Use of Indocyanine Green Near-Infrared Imaging for Sentinel Lymph Node Biopsy in Early Oral Squamous Cell Carcinoma: A Pilot Study.

PURPOSE: The current established technique for sentinel lymph node (SLN) biopsy is preoperative injection of 99mtechnetium-labeled nanosized colloids (99mTc) followed by single photon emission computed tomography and standard computed tomography (SPECT/CT) with subsequent intraoperative gamma probe-guided excision of the SLN. It is however time and resource consuming, causes radiation exposure and morbidity for the patient as the injection is done in the awake patient. Recently near-infrared imaging with indocyanine green (ICG) gained importance in SLN biopsy as a faster and more convenient technique. The objective of our study was to investigate the feasibility of SLN biopsy using ICG-imaging in early oral squamous cell carcinoma (OSCC). METHODS: Single-centre pilot study of five patients with early-stage OSCC. For all patients, both techniques (99mTc and ICG) were performed. We injected 99mTc preoperatively in the awake patient, followed by SPECT/CT imaging. Intraoperatively ICG was injected around the primary tumor. Then the neck incision was performed according to the SPECT/CT images and SLN were detected by using a gamma probe and near-infrared fluorescence imaging of the ICG-marked lymph nodes intraoperatively. The excised lymph nodes were sent to histopathological examination according to the SLN dissection protocol. RESULTS: In all five patients sentinel lymph nodes were identified. A total of 7 SLN were identified after injection of 99mTc, imaging with SPECT/CT and intraoperative use of a gamma probe. All these SLN were fluorescent and visible with the ICG technique. In two patients, we could identify additional lymph nodes using the ICG technique. Pathological analysis demonstrated occult metastasis in two of the cases. CONCLUSIONS: Our study shows that ICG-guided SLN biopsy is a feasible technique, especially in combination with conventional radioisotope method and may help for intraoperative localization of SLN. Validation studies with bigger patient cohorts are needed to prove our results.

Head and neck reconstruction with the superficial circumflex iliac artery perforator (SCIP) free flap: Lessons learned after 73 cases.

BACKGROUND: Head and neck tissue defects after ablative surgery often require complex and composite reconstructions. The superficial circumflex iliac artery perforator (SCIP) flap is an extremely versatile perforator-based flap with minimal donor site morbidity, which may represent the optimal procedure in this setting. Over the last 5 years, we collected a large base of experience, including both simple and chimeric SCIP-based reconstruction, making this flap our first choice for head and neck reconstructions. PATIENTS AND METHODS: Seventy-three patients undergoing ablative head and neck surgery for oncologic pathologies were treated by means of a SCIP flap reconstruction. Patients' mean age was 67 years old (range 37-89), 51 were males and 22 were females. Fifty-eight flaps were simple and 15 were chimeric reconstruction patterns. Indocyanine green perfusion imaging was performed in all cases. RESULTS: All the patients were successfully treated with no flap losses were encountered. Twelve patients encountered postoperative complications: in four cases revision surgery was required for venous congestion, while the remaining cases were managed conservatively (four wound dehiscence and three infections). No patients showed donor site complications. The mean follow-up period was 11 months (range 3-24). CONCLUSIONS: Our case series demonstrates the reliability and versatility of the SCIP flap for different kinds of head and neck reconstructions. The chimeric options combined with bone, double skin paddle, and muscle offer a broad variety of functional reconstructive solutions for complex head and neck surgeries. Intraoperative indocyanine green perfusion examination provides a valuable tool to assess and ascertain proper vascularization and post-anastomosis vessel patency in complex microvascular flap-based reconstructions.

In Vitro Assessment of Wound-Healing Efficacy of Stabilized Basic Fibroblast Growth Factor (FGF-2) Solutions.

