Breathing-Swallowing discoordination after definitive chemoradiotherapy for head and neck cancers is associated with aspiration pneumonia.

PURPOSE: Swallowing dysfunction and the risk of aspiration pneumonia are frequent clinical problems in the treatment of head and neck squamous cell carcinomas (HNSCCs). Breathing-swallowing coordination is an important factor in evaluating the risk of aspiration pneumonia. To investigate breathing-swallowing discoordination after chemoradiotherapy (CRT), we monitored respiration and swallowing activity before and after CRT in patients with HNSCCs. METHODS: Non-invasive swallowing monitoring was prospectively performed in 25 patients with HNSCCs treated with CRT and grade 1 or lower radiation-induced dermatitis. Videoendoscopy, videofluoroscopy, Food Intake LEVEL Scale, and patient-reported swallowing difficulties were assessed. RESULTS: Of the 25 patients selected for this study, four dropped out due to radiation-induced dermatitis. The remaining 21 patients were analyzed using a monitoring system before and after CRT. For each of the 21 patients, 405 swallows were analyzed. Swallowing latency and pause duration after the CRT were significantly extended compared to those before the CRT. In the analysis of each swallowing pattern, swallowing immediately followed by inspiration (SW-I pattern), reflecting breathing-swallowing discoordination, was observed more frequently after CRT (p = 0.0001). In 11 patients, the SW-I pattern was observed more frequently compared to that before the CRT (p = 0.00139). One patient developed aspiration pneumonia at 12 and 23 months after the CRT. CONCLUSION: The results of this preliminary study indicate that breathing-swallowing discoordination tends to increase after CRT and could be involved in aspiration pneumonia. This non-invasive method may be useful for screening swallowing dysfunction and its potential risks.

Impact of the COVID-19 Infection on Head and Neck Cancer Treatment During Hospitalization.

Objective The after-effects of coronavirus disease 2019 (COVID-19) infection are still unknown; therefore, we investigate the possibility that COVID-19 may interrupt cancer treatment and impact prognosis. Methods We examined the characteristics, prognosis, and changes in treatment options before and after COVID-19 in 11 head and neck cancer patients who were infected with COVID-19 after admission for cancer treatment at Gifu University Hospital. These patients were compared to 110 patients unaffected by COVID-19 during the same period. To identify the effects of COVID-19 on the cancer treatment sequence, we examined the rates of overall survival, progression-free survival, and completion, as well as radiation dosage in radiotherapy and cisplatin dosage in chemoradiotherapy. Results All 11 patients with COVID-19 had their planned cancer treatment postponed or interrupted. There was no significant difference in overall or progression-free survival compared to patients without COVID-19. Notably, only 3/6 of the COVID-19-affected patients completed radiotherapy compared to 42/46 unaffected patients. The ratio of actual radiation dose to planned dose was significantly impaired in COVID-19 affected patients group (98.3% vs. 88.6%). Cisplatin dosage in chemoradiation was not significantly different in either the radical (100 mg/m2, every three weeks) or adjuvant (40 mg/m2, every one week) treatment groups. Conclusion COVID-19 infection in head and neck cancer patients had no apparent impact on cancer prognosis. However, when restricted to irradiation, the treatment completion rate and the ratio of planned to actual dose decreased significantly, underscoring the impact of COVID-19 infection on cancer treatment. The difference in irradiation may affect the success of patients' treatment going forward, and it should be explored whether irradiation can be continued without delay.

FDG uptake in the cervical muscles after neck dissection: imaging features and postoperative natural course on 18F­FDG­PET/CT.

