Association of neutrophil-to-lymphocyte ratio with severe radiation-induced mucositis in pharyngeal or laryngeal cancer patients: a retrospective study.

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a marker of systemic inflammation that informs clinical decisions regarding recurrence and overall survival in most epithelial cancers. Radiotherapy for head and neck cancer leads to mucositis in almost all patients and severe radiation-mucositis affects their quality of life (QOL). However, little is known about the NLR for severe mucositis. Therefore, this study aimed to show the association between the NLR and severe radiation-induced mucositis in hypopharyngeal or laryngeal cancer patients. METHODS: In this retrospective study, we determined the incidence of grade 3 mucositis in 99 patients who were receiving definitive radiotherapy or chemoradiotherapy (CRT) for hypopharyngeal or laryngeal cancer. We performed univariate and multivariate logistic regression analyses to investigate the characteristics of grade 3 mucositis. Kaplan-Meier curves and log-rank tests were used to evaluate the occurrence of grade 3 mucositis between two groups with high (NLR > 5) or low (NLR < 5) systemic inflammation. RESULTS: The incidence of grade 3 mucositis was 39%. Univariate logistic regression analysis showed that the NLR (Odd ratio [OR] = 1.09; 95% confidence interval [CI] = 1.02-1.16; p = 0.016) and smoking (OR = 1.02; 95% CI = 1.00-1.03; p = 0.048) were significantly associated with grade 3 mucositis. Multivariate logistic regression analysis showed that the NLR was independently associated with grade 3 mucositis (OR = 1.09; 95% CI = 1.01-1.17; p = 0.021). Kaplan-Meier curves also showed that patients with higher NLR (NLR > 5) prior to radiotherapy developed grade 3 mucositis more frequently than those with lower NLR during radiotherapy (p = 0.045). CONCLUSION: This study suggests that a higher NLR is a risk factor and predictor of severe radiation-induced mucositis in hypopharyngeal or laryngeal cancer patients.

Biomarkers for Malignant Potential in Vocal Fold Leukoplakia: A State of the Art Review.

OBJECTIVE: To explore biomarkers that are candidates for understanding potential degeneration to malignancy of vocal fold leukoplakia (VFL), with the goal of guiding future diagnostic and treatment recommendations. DATA SOURCES: PubMed and Medline search engines. REVIEW METHODS: A systematic review was conducted by searching the following key words: vocal fold or laryngeal, coupled with leukoplakia or dysplasia, and combined with the term prognostic markers. We collated the biomarkers and their significance, followed by observing the power of their evidence by assessing the quality of the studies according to guidelines of tumor marker prognostic studies (REMARK). CONCLUSIONS: Prognostic biomarkers in the 16 studies are generally divided into 3 categories according to their biological roles: proliferation (Ki-67, CK-1 RS14024 SNP), cell cycle control (P53, p16, cyclin D1, p57kip2, interleukin-10 [IL-10], miR-10a, and miR-34c), cell adhesion, and invasion (neutrophil-to-lymphocyte ratio, OPN/CD44v6 axis, MMP-1, vascular endothelial growth factor A, MMP-9, serpin peptidase inhibitor 1, plasminogen activator, CTNN/B1, ß-catenin, NANOG, HERG1). The prognostic use of these biomarkers is limited due to the variable methodologies, study design, assay methods, and statistical analysis performed. IMPLICATIONS FOR PRACTICE: Prognostic factors in vocal fold leukoplakia have important clinical implications regarding the potential for malignant degeneration. Although further study is needed, the currently available evidence suggests that p53, p16, cyclin D1, IL-10, NLR, OPN and CD44v6, CTNNB1, and CTTN and FAK might be of particular interest in determining prognosis of VFL as related to malignancy. Future, large, well-designed, prospective studies are expected to determine the prognostic power of these biomarkers before their implementation in routine clinical practice.

Clinical predictors of descending necrotizing mediastinitis after deep neck infections.

