Oscillatory control of embryonic development.

Proper embryonic development depends on the timely progression of a genetic program. One of the key mechanisms for achieving precise control of developmental timing is to use gene expression oscillations. In this Review, we examine how gene expression oscillations encode temporal information during vertebrate embryonic development by discussing the gene expression oscillations occurring during somitogenesis, neurogenesis, myogenesis and pancreas development. These oscillations play important but varied physiological functions in different contexts. Oscillations control the period of somite formation during somitogenesis, whereas they regulate the proliferation-to-differentiation switch of stem cells and progenitor cells during neurogenesis, myogenesis and pancreas development. We describe the similarities and differences of the expression pattern in space (i.e. whether oscillations are synchronous or asynchronous across neighboring cells) and in time (i.e. different time scales) of mammalian Hes/zebrafish Her genes and their targets in different tissues. We further summarize experimental evidence for the functional role of their oscillations. Finally, we discuss the outstanding questions for future research.

Pairing of segmentation clock genes drives robust pattern formation.

Gene expression is an inherently stochastic process1,2; however, organismal development and homeostasis require cells to coordinate the spatiotemporal expression of large sets of genes. In metazoans, pairs of co-expressed genes often reside in the same chromosomal neighbourhood, with gene pairs representing 10 to 50% of all genes, depending on the species3-6. Because shared upstream regulators can ensure correlated gene expression, the selective advantage of maintaining adjacent gene pairs remains unknown6. Here, using two linked zebrafish segmentation clock genes, her1 and her7, and combining single-cell transcript counting, genetic engineering, real-time imaging and computational modelling, we show that gene pairing boosts correlated transcription and provides phenotypic robustness for the formation of developmental patterns. Our results demonstrate that the prevention of gene pairing disrupts oscillations and segmentation, and the linkage of her1 and her7 is essential for the development of the body axis in zebrafish embryos. We predict that gene pairing may be similarly advantageous in other organisms, and our findings could lead to the engineering of precise synthetic clocks in embryos and organoids.

Regulatory mechanisms ensuring coordinated expression of functionally related genes.

Coordinated spatiotemporal expression of large sets of genes is required for the development and homeostasis of organisms. To achieve this goal, organisms use myriad strategies where they form operons, utilize bidirectional promoters, cluster genes, share enhancers among genes by DNA looping, and form topologically associated domains and transcriptional condensates. Coexpression achieved by these different strategies is hypothesized to have functional importance in minimizing gene expression variability, establishing dosage balance to ensure stoichiometry of protein complexes, and minimizing accumulation of toxic intermediate metabolites. By combining gene-editing tools with computational modeling, recent studies tested the advantages of adjacent genes located in pairs and clusters. We propose that with the advancement of gene editing, single-cell sequencing, and imaging tools, one could readily test the functional importance of different coexpression strategies in a variety of biological processes.

Zebrafish as a model to investigate a biallelic gain-of-function variant in MSGN1, associated with a novel skeletal dysplasia syndrome.

