomes after TORS. Indeed, dysphagia is among the most commonly cited functional impairments in OPSCC survivors treated by surgeries with an open approach or conventional radiotherapy. We performed a review of the literature and analysed functional outcomes after TORS. Althought the technique is very recent, early functional and oncologic outcome data are promising and the major studies analysing these parameters support that TORS is feasible and safe as well as oncologically and functionally efficacious.

Transoral robotic tongue base reduction in surgical management of obstructive sleep apnea syndrome.

Management of base of tongue (BOT) is a challenging topic in surgical management of obstructive sleep apnea syndrome. After the introduction of transoral robotic surgery technology (TORS) into the otolaryngology practice, surgery on the BOT was performed more effectively. Base of tongue reduction can be performed alone or as a part of a multilevel surgery. Patient selection is important and will be discussed further in this study. Available studies show promising and encouraging results for TORS future use in BOT.

Use of cidofovir in HPV patients with recurrent respiratory papillomatosis.

Recurrent respiratory papillomatosis is a viral-induced disease, associated with exophytic epithelial lesions affecting the upper airways. Problem of treatment is the high recurrence of papilloma growth after surgical removal; therefore, adjuvant therapy schemes have been established. We used cidofovir, 7.5 mg/ml, in adjuvant therapy in the past years. Out of 31 adult patients treated with the drug, 26 (83.9 %) are at the moment in complete response. 19 (73 % of pts with CR) of those 26 patients were cured with a number of injections between 1 and 4 (mean 2.5). We did not see any clinical manifestation of renal toxicity or neutropenia (superinfection) necessitating a blood test. Six patients presented dysplasia during the treatment with the drug, while six patients had dysplasia prior to cidofovir injection. Due to recurrent nature of the disease and the high number of mechanical and laser surgeries required we treated one tracheal stenosis, two scarred larynx, and two glottic synechiaes. There is still an ongoing discussion within the European Laryngological Society about the effectiveness and possible side effects of this drug. Results show promising long-term effects of adjuvant use of cidofovir, without any relevant side effects.

Vocal fold scars: current concepts and future directions. Consensus report of the Phonosurgery Committee of the European Laryngological Society.

Scarring of the vocal folds leads to a deterioration of the highly complex micro-structure with consecutively impaired vibratory pattern and glottic insufficiency. The resulting dysphonia is predominantly characterized by a reduced vocal capacity. Despite the considerable progress in understanding of the underlying pathophysiology, the treatment of scarred vocal folds is still an unresolved chapter in laryngology and phonosurgery. Essential for a successful treatment is an individual, multi-dimensional concept that comprises the whole armamentarium of surgical and non-surgical (i.p. voice therapy) modalities. An ideal approach would be to soften the scar, because the reduced pliability and consequently the increased vibratory rigidity impede the easiness of vibration. The chosen phonosurgical method is determined by the main clinical feature: Medialization techniques for the treatment of glottic gap, or epithelium freeing techniques for improvement of vibration characteristics often combined with injection augmentation or implantation. In severe cases, buccal mucosa grafting can be an option. New developments, include treatment with anxiolytic lasers, laser technology with ultrafine excision/ablation properties avoiding coagulation (Picosecond infrared laser, PIRL), or techniques of tissue engineering. However, despite the promising results by in vitro experiments, animal studies and first clinical trials, the step into clinical routine application has yet to be taken.

Endoscopic treatment of anterior glottic webs according to Lichtenberger technique and results on 18 patients.

Anterior glottic webs are most frequently acquired and result in a major vocal handicap. Many treatment modalities have been reported in the literature. None of them achieves perfect morphological or functional results. We present our series treated by an endoscopic technique based on CO(2) laser section of the web, mitomycin application and placement of a temporary silastic stent. We retrospectively reviewed the charts of 18 consecutive patients with anterior webs treated at our university hospital between 2003 and 2010. The endoscopic technique consisted of the section of the web with the CO(2) Acublade system, immediate application of mitomycin C and placement of a silastic stent. No tracheostomy was required. The stent was removed 3 weeks later. Patients had a vocal evaluation pre and postoperatively. It consisted of a video-stroboscopic examination, the global score of the Voice Handicap Index, the global and roughness scores of the perceptive voice evaluation according to Hirano, acoustic and aerodynamic parameters. Eighteen patients were included in the study with a mean age of 46 years (min. = 5, max. = 76). Twenty-two percent were women. All patients had postoperative speech therapy. The mean follow-up is 48.4 months (3-87 months). At the last follow-up, none of the patients had recurrence of the laryngeal web. The grade G of dysphonia significantly decreased from 2 to 1 (p = 0.035). CO(2) laser resection of anterior webs with mitomycin C application and placement of a silastic stent for 3 weeks induces a good morphological result with absence of web reformation but without substantial voice improvement observed in our series.

Altered dendritic cell function in normal pregnancy.

In pregnancy, maternal immunity is skewed to favour maintenance of gestation and immune tolerance of a semi-allogeneic fetus. Dendritic cells are thought to play a crucial role in mediating the balance between immunity and tolerance, and determining the type of T helper cell response. We postulated that myeloid dendritic cells would be modified in pregnancy to favour type 2 T helper cell responses. We show that the proportion of circulating myeloid dendritic cells expressing CD86 and staining for HLA-DR were significantly lower in the third trimester of pregnancy compared with non-pregnant women. As pregnancy progressed through the third trimester to term, CD86 expression increased. Furthermore, monocytes from pregnant women differentiated into less phenotypically mature dendritic cells which expressed lower levels of CD80, CD86 and HLA-DR molecules compared with non-pregnant women. In response to inflammatory stimuli, monocyte-derived dendritic cells, from pregnant women up-regulated CD86 more than CD80, and secreted less IL-12p70 but more IL-10, compared with monocyte-derived dendritic cells from non-pregnant controls. Our results demonstrate that, in pregnancy, the dendritic cell system is modified to favour type 2 T helper cell responses.

Regulation of dendritic cell interleukin-12 secretion by tumour cell necrosis.

Dendritic cells (DCs) play a key role in the induction and regulation of antigen-specific immunity. Studies have shown that, similar to infection, cellular necrosis can stimulate DC maturation. However, the ability of necrotic cell death to modulate DC cytokine secretion has yet to be explored. We investigated the regulation of interleukin (IL)-12 secretion by human DCs in response to tumour cell necrosis in an in vitro culture model. Two human tumour cell lines (K562 and JAr) were induced to undergo necrosis using heat injury and repeated cycles of freezing and thawing. Both types of tumour cells tested in this study, when injured, induced secretion of monomeric IL-12p40 by monocyte-derived DCs. Furthermore, priming DCs with necrotic cells augmented IL-12p70 secretion significantly in conjunction with CD40 cross-linking. This was physiologically relevant because cell death-pulsed DCs were more potent than non-pulsed DCs at stimulating T cells to proliferate and secrete interferon (IFN)-gamma. The Toll-like receptor 4 (TLR4) played a role in mediating the DC response to heat-killed, but not freeze/thaw-killed necrotic cells. For both methods of injury, proteins contributed to the effect of necrosis on dendritic cells, whereas DNA was involved in the effect of freeze/thawed cells only. These findings indicate that necrotic tumour cell death is not sufficient to induce bioactive IL-12p70, the Th1 promoting cytokine, but acts to augment its secretion via the CD40/CD40L pathway. The results also highlight that the mode of cell death may determine the mechanism of dendritic cell stimulation.