Metabolomics of head and neck cancer in biofluids: an integrative systematic review.

INTRODUCTION: Head and neck cancer (HNC) is the fifth most common cancer globally. Diagnosis at early stages are critical to reduce mortality and improve functional and esthetic outcomes associated with HNC. Metabolomics is a promising approach for discovery of biomarkers and metabolic pathways for risk assessment and early detection of HNC. OBJECTIVES: To summarize and consolidate the available evidence on metabolomics and HNC in plasma/serum, saliva, and urine. METHODS: A systematic search of experimental research was executed using PubMed and Web of Science. Available data on areas under the curve was extracted. Metabolic pathway enrichment analysis were performed to identify metabolic pathways altered in HNC. Fifty-four studies were eligible for data extraction (33 performed in plasma/serum, 15 in saliva and 6 in urine). RESULTS: Metabolites with high discriminatory performance for detection of HNC included single metabolites and combination panels of several lysoPCs, pyroglutamate, glutamic acid, glucose, tartronic acid, arachidonic acid, norvaline, linoleic acid, propionate, acetone, acetate, choline, glutamate and others. The glucose-alanine cycle and the urea cycle were the most altered pathways in HNC, among other pathways (i.e. gluconeogenesis, glycine and serine metabolism, alanine metabolism, etc.). Specific metabolites that can potentially serve as complementary less- or non-invasive biomarkers, as well as metabolic pathways integrating the data from the available studies, are presented. CONCLUSION: The present work highlights utility of metabolite-based biomarkers for risk assessment, early detection, and prognostication of HNC, as well as facilitates incorporation of available metabolomics studies into multi-omics data integration and big data analytics for personalized health.

The surgical treatment of acquired subglottic stenosis in children with double-stage laryngotracheal reconstruction.

OBJECTIVES: The aim of this study is to report our experience with double-stage laryngotracheal reconstruction with anterior or antero-posterior cartilage grafting in the management of acquired laryngotracheal stenosis in children. Patients were treated by the same surgeon at the UMC National Research Center for Maternal and Child Health of Astana (Kazakhstan), and Sfendiyarov Kazakh National Medical University, Almaty (Kazakhstan). METHODS: From November 2011 to September 2019, 9 children underwent surgery for grade III and IV laryngotracheal stenosis according to the European Laryngological Society classification (mean age of 6 years, range of 2-12 years). RESULTS: Six patients underwent double-stage laryngotracheal reconstruction with anterior and posterior cartilage graft, and 3 patients underwent double-stage laryngotracheal reconstruction with single anterior cartilage graft. In all patients, a T-tube was used to stabilize the airway (mean time of 5.8 months, range of 5-9 months). One patient required additional dilation with bougies to obtain a viable laryngotracheal diameter. No postoperative complications were observed. One patient experienced recurrence of the stenosis 5 months after double-stage laryngotracheal reconstruction with double anterior and posterior cartilage grafts and is waiting for revision surgery. After a mean follow-up of 14 months (range of 4-36 months), 8 patients are tracheostomy-free, and all patients are feeding tube-free. CONCLUSIONS: Double-stage laryngotracheal reconstruction with a single or double cartilage grafting represents a safe and effective option in the management of complete or severe laryngotracheal stenosis.

Transoral-transpharyngeal CO2 laser en bloc excision of voluminous left recurrent laryngeal nerve schwannoma: Case report and review of the literature.

Recurrent nerve laryngeal schwannoma is a rare benign tumor that, in expert hands, can be treated by transoral CO2 laser surgery.

Compartmental Surgery With Microvascular Free Flap Reconstruction in Patients With T1-T4 Squamous Cell Carcinoma of the Tongue: Analysis of Risk Factors, and Prognostic Value of the 8th Edition AJCC TNM Staging System.