Chronic tympanic membrane perforations (TMP) pose a significant clinical challenge, but basic fibroblast growth factor (FGF-2) shows promise for their treatment, despite its instability in aqueous solutions which hampers the sustained delivery crucial for the healing process. Addressing this, our research focused on the development of stabilized FGF-2 formulations, F5 and F6, incorporating dual, generally regarded as safe (GRAS) excipients to enhance stability and therapeutic efficacy. F5 combined FGF-2 (1600 ng/mL) with 0.05% w/v methylcellulose (MC) and 20 mM alanine, while F6 used FGF-2 with 0.05% w/v MC and 1 mg/mL human serum albumin (HSA). Our findings demonstrate that these novel formulations not only significantly improve the cytoproliferation of human dermal fibroblasts but also exhibit the most potent chemoattractant effects, leading to the highest fibroblast monolayer closure rates (92.5% for F5 and 94.1% for F6 within 24 h) compared to other FGF-2 solutions tested. The comparable performance of F5 and F6 underscores their potential as innovative, less invasive, and cost-effective options for developing otic medicinal products aimed at the effective treatment of chronic TMP.

Chondrosarcoma of the petrous apex with nerve abducens involvement in a woman with pre-existing contralateral amblyopia.

We report about a case of a woman in her 50s with a chondrosarcoma of the petrous apex. She has a strabism due to a right-sided amblyopia since childhood and noticed a slowly progressive squint angle in the last months. Her general practitioner (GP) referred her to an ophthalmologist who diagnosed a left abducens paresis and initiated an MRI demonstrating a mass in the left petrous apex. A transnasal endoscopic transsphenoidal biopsy revealed a grade I chondrosarcoma. The patient underwent an endoscopic transsphenoidal anterior petrosectomy approach with complete removal of the tumour. After surgery the squint angle gradually improved to previous levels, so that the patient was able to resume her work. This report demonstrates that even slight changes of a squint angle without diplopia, in this case because of pre-existing amblyopia, could be a hallmark of an intracranial process.

Event-Related Potentials of Single-Sided Deaf Cochlear Implant Users: Using a Semantic Oddball Paradigm in Noise.

INTRODUCTION: In individuals with single-sided deafness (SSD), who are characterised by profound hearing loss in one ear and normal hearing in the contralateral ear, binaural input is no longer present. A cochlear implant (CI) can restore functional hearing in the profoundly deaf ear, with previous literature demonstrating improvements in speech-in-noise intelligibility with the CI. However, we currently have limited understanding of the neural processes involved (e.g., how the brain integrates the electrical signal produced by the CI with the acoustic signal produced by the normal hearing ear) and how modulation of these processes with a CI contributes to improved speech-in-noise intelligibility. Using a semantic oddball paradigm presented in the presence of background noise, this study aims to investigate how the provision of CI impacts speech-in-noise perception of SSD-CI users. METHOD: Task performance (reaction time, reaction time variability, target accuracy, subjective listening effort) and high density electroencephalography from twelve SSD-CI participants were recorded, while they completed a semantic acoustic oddball task. Reaction time was defined as the time taken for a participant to press the response button after stimulus onset. All participants completed the oddball task in three different free-field conditions with the speech and noise coming from different speakers. The three tasks were: (1) CI-On in background noise, (2) CI-Off in background noise, and (3) CI-On without background noise (Control). Task performance and electroencephalography data (N2N4 and P3b) were recorded for each condition. Speech in noise and sound localisation ability were also measured. RESULTS: Reaction time was significantly different between all tasks with CI-On (M [SE] = 809 [39.9] ms) having faster RTs than CI-Off (M [SE] = 845 [39.9] ms) and Control (M [SE] = 785 [39.9] ms) being the fastest condition. The Control condition exhibited significantly shorter N2N4 and P3b area latency compared to the other two conditions. However, despite these differences noticed in RTs and area latency, we observed similar results between all three conditions for N2N4 and P3b difference area. CONCLUSION: The inconsistency between the behavioural and neural results suggests that EEG may not be a reliable measure of cognitive effort. This rationale is further supported by different explanations used in past studies to explain N2N4 and P3b effects. Future studies should look to alternative measures of auditory processing (e.g., pupillometry) to gain a deeper understanding of the underlying auditory processes that facilitate speech-in-noise intelligibility.

A Study of Event-Related Potentials During Monaural and Bilateral Hearing in Single-Sided Deaf Cochlear Implant Users.