OBJECTIVES/HYPOTHESIS: To identify the clinical predictors of descending necrotizing mediastinitis (DNM) secondary to deep neck infections (DNIs) before treatment. STUDY DESIGN: Retrospective case series. METHODS: We reviewed 73 patients with DNIs who had been treated with external drainage at our institute between April 2009 and March 2019. We divided these patients into either a DNI group without mediastinitis (n = 55) or a DNM group secondary to DNI (n = 18). We collected clinical data and compared them between the groups, conducting univariate and multiple logistic regression analysis to identify the predictors of DNM. RESULTS: We identified age, C-reactive protein (CRP), neutrophil percentage, lymphocyte percentage, neutrophil to lymphocyte ratio (NLR), presence of comorbidities, presence of gas, and abscess extension below the hyoid bone as statistically significant by univariate analysis. Moreover, multiple logistic regression analysis showed that age ≥55 years, NLR ≥13, and CRP ≥30 mg/dL were statistically significant. CONCLUSIONS: We identified age ≥55, NLR ≥13, and CRP ≥30 before DNI treatment as clinical predictors of a DNM complication. LEVEL OF EVIDENCE: 4 Laryngoscope, 130:E567-E572, 2020.

[The significance of lymphocyte to monocyte ratio in peripheral blood of patients with benign and malignant laryngeal lesions].

Objective:The aim of this study is to investigate the value of preoperative peripheral blood lymphocyte to monocyte ratio (LMR) in differentiating laryngeal squamous cell carcinoma (LSCC), laryngeal precancerous lesions (LPL) and laryngeal benign lesions (LBL). Method:Four hundred and five cases of laryngeal lesions diagnosed by pathology (154 cases of LSCC, 83 cases of LPL and 168 cases of LBL) were collected. LSCC group was further divided into T1 group, T2 group and T3-4 group based on T stage. The levels of neutrophils, lymphocytes, monocytes, hemoglobin, platelet and other blood indexes were measured, as well as compared the LMR, neutrophil to lymphocyte ratio (NLR) and other parameters in each group. Result:The LMR and NLR in LBL, LPL and LSCC groups was 4.88±1.65 and 4.61±1.59, 3.92±1.77 and 2.11±0.79, 2.08±0.77 and 2.63±1.69, respectively. The LMR in the LSCC group was significantly lower than those in the LBL and LPL group (P<0.01), whereas the NLR was significantly higher than those in LBL and LPL group (P<0.05). Either LMR or NLR between the LBL and LPL group was not statistically different (P>0.05). The LMR of patients with local advanced (T3-4) stage in the LSCC group was lower than that in the early or medium stage (T1-2), while the NLR was higher and the difference was statistically significant (P<0.05). There was no significant difference in platelet, white blood cell and neutrophil count between LBL, LPL and LSCC (P>0.05). Conclusion:We, for the first time, compared LMR in different laryngeal lesions and found that LMR and NLR as a systemic inflammatory index have a certain reference value for to differentiate LSCC from LPL and LBL.

Correlations Between Serum Apolipoprotein A-I and Formation of Vocal Cord Polyp.

OBJECTIVE: This study aims to investigate the correlations between serum apolipoprotein A-I (ApoA-I) and the formation of vocal cord polyps (VCPs). STUDY DESIGN: This study used the nonmatched case-control study method. METHODS: The serum total cholesterol (TC), triglyceride, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, ApoA-I, apolipoprotein B (ApoB), and ApoA-I/ApoB levels of 89 VCP patients and 87 normal volunteers were compared. Additionally, such VCP-related factors as excessive vocal use, vocal abuse, smoking, drinking, and the size of VCPs were analyzed. RESULTS: The two groups did not significantly differ with regard to triglyceride, low-density lipoprotein cholesterol, ApoB, and ApoA-I/ApoB levels (P > 0.05), whereas they did significantly differ with regard to TC, HDL-C, and ApoA-I levels (P < 0.05) according to independent t tests. Logistic regression analysis showed that excessive vocal use and vocal abuse were risk factors for VCPs (P < 0.05), with odds ratio values of 5.675 and 12.781, respectively. The ApoA-I level was negatively associated with VCPs (P < 0.05), with an odds ratio of 0.511; however, TC and HDL-C were not associated with the formation of VCPs (P > 0.05). The size of VCPs in females was negatively correlated with the serum ApoA-I level (r = -0.349, P = 0.032), whereas that in males was not (P > 0.05). CONCLUSIONS: As the serum ApoA-I level was negatively correlated with the formation of VCPs, ApoA-I may reduce the risk of VCPs. These findings may facilitate the prevention and treatment of VCPs.

