The aim of the study was to utilize a quantitative assessment of the vibratory characteristics of vocal folds in diagnosing benign and malignant lesions of the glottis using high-speed videolaryngoscopy (HSV).
METHODS: Case-control study including 100 patients with unilateral vocal fold lesions in comparison to 38 normophonic subjects. Quantitative assessment with the determination of vocal fold oscillation parameters was performed based on HSV kymography. Machine-learning predictive models were developed and validated.
RESULTS: All calculated parameters differed significantly between healthy subjects and patients with organic lesions. The first predictive model distinguishing any organic lesion patients from healthy subjects reached an area under the curve (AUC) equal to 0.983 and presented with 89.3% accuracy, 97.0% sensitivity, and 71.4% specificity on the testing set. The second model identifying malignancy among organic lesions reached an AUC equal to 0.85 and presented with 80.6% accuracy, 100% sensitivity, and 71.1% specificity on the training set. Important predictive factors for the models were frequency perturbation measures.
CONCLUSIONS: The standard protocol for distinguishing between benign and malignant lesions continues to be clinical evaluation by an experienced ENT specialist and confirmed by histopathological examination. Our findings did suggest that advanced machine learning models, which consider the complex interactions present in HSV data, could potentially indicate a heightened risk of malignancy. Therefore, this technology could prove pivotal in aiding in early cancer detection, thereby emphasizing the need for further investigation and validation.

Paraneoplastic IgA nephropathy (IgAN) is an underrecognized condition in which malignancy manifests as symptoms of IgAN, and it remains controversial regarding their mechanistic relation between IgAN and malignancy. Herein, we report a case of a 68-year-old Japanese man with glottic cancer who developed nephrotic syndrome as a clinical manifestation of IgAN. Renal biopsy revealed diffuse proliferative glomerulonephritis with glomerular capillary IgA deposition that is a rare subtype of IgAN. After complete remission of the glottic cancer by irradiation, proteinuria and hematuria disappeared. Based on his clinical course, we diagnosed paraneoplastic IgAN. Therefore, we should consider the possibility that IgAN with glomerular capillary IgA deposition might be paraneoplastic glomerulopathy especially before initiating immunosuppressive therapy. The patient thereafter developed prostate cancer and hepatocellular cancer, but IgAN did not recur. The association of IgAN specifically with the glottic cancer in this triple-cancer patient may suggest a potential link between IgAN and mucosal cancer. Because galactose-deficient IgA1 (Gd-IgA1) was observed in the similar pattern as IgA, Gd-IgA1 also may play an important role in the pathogenesis of paraneoplastic IgAN.

BACKGROUND: We report the case of a patient with smoking-induced radiation laryngeal necrosis (RLN) after undergoing definitive radiotherapy (RT) alone for T1a glottic squamous cell carcinoma.
METHODS: The patient was a 63-year-old man who had a history of heavy smoking. He quit smoking when he was diagnosed with glottic squamous cell carcinoma. The RT dose was 63 Gy, delivered in 28 fractions with the three-dimensional conventional RT technique for the larynx. After RT completion, the initial treatment response was complete response. He then underwent follow-up examinations. At 13 months after RT, the patient resumed smoking. At 2 months after resuming smoking, he had severe sore throat and hoarseness. Laryngoscopy revealed a large tumor in the glottis. Surgical excision was performed, and the patient was histologically diagnosed with RLN, as late toxicity without cancer recurrence. At 3 weeks postoperatively, the patient had dyspnea, and laryngoscopy revealed total laryngeal paralysis. Thus, he underwent an emergent tracheostomy. The administration of steroids affected RLN, and laryngeal paralysis gradually improved.
CONCLUSIONS: This case suggests that smoking may have the potential to induce RLN after RT. Moreover, continuing smoking cessation is significantly important for patients with glottic cancer who receive RT. Rather than leaving smoking cessation up to the patient, it would be necessary for clinicians to actively intervene to help patients continue their effort to quit smoking.