PURPOSE: This study aimed to assess the imaging features and postoperative natural course of 18F-fluorodeoxyglucose (FDG) uptake in the cervical muscles after neck dissection. MATERIALS AND METHODS: This study included 83 patients who underwent preoperative and postoperative 18F-FDG-PET/CT and were diagnosed with head and neck malignancy after neck dissection. Postoperative 18F-FDG-PET/CT was performed within 5 years after neck dissection. Preoperative and postoperative FDG uptake of the trapezius, sternocleidomastoid, scalene, pectoralis major, and deltoid muscles was visually assessed. Increased postoperative uptake was visually defined as higher postoperative FDG uptake than the preoperative one in the corresponding muscle. The maximum standardized uptake value (SUVmax) was measured in cases with increased postoperative uptakes. RESULTS: Increased postoperative uptakes were observed in 43 patients (52%). The trapezius (31/83, 37%), sternocleidomastoid (19/83, 23%), and scalene (12/83, 14%) muscles were involved, as opposed to the pectoralis major and deltoid muscles were not. Increased postoperative uptakes were observed on the dissected side in all 43 patients. Significant differences between SUVmax estimated from the mixed-effects model and postoperative months were observed in the trapezius muscle (Coefficient (ß) = -0.038; 95% confidence interval (CI): [-0.047, -0.028]; p < 0.001) and sternocleidomastoid muscle (ß = -0.015; 95% CI: [-0.029, -0.001]; p = 0.046). CONCLUSIONS: Increased postoperative uptakes in the cervical muscles were observed on the dissected side in approximately half of the patients after neck dissection. The SUVmax in the trapezius and sternocleidomastoid muscles decreased after surgery over time.

Prognostic value of radiological T category using conventional MRI in patients with oral tongue cancer: comparison with pathological T category.

PURPOSE: This study aimed to compare the radiological tumor (T)-category using multiparametric MRI with the pathological T category in patients with oral tongue squamous cell carcinoma (OTSCC) and to examine which is a better predictor of prognosis. METHODS: This retrospective study included 110 consecutive patients with surgically resected primary OTSCC who underwent preoperative contrast-enhanced MRI. T categories determined by maximum diameter and depth of invasion were retrospectively assessed based on the pathological specimen and multiparametric MRI. The MRI assessment included the axial and coronal T1-weighted image (T1WI), axial T2-weighted image (T2WI), coronal fat-suppressed T2WI, and axial and coronal fat-suppressed contrast-enhanced T1WI (CET1WI). Axial and coronal CET1WI measurements were divided into two groups: measurements excluding peritumoral enhancement (MEP) and measurements including peritumoral enhancement. The prognostic values for recurrence and disease-specific survival after radiological and pathological T categorization of cases into T1/T2 and T3/T4 groups were compared. RESULTS: The T category of MEP on coronal CET1WI was the most relevant prognostic factor for recurrence [hazard ratio (HR) = 3.30, p = 0.001] and the HR was higher than the HR for pathological assessment (HR = 2.26, p = 0.026). The T category determined by MEP on coronal CET1WI was also the most relevant prognostic factor for disease-specific survival (HR = 3.12, p = 0.03), and the HR was higher than the HR for pathological assessment (HR = 2.02, p = 0.20). CONCLUSION: The T category determined by MEP on the coronal CET1WI was the best prognostic factor among all radiological and pathological T category measurements.

Summary of Japanese clinical practice guidelines for head and neck cancer - 2022 update edited by the Japan society for head and neck cancer.

The aim of the "Japanese Clinical Practice Guidelines for Head and Neck Cancer - 2022 Update" is to review the latest evidence regarding head and neck cancer and to present the current standard approaches for diagnosis and treatment. These evidence-based recommendations were created with the consensus of the Guideline Committee, which is composed of otorhinolaryngologists and head and neck surgeons, together with radiologists, radiation oncologists, medical oncologists, plastic surgeons, dentists, palliative care physicians, and rehabilitation physicians. These guidelines were created by the Clinical Practice Guideline Committee of the Japan Society for Head and Neck Cancer based on the "Head and Neck Cancer Treatment Guidelines 2018 Edition," and the revised draft was compiled after evaluation by the Assessment Committee and public comments. The 'Clinical questions and recommendations' section consists of 13 categories, and 59 clinical questions are described in total. Here we describe 6 clinical questions specific to other sets of guidelines with recommendations and comments.

Botulinum toxin injection for abductor spasmodic dysphonia under cervical ultrasonography guidance.

Ultrasound (US) imaging effectively provides real-time anatomical information for clinical examinations. In otolaryngology, US imaging can visualize laryngeal muscles as well as cervical muscles. Here we present the case where US imaging was used while injecting botulinum toxin (BT) for the treatment of abductor spasmodic dysphonia, which provided definite results. We could visualize not only the injection pathway but also the infiltration of the BT solution into the posterior cricoarytenoid muscles. Therefore, our laryngeal US imaging is useful for both improving the success rate and avoiding injection complications of BT.

