A Phase 1 Study of Ensitrelvir Fumaric Acid Tablets Evaluating the Safety, Pharmacokinetics and Food Effect in Healthy Adult Populations.

BACKGROUND: A reported clinical pharmacokinetics and safety study of suspension formulation of ensitrelvir, a therapeutic agent used in severe acute respiratory syndrome coronavirus 2 infection, demonstrated favorable pharmacokinetics and was well tolerated in healthy male Japanese and White participants. Understanding the safety and pharmacokinetic features of ensitrelvir (using the formulation approved for clinical use) in various populations, and the effect of food, is crucial for optimal clinical use. OBJECTIVES: The objectives of this study were to (1) assess the safety, tolerability, and pharmacokinetics of ensitrelvir following multiple-dose administration of ensitrelvir tablets in populations with different races, ages, and sex; and (2) assess the effect of food on the pharmacokinetics of ensitrelvir tablets in the fasted or fed state. METHODS: A phase 1, multicenter, double-blinded, randomized, placebo-controlled study was conducted to evaluate the safety and pharmacokinetics of once-daily ensitrelvir tablets at loading/maintenance doses of 375/125 mg or 750/250 mg for 5 days in healthy Japanese females, Japanese elderly (only 375/125 mg), and White male and female participants. An open-label, two-group, two-period crossover study was also conducted to estimate the effect of food on the pharmacokinetics of ensitrelvir at single dose of 375 mg. The nature, frequency, and severity of treatment-emergent adverse events were evaluated and recorded in safety assessments in both studies. RESULTS: The maximum plasma concentration (Cmax) and area under the plasma concentration-time curve (AUC) were similar within these populations. The geometric mean half-life of ensitrelvir following multiple-dose administration was 48.7-58.9 h across all cohorts. The Cmax and AUC increased in a dose-proportional manner in Japanese female participants, and increased in a less than dose-proportional manner in White participants. Furthermore, there was no clear relationship between the dose and geometric mean half-life of ensitrelvir. The plasma concentration at 24 h (C24) after an initial dose of 375/125 mg exceeded the target plasma concentration (6.09 µg/mL) in all populations. Regarding the effect of food on the pharmacokinetics of ensitrelvir, although time to Cmax in the fed state was delayed, there was no clinically meaningful difference in the exposure levels (Cmax and AUC) of ensitrelvir between the fasted and fed states. Most treatment-emergent adverse events were mild in nature and had resolved. CONCLUSION: Ensitrelvir (375/125 mg and 750/250 mg tablet formulation) was well tolerated, without any major safety concerns. The pharmacokinetics of ensitrelvir between all populations in the study were similar and C24 exceeded the target plasma concentration at 375/125 mg. These results suggest that ensitrelvir can be effectively administered with no necessity for dose adjustment for age, sex, and race without food restriction. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials identifier: jRCT2031210202, registered on 16 July 2021.

Factors Associated with Complications after Total Pharyngo-Laryngo-Esophagectomy and Free Jejunal Flap Reconstruction.

INTRODUCTION: Free jejunal flap (FJF) reconstruction is a standard procedure for pharyngeal and cervical esophageal defects resulting from head and neck cancer resection. However, improvements in patients' quality of life after surgery require a further statistical approach. METHODS: An observational, retrospective, multivariate analysis was designed to report the incidence of postoperative complications and their association with clinical factors in 101 patients who underwent total pharyngo-laryngo-esophagectomy and FJF reconstruction for head and neck cancer at a university hospital between January 2007 and December 2020. RESULTS: Postoperative complications were observed in 69% of patients. In the reconstructive site, anastomotic leak, observed in 8% of patients was associated with vascular anastomosis in the external jugular vein system (age-adjusted odds ratio [OR]: 9.05, p = 0.044) and anastomotic stricture, observed in 11% of patients was associated with postoperative radiotherapy (age-adjusted OR: 12.60, p = 0.02). Cervical skin flap necrosis was the most common complication (34%) and was associated with vascular anastomosis on the right cervical side (age- and sex-adjusted OR: 4.00, p = 0.005). CONCLUSION: Although FJF reconstruction is a useful procedure, 69% of patients suffer a postoperative complication. We suppose that anastomotic leak is related to the low blood flow resistance of the FJF and inadequate drainage of the external jugular venous system, and anastomotic stricture is related to the vulnerability of the intestinal tissue to radiation. Furthermore, we hypothesized that the location of the vascular anastomosis may affect the mesenteric location of the FJF and the dead space in the neck, leading to the development of cervical skin flap necrosis. These data contribute to increasing our knowledge about postoperative complications related to FJF reconstruction.