OBJECTIVES: Single-sided deafness (SSD) is characterized by a profoundly deaf ear and normal hearing in the contralateral ear. A cochlear implant (CI) is the only method to restore functional hearing in a profoundly deaf ear. In a previous study, we identified that the cortical processing of a CI signal differs from the normal-hearing ear (NHE) when directly compared using an auditory oddball paradigm consisting of pure tones. However, exactly how the brain integrates the electrical and acoustic signal is not well investigated. This study aims to understand how the provision of the CI in combination with the NHE may improve SSD CI users' ability to discriminate and evaluate auditory stimuli. DESIGN: Electroencephalography from 10 SSD-CI participants (4 participated in the previous pure-tone study) were recorded during a semantic acoustic oddball task, where they were required to discriminate between odd and even numbers. Stimuli were presented in four hearing conditions: directly through the CI, directly to the NHE, or in free field with the CI switched on and off. We examined task-performance (response time and accuracy) and measured N1, P2, N2N4, and P3b event-related brain potentials (ERPs) linked to the detection, discrimination, and evaluation of task relevant stimuli. Sound localization and speech in noise comprehension was also examined. RESULTS: In direct presentation, task performance was superior during NHE compared with CI (shorter and less varied reaction times [~720 versus ~842 msec], higher target accuracy [~93 versus ~70%]) and early neural responses (N1 and P2) were enhanced for NHE suggesting greater signal saliency. However, the size of N2N4 and P3b target-standard effects did not differ significantly between NHE and CI. In free field, target accuracy was similarly high with the CI (FF-On) and without the CI (FF-Off) (~95%), with some evidence of CI interference during FF-On (more variable and slightly but significantly delayed reaction times [~737 versus ~709 msec]). Early neural responses and late effects were also greater during FF-On. Performance on sound localization and speech in noise comprehension (S CI N NHE configuration only) was significantly greater during FF-On. CONCLUSIONS: Both behavioral and neural responses in the semantic oddball task were sensitive to CI in both direct and free-field presentations. Direct conditions revealed that participants could perform the task with the CI alone, although performance was suboptimal and early neural responses were reduced when compared with the NHE. For free-field, the addition of the CI was associated with enhanced early and late neural responses, but this did not result in improved task performance. Enhanced neural responses show that the additional input from the CI is modulating relevant perceptual and cognitive processes, but the benefit of binaural hearing on behavior may not be realized in simple oddball tasks which can be adequately performed with the NHE. Future studies interested in binaural hearing should examine performance under noisy conditions and/or use spatial cues to allow headroom for the measurement of binaural benefit.

Functional reconstruction of the unilateral supraglottis and piriform sinus with a triple chimeric superficial circumflex iliac artery perforator flap after supraglottic laryngectomy: A case report.

Preservation of laryngeal functions after supraglottic laryngectomy depends on both the extent of surgical resection and the type of reconstruction. Any reconstructive modality faces the challenges of preserving voice and swallow function due to the complex and dynamic anatomy of the larynx. In this report, we present a case in which the entire affected unilateral supraglottis and piriform sinus were functionally reconstructed using a triple chimeric superficial circumflex iliac artery perforator (SCIP) free flap. An extended unilateral supraglottic laryngectomy and neck dissection were performed in a 78-year-old male patient presenting with a supraglottic cT4a cN0 cM0 laryngeal cancer. The resulting defect was reconstructed using a triple chimeric SCIP flap from the right inguinal region intended to reconstruct the different affected compartments. It was based on three perforators and consisted of a 4 cm × 3 cm fascial flap from the external oblique muscle and two fasciocutaneous paddles measuring 6 cm × 2 cm and 3 cm × 4 cm. The arterial and venous vessels were anastomosed to the superior thyroid artery and internal jugular vein. The fascial flap was used to reconstruct the aryepiglottic fold. The smaller fasciocutaneous paddle was utilized to reconstruct the affected piriform sinus and former thyroid cartilage compartment, while the larger fasciocutaneous paddle served as a monitor skin flap. The postoperative recovery was uneventful. Laryngeal functions including voice and deglutition were well-preserved after 4 months of rehabilitation. The patient showed no signs of chronic aspiration or tumor recurrence 6 and 12 months postoperatively. The pliable and versatile triple chimeric SCIP flap provides a useful free flap option for a tailored functional reconstruction after an extended supraglottic laryngectomy. Restoration of larynx elevation and mobility with the presented technique substantially improves swallow rehabilitation while preserving the voice.