Laryngeal microsurgery under general anesthesia using small-bore endotracheal tubes: blood gas analysis.

This study reports variations observed under general anesthesia through small-bore endotracheal tubes in PO2, PCO2, HCO3, percentage saturation of O2, and pH levels in 39 patients who underwent laryngeal microsurgery lasting from 10 to 100 minutes. The tendency to an increase in PCO2 levels reached statistical significance only at the 100th minute but did not constitute a risk for patients as values remained within the limits of "permitted hypercapnia." PO2, percentage saturation of oxygen, and HCO3 levels did not vary significantly. pH values tended to fall (respiratory acidosis) in correlation to the increase in PCO2. Small-bore endotracheal tubes can safely be used for laryngeal microsurgery when operating times are not longer than 100 minutes.

Anesthesia for carbon dioxide laser microsurgery of the larynx.

Jet ventilation via the Sanders injector during intravenous general anesthesia provides excellent operative conditions for CO2 laser microsurgery of the larynx. This technique, which includes complete muscle relaxation, is superior to traditional methods of anesthesia because the endotracheal tube is eliminated, thus improving the surgical field and reducing burn hazards owing to ignition of the tube. The laryngoscope has been modified to carry multiple ports into which a 14-gauge needle is inserted and the tip advanced just distal to the vocal cords. This needle is securely attached to the injector and pressure from the oxygen source is adjusted according to the patient's build and total compliance. Satisfactory arterial blood gases, superb operating conditions, safety, and rapid awakening make this the method of choice for most patients.

Mucosal blood volume and oxygen saturation in the human vocal fold.

With a newly developed spectrophotometric analyzer we were able to measure hemoglobin (Hb) concentration and its oxygen saturation in the human vocal and ventricular folds. Studies were made on 30 subjects including 18 normal controls. In laryngomicrosurgery under general anesthesia, measurements were made with a fiber probe touching the laryngeal mucosa. Results were as follows: In normal mucosa of the vocal fold, the mean value of IHb was 40 and the ISO2 was 55, while in that of the ventricular fold, the mean values were 74 and 56, respectively. Thus, in spite of the influence of general anesthesia, the mucosal blood volume was lower in the vocal fold than in the ventricular fold. The mean value of IHb was 30 in the vocal fold polyps, 122 in the vocal fold nodule, 43 in the polypoid degenerations, 17 in the vocal fold cyst, 62 in the granuloma, 6 in the sulcus vocalis and 19 in the hyperkeratoses. This method is considered useful for objective and quantitative analysis of pathological conditions in the vocal fold.

Abnormal sensations of the pharyngo-larynx.

By use of a chart questionnaire, abnormal sensations of the pharyngo-larynx (ASPL) were analyzed between May 1-October 30, 1984 and followed up uintil 1 year after the first consultation date. Two hundred ninety-one patients from the total were found to suffer from ASPL, the ratio of ASPL to all out-patients being 1.47%. The ratio of sex distinction was 6.2 (males): 10 (females). A significant number of ASPL cases occured between the ages of 30-59 years old. ASPL patients were divided into the following categories: (1) causes originating from the ENT field, (2) internal medicine origin, (3) psychological internal medicine, (4) malignant origin and (5) unknown origin. The authors also conducted an investigation of the relationship between iron deficiency and abnormal sensations of the pharyngo-larynx. ASPL in females aged between 30 to 40 years indicated a significant relation to anemia of latent iron deficiency. The authors also investigated from the psychological internal medicine view and the results revealed sticky sensations of the pharyngo-larynx and autonomic imbalances with position reaction to psychosomatic and neurotic symptoms.

A prospective evaluation of the feasibility of day-case microlaryngeal surgery.

An increasing number of surgical procedures are being performed on a day-case basis. In the UK otolaryngologists have been reluctant to introduce same day discharge in microlaryngeal surgery (MLS). The reason for this is the perceived risk to the airway from bleeding and oedema after MLS. The aim of this study was to investigate the feasibility of establishing a same day discharge service for MLS patients. One hundred consecutive patients under the care of one consultant otolaryngologist were recruited. A clinical street-fit assessment and objective measures of peak expiratory flow rate (PEFR) and oxygen saturation (SaO2) were recorded pre- and post-operatively. Results indicate that the PEFR and SaO2 did not change significantly during the course of the study. The street-fit criteria for discharge were satisfied in 80 per cent of patients following surgery. By combining the ASA score (American Society of Anaesthesiologists) with street-fitness 63 per cent of our patients were eligible for same day discharge.

[Phenotype expression and production of IL-2 by tonsillar and blood lymphocytes in patients with tonsil pathology]. / Espressione fenotipica e produzione di IL-2 da parte di linfociti tonsillari ed ematici in soggetti con patologia tonsillare.

In recent years several studies have attempted to investigate immunological responses in different tonsillar pathologies, including recurrent tonsillitis and focal infections. The present study was performed on ten patients who had undergone tonsillectomy for a) simple hypertrophy, b) recurrent tonsillitis and c) recurrent tonsillitis with focal manifestations. The blood (PBMNC) and tonsillar (TMNC) lymphocytes were tested separately. A subsequent investigation was performed on the PBMNC six months after surgery. The phenotypical aspects of the different subpopulations were studied using fluorescent antiserums and monoclonal antibodies. A second field of investigation concerned the in vitro blastogenesis, which was measured under spontaneous and PHA-P induced conditions. Finally, the IL-2 production was evaluated using the induced-growth capacity of an IL-2 dependent clone of a T murine cell line. The most interesting findings are presented. The phenotypical studies confirmed some peculiar aspects of the representation of tonsillar subsets. According to the hyperactivation ratio, the proliferation data proved to be higher in the tonsil than in the blood. A greater number of positive HLA-DR and IL-2 receptor cells (both antibodies being activated cell markers) was seen in the tonsil than in the blood and this, as well as the sporadic presence of spontaneous blastogenesis, suggests the possibility of an in vivo pre-activated condition. As far as the secretion of IL-2 is concerned, when compared to the peripheral blood ratio, greater production was found in the tonsil. Finally, a different production kinetic appears to be a constant result of the present study. The performed tests were unable to demonstrate any particular differences among the three different groups of pathologies.

[Application of high frequency jet ventilation during microsurgery of the larynx under suspending laryngoscopy]. / Aplicación de la ventilación con jet a alta frecuencia durante la microcirugía de laringe bajo laringoscopia en suspensión.

OBJECTIVES: This study describes the results obtained with high frequency jet ventilation (HFJV) in 19 patients who underwent laryngeal microsurgery under suspending laryngoscopy. MATERIAL AND METHODS: After premedication and anesthetic induction with propofol (Diprivan R, ICI-Farma), we performed an endotracheal intubation (28F tube) under succinyl-choline facilitation. Conventional ventilation was started at a rate of 14-16 cpm with a minute volume of 8-10 l, and a FiO2 of 0.4 (air-oxygen). The endotracheal tube was replaced by an insufflation catheter of 2 mm internal diameter and HFJV was initiated at a rate of 100 cpm, inspiratory time equal to the 33% of the total cycle, generator pressure of 2.5-3.6 kg/cm2, and similar FiO2. We used an Ergojet CVT (Temel SA) respirator that allowed continuous monitoring of the injector released volume during each cycle (Vjet) as well as the air way pressure. Anesthesia was maintained with continuous propofol perfusion. RESULTS: During HFJV there were no significant hemodynamic alterations and surgeons considered that the condition of the surgical field was excellent. Air way pressure was maintained at low levels in all cases, although brief hypertensive episodes occurred during laryngeal manipulation. Oxygenation was satisfactory in all except one patient with chronic obstructive pulmonary disease. Conventional ventilation and HFJV did not induce significant differences in alveolar ventilation nor in PaCO2. However, during HFJV oxygenation and ventilatory levels suffered a high degree of interindividual variability. This phenomenon could be due to the existence of variable degrees of gas reflux during insufflation. CONCLUSIONS: We conclude that HFJV is a very useful technique for anesthesia in laryngeal microsurgery. However, an appropriate monitoring of ventilatory dynamics and a detailed knowledge of the influences of patient's characteristics on HFJV are required.