Compartmental surgery and primary reconstruction with microvascular free flaps represent the gold-standard in the treatment of oral tongue squamous cell carcinoma (OTSCC). However, there are still unclear clinical features that negatively affect the outcomes. This retrospective study included 80 consecutive patients with OTSCC who underwent compartmental surgery and primary reconstruction by free flap. The oncologic outcomes, the reliability of the 8th edition American Joint Committee on Cancer (AJCC) staging system and the prognostic factors were evaluated. Fifty-nine males and 21 females (mean age 57.8 years, range 27-81 years) were treated between November 2010 and March 2018 (one patient had two metachronous primaries). Seventy-one patients (88.75%, 52 males, 19 females, mean age of 57.9 years, range of 27-81 years) had no clinical history of previous head and neck radiotherapy and were considered as naive. Histology showed radical surgery on 80/81 lesions (98.8%), with excision margins >0.5 cm, while in 1 case (1.2%), a close posterior margin was found. According to the 8th AJCC classification, 37 patients (45.7%) were upstaged shifting from the clinical to the pathological stage, and 39 (48.1%) showed an upstaging while shifting from the 7th to the 8th AJCC staging system (no tumors were downstaged). Nodal involvement was confirmed in 33 patients (40.7%). Perineural and lymphovascular invasion were present in 9 (11.1%) and 11 (13.6%) cases, respectively. Twenty-two patients (27.1%) underwent adjuvant therapy. The 5-years disease-specific, overall, overall relapse-free, locoregional relapse-free and distant metastasis-free survival rates were 73.2, 66.8, 62.6, 67.4, and 86%, respectively. Patients with a lymph node ratio >0.09 experienced significantly worse outcomes. Univariate analysis showed that patients with previous radiotherapy, stage IV disease, nodal involvement, and lymphovascular invasion had significantly worse outcomes. Multivariate analysis focused naive patients and showed that lymphovascular invasion, advanced stage of disease, and node involvement resulted reliable prognostic factors, and patients with the same tumor stage and histological risk factors who did not undergo adjuvant therapy experienced significantly worse outcomes. In our series, surgery played a major role in the treatment of local extension; adjuvant therapy resulted strictly indicated in patients with advanced-stage disease associated with risk factors.

Single and double mucosal microflap CO2 laser "sliding" technique in the management of iatrogenic glottic web: anatomical and functional results.

PURPOSE: An anterior glottic web consists of the formation of a bridge of scar tissue covered by epithelium between the anterior free edges of the true vocal cords and represents one of the most common complications of laryngeal endoscopic surgery for tumors involving the anterior commissure. Endoscopic surgery is the therapy of choice, but simple section of the web is burdened by a high recurrence rate. Topical application of mitomycin C, intracordal stents, and the use of mucosal microflaps have been proposed to improve outcomes. We report our experience with the use of single and double mucosal microflaps (sliding technique) during the management of iatrogenic anterior glottic web (IAGW). METHODS: From November 2010 to December 2018, 30 patients (29 males, 1 female, mean age 65 years, range 47-87 years) were observed for IAGW, and 11 of these patients (36.7%) required surgical treatment. The Voice Handicap Index (VHI) and the GRBAS were used for the perceptive evaluation of pre- and post-operative voice quality. RESULTS: A reduction of the web length was observed in all cases, and we did not observe any residual web at the mid-third of the glottis. The mean post-operative VHI score decreased from 45 to 24, and the mean post-operative GRBAS values were reduced from 2.8, 2.4, 2.3, 2.1, and 1.1 to 1.9, 1.4, 1.3, 1.1, and 0, respectively. CONCLUSIONS: The microflap technique represents an effective and reproducible one-step procedure that, in expert hands, allows to obtain good anatomical and functional results in a high percentage of cases.

CO2 Transoral Microsurgery for Supraglottic Squamous Cell Carcinoma.

The present study analyzed the results of the endoscopic approach to T1, T2 and selected T3 supraglottic carcinoma with the aim of reviewing functional and oncologic outcomes after different types of endoscopic supraglottic laryngectomies. This is a retrospective clinical study of 42 consecutive patients (mean age of 61.8 years, 33 males, 9 females) treated by the senior author for supraglottic squamous cell carcinoma with a transoral CO2 laser approach and reviewed from November 2010 to September 2017. Surgical procedures were classified according to the European Laryngological Society. In addition to the standardized transoral supraglottic laryngectomies, we introduced a modified type IVb by sparing the inferior third of the arytenoid if not directly involved in the tumor. Swallowing was evaluated with the Swallowing Performance Status Scale reported by the Multinational Association of Supportive Care in Cancer/International Society of Oral Oncology. Survival probabilities were estimated using Kaplan-Meier curves. Two type I, 2 type IIa, 2 type IIb, 3 type IIIa, 12 type IIIb, 13 type IVa, 3 type modified IVb, and 5 type IVb supraglottic laryngectomies were performed. Twenty-one patients (50%) underwent primary neck dissection. The pathologic TNM classification according to the 8th edition of the American Joint Committee on Cancer system was as follows: 9 pT1cN0, 2 pT1N0, 1 pT1N1, 7 pT2cN0, 1 rypT2cN0, 9 pT2N0, 4 pT2N1, 2 ypT2N1, 2 pT3cN0, 2 rypT3cN0, 1 pT3N1, and 2 pT3N2b. Mean follow-up was 3.4 years (range of 9 months to 6 years). According to the Kaplan-Meier analysis, 5-year disease-specific survival, local-relapse-free survival, nodal-relapse-free survival, overall laryngeal preservation and overall survival of patients without previous head and neck radiotherapy/open surgery were 100%, 95.2%, 87.8%, 100%, and 64.6%, respectively. Patients who underwent type I, IIa, and IIb resections (n = 6) started oral feeding the day after surgery, patients who underwent type III-IVb modified resections (n = 31) started oral feeding 3-4 days after surgery, and patients who underwent standard type 4b resections (n = 5) started oral feeding 7 days after surgery. Three months after surgery, patients without a clinical history of previous head and neck radiotherapy/open surgery who underwent type III, IVa, and modified IVb resections showed significantly better swallowing compared to patients who underwent standard type IVb resection: grade 4-6 impairment of swallowing in 8 and 66.7% of cases, respectively (p = 0.006072); patients with a clinical history of previous head and neck radiotherapy/open surgery who underwent type III, IVa, and modified IVb resections showed not statistically significant better swallowing compared to patients who underwent standard type IVb resection: grade 4-6 impairment of swallowing at 3 months in 16.7% and 50% of cases, respectively (p = 0.23568). Transoral CO2 laser supraglottic laryngectomy is an oncologic sound alternative to traditional open neck surgery and chemo-radiotherapy. Recovery of swallowing is significantly worsened after total resection of the arytenoid. Modified type IVb procedure leaving intact, when possible, the inferior third of the arytenoid and consequently the glottic competence, improves functional outcome.