Effect of Cochlear Implant Electrode Insertion Depth on Speech Perception Outcomes: A Systematic Review.

Objective: The suitable electrode array choice is broadly discussed in cochlear implantation surgery. Whether to use a shorter electrode length under the aim of structure preservation versus choosing a longer array to achieve a greater cochlear coverage is a matter of debate. The aim of this review is to identify the impact of the insertion depth of a cochlear implant (CI) electrode array on CI users' speech perception outcomes. Databases Reviewed: PubMed was searched for English-language articles that were published in a peer-reviewed journal from 1997 to 2022. Methods: A systematic electronic search of the literature was carried out using PubMed to find relevant literature on the impact of insertion depth on speech perception. The review was conducted according to the preferred reporting items for systematic reviews and meta-analyses guidelines of reporting. Studies in both, children and adults with pre- or postlingual hearing loss, implanted with a CI were included in this study. Articles written in languages other than English, literature reviews, meta-analyses, animal studies, histopathological studies, or studies pertaining exclusively to imaging modalities without reporting correlations between insertion depth and speech outcomes were excluded. The risk of bias was determined using the "Risk of Bias in Nonrandomized Studies of Interventions" tool. Articles were extracted by 2 authors independently using predefined search terms. The titles and abstracts were screened manually to identify studies that potentially meet the inclusion criteria. The extracted information included: the study population, type of hearing loss, outcomes reported, devices used, speech perception outcomes, insertion depth (linear insertion depth and/or the angular insertion depth), and correlation between insertion depth and the speech perception outcomes. Results: A total of 215 relevant studies were assessed for eligibility. Twenty-three studies met the inclusion criteria and were analyzed further. Seven studies found no significant correlation between insertion depth and speech perception outcomes. Fifteen found either a significant positive correlation or a positive effect between insertion depth and speech perception. Only 1 study found a significant negative correlation between insertion depth and speech perception outcomes. Conclusion: Although most studies reported a positive effect of insertion depth on speech perception outcomes, one-third of the identified studies reported no correlation. Thus, the insertion depth must be considered as a contributing factor to speech perception rather than as a major decisive criterion. Registration: This review has been registered in PROSPERO, the international prospective register of systematic reviews (CRD42021257547), available at https://www.crd.york.ac.uk/PROSPERO/.

Odd-even oddball task: Evaluating event-related potentials during word discrimination compared to speech-token and tone discrimination.

Tonal and speech token auditory oddball tasks have been commonly used to assess auditory processing in various populations; however, tasks using non-word sounds may fail to capture the higher-level ability to interpret and discriminate stimuli based on meaning, which are critical to language comprehension. As such, this study examines how neural signals associated with discrimination and evaluation-processes (P3b) from semantic stimuli compare with those elicited by tones and speech tokens. This study comprises of two experiments, both containing thirteen adults with normal hearing in both ears (PTA ≤ 20 dB HL). Scalp electroencephalography and auditory event related potentials were recorded in free field while they completed three different oddball tasks: (1) tones, (2) speech tokens and (3) odd/even numbers. Based on the findings of experiment one, experiment two was conducted to understand if the difference in responses from the three tasks was attributable to stimulus duration or other factors. Therefore, in experiment one, stimulus duration was not controlled and in experiment two, the duration of each stimulus was modified to be the same across all three tasks (∼400 ms). In both experiments, P3b peak latency was significantly different between all three tasks. P3b amplitude was sensitive to reaction time, with tasks that had a large reaction time variability resulting in the P3b amplitude to be smeared, thereby reducing the amplitude size. The findings from this study highlight the need to consider all factors of the task before attributing any effects to any additional process, such as semantic processing and mental effort. Furthermore, it highlights the need for more cautious interpretation of P3b results in auditory oddball tasks.

Minimally Traumatic Cochlear Implant Surgery: Expert Opinion in 2010 and 2020.