Reconstruction for Bilateral Internal Jugular Vein Perfusion Disruption.

When resecting the internal jugular veins bilaterally in surgery for head and neck cancer, it is necessary to perform neck dissection in two stages or to reconstruct the internal jugular veins in one stage. Reconstruction of the internal jugular vein using grafting or direct anastomosis to the external jugular vein have both been reported. We report the case of a 53-year-old man with accidental injury to the left internal jugular vein after resection of the right internal jugular vein for supraglottic cancer. The left internal jugular vein was damaged near the inflow of the subclavian vein, making vein grafting difficult. Therefore, internal jugular venous return was reestablished by end-to-side anastomosis of the left internal jugular vein to the left external jugular vein system. In this surgical procedure, by incising the internal jugular vein obliquely, it was not necessary to match the calibers of the internal jugular vein and the external jugular vein system, and a smooth hemodynamic body was reconstructed. In addition, we were able to reconstruct the internal jugular vein while preserving blood flow in the external jugular vein system. End-to-side anastomosis of the internal jugular vein to the external jugular system is an option for internal jugular vein reconstruction.

Evaluation of the Drug-Drug Interaction Potential of Ensitrelvir Fumaric Acid with Cytochrome P450 3A Substrates in Healthy Japanese Adults.

BACKGROUND: Management of drug-drug interactions (DDIs) for ensitrelvir, a novel 3-chymotrypsin-like protease inhibitor of SARS-CoV-2 infection is crucial. A previous clinical DDI study of ensitrelvir with midazolam, a clinical index cytochrome P450 (CYP) 3A substrate, demonstrated that ensitrelvir given for 5 days orally with a loading/maintenance dose of 750/250 mg acted as a strong CYP3A inhibitor. OBJECTIVES: The objectives of this study were to investigate the effect of ensitrelvir on the pharmacokinetics of CYP3A substrates, dexamethasone, prednisolone and midazolam, and to assess the pharmacokinetics, safety, and tolerability of ensitrelvir following multiple-dose administration of ensitrelvir. METHODS: This was a Phase 1, multicenter, single-arm, open-label study in healthy Japanese adult participants. The effects of multiple doses of ensitrelvir in the fasted state on the pharmacokinetics of dexamethasone, prednisolone, and midazolam were investigated. Ensitrelvir was administered from Day 1 through Day 5, with a loading/maintenance dose of 750/250 mg for the dexamethasone and prednisolone cohorts whereas 375/125 mg for the midazolam cohort. Either dexamethasone, prednisolone, or midazolam was administered alone (Day - 2) or in combination with ensitrelvir (Day 5) in each of the cohorts. Additionally, dexamethasone or prednisolone was administered on Days 9 and 14. The pharmacokinetic parameters of ensitrelvir, dexamethasone, prednisolone, and midazolam were calculated based on their plasma concentration data with non-compartmental analysis. In safety assessments, the nature, frequency, and severity of treatment-emergent adverse events were evaluated and recorded. RESULTS: The area under the concentration-time curve (AUC) ratio of dexamethasone on Day 5 was 3.47-fold compared with the corresponding values for dexamethasone alone on Day - 2 and the effect diminished over time after the last dose of ensitrelvir. No clinically meaningful effect was observed for prednisolone. The AUC ratio of midazolam was 6.77-fold with ensitrelvir 375/125 mg suggesting ensitrelvir at 375/125 mg strongly inhibits CYP3A similar to that at 750/250 mg. No new safety signals with ensitrelvir were reported during the study. CONCLUSION: The inhibitory effect for CYP3A was confirmed after the last dose of ensitrelvir, and the effect diminished over time. In addition, ensitrelvir at 375/125 mg showed CYP3A inhibitory potential similar to that at 750/250 mg. These findings can be used as a clinical recommendation for prescribing ensitrelvir with regard to concomitant medications. CLINICAL TRIAL REGISTRATION: Japan Registry of Clinical Trials identifier: jRCT2031210202.