Immunohistochemical localization of CD31, CD34, and periostin in vocal fold polyps.

BACKGROUND: Long-term voice-abuse or sudden vocal fold microvascular disruption can lead to injury and subsequent repair/remodeling of the vocal fold mucosa. Periostin is known to be involved in airway remodeling and in various otolaryngological diseases. In ischemic heart disease, increased CD31 expression has been observed around cardiomyocytes during remodeling, and endothelial proliferation has been reported to occur at these sites. OBJECTIVES: We investigated the expression and the roles of CD31, CD34, and periostin in the formation of vocal fold polyps. MATERIALS AND METHODS: Fifty-seven samples of vocal fold polyps were investigate histopathologically and immunohistochemically. RESULT: Expression of CD31 and CD34 was detected in 41 (71.9%) and 53 (93.0%) samples, respectively, obtained from patients with vocal fold polyp. Expression of periostin was detected in 41 (71.9%) samples obtained from patients with vocal polyps. The vocal polyp samples could be classified into three histological subtypes. Three patterns of CD31 and CD34 expression were observed in the vocal polyp. Four patterns of periostin expression were observed in vocal polyps. An association was observed between the CD31 expression pattern and the histological subtype of vocal fold polyps. CONCLUSION AND SIGNIFICANCE: In vocal fold polyps, evaluation of vascular endothelial markers may be useful for staging.

A Rare Case of Adult Vocal Cord Hemangioma: A Case Report and Literature Review.

Infantile laryngeal hemangiomas are relatively common. However, adult vocal cord hemangiomas are extremely rare. A 46-year-old woman was referred to our department for hoarseness, which continued for 18 months. A laryngeal fiberscope revealed a small protuberant tumor resembling a polyp on her right vocal cord, and the narrow-band imaging showed abundant vascularity. Laryngeal microsurgery with a cold instrument under general anesthesia completely resected the tumor on the vocal cord. Histopathologically, the resected tumor consisted of vessels with thick walls and was diagnosed as a cavernous hemangioma of the vocal cord. After the surgery, she has never complained of hoarseness and has had no local recurrence for six months.

Salivary gland cancer organoids are valid for preclinical genotype-oriented medical precision trials.

Salivary gland cancers (SGCs) are heterogeneous tumors, and precision oncology represents a promising therapeutic approach; however, its impact on SGCs remains obscure. This study aimed to establish a translational model for testing molecular-targeted therapies by combining patient-derived organoids and genomic analyses of SGCs. We enrolled 29 patients, including 24 with SGCs and 5 with benign tumors. Resected tumors were subjected to organoid and monolayer cultures, as well as whole-exome sequencing. Organoid and monolayer cultures of SGCs were successfully established in 70.8% and 62.5% of cases, respectively. Organoids retained most histopathological and genetic profiles of their original tumors. In contrast, 40% of the monolayer-cultured cells did not harbor somatic mutations of their original tumors. The efficacy of molecular-targeted drugs tested on organoids depended on their oncogenic features. Organoids recapitulated the primary tumors and were useful for testing genotype-oriented molecular targeted therapy, which is valuable for precision medicine in patients with SGCs.

Prognostic Factors of Pretreatment Magnetic Resonance Imaging for Predicting Clinical Outcome in Patients With Parotid Gland Cancer.

PURPOSE: This study aimed to assess the utility of pretreatment magnetic resonance imaging (MRI) in predicting the clinical outcomes of patients with parotid gland cancer. METHODS: A total of 43 patients with histopathologically confirmed primary parotid gland cancer, who underwent pretreatment MRI, were enrolled in this study. All images were retrospectively reviewed, and MRI features were evaluated as possible prognostic factors influencing the progression-free survival (PFS) using the Kaplan-Meier method and Cox proportional hazards regression model. Cox regression analysis was used to estimate the hazard ratios (HRs) with 95% confidence interval (95% CI) values. RESULTS: Kaplan-Meier survival analysis showed that old age (>73 years, P < 0.01), large maximum tumor diameter (>33 mm, P < 0.01), low apparent diffusion coefficient value (≤1.29 ×10 -3 mm 2 /s, P < 0.01), ill-defined margin ( P < 0.01), skin invasion ( P < 0.01), regional nodal metastasis ( P < 0.01), heterogeneous enhancement ( P < 0.05), and high signal intensity ratio on gadolinium-enhanced fat-suppressed T1-weighted images (>2.017, P < 0.05) were significant predictors of worse PFS. Cox proportional hazards regression analysis revealed that regional nodal metastasis (HR, 32.02; 95% CI, 6.42-159.84; P < 0.01) and maximum tumor diameter (HR, 1.04; 95% CI, 1.01-1.08; P < 0.05) were independent predictors of PFS. CONCLUSION: Pretreatment MRI parameters could be prognostic factors of patients with parotid gland cancer. In particular, the maximum tumor diameter and regional nodal metastasis, which were closely associated with T and N classifications, were important prognostic factors in predicting the PFS.

Comprehensive Genome profile testing in head and neck cancer.

OBJECTIVE: Head and neck cancer (HNC) is a tumor occurring in various primary sites with limited chemotherapy options for its treatment. Recently, comprehensive genomic profiling (CGP) testing has become clinically widespread. In this study, we examined the utility of CGP in diagnosing and treating HNC. METHODS: This study included 29 patients with HNC who underwent CGP testing at the Gifu University Hospital between December 2019 and April 2022. We analyzed the types of gene mutations and tumor mutational burden (TMB) based on the CGP results. Squamous cell carcinoma accounted for 55.2%, and other cancers accounted for 44.8%. And we investigated the correlation of prognosis with gene mutations and TMB. RESULTS: Gene mutations were detected in TP53(48.3%), CDKN2A (27.6%), CDKN2B (17.2%), NOTCH1 (17.2%), PIK3CA (17.2%), ARID1A (13.8%), and NF1 (13.8%). TP53, CDKN2A and CDKN2B mutations significantly decreased survival rate in HNC. Five cases (17.2%) were TMB-high and 82.8% were TMB-low. In SCC cases treated with immune checkpoint inhibitors, TMB-high had better Overall survival than TMB-low. And all patients with TMB-high were oropharyngeal cancer. CONCLUSION: Although there were no cases in which effective treatment was actually performed based on the results of CGP, many gene mutations have been detected and several gene mutations correlated with prognosis. Furthermore, TMB can be used as a biomarker to predict the therapeutic effects of immune checkpoint inhibitors in cases of SCC.

Immunohistochemical Localization of D-ß-Aspartic Acid and Periostin in Vocal Fold Polyps.

Long-term voice abuse or sudden vocal fold microvascular disruption may lead to injury and subsequent repair/remodeling in the vocal fold mucosa. Periostin is known to be involved in airway remodeling and also in various otolaryngological diseases. D-ß-aspartic acid is the major isomer of D-aspartic acid found in elderly tissue. In this study we investigated the expression and the role of D-ß-aspartic acid and periostin in the formation of vocal fold polyps. The expression patterns of D-ß-aspartic acid and periostin in 36 surgical specimens of vocal fold polyps from 36 patients were investigated immunohistochemically. In the epithelium of vocal polyps, D-ß-aspartic acid was expressed in all cases. Expression of D-ß-aspartic acid was detected in 25 samples obtained from patients with vocal fold polyps stroma. Expression of periostin was detected in 28 samples obtained from patients with vocal fold polyps. Two patterns of D-ß-aspartic acid expression were observed in vocal fold polyps stroma: positive type and negative type. The following four patterns of periostin expression were observed in vocal fold polyps: negative type, superficial type, infiltrative type, and diffuse type. An association was observed between D-ß-aspartic acid expression patterns and periostin expression patterns. From these findings we speculate that periostin and D-ß-aspartic acid participate in certain pathological changes in vocal fold polyps, such as extracellular matrix accumulation, local fibrosis, and the formation and development of vocal fold polyps.

MRI findings of sporadic/simple lymphoepithelial cyst of the parotid gland.