This study aimed to discover expert opinion on the surgical techniques and materials most likely to achieve maximum postoperative residual hearing preservation in cochlear implant (CI) surgery and to determine how these opinions have changed since 2010. A previously published questionnaire used in a study published in 2010 was adapted and expanded. The questionnaire was distributed to an international group of experienced CI surgeons. Present results were compared, via descriptive statistics, to those from the 2010 survey. Eighteen surgeons completed the questionnaire. Respondents clearly favored the following: round window insertion, slow array insertion, and the peri- and postoperative use of systematic antibiotics. Insertion depth was regarded as important, and electrode arrays less likely to induce trauma were preferred. The usefulness of dedicated soft-surgery training was also recognized. A lack of agreement was found on whether the middle ear cavity should be flushed with a non-aminoglycoside antibiotic solution or whether a sheath or insertion tube should be used to avoid contaminating the array with blood or bone dust. In conclusion, this paper demonstrates how beliefs about CI soft surgery have changed since 2010 and shows areas of current consensus and disagreement.

Systematic Literature Review of Hearing Preservation Rates in Cochlear Implantation Associated With Medium- and Longer-Length Flexible Lateral Wall Electrode Arrays.

Background: The last two decades have demonstrated that preoperative functional acoustic hearing (residual hearing) can be preserved during cochlear implant (CI) surgery. However, the relationship between the electrode array length and postoperative hearing preservation (HP) with lateral wall flexible electrode variants is still under debate. Aims/Objectives: This is a systematic literature review that aims to analyze the HP rates of patients with residual hearing for medium-length and longer-length lateral wall electrodes. Method: A systematic literature review methodology was applied following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) recommendations to evaluate the HP rates of medium-length and longer-length lateral wall electrodes from one CI manufacturer (medium length FLEX 24, longer length FLEX 28 and FLEX SOFT, MED-EL, Innsbruck, Austria). A search using search engine PubMed (https://www.ncbi.nlm.nih.gov/pubmed/) was performed using the search terms "hearing preservation" or "residual hearing" and "cochlear implant" in "All fields." Articles published only in English between January 01, 2009 and December 31, 2020 were included in the search. Results: The HP rate was similar between medium-length (93.4%-93.5%) and longer (92.1%-86.8%) electrodes at 4 months (p = 0.689) and 12 months (p = 0.219). In the medium-length electrode group, patients under the age of 45 years had better HP than patients above the age of 45 years. Conclusions: Both medium-length and longer electrode arrays showed high hearing preservation rates. Considering the hearing deterioration over time, implanting a longer electrode at primary surgery should be considered, thus preventing the need for future reimplantation.

Worldwide Variation in Cochlear Implant Candidacy.

BACKGROUND: The aim of this study was to find out how candidacy criteria have evolved differently across the globe. METHODS: Candidacy criteria and outcome measurements applied in 19 HEARRING clinics were analyzed. RESULTS: Candidacy criteria vary between clinics. Overall, both bilateral implantation and cochlear implantation in patients with single-sided deafness are becoming more frequent. CONCLUSION: Standardized outcome measurement instruments need to be applied to provide access to the hearing world to all patients with hearing loss who would benefit from cochlear implantation.

Suitable Electrode Choice for Robotic-Assisted Cochlear Implant Surgery: A Systematic Literature Review of Manual Electrode Insertion Adverse Events.