[Interrelations of lysosomal enzymes of leukocytes in patients with cicatricial stenosis of the larynx]. / Vzaimosviazi lizosomal'nykh fermentov leikotsitov u bol'nykh s rubtsovym stenozom gortani.

Activities of acid and alkaline phosphatases, cathepsin B, leucine aminopeptidase, N-acetyl-beta-D-hexosaminidases, beta-D-galactosidase and beta-D-glucuronidase were studied in leukocytes of two groups of patients with normal and pathological healing of wounds after surgical treatment of scar stenosis of larynx. Analysis of the enzymatic activity, calculated by means of Student's test using the data of a single estimation of the activity in leukocytes before surgical treatment, did not exhibit any distinct differences in these two groups of patients. The study of interrelationship between the activities of individual enzymes by means of principles of regression analysis enabled to show that the enzymes studied were in the positive regressive relation. Pattern of enzymatic activity in leukocytes of patients with pathological wound healing was distinctly different from that of patients with normal healing in the shape of regression and, especially, in relaxation of the interrelations between phosphatases and other enzymes. The principle of regression enabled to evaluate the prognosis of postoperative development of wound healing using the preliminary estimation of enzymatic activity in leukocytes of patients with scar stenosis of larynx.

[Lectin-reactive immune complexes in plasma in ENT diseases]. / Lektin-reaktivnye immunnye kompleksy v plazme krovi pri LOR-zabolevaniiakh.

The content of circulating immune complexes (IC) interacting with plant lectins from Canavalia ensiformis (Con A), phaseolus vulgaris (PHA) and wheat germ (WGA) was examined in blood plasma of healthy donors and patients with ENT diseases (n = 36). It was found that the level of PHA- and WGA-reactive IC in patients with laryngeal carcinoma was significantly higher than in control, whereas only the level of WGA-reactive IC was elevated in patients with scleroma. The level of ConA-reactive IC was statistically uniform in control and both ENT diseases.

Elevated neutrophil-to-lymphocyte ratio in squamous cell carcinoma of larynx compared to benign and precancerous laryngeal lesions.

BACKGROUND: Laryngeal carcinogenesis is a multifactorial process that has not been fully elucidated. Despite extensive research, reliable markers with diagnostic and prognostic value are still lacking. It was recently reported that an elevated preoperative neutrophil-to-lymphocyte ratio (NLR) may correlate with an increased risk of recurrence, tumor aggressiveness and poorer prognosis in various malignancies. The aim of this study was to examine whether NLR could be used as an inflammatory marker to differentiate laryngeal squamous cell carcinoma (LSCC) patients from benign laryngeal lesion (BLL) and precancerous laryngeal lesion (PLL) patients. MATERIALS AND METHODS: This retrospective study was performed on 209 patients admitted to a tertiary referral center with laryngeal lesions and undergoing biopsies to establish their histopathological diagnosis. We reviewed the patient files for their clinical, histopathological and laboratory data. The patients were divided into three groups according to their histopathological findings, as BLL, PLL and LSCC groups. The patients in the PLL group were also divided into three subgroups as mild, moderate and severe dysplasia/ carcinoma in situ (CIS) subgroups. The groups were compared for NLR and the other laboratory data. RESULTS: The mean NLRs of the BLL, PLL and the LSCC groups were 2.12 ± 0.86, 2.32 ± 0.68 and 3.46 ± 1.51, respectively, and the difference was statistically significant (p = 0.001). The mean NLRs of the patients with PLL and LSCC were significantly higher than the patients with BLL (p = 0.031 and p = 0.001, respectively). The mean NLRs were similar among mild dysplasia, moderate dysplasia and severe dysplasia / CIS groups (p > 0.05). CONCLUSIONS: To our knowledge, this is the first study investigating NLR in BLL, PLL and LSCC. NLR is an inexpensive, reproducible and widely available blood test, and could be a useful inflammatory marker to differentiate LSCC from BLL and PLL.