BACKGROUND/OBJECTIVES: Rare genetic disorders causing specific congenital developmental abnormalities often manifest in single families. Investigation of disease-causing molecular features are most times lacking, although these investigations may open novel therapeutic options for patients. In this study, we aimed to identify the genetic cause in an Iranian patient with severe skeletal dysplasia and to model its molecular function in zebrafish embryos. RESULTS: The proband displays short stature and multiple skeletal abnormalities, including mesomelic dysplasia of the arms with complete humero-radio-ulna synostosis, arched clavicles, pelvic dysplasia, short and thin fibulae, proportionally short vertebrae, hyperlordosis and mild kyphosis. Exome sequencing of the patient revealed a novel homozygous c.374G > T, p.(Arg125Leu) missense variant in MSGN1 (NM_001105569). MSGN1, a basic-Helix-Loop-Helix transcription factor, plays a crucial role in formation of presomitic mesoderm progenitor cells/mesodermal stem cells during early developmental processes in vertebrates. Initial in vitro experiments show protein stability and correct intracellular localization of the novel variant in the nucleus and imply retained transcription factor function. To test the pathogenicity of the detected variant, we overexpressed wild-type and mutant msgn1 mRNA in zebrafish embryos and analyzed tbxta (T/brachyury/ntl). Overexpression of wild-type or mutant msgn1 mRNA significantly reduces tbxta expression in the tailbud compared to control embryos. Mutant msgn1 mRNA injected embryos depict a more severe effect, implying a gain-of-function mechanism. In vivo analysis on embryonic development was performed by clonal msgn1 overexpression in zebrafish embryos further demonstrated altered cell compartments in the presomitic mesoderm, notochord and pectoral fin buds. Detection of ectopic tbx6 and bmp2 expression in these embryos hint to affected downstream signals due to Msgn1 gain-of-function. CONCLUSION: In contrast to loss-of-function effects described in animal knockdown models, gain-of-function of MSGN1 explains the only mildly affected axial skeleton of the proband and rather normal vertebrae. In this context we observed notochord bending and potentially disruption of pectoral fin buds/upper extremity after overexpression of msgn1 in zebrafish embryos. The latter might result from Msgn1 function on mesenchymal stem cells or on chondrogenesis in these regions. In addition, we detected ectopic tbx6 and bmp2a expression after gain of Msgn1 function in zebrafish, which are interconnected to short stature, congenital scoliosis, limb shortening and prominent skeletal malformations in patients. Our findings highlight a rare, so far undescribed skeletal dysplasia syndrome associated with a gain-of-function mutation in MSGN1 and hint to its molecular downstream effectors.

Oncological Outcomes of Transoral Laryngeal Microsurgery with Fiber-Optic Diode Laser for Early Glottic Cancer: A Single-Center Experience.

Backgroud/Objectives: Transoral laser laryngeal microsurgery (LTLM) has been widely used in the treatment of early-stage glottic laryngeal squamous cell carcinoma (LSCC) for the past few decades. Although T stage, tumor grade, anterior commissure involvement, type of cordectomy, positive surgical margin, and postoperative additional therapies were accused as the prognostic factors for recurrence, there is still controversy about these data in the literature. The purpose of this study was to evaluate the oncological results of our patients with early glottic LSCC treated with LTLM as a single-modality therapy in a single-center study. METHODS: Patients with early-stage (Tis-1-2/N0) glottic LSCC who underwent LTLM as a primary treatment from 2011 to 2019 were retrospectively reviewed. The clinicopathological factors and oncologic outcomes were analyzed. RESULTS: One hundred and sixty-one patients were enrolled in this study. The 5-year overall (OS), disease-specific (DSS), disease-free (DFS), and laryngectomy-free survival rates were 84.5%, 97.9%, 79.2%, and 93.5%, respectively. The most common stage, histopathological type, and type of endoscopic cordectomy were T1 stage, well-differentiated cancer, and type 2 cordectomy, respectively. A positive surgical margin was defined in 20 (12.4%) patients. There was a significant relationship between histopathological grade and positive surgical margins (p = 0.038). OS and DSS rates of "wait and see" modality were lower, while DFS of radiotherapy was lower than that of other treatment modalities in patients with positive surgical margins, but the differences were not statistically significant. Nineteen (11.8%) patients had a recurrence. DSS was statistically significantly lower in patients with recurrence (p < 0.001). CONCLUSION: The results of our study showed that anterior commissure involvement, surgical margin positivity, and higher T stage statistically did not reduce survival rates in early-stage LSCC patients treated with LTLM. As the histopathological grade of the tumor worsens, the risk of surgical margin positivity increases. RT may have a negative effect on recurrence and organ preservation in the additional treatment of patient with positive surgical margins.

Is Septal Cartilage Graft via Transmastoid Approach Safe Enough in the Repair of Large Tegmen Defects?