Background and Objective: The cochlear implant (CI) electrode insertion process is a key step in CI surgery. One of the aims of advances in robotic-assisted CI surgery (RACIS) is to realize better cochlear structure preservation and to precisely control insertion. The aim of this literature review is to gain insight into electrode selection for RACIS by acquiring a thorough knowledge of electrode insertion and related complications from classic CI surgery involving a manual electrode insertion process. Methods: A systematic electronic search of the literature was carried out using PubMed, Scopus, Cochrane, and Web of Science to find relevant literature on electrode tip fold over (ETFO), electrode scalar deviation (ESD), and electrode migration (EM) from both pre-shaped and straight electrode types. Results: A total of 82 studies that include 8,603 ears implanted with a CI, i.e., pre-shaped (4,869) and straight electrodes (3,734), were evaluated. The rate of ETFO (25 studies, 2,335 ears), ESD (39 studies, 3,073 ears), and EM (18 studies, 3,195 ears) was determined. An incidence rate (±95% CI) of 5.38% (4.4-6.6%) of ETFO, 28.6% (26.6-30.6%) of ESD, and 0.53% (0.2-1.1%) of EM is associated with pre-shaped electrodes, whereas with straight electrodes it was 0.51% (0.1-1.3%), 11% (9.2-13.0%), and 3.2% (2.5-3.95%), respectively. The differences between the pre-shaped and straight electrode types are highly significant (p < 0.001). Laboratory experiments show evidence that robotic insertions of electrodes are less traumatic than manual insertions. The influence of round window (RW) vs. cochleostomy (Coch) was not assessed. Conclusion: Considering the current electrode designs available and the reported incidence of insertion complications, the use of straight electrodes in RACIS and conventional CI surgery (and manual insertion) appears to be less traumatic to intracochlear structures compared with pre-shaped electrodes. However, EM of straight electrodes should be anticipated. RACIS has the potential to reduce these complications.

Superficial Circumflex Iliac Artery Perforator Flap in Advanced Head and Neck Reconstruction: From Simple to Its Chimeric Patterns and Clinical Experience with 22 Cases.

BACKGROUND: Head and neck tissue defects after ablative head and neck surgery often require complex and composite reconstructions. The superficial circumflex iliac artery perforator (SCIP) flap is an extremely versatile perforator-based flap with minimal donor-site morbidity. The authors present their experience with both simple and chimeric SCIP flap reconstructions for complex defects in various head and neck regions. METHODS: Twenty-two patients undergoing ablative head and neck surgery for oncologic abnormalities were treated by means of a SCIP flap reconstruction. Patients' mean age was 62 years; 21 were men and one was a woman. Seventeen flaps were simple and five were chimeric reconstruction patterns. Indocyanine green perfusion imaging was performed in all cases. RESULTS: Twenty-one of 22 patients (95.5 percent) were successfully treated with good aesthetic and functional results. Two patients (9 percent) showed minor donor-site complications that were managed conservatively. The mean follow-up period was 5.3 months (range, 2 to 8 months). CONCLUSIONS: This case series demonstrates the reliability and versatility of the SCIP flap for head and neck reconstruction. The chimeric options combined with bone, double-skin paddle, and muscle offer a broad variety of functional reconstructive solutions for complex head and neck surgery. Intraoperative indocyanine green perfusion examinations are a valuable tool to assess and ascertain proper inset, vitality, and postanastomosis vessel patency in these complex microvascular flap reconstructions. . CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Stabilisation of Recombinant Human Basic Fibroblast Growth Factor (FGF-2) against Stressors Encountered in Medicinal Product Processing and Evaluation.

Basic fibroblast growth factor (FGF-2) is a highly labile protein with strong potential for tissue engineering. The aim of this study was to develop FGF-2 formulations that are stable against physical stressors encountered in pharmaceutical processing and evaluation. Pharmaceutical excipients, alone or in combination, were added to aqueous FGF-2 (770 ng/mL) solution and the stability of the resulting solutions on storage at 4-37 °C was evaluated. Stability of the solutions to repeated freeze-thaw cycles and lyophilisation was also evaluated, as well as the stability of the lyophilised stabilised protein to storage at -4, 4 and 18 °C for up to 12 months. In all of these experiments FGF-2 was quantified by ELISA assay. The as-received FGF-2, when dissolved in water, was highly unstable, retaining only 50% of baseline protein content after 30 min at 37 °C or 1 h at 25 °C. By contrast, FGF-2 solutions prepared with 0.5% w/v methylcellulose (MC) and 20 mM alanine (formulation F5) or with 0.5% w/v MC and 1 mg/mL human serum albumin (HSA) (formulation F6) were highly stable, having residual FGF-2 content comparable to baseline levels even after 2 h at 37 °C and 5 h at 25 °C. F5 and F6 were also highly stable to repeated freeze-thaw cycles, with >99% of FGF-2 load remaining after the third cycle. In addition, F5 and F6 were stable to lyophilisation, and the lyophilised products could be stored at -4, 4 or 18 °C for at least 12 months, with less than 1% loss in mean FGF-2 content. Thus, FGF-2 solution is effectively stabilised against both thermal and processing stressors in the presence of MC and alanine (F5), or MC and HSA (F6). The resultant FGF-2 solutions may be applied as medicinal products or further processed into more advanced medicinal products, e.g., scaffolds, for wound healing and tissue regeneration.