Prospective, double-blind, placebo-controlled trials of ecallantide for acute attacks of hereditary angioedema.

Hereditary angioedema (HAE) is a rare genetic disorder characterized by unpredictable, episodic, incapacitating attacks of well-demarcated angioedema in the absence of urticaria and pruritus. HAE is due to deficient or dysfunctional C1-esterase inhibitor activity, which results in unopposed activation of plasma kallikrein, resulting in increased levels of bradykinin. Ecallantide is a potent and specific plasma kallikrein inhibitor approved for the treatment of acute attacks of HAE affecting any anatomic site. In Phase III clinical trials, subcutaneously administered ecallantide demonstrated significant, rapid and durable symptom relief. Ecallantide was effective for all attack types, including potentially life-threatening laryngeal attacks. The main safety concern is potentially serious hypersensitivity reactions, including anaphylaxis. Ecallantide represents an important treatment option for the management of acute attacks of HAE.

[Asthma or laryngeal amyloidosis? A report of a case and literature review]. / Asma o amiloidosis laríngea? Comunicación de un caso y revisión de la literatura.

The laryngeal amyloidosis is an uncommon disease accounting for 1% of all benign lesions of larynx. The commonest symptom is the dysphonia, sometimes accompanied by stridor, laryngeal globus sensation, dysphagia and, in rare occasions, cough, dyspnea and hemoptysis, specially when the tracheobronchial tree is also affected. This paper describes the case of a 30-year-old female patient, whose main symptoms were progressive dysphonia and dyspnea, admitted at allergy service to rule out asthma. The respiratory function tests showed obstruction in the medium and small caliber ways without reversibility with salbutamol. Biopsies of ventricular band, vocal cord and arytenoid stained with positive Congo red for amyloid tissue, established the laryngeal amyloidosis diagnosis. The complementary studies to rule out amyloid tissue in the remaining tracheobronchial tree were negative. Dyspnea had characteristics of laryngeal origin, caused by a pulmonary ventilation disorder provoked by the difficult arrival of air to alveoli, which caused the decreased partial pressure of oxygen and CO2.

[Ventilation in laryngeal laser-surgical interventions using superimposed high frequency jet ventilation (SHFJV)--a further revision of jet ventilation technique for laryngeal interventions]. / Beatmung bei laryngealen laserchirurgischen Eingriffen mittels der Superponierten Hochfrequenz Jet-Ventilation (SHFJV)--Eine Weiterentwicklung der Jet-Ventilationstechnik für laryngeale Eingriffe.

In laser surgery of the larynx the surgeon and the anaesthesist have to compete for the limited space available. The surgeon requiring good visibility and an undisturbed operating area whereas the anesthetist has to ensure sufficient ventilation of the patient. Further, complications of anaesthesia and laser must be avoided. These requirements are met by using the jet-tube (jet-laryngoscope) with two integrated nozzles applying simultaneously low- and high-frequency jet-ventilation giving the surgeon total access to the area operated on, and at the same time enables safe ventilation of the patient. Of 334 operations with the tubeless ventilation technique 76 cases were laser surgical interventions. In 6 patients stenoses were enlarged. The average duration of the jet-ventilation was 25 +/- 10 minutes. The maximum duration of a laser surgical intervention was 140 minutes. The age distribution of the patients was 18 months to 82 years. In all patients pulmonary gas exchange was satisfactory. We believe that the advantage of the tubeless jet-ventilation is: optimal visibility and surgical freedom for the surgeon, no time limitation, even in very severe stenoses. Since no volatile anaesthetics or any type of endotracheal tube are applied there is no danger of interaction with the laser when using the SHFJV via the jet-laryngoscope. Application of the tubeless jet-ventilation technique is however limited if patients suffer from severe pulmonary obstruction; likewise highly obese patients and patients in whom massive bleeding occurs are not amenable to tubeless jet-ventilation.