INTRODUCTION: Tegmen defect (TD) has a potential of intracranial spread of middle ear infection, meningoencephalic herniation (MEH), and cerebrospinal fluid leakage (CSFL). Especially the defects >1 cm with MEH or CSFL are generally repaired via the classical middle fossa or minicraniotomy technique. The aim of this study was to show the efficiency of the intracranial, extradural placement of the septal cartilage graft in the closure of the TD larger than 1 cm via the transmastoid (TM) approach. METHODS: The demographic, preoperative, intraoperative, and postoperative data of 11 patients with chronic otitis media (COM) who had TD larger than 1 cm were reviewed retrospectively. Hospitalization time and hearing preservation with respect to MEH or CSFL were analyzed. RESULTS: The most common etiology of TD was cholesteatoma (82%), and 91% of the patients had multiple COM surgery history. The mean TD size was 15.4 (10-25) mm. Fifty-five percent of the patients presented with either MEH or CSFL. The mean follow-up of the patients was 22.5 (8-42) months. There was no significant difference between preoperative and postoperative mean bone conduction thresholds. Mean hospitalization time was 5.2 (3-10) days. There was no significant difference in the hospitalization time between patients with MEH or CSFL and without MEH or CSFL. Neither recurrence nor graft infection was encountered. CONCLUSION: Extradural grafting with the septal cartilage in the large TD up to 25 mm can be repaired efficiently via the TM approach without application of a lumbar drainage.

Is There Any Effect of Subjective Tinnitus on Vestibular Evoked Myogenic Potentials.

Idiopathic subjective tinnitus has a complex pathophysiology in which not only cochlear and central classical auditory pathways but also nonclassical auditory pathways of different parts of the brain are involved. Vestibuloocular and vestibulocollic pathways are the central projections of utricle and saccule used in the vestibular evoked myogenic potential (VEMP) test. Aim of this study was to investigate the effects of idiopathic subjective tinnitus on vestibuloocular and vestibulocollic pathways via VEMP. We prospectively analyzed 30 unilateral idiopathic subjective tinnitus patient's cervical, ocular VEMP tests, tinnitus handicap index scores, symptom duration and compared with contralateral ear and 35 healthy volunteers. The latencies and amplitudes of P1 and N1 waves were recorded and pathologic wave criteria was calculated according to healthy volunteer's data. In cervical VEMP there were significant longer latencies of P1 and N1 waves with respect to contralateral ear and control group. In ocular VEMP test, N1 and P1 latencies and amplitudes were not significantly different. The percentages of pathologic wave of the tinnitus side were not significantly higher in both cervical VEMP and ocular VEMP tests with respect to contralateral side. Tinnitus handicap index scores and symptom duration had no relationship with latency and amplitude of VEMP tests. Although cervical VEMP P1 and N1 latencies were significantly longer, subjective tinnitus did not result in pathological alterations in the VEMP test. Presence of subjective tinnitus is not an influencing factor in the VEMP interpretation.

Impact of fetal brain tissue derived mesenchymal stem cell and fibrin glue on facial nerve crash injury

Background/aim: To evaluate the clinical and histopathological effects of fetal brain tissue derived mesenchymal stem cells (FBTMSC) and fibrin glue (FG) on the facial nerve (FN) regeneration in rats with traumatic FN injury. Materials and methods: Twenty-eight Sprague Dawley rats were included in the study and divided into 4 groups. Traumatic FN injury (FP) was created by a surgical clamp compression to the main trunk of left FN in all groups. In the control group (group 1) no treatment was applied, in group 2 (FBTMSC group) 2 × 106 FBTMSC was injected, in group 3 (FG group) only FG was applied, in group 4 (FBTMSC and FG groups) both FBTMSC and FG were applied to the injured section of the nerve. The FN functions were evaluated clinically, immediately after the procedure and at 3rd, 5th, and 8th weeks postoperatively. The FNs of all subjects were excised after the 8th week; then the rats were sacrificed. The presence of stem cells in the injured zone was assessed using bromo-deoxyuridine (BrdU), and apoptosis was determined by the TUNEL method. Results: After the damage, total FP was observed in all subjects. Statistically significant functional improvement was observed in group 4 compared to all other groups (P < 0.005). TUNEL-positive cell count was statistically significantly higher in the control group than the other groups (P < 0.001). TUNEL-positive cell count was statistically significantly lower in group 4 than the other groups. The proportion of BrdU-stained cells in group 4 (5%) was higher than group 2 (2%). Conclusion: Clinically and histopathologically FBTMSC applied with FG may play a promising role as a regenerative treatment in posttraumatic FP.

Prognostic role of homeostasis model assessment and oral glucose tolerance test in nondiabetic patients with Bell's palsy

Background/aim: We aimed to revealthe incidence and predictive role of insulin resistance and distorted oral glucose tolerance test in nondiabetic patients withBell's Palsy (BP). Materials and methods: Eighty-sixpatients with BP and 28 control subjects; all with normal blood glucose levels and no history of diabetes, were enrolled in the study. We investigated insulin resistance (IR) in all subjects, in terms of HOMA-IR greater than 2.7. Sixty-two of the patients also underwent an oral glucose tolerance test (OGTT). Results: The mean HOMA-IR value was significantly increased in patients, compared to the control group (3.2 vs 1.6; P < 0.01). IR was detected more in BP patients than in controls (P < 0.05). The patients with higher HOMA-IR values had more severe facial dysfunction at the initial presentation and complete recovery time took longer than the patients with normal HOMA-IR value (75 days vs 42 days; P < 0.05). Following a 2h-OGTT, impaired glucose tolerance and newly diagnosed DM were found in 60% of the patients. Recovery time was significantly longer in prediabetics and newly diagnosed diabetic patients than in patients with normal glycemia (68 days, 52 days, and 32 days, respectively; P < 0.01). Conclusion: There is a strong linkage between HOMA-IR value and BP prognosis so HOMA-IR value may have a significant role of predicting BP prognosis at presentation.

Addition of intratympanic steroid or hyperbaric oxygen treatment to systemic steroid treatment in sudden idiopathic sensorineural hearing loss treatment, and long-term results of salvage treatment

Background/aim: This study aims to determine the therapeutic superiority of the addition of intratympanic steroid or hyperbaric oxygen therapy to systemic steroid treatment in idiopathic sudden sensorineural hearing loss as initial treatment, and evaluate the long- term results of salvage treatment. Materials and methods: This study was a retrospective clinical trial with a total of 96 patients with idiopathic sudden sensorineural hearing loss. Patients were divided into 3 groups. Group 1 (n: 32) received systemic steroid treatment. Group 2 (n: 32) received the Group 1 protocol plus intratympanic steroid treatment. Group 3 (n: 32) received the Group 1 protocol plus hyperbaric oxygen treatment. Pretreatment and postinitial audiologic evaluations were performed, and the hearing outcome was analyzed with Furuhashi criteria. All patients, except those who experienced total recovery after initial treatment, were directed to salvage treatment. Audiologic assessment was performed again after salvage treatment and a mean follow-up period of 36.5 months. Results: Each group was homogenous according to demographics, audiologic data, and prognostic factors. There was no statistically significant difference in recovery and success rate within the 3 groups after initial treatment. (P: 0.66, P: 0.248, respectively). Successful results were obtained after salvage treatment in only 3 patients (5%). These patients received follow-up treatment at a mean of 36.5 months, but there was no spontaneous recovery after the end of salvage treatment. Conclusion: The addition of intratympanic steroids or hyperbaric oxygen to systemic steroids caused no significant hearing improvement as the initial treatment of idiopathic sudden sensorineural hearing loss. The efficacy of salvage treatment was limited, and there was no spontaneous hearing improvement after the long-term follow-up.

Laryngeal electromyographic changes in postthyroidectomy patients with normal vocal cord mobility.

Thyroidectomy has been used for the treatment of thyroid disease for more than 100 years. In spite of the advancement of surgical techniques, there is still a risk of laryngeal nerve injury. The risk of partial or complete injury still depends on some surgical and disease-related factors. The aim of this study is to show the partial injury and to establish these risk factors via laryngeal electromyographic analysis (LEMG) in postthyroidectomy patients with normal vocal cord motion and mucosal anatomy. Patients who had undergone thyroid surgery were enrolled in this prospective study. LEMG analysis was performed to all patients with normal vocal cord mobility preoperatively and was repeated after the first and the third months of surgery. Thyroarytenoid (TA) and cricothyroid (CT) muscles were used to evaluate recurrent and external branch of superior laryngeal nerves, respectively. Four of the 32 patients had mild-to-moderate degrees of partial LEMG changes during preoperative LEMG analysis of TA and CT muscles on each side. After 3 months of surgery, there was a statistically significant worsening of LEMG findings in the right and left external branches of superior and left recurrent laryngeal nerves. Disease and surgery-related risk factors were analyzed. However, there was no significant relationship on the progression of LEMG findings according to these parameters. This is the first prospective study which supports the risk of progression of LEMG changes in patients with normal laryngoscopic examination after thyroid surgery. No reliable significant risk factor was found influencing the LEMG progression.

Can Cochlear Nerve Size Assessment With Magnetic Resonance Enhance the Understanding of Idiopathic Sudden Sensorineural Hearing Loss?

BACKGROUND AND OBJECTIVES: Idiopathic sudden sensorineural hearing loss (ISSHL) is a rapid loss of hearing, exceeding 30 dB in at least 3 consecutive frequencies within 3 days, without any identifiable cause despite thorough investigations. Currently, the etiology and pathogenesis of ISSHL have not been fully elucidated. This study aimed to assess the size of the cochlear nerve in patients with ISSHL and explore its relationship with pretreatment audiograms and treatment response. Subjects and. METHODS: A total of 125 patients (59 [47.2%] women; mean age 47.7±13.8 years [minimum-maximum: 21-76]) and 60 healthy participants (27 [45%] women; mean age 45.7±16.8 years [minimum-maximum: 20-76]) as a control group were included in this study. The size of the cochlear nerve was assessed on the affected side, compared to the control group, as well as on the unaffected side. Pretreatment and posttreatment audiological values were also analyzed. RESULTS: The cross-sectional area (CSA), vertical diameter (VD), and horizontal diameter (HD) of the CN were found to be smaller on the affected side of ISSHL patients compared to the control group (p<0.01; p=0.04; p=0.02, respectively). In the study group (affected side of ISSHL patients), there were no significant differences in VD, HD, and CSA values between pretreatment audiogram types (p=0.23; p=0.53; p=0.39, respectively), and initial hearing levels (p=0.16; p=0.22; p=0.23, respectively). Furthermore, there were no significant differences in VD, HD, and CSA values between the recovery groups according to Furuhashi criteria (p=0.18; p=0.37; p=0.27, respectively). CONCLUSIONS: The size of the CN may be a risk factor for ISSHL, but it does not affect the type of audiogram curves and was not prognostic in terms of treatment response.

Could the thick of retinal nerve fiber layer be a potential measure of axonal loss in hearing loss?

OBJECTIVE: The objective of the study is to compare the optic coherence tomography (OCT) parameters of the healthy and affected sides of patients with idiopathic sudden sensorineural hearing loss (ISSNHL) and to investigate the relationships between these and the improvement in hearing levels. METHODS: A bilateral eye evaluation of patients diagnosed with ISSNHL was performed with OCT. The ganglion cell complex (GCC) and retina nerve fiber layer (RNFL) thickness values were recorded and the differences between the two eyes were examined. RESULTS: An evaluation was made of 39 patients with a mean age of 44.82 ± 14.90 years. The RNFL thickness of the eyes was determined to be mean 89.87 ± 3.65 µm on the affected side and 103.87 ± 3.98 µm on the healthy control side (p = 0.0001). The mean GCC was determined to be mean 90.46 ± 3.49 µm on the affected side and 103.77 ± 3.96 µm on the healthy control side (p = 0.0001). CONCLUSIONS: A statistically significant difference was observed between the healthy and affected eyes of patients with ISSNHL with respect to mean GCC and mean RNFL thickness. OCT could be a useful technique for measuring this neural degeneration.