Overall Neutrophil-to-Lymphocyte Ratio and SUVmax of Nodal Metastases Predict Outcome in Head and Neck Cancer Before Chemoradiation.

INTRODUCTION: This study investigates the pretherapeutic neutrophil-to-lymphocyte ratio (NLR) with markers of tumor metabolism in 18-fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) and their potential prognostic value in head and neck cancer patients prior to primary chemoradiation. MATERIALS AND METHODS: NLR and metabolic markers of primary tumor and nodal metastases including maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were retrospectively assessed in a consecutive cohort of head and neck squamous cell cancer patients undergoing primary chemoradiation. The main outcome measure was survival. RESULTS: The study included 90 patients of which 74 had lymph node metastases at diagnosis. Median follow-up time of nodal positive patients (n=74) was 26.5 months (IQR 18-44). The NLR correlated significantly with metabolic markers of the primary tumor (TLG: rs=0.47, P<0.001; MTV: rs=0.40, P<0.001; SUVmax: rs=0.34, P=0.003), but much less with FDG-PET/CT surrogate markers of metabolic activity in nodal metastases (TLG: rs=0.15, P=0.19; MTV: rs=0.25, P=0.034; SUVmax: rs=0.06, P=0.63). For nodal positive cancer patients, multivariate analysis showed that an increased NLR (HR=1.19, 95% CI=1.04-1.37, P=0.012) and SUVmax of lymph node metastasis (HR=1.09; 95% CI=0.99-1.19; P=0.081) are independently predictive of disease-specific survival. High NLR had a negative prognostic value for overall survival (HR=1.16, 95% CI=1.02-1.33, P=0.021). CONCLUSION: NLR correlates positively with metabolic markers of the primary tumor, suggestive of an unspecific inflammatory response in the host as a possible reflection of increased metabolism of the primary tumor. SUVmax of lymph node metastases and the NLR, however, show no correlation and are independently predictive of disease-specific survival. Therefore, their addition could be used to improve survival prediction in nodal positive head and neck cancer patients undergoing primary chemoradiation.

Free double-paddle posterior tibial artery perforator flap for hypopharynx reconstruction: A case report and literature review.

Microsurgical free tissue transfer is nowadays considered to be one of the main options for head and neck reconstruction. The free posterior tibial artery perforator (PTAP) flap is a well-known reconstructive technique for local defect coverage in the distal leg, and only recently has been employed for head and neck reconstructions. Being a very thin and pliable flap, with low donor site morbidity and constant anatomy, the PTA perforator-based flap could be a great alternative to the more commonly-employed radial forearm free flap (RFFF). The present case report shows a complex head and neck defect coverage by means of a free double-paddle PTA flap, with a concise literature review of previous PTA flap descriptions in this setting. A 59-year-old male patient presented with a hypopharynx leakage after radiotherapy due to hypopharynx carcinoma. Since the patient had an occluded ulnar artery on the left side and an arterial line in the radial artery on the right side, both a RFFF and an ulnar artery perforator (UAP) flap were contraindicated. Moreover, two different cutaneous flaps were needed to reconstruct a 6 × 8 cm2 defect, one for the reconstruction of the hypopharynx and one for the resurfacing of the neck, since previous surgeries and radiotherapy led to severe fibrosis of the neck. The patient had a BMI of 25.4 kg/m2, which led us to exclude the anterolateral thigh (ALT) flap because of its thickness. For the forementioned reasons, an unconventional double-paddle PTAP flap based on two perforator vessels was chosen. Based on two perforators, two skin islands were harvested, building a double-paddle PTA perforator-based flap. The proximal skin island was 6 × 7 cm2 and the distal one was 6 × 4 cm2 . The larger skin flap was set at the leakage of the hypopharynx. The smaller skin island was used to monitor the survival of the whole flap and for resurfacing the outer side of the neck. The postoperative course was uneventful and at 3 months follow up the reconstructive result was good with no functional drawback. In view of the obtained result, we can consider that the PTA flap might be a reliable alternative to the much widely used RFFF, with a minor donor site morbidity, for delicate head and neck reconstructions.