OBJECTIVE: The value of margin status after TLM for glottic cancer is debatable, due to difficulties in specimen orientation and margin analysis. To reduce these difficulties, we recently introduced a standardized protocol of oriented fixation of TLM specimens. This proved feasible and resulted in high margin evaluability rates and a decreased rate of false positive deep margins, when compared to a historical TLM cohort. For the patients whose specimens were processed according to this protocol, we prospectively analyzed oncological outcomes, identified prognostic factors and assessed the influence of the protocol introduction on outcomes compared with a historical TLM cohort.
METHODS: Ninety-six patients with glottic malignancies treated with TLM were included. Resection specimens were processed according to the new protocol. Descriptive statistics and survival analyses were used to determine oncological outcomes. To assess the effect of the protocol introduction on outcomes, a matched-case-control analysis was performed, using a historical TLM-cohort as controls. The Cox proportional hazards model was used to analyze prognostic effects of patient and treatment characteristics, including the pathology protocol introduction, on overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS) and local recurrence-free survival (LRFS).
RESULTS: Two-year outcomes were favorable: 88.5% OS, 97.0% DSS, and 87.6% LRFS. At multivariable analysis, the presence of multiple positive superficial margins was a negative prognosticator for OS (HR 4.102) and increasing cT classification proved a negative prognosticator for DFS (HR 2.828) and LRFS (HR 2.676). Matched case-control analysis did not reveal a significant difference in oncological outcomes between cohorts. Deep margin status had a strong differential effect for DFS (p-value for interaction = 0.0205) and for LRFS (p-value for interaction = 0.0176) between cohorts, indicating a prognostic effect of deep margin status on both outcomes in the current cohort, but not in the historical cohort.
CONCLUSIONS: The introduction of a new standardized technique of oriented fixation of TLM specimens did not affect oncological outcomes when compared to a historical TLM cohort, but assigned a significant prognostic effect to deep margin status for DFS and LRFS, facilitating the decision making process with regards to planning of second-look procedures, administration of adjuvant radiotherapy or determination of follow-up intensity.

OBJECTIVE: To propose, in patients presenting a difficult laryngeal exposure, a surgical innovation allowing to perform a transoral laser cordectomy for cancers reaching the anterior commissure or the anterior third of vocal folds (according to the European Laryngological Society classification of laryngeal endoscopic cordectomies).
METHODS: Our surgical technique consisted of adding to conventional cordectomies a modified relaxation thyroplasty proposed by Isshiki (type III), also called relaxation thyroplasty by a medial approach in the European Laryngological Society classification system. The anterior commissure retrusion is usually employed in the management of high-pitched voice disorders, but can also allow a better exposure of the anterior commissure.
RESULTS: We described here this surgical innovation through the example of our first two patients. For both patients, the definitive histologic analysis showed negative microscopic margins and there was no post-operative complication. There was no need for a tracheostomy. They were allowed to take a normal diet after 2 days and were discharged after 4 days. The voice was breathy and hoarse as expected in case of extended cordectomy.
CONCLUSIONS: This surgical innovation corresponding to the addition of an anterior commissure retrusion by a bilateral thyrotomy could be useful in the ELS classification of endoscopic cordectomies. It should allow surgeons to carry out a transoral CO2 laser cordectomy in patients with a T1 and sometimes T2 glottic carcinoma, even with a difficult laryngeal exposure.

The aim of the present study was to report an unusual case of multiple lower cranial nerve palsies in a patient with Wegener\'s granulomatosis (WG) during radiotherapy for glottic cancer. WG is an autoimmune disease characterized by necrotizing granulomas mainly in the upper and lower respiratory tract or kidneys; however, the involvement of cranial nerves is not uncommon. Prior to the use of cyclophosphamide (CYC) the 1-year mortality rate was ~82%; the introduction of rituximab (RTX) has revolutionized the course of the WG, with remission rates comparable to those of CYC and superior effectiveness in relapsing patients. Hypogammaglobulinemia and B-cell depletion are the best known monitored side effects affecting survival due to secondary infections. Immunodepression and relapse with lower cranial nerve palsy have a negative impact on prognosis. We herein present the case of a heavily pre-treated GPA patient with secondary immunosuppression, who underwent radiotherapy for glottic cancer and developed multiple low cranial nerve palsies during treatment, which was interrupted at 60 Gy. The possible related causes and the association between previous immunosuppressive treatments and radiotherapy were also analyzed to elucidate the cause of this complication.