OBJETIVO: Comparar e investigar los parámetros de la tomografía de coherencia óptica (OCT) de los lados sanos y afectados de pacientes con pérdida auditiva neurosensorial súbita idiopática (PANSI). MÉTODO: La evaluación ocular bilateral de los pacientes diagnosticados con PANSI se realizó con OCT. Se registraron los valores de espesor del complejo de células ganglionares (CCG) y de la capa de fibras nerviosas de la retina (CFNR), y se examinaron las diferencias entre los dos ojos. RESULTADOS: Se evaluaron 39 pacientes, con una edad media de 44.82 ± 14.90 años. Se determinó que el grosor de la CFNR de los ojos era una media de 89.87 ± 3.65 µm en el lado afectado y 103.87 ± 3.98 µm en el lado de control sano (p = 0.0001). Se determinó que el CCG medio era 90.46 ± 3.49 µm en el lado afectado y 103.77 ± 3.96 µm en el lado de control sano (p = 0.0001). CONCLUSIONES: Se encontró una diferencia estadísticamente significativa entre los ojos sanos y afectados de pacientes con PANSI con respecto al CCG medio y al espesor medio de la CFNR. La OCT podría ser una técnica útil para medir esta degeneración neuronal.

Disrupted harmony of the skull skeleton: Middle ear resonance in acromegaly.

OBJECTIVES: This study aims to investigate whether the middle ear resonance frequency (RF) is affected in acromegaly, which causes growth in the skull bone. METHODS: Thirty acromegaly patients and 38 volunteers were included in the study. Pure tone average scores and middle ear RF values of the groups that underwent pure tone audiometry, tympanometry, and multifrequency tympanometry tests were compared. RESULTS: The pure tone mean was 14.95 ± 12.13 in acromegaly patients and 5.70 ± 8.52 in the control group (p:0.18). Sensorineural hearing loss(SNHL) was observed in 16.6% of the patients. The average middle ear RF was calculated as 815 ± 179.05 Hz in patients with acromegaly and 773 ± 127.15 in the control group. (p = 0.0001). CONCLUSION: This study is the first to evaluate middle-ear RF in acromegaly patients. Acromegaly-induced changes in soft tissues and bone structures impact middle ear functions. In this patient group, we found an increase in middle ear RF without conductive-type hearing loss and a 16.6% rate of SNHL.

Using single-molecule fluorescence in situ hybridization and immunohistochemistry to count RNA molecules in single cells in zebrafish embryos.

Taming gene expression variability is critical for robust pattern formation during embryonic development. Here, we describe an optimized protocol for single-molecule fluorescence in situ hybridization and immunohistochemistry in zebrafish embryos. We detail how to count segmentation clock RNAs and calculate their variability among neighboring cells. This approach is easily adaptable to count RNA numbers of any gene and calculate transcriptional variability among neighboring cells in diverse biological settings. For complete details on the use and execution of this protocol, please refer to Keskin et al. (2018),1 Zinani et al. (2021),2 and Zinani et al. (2022).3.

Stochastic gene expression and environmental stressors trigger variable somite segmentation phenotypes.

Mutations of several genes cause incomplete penetrance and variable expressivity of phenotypes, which are usually attributed to modifier genes or gene-environment interactions. Here, we show stochastic gene expression underlies the variability of somite segmentation defects in embryos mutant for segmentation clock genes her1 or her7. Phenotypic strength is further augmented by low temperature and hypoxia. By performing live imaging of the segmentation clock reporters, we further show that groups of cells with higher oscillation amplitudes successfully form somites while those with lower amplitudes fail to do so. In unfavorable environments, the number of cycles with high amplitude oscillations and the number of successful segmentations proportionally decrease. These results suggest that individual oscillation cycles stochastically fail to pass a threshold amplitude, resulting in segmentation defects in mutants. Our quantitative methodology is adaptable to investigate variable phenotypes of mutant genes in different tissues.