Prognostic value of age, subglottic, and anterior commissure involvement for early glottic carcinoma treated with CO2 laser transoral microsurgery: a retrospective, single-center cohort study of 261 patients.

PURPOSE:  CO2 laser transoral microsurgery for glottic carcinoma, when indicated, has the well-established advantages of low morbidity and positive oncological outcomes. The present study aims to determine how patient age, and tumor site could negatively impact prognosis; other variables such as the status of the margins of resection, tobacco and alcohol intake, and the grade of differentiation of the tumors have been evaluated. METHODS: This was a retrospective analysis on 261 patients with a glottic carcinoma who underwent CO2 laser transoral microsurgery. The impact of different variables was calculated using univariate and multivariate analyses. RESULTS: The study included 248 males and 13 females. The median follow-up period was 4.3 years. Five-year disease-specific survival, recurrence-free survival, local control with laser alone, overall laryngeal preservation, and overall survival rates were 99.4, 92.2, 93.8, 97.6, and 85.5%, respectively. Equivalent results were observed in young and elderly patients. Patients with positive margins after CO2 laser transoral microsurgery showed a reduced local control with laser alone. T2 patients with true subglottic spreading and patients with anterior commissure involvement of grade 3 (Rucci's classification) experienced worse local control rates, despite free surgical margins confirmed by histology. CONCLUSIONS:  CO2 laser transoral microsurgery is an effective and reproducible single-stage modality therapy for young and elderly patients with glottic carcinoma. Superficial close margins can be managed by a careful wait-and-see policy, while positive margins should undergo surgical enlargement. In our experience, undifferentiated tumors, true subglottic extension, and anterior commissure involvement of grade 3 were associated with worse outcomes.

Metabolomic analysis of urine with Nuclear Magnetic Resonance spectroscopy in patients with idiopathic sudden sensorineural hearing loss: A preliminary study.

OBJECTIVE: Idiopathic sudden sensorineural hearing loss is a frequent emergency, with unknown aetiology and usually treated with empiric therapy. Steroids represent the only validated treatment but prognosis is unpredictable and the possibility to select the patients who will not respond to steroids could avoid unnecessary treatments. Metabolomic profiling of the biofluids target the analysis of the final product of genic expression and enzymatic activity, defining the biochemical phenotype of a whole biologic system. METHODS: We studied the metabolomics of the urine of a cohort of patients with idiopathic sudden sensorineural hearing loss, correlating the metabolic profiles with the clinical outcomes. Metabolomic profiling of urine samples was performed by 1H Nuclear Magnetic Resonance spectroscopy in combination with multivariate statistical approaches. RESULTS: 26 patients were included in the study: 5 healthy controls, 13 patients who did not recover after treatment at 6 months while the remaining 8 patients recovered from the hearing loss. The orthogonal partial least square-discriminant analysis score plot showed a significant separation between the two groups, responders and non-responders after steroid therapy, R2Y of 0.83, Q2 of 0.38 and p value <0.05. The resulting metabolic profiles were characterized by higher levels of urinary B-Alanine, 3-hydroxybutyrate and Trimethylamine N-oxide, and lower levels of Citrate and Creatinine in patients with worst outcome. CONCLUSION: Idiopathic sudden sensorineural hearing loss is a specific disease with unclear systemic changes, but our data suggest that there are different types of this disorder or patients predisposed to effective action of steroids allowing the recover after treatment.