A Synchrotron and Micro-CT Study of the Human Endolymphatic Duct System: Is Meniere's Disease Caused by an Acute Endolymph Backflow?

Background: The etiology of Meniere's disease (MD) and endolymphatic hydrops believed to underlie its symptoms remain unknown. One reason may be the exceptional complexity of the human inner ear, its vulnerability, and surrounding hard bone. The vestibular organ contains an endolymphatic duct system (EDS) bridging the different fluid reservoirs. It may be essential for monitoring hydraulic equilibrium, and a dysregulation may result in distension of the fluid spaces or endolymphatic hydrops. Material and Methods: We studied the EDS using high-resolution synchrotron phase contrast non-invasive imaging (SR-PCI), and micro-computed tomography (micro-CT). Ten fresh human temporal bones underwent SR-PCI. One bone underwent micro-CT after fixation and staining with Lugol's iodine solution (I2KI) to increase tissue resolution. Data were processed using volume-rendering software to create 3D reconstructions allowing orthogonal sectioning, cropping, and tissue segmentation. Results: Combined imaging techniques with segmentation and tissue modeling demonstrated the 3D anatomy of the human saccule, utricle, endolymphatic duct, and sac together with connecting pathways. The utricular duct (UD) and utriculo-endolymphatic valve (UEV or Bast's valve) were demonstrated three-dimensionally for the first time. The reunion duct was displayed with micro-CT. It may serve as a safety valve to maintain cochlear endolymph homeostasis under certain conditions. Discussion: The thin reunion duct seems to play a minor role in the exchange of endolymph between the cochlea and vestibule under normal conditions. The saccule wall appears highly flexible, which may explain occult hydrops occasionally preceding symptoms in MD on magnetic resonance imaging (MRI). The design of the UEV and connecting ducts suggests that there is a reciprocal exchange of fluid among the utricle, semicircular canals, and the EDS. Based on the anatomic framework and previous experimental data, we speculate that precipitous vestibular symptoms in MD arise from a sudden increase in endolymph pressure caused by an uncontrolled endolymphatic sac secretion. A rapid rise in UD pressure, mediated along the fairly wide UEV, may underlie the acute vertigo attack, refuting the rupture/K+-intoxication theory.

Temporal Pitch Perception in Cochlear-Implant Users: Channel Independence in Apical Cochlear Regions.

Two-electrode stimuli presented on adjacent mid-array contacts in cochlear-implant users elicit pitch percepts that are not consistent with a summation of the two temporal patterns. This indicates that low-rate temporal rate codes can be applied with considerable independence on adjacent mid-array electrodes. At issue in this study was whether a similar independence of temporal pitch cues can also be observed for more apical sites of stimulation, where temporal cues have been shown to be more reliable than place cues, in contrast to middle and basal sites. In cochlear-implant recipients with single-sided deafness implanted with long lateral-wall electrode arrays, pitch percepts were assessed by matching the pitch of dual-electrode stimuli with pure tones presented to the contralateral normal-hearing ear. The results were supported with an additional pitch-ranking experiment, in a different subject population with bilateral deafness. Unmodulated pulse trains with 100, 200, and 400 pulses per second were presented on three pairs of adjacent electrodes. Pulses were separated by the minimal interchannel delay (1.7 µs) in a short-delay configuration and by half the pulse period in a long-delay configuration. The hypothesis was that subjects would perceive a pitch corresponding to the doubled temporal pattern for the long-delay stimuli due to the summation of excitation patterns from adjacent apical electrodes, if those electrodes were to activate largely overlapping neural populations. However, we found that the mean matched acoustic pitch of the long-delay pulses was not significantly different from that of the short-delay pulses. These findings suggest that also in the apical region in long-array cochlear-implant recipients, temporal cues can be transmitted largely independently on adjacent electrodes.