Gene copy number and negative feedback differentially regulate transcriptional variability of segmentation clock genes.

Timely progression of a genetic program is critical for embryonic development. However, gene expression involves inevitable fluctuations in biochemical reactions leading to substantial cell-to-cell variability (gene expression noise). One of the important questions in developmental biology is how pattern formation is reproducibly executed despite these unavoidable fluctuations in gene expression. Here, we studied the transcriptional variability of two paired zebrafish segmentation clock genes (her1 and her7) in multiple genetic backgrounds. Segmentation clock genes establish an oscillating self-regulatory system, presenting a challenging yet beautiful system in studying control of transcription variability. In this study, we found that a negative feedback loop established by the Her1 and Her7 proteins minimizes uncorrelated variability whereas gene copy number affects variability of both RNAs in a similar manner (correlated variability). We anticipate that these findings will help analyze the precision of other natural clocks and inspire the ideas for engineering precise synthetic clocks in tissue engineering.

Management of deep neck infections in adults and importance of clinical and laboratory findings.

This study aimed to analyze laboratory and radiological imaging results in the prediction of treatment strategy in patients with deep neck infections. Eighty-three patients (55 (66.3%) men, mean age: 38.2±14.5 years) were included in the study. Patients were divided into three groups according to the treatment strategy: group 1 received only antibiotic treatment, group 2 underwent abscess drainage with needle puncture in addition to antibiotic treatment, and group 3 underwent surgical drainage with antibiotic treatment. Laboratory outcomes, imaging methods, duration of hospital stay, treatment strategy, and clinical outcomes were analyzed.According to the laboratory results, complete blood count values did not vary among the three groups, but C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) values were higher in group 3 (p<0.01). Based on receiver operating characteristic (ROC) analysis, the cut-off levels for CRP and ESR associated with the need for surgical drainage were 133 mg/L and 42.5, respectively. According to radiological imaging results, the number of involved neck spaces was significantly different among the three groups (p=0.03), and group 3 had more spaces involved when compared with groups 1 and 2 (p=0.04). Gas formation in the neck tissues was noted in 10 patients in group 3 and 5 patients in groups 1 and 2 (p=0.02). ESR and CRP levels were higher in patients who underwent surgical drainage. In patients with deep neck space infections, the involvement of two or more neck spaces and gas formation on radiological images might indicate surgical drainage as a treatment strategy.

Occult lymph node metastasis in patients with laryngeal cancer and relevant predicting factors: a single-center experience.

OBJECTIVE: To reveal the incidence and predictive parameters of occult cervical lymph node metastasis (LNM) in patients with cN0 laryngeal squamous cell cancer (LSCC) who underwent surgery as definitive treatment. METHODS: Patients with cN0 laryngeal cancer who had undergone elective neck dissection together with partial or total laryngectomy between January 2006 and November 2020 were retrospectively analyzed. Clinical and histopathologic predictors of occult metastasis were also analyzed. Follow-up data were used to obtain recurrence and survival analysis. RESULTS: A total of 86 patients with a mean age of 62.5 years were included in the study. Occult LNM was detected in 15 (17.4%) patients. Tumor grade, pT stage, thyroid cartilage invasion, and extralaryngeal extension were found to predict occult neck metastasis in univariate analysis. The mean follow-up time was 60.7 months and in the survival/recurrence analysis, pT stage, tumor location, tumor grade, presence of occult metastasis, pre-epiglottic space involvement. and extralaryngeal extension were found to predict poorer outcome. CONCLUSION: Overall occult LNM is low (17.4%) in N0 laryngeal cancer, but the presence of LNM is a poor prognostic factor. Correct determination of the neck status and proper treatment is crucial. The incidence of LNM is very low in T1-T2 stages and well-differentiated tumors. The "wait and see" strategy may be applied in T1-T2 cases as well as selected T3 cases with well-differentiated tumors.