Various mechanisms such as second primary lesion, tumour seeding or lymphogenous and haematogenous metastasis could be proposed to explain the nature of dual malignant lesions. We report the case of a glottic laryngeal carcinoma combined with a secondary endotracheal tumour. Following the imaging modalities, the patient underwent total laryngectomy and wide excision of the trachea. Histopathology ultimately established that the tracheal lesion was a metastatic tumour secondary to regional lymphatic spread of the glottic tumour. To our knowledge, there is no previous report in the English literature concerning tracheal lymphogenous metastatic involvement in the context of laryngeal malignancy. Paradoxical lymphatic spread must always remain an issue of head and neck oncology.

To identify and compare treatment and system factors associated with survival in early-stage glottic cancer.
Retrospective study of cases in the Commission on Cancer National Cancer Database.
Adult patients with early glottic cancer (stage I or II) diagnosed between January 1, 2004, and December 31, 2012, were included. Demographic, tumor, and survival variables were included in the analyses. Multivariate Cox regressions as well as univariate Kaplan-Meier analyses were conducted.
In total, 5,627 patients were included in the study. Treatment factors associated with improved survival included larynx-preserving surgery alone (hazard ratio [HR] 0.740; P = 0.001) and larynx-preserving surgery with radiation (HR 0.837; P = 0.010) when compared to radiotherapy alone. System factors associated with worse survival included intermediate- (HR 1.123; P = 0.047) or low- (HR 1.458; P = 0.017) volume centers; Medicaid (HR 1.882; P < 0.001), Medicare (HR 1.532; P < 0.001), or other government insurance (HR 2.041; P < 0.001); and delay between diagnosis and treatment greater than 100 days (HR 1.605; P = 0.006).
A number of treatment and system factors were found to be significantly associated with survival when controlling for patient and tumor factors. These may present targets for the improvement of outcomes in early-stage glottic cancers.
4. Laryngoscope, 127:616-622, 2017.

Radiation therapy (RT) and endolaryngeal surgery are standard treatments for early-stage glottic cancer. They have closely matched oncological outcomes; however, it is debatable which method is superior in terms of functional outcomes. Several dosimetric studies have demonstrated that, compared with conventional RT, intensity-modulated RT (IMRT) reduces unnecessary radiation of the adjacent normal tissues, including the carotid artery and thyroid gland. However, RT targets the whole larynx, whereas endolaryngeal surgery is a highly focused treatment involving the en bloc resection of a tumor with safety margins. For T1a glottic cancer, in which the tumor is limited to one vocal cord, the technical feasibility of targeting IMRT on the single vocal cord affected has been investigated; however, the clinical feasibility and the possibility of inferior local control remain to be elucidated. In the present case study, IMRT was used to treat the whole larynx first, and then to treat a single vocal cord. The patient in the present study had T1a glottic cancer, and received volumetric modulated arc therapy with a total dose of 63 Gy/28 fractions. The first treatment phase (40.5 Gy/18 fractions) targeted the whole larynx to eliminate subclinical disease. The second treatment phase (22.5 Gy/10 fractions) targeted only the involved vocal cord. During this treatment phase, the exposure of the non-involved right vocal cord, the right carotid artery and the thyroid gland to the radiation was lower compared with the continuation of the initial treatment approach. These findings suggested that changing the target volume from the whole larynx to the affected vocal cord during the course of IMRT is feasible for T1a glottic cancer, and that it may reduce functional side effects while maintaining oncological outcomes.