PURPOSE: This study aimed to determine the MRI features of sporadic/simple lymphoepithelial cyst (SLEC) of the parotid gland. METHODS: Ten patients (seven men, three women; mean age, 60 years; age range, 38-77 years) with histopathologically and clinically proven SLEC of the parotid gland who underwent MRI before surgical resection were enrolled in this study. No enrolled patient had HIV infection or Sjögren syndrome. MRI findings of SLEC were retrospectively assessed. RESULTS: We confirmed 10 SLECs larger than 10 mm with a mean maximum diameter of 26.6 mm (range, 12-42 mm). Nine patients (90%) had a single cyst, and one (10%) had a large cyst accompanied by small cysts (<10 mm) within the ipsilateral parotid gland. Eight SLECs (80%) were unilocular, and two (20%) were bilocular, with complete septa. Among seven SLECs (70%) with internal septa, five unilocular SLECs (50%) had incomplete septa. Six SLECs (60%) had eccentric cyst wall thickening, and five (50%) were surrounded by small solid nodules that were isointense relative to lymph node. On T1-weighted images, all cyst contents were homogeneously hyperintense relative to cerebrospinal fluid. CONCLUSION: SLECs of the parotid gland are usually single unilocular lesions. Internal septa, eccentric cyst wall thickening, and small solid nodules surrounding the lesion were often observed. Cyst contents are always homogeneously hyperintense on T1-weighted images.

Long Non-Coding RNAs Associated with Mitogen-Activated Protein Kinase in Human Pancreatic Cancer.

Long non-coding RNAs (lncRNAs) have emerged as a significant player in various cancers, including pancreatic cancer. However, how lncRNAs are aberrantly expressed in cancers is largely unknown. We hypothesized that lncRNAs would be regulated by signaling pathways and contribute to malignant phenotypes of cancer. In this study, to understand the significance of mitogen-activated protein kinase/extracellular signal-regulated kinase (MAPK/ERK), which is a major aberrant signaling pathway in pancreatic cancer, for the expression of lncRNAs, we performed comparative transcriptome analyses between pancreatic cancer cell lines with or without activation of MAPK. We identified 45 lncRNAs presumably associated with MAPK in pancreatic cancer cells; among these, LINC00941 was consistently upregulated by MAPK. The immediate genomic upstream region flanking LINC00941 was identified as a promoter region, the activity of which was found to be preferentially associated with MAPK activity via ETS-1 binding site. LINC00941 promoted cell proliferation in vitro. Moreover, TCGA data analysis indicated that high expression of LINC00941 was associated with poor prognosis of patients with pancreatic cancer. Transcriptomes comparing transcriptions between cells with and without LINC00941 knockdown revealed 3229 differentially expressed genes involved in 44 biological processes, including the glycoprotein biosynthetic process, beta-catenin-TCF complex assembly, and histone modification. These results indicate that MAPK mediates the aberrant expression of lncRNAs. LINC00941 is the lncRNA by MAPK most consistently promoted, and is implicated in the dismal prognosis of pancreatic cancer. MAPK-associated lncRNAs may play pivotal roles in malignant phenotypes of pancreatic cancer, and as such might represent both potentially valid therapeutic targets and diagnostic biomarkers.

Usefulness of intraoperative monitoring for mesenteric lymph node metastasis in transplanted free jejunum.

We herein report a rare case of a patient with hypopharyngeal squamous cell carcinoma (SCC) who presented with recurrent metastasis in the mesenteric lymph node of a transplanted jejunum. Removal of the metastatic lymph node required resection of the nutrient vessels which risked the current state of the transplanted jejunum. Importantly, although the nutrient vessels were resected, the jejunum did not become necrotic. This case and another similar case indicate that it may be possible to predict the viability of a transplanted jejunum where jejunal nutrient vessels must subsequently be resected. Key indicators for jejunal survival include determining jejunal blood flow by intraoperative indocyanine green fluorescence imaging, confirming good jejunal color and observation of peristaltic movement by intraoperative blood flow blockage of nutrient vessels. In conclusion, if intraoperative indocyanine green fluorescence imaging in the entire jejunum can be confirmed, there is a high possibility that the jejunum can be well preserved. The clinical presentation and clinical course are described with a proposed new schema of the resectable site of the transplanted jejunal mesentery.

Two cases of flow void sign of temporal bone metastasis from follicular thyroid carcinoma.

This report describes CT and MRI findings of temporal bone metastasis from follicular thyroid carcinoma in two cases. Both of these had large, osteolytic, hypervascular masses of the temporal bone, accompanied by internal scattered bone fragments and extraosseous mass formation on unenhanced and contrast-enhanced CT images. In the first case, several dilated and tortuous vessels within the markedly hypervascular mass were observed on the arterial phase of dynamic contrast-enhanced CT images. Compared with the signal intensity of the cerebellum, temporal bone masses showed slightly hypo- to slightly hyperintense on T1-weighted images and slightly hypo- to moderately hyperintense on T2-weighted images. Both cases had flow voids in abnormally dilated vessels within the mass on T1- and T2-weighted images. Thyroid follicular carcinoma rarely metastasizes the temporal bone and presents with an osteolytic hypervascular mass with flow void sign.

Current status of diffusion-weighted imaging in differentiating parotid tumors.

Recently, diffusion-weighted imaging (DWI) is an essential magnetic resonance imaging (MRI) protocol for head and neck imaging in clinical practice as it plays an important role in lesion detection, tumor extension evaluation, differential diagnosis, therapeutic effect prediction, therapy evaluation, and recurrence diagnosis. Especially in the parotid gland, several studies have already attempted to achieve accurate differentiation between benign and malignant tumors using DWI. A conventional single-shot echo-planar-based DWI is widely used for head and neck imaging, whereas advanced DWI sequences, such as intravoxel incoherent motion, diffusion kurtosis imaging, periodically rotated overlapping parallel lines with enhanced reconstruction, and readout-segmented echo-planar imaging (readout segmentation of long variable echo-trains), have been used to characterize parotid tumors. The mean apparent diffusion coefficient values are easily measured and useful for assessing cellularity and histological characteristics, whereas advanced image analyses, such as histogram analysis, texture analysis, and machine and deep learning, have been rapidly developed. Furthermore, a combination of DWI and other MRI protocols has reportedly improved the diagnostic accuracy of parotid tumors. This review article summarizes the current state of DWI in differentiating parotid tumors.

Posterior ischemic optic neuropathy following postoperative bleeding and internal jugular vein compression.

Perioperative blindness, especially posterior ischemic optic neuropathy (PION), is an uncommon but potentially devastating complication. We report a case of a 65-year-old male patient who underwent laryngopharyngectomy, bilateral neck dissection, and free jejunum flap reconstruction, but then experienced PION in his right eye following postoperative bleeding and bilateral internal jugular veins (IJVs) compression. Despite systemic corticosteroid therapy, his visual recovery prognosis was poor. The specific mechanism responsible for PION remains unclear, and no therapy has been shown to improve this condition. As such, prevention of perioperative PION remains the only available strategy. Surgeons should be aware of this rare potential complication and its risk factors and strive to avoid it. As postoperative bleeding and IJV compression are one of important risk factors for PION, avoiding these are critical.

Metabolic profiling analysis of head and neck squamous cell carcinoma.

OBJECTIVE: Tumor cells can acquire a large amount of energy and structural components by reprogramming energy metabolism; moreover, metabolic profiles slightly differ according to cancer type. This study compared and assessed the metabolic profile of head and neck squamous cell carcinoma (HNSCC) and normal tissues, which were collected from patients without cancer. SUBJECTS AND METHODS: Overall, 23 patients with HNSCC and 6 patients without cancer were included in the analysis. Metabolomic profiles were analyzed using capillary electrophoresis-mass spectrometry. Gene expression was evaluated using real-time reverse transcription-polymerase chain reaction. RESULTS: Glycolysis, the pentose phosphate pathway, tricarboxylic acid cycle, and glutamine metabolism were upregulated in HNSCC tissues based on gene expression analysis. HNSCC could then have enhanced energy production and structural component. The levels of lactate, succinate, glutathione, 2-hydroxyglutarate, and S-adenosylmethionine, considered as oncometabolites, increased and these had accumulated in HNSCC tissues. CONCLUSIONS: The level of metabolites and the expression of enzymes differ between HNSCC and normal tissues. Reprogramming metabolism in HNSCC provides an energy source as well as structural components, creating a system that offers rapid proliferation, progression, and is less likely to be eliminated.