Olanzapine for The Prevention of Nausea and Vomiting Caused by Chemoradiotherapy with High-Dose Cisplatin for Head and Neck Cancer.

Background: Chemotherapy-induced nausea and vomiting (CINV) are the most common and distressing adverse events in patients receiving anticancer therapy. Radiotherapy also induces nausea and vomiting, so concurrent chemoradiotherapy-induced nausea and vomiting (CRINV) are significant problems for patients undergoing chemoradiotherapy. Conventionally, three-drug combination therapy with dexamethasone, 5-hydroxytryptamine type 3 (5-HT3) receptor antagonist, and neurokinin-1 (NK1) receptor antagonist has been used to prevent CRINV induced by concurrent chemoradiotherapy with cisplatin for patients with head and neck cancer (HNC). Nonetheless, CRINV still remains a problem. The effectiveness of adding olanzapine to prevent CINV has been reported, suggesting the efficacy of four-drug combination therapy for CRINV. However, its effectiveness has hardly been reported in patient receiving chemoradiotherapy for HNC. Methods: A total of 109 patients with HNC who received concurrent chemoradiotherapy with cisplatin from April 2014 to March 2021 were included and divided into the following two groups according to antiemetic treatment regimen: the conventional group (Con group; n = 78) who received three-drug combination therapy and the olanzapine group (Olz group; Olz group, n = 31) who received four-drug combination therapy with olanzapine. Acute (0 to 24 h from cisplatin) and delayed (25 to 120 h from cisplatin) CRINV were then compared using the Common Terminology Criteria for Adverse Events. Results: No significant difference in acute CRINV were observed between both groups (P = 0.5761, Fisher's exact test). However, the Olz group had a significantly lower incidence rate of delayed CRINV over Grade 3 compared to the Con group (P = 0.0318, Fisher's exact test). Conclusion: Four-drug combination therapy with olanzapine was effective in suppressing delayed CRINV due to chemoradiotherapy with cisplatin for HNC.

Evaluation of Drug-Drug Interactions of Ensitrelvir, a SARS-CoV-2 3CL Protease Inhibitor, With Transporter Substrates Based on In Vitro and Clinical Studies.

Drug-drug interaction potentials of ensitrelvir, a novel oral inhibitor of 3C-like protease of severe acute respiratory syndrome coronavirus 2, for drug transporters were evaluated by in vitro and clinical studies. The target drug transporters assessed were P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, organic cation transporter (OCT) 1, OCT2, and multidrug and toxin extrusion 1 and 2K. In vitro study revealed that ensitrelvir is a substrate for P-gp and BCRP and inhibits P-gp, BCRP, OATP1B1, OATP1B3, OCT1, and OAT3. Based on these results, a clinical drug-drug interaction study to evaluate the effect of ensitrelvir on the pharmacokinetics of P-gp, BCRP, OATP1B1, OATP1B3, and OCT1 substrates was conducted with a cocktail approach using digoxin (P-gp substrate), rosuvastatin (BCRP, OATP1B1, and OATP1B3 substrate), and metformin (OCT1 substrate). The cocktail was administered first, and after the washout period, the cocktail was coadministered with 500 mg of ensitrelvir. No treatment-emergent adverse events were observed. Pharmacokinetic analyses demonstrated that the ratios (90% confidence intervals) of "cocktail with ensitrelvir" to "cocktail without ensitrelvir" for maximum plasma concentration and area under the plasma concentration-time curve were, respectively, 2.17 (1.72-2.73) and 1.31 (1.13-1.52) for digoxin, 1.97 (1.73-2.25) and 1.65 (1.47-1.84) for rosuvastatin, and 1.03 (0.91-1.16) and 1.02 (0.94-1.11) for metformin. The results indicate that the exposure levels of digoxin and rosuvastatin increased when coadministered with ensitrelvir, but those of metformin were not changed. In conclusion, ensitrelvir has an impact on the exposure levels of P-gp, BCRP, OATP1B1, and OATP1B3 substrates.

Photoimmunotherapy with surgical navigation and computed tomography guidance for recurrent maxillary sinus carcinoma.

Photoimmunotherapy (PIT) using lasers to target treatment areas is effective for unresectable locally advanced or unresectable locoregionally recurrent head and neck cancer; however, there are only two devices to target the treatment area. One illuminates tumour tissue through a needle, and the other illuminates tumour tissue superficially. Treating lesions surrounded by bone, such as in maxillary sinus cancer, is difficult. We report the first case of PIT for unresectable recurrent maxillary sinus cancer employing surgical navigation and computed tomography guidance in a 56-year-old man. Although he underwent concurrent chemoradiotherapy for cT4bN0M0 maxillary sinus cancer, the tumour recurred at the primary site 6 months post treatment. Chemotherapy was performed for approximately 1 year; however, the tumour progressed. The tumour involved the anterior wall of the maxillary sinus and caused bone destruction; thus, we believed that PIT with a needle device was possible if the puncture was carefully performed. We used a surgical navigation system for neurosurgery and computed tomography guidance to ensure that intraoperative punctures were accurately performed. The operation time was 1 h 52 min and the treatment was completed as planned. Tumour necrosis and volume reduction were obtained with no severe adverse events, which reduced the patient's pain.

Risk Factors of Free Flap Complications in Reconstruction for Head and Neck Cancer.

Background: Although head and neck reconstruction using free flaps has become a common procedure, flap complications remain a concern. This study aimed to analyze the risk factors of free flap complications and to identify the causes of these complications. Methods: We studied 97 patients with head and neck cancer with intraoral defects who underwent reconstruction using free flaps at Tottori University Hospital between 2011 and 2020. We used a retrospective cohort study design to investigate whether flap complications, including flap necrosis (total and partial) and flap dehiscence, were related to various factors, including the underlying disease condition, treatment status, and surgical factors. Results: Of the 97 patients analyzed, total flap necrosis was observed in one patient (1.0%). The incidence rate of flap complications, including flap necrosis and flap dehiscence, was 29.9%. When the time taken to perform one vascular anastomosis, including preparation of the recipient vessel and flap vessel, exceeded 30 min, the incidence rates of flap necrosis (total and partial) (odds ratio, 8.30; 95% confidence interval, 1.91-36.00; P = 0.005) and flap dehiscence (odds ratio, 3.46; 95% confidence interval, 1.05-11.36; P = 0.041) increased significantly. Conclusion: The time taken to perform one vessel anastomosis was the factor that contributed the most to the incidence of flap complications. Reconstructive surgeons should reduce the incidence of flap complications by keeping the known risk factors of the surgery in mind and by aiming to complete a vascular anastomosis time, including the time taken for the preparation of vessels, of ≤ 30 min per vessel during surgery.

Safety, Tolerability, and Pharmacokinetics of the Novel Antiviral Agent Ensitrelvir Fumaric Acid, a SARS-CoV-2 3CL Protease Inhibitor, in Healthy Adults.

Ensitrelvir is a novel selective inhibitor of the 3C-like protease of SARS-CoV-2, which is essential for viral replication. This phase 1 study of ensitrelvir assessed its safety, tolerability, and pharmacokinetics of single (part 1, n = 50) and multiple (part 2, n = 33) ascending oral doses. Effect of food on the pharmacokinetics of ensitrelvir, differences in pharmacokinetics of ensitrelvir between Japanese and white participants, and effect of ensitrelvir on the pharmacokinetics of midazolam (a cytochrome P450 3A [CYP3A] substrate) were also assessed. In part 1, Japanese participants were randomized to placebo or ensitrelvir at doses of 20, 70, 250, 500, 1,000, or 2,000 mg. In part 2, Japanese and white participants were randomized to placebo or once-daily ensitrelvir at loading/maintenance dose 375/125 mg or 750/250 mg for 5 days. Most treatment-related adverse events observed were mild in severity and were resolved without treatment. Plasma exposures showed almost dose proportionality, and geometric mean half-life of ensitrelvir following the single dose was 42.2 to 48.1 h. Food intake reduced Cmax and delayed Tmax of ensitrelvir but did not impact the area under the curve (AUC), suggesting suitability for administration without food restriction. Compared with Japanese participants, plasma exposures were slightly lower for white participants. Ensitrelvir affected the pharmacokinetics of CYP3A substrates because of increase in AUC of midazolam coadministered with ensitrelvir 750/250 mg on day 6. In conclusion, ensitrelvir was well-tolerated and demonstrated favorable pharmacokinetics, including a long half-life, supporting once-daily oral dosing. These results validate further assessments of ensitrelvir in participants with SARS-CoV-2 infection.

A Randomized Phase 2/3 Study of Ensitrelvir, a Novel Oral SARS-CoV-2 3C-Like Protease Inhibitor, in Japanese Patients with Mild-to-Moderate COVID-19 or Asymptomatic SARS-CoV-2 Infection: Results of the Phase 2a Part.

This multicenter, double-blind, phase 2a part of a phase 2/3 study assessed the efficacy and safety of ensitrelvir, a novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) 3C-like protease inhibitor, in Japanese patients with mild-to-moderate coronavirus disease 2019 (COVID-19) or asymptomatic SARS-CoV-2 infection. Sixty-nine patients were randomized (1:1:1) to orally receive 5-day ensitrelvir fumaric acid (375 mg on day 1 followed by 125 mg daily, or 750 mg on day 1 followed by 250 mg daily) or placebo and followed up until day 28. The primary outcome was the change from baseline in the SARS-CoV-2 viral titer. A total of 16, 14, and 17 patients in the ensitrelvir 125 mg, ensitrelvir 250 mg, and placebo groups, respectively, were included in the intention-to-treat population (mean age: 38.0 to 40.4 years). On day 4, the change from baseline in SARS-CoV-2 viral titer (log10 50% tissue culture infectious dose/mL) in patients with positive viral titer and viral RNA at baseline was greater with ensitrelvir 125 mg (mean [standard deviation], -2.42 [1.42]; P = 0.0712) and 250 mg (-2.81 [1.21]; P = 0.0083) versus placebo (-1.54 [0.74]); ensitrelvir treatment reduced SARS-CoV-2 RNA by -1.4 to -1.5 log10 copies/mL versus placebo. The viral titer and viral RNA were similar across groups on and after day 6. The median time to infectious viral clearance decreased by approximately 50 h with ensitrelvir treatment. All adverse events were mild to moderate. Ensitrelvir treatment demonstrated rapid SARS-CoV-2 clearance and was well tolerated (Japan Registry of Clinical Trials identifier: jRCT2031210350).

Pharmacokinetic Assessment and Treatment Effect of Lusutrombopag in Child-Pugh Class C Patients: Review of Patient Data from Two Clinical Studies and Post-Marketing Surveillance.

INTRODUCTION: Patients with thrombocytopenia and chronic liver disease are at increased risk of bleeding during invasive procedures due to low platelet counts. Lusutrombopag, an orally active thrombopoietin receptor agonist, increases platelet count and reduces the need for platelet transfusion in chronic liver disease patients with thrombocytopenia undergoing a planned invasive procedure. The safety of lusutrombopag in patients with Child-Pugh class C chronic liver disease is not known. The present analysis was performed to determine the pharmacokinetics, efficacy, and safety of lusutrombopag in patients with Child-Pugh class C chronic liver disease. METHODS: Data for patients with Child-Pugh class C chronic liver disease were collected from three data sets: a phase 1/2 Child-Pugh class C study (n = 5) (JapicCTI-163289 [Japan Pharmaceutical Information Center]), a phase 3 pivotal study (L-PLUS 2, n = 3) (NCT02389621 [Clinicaltrials.gov]), and ongoing post-marketing surveillance (n = 27) (JapicCTI-163432 [Japan Pharmaceutical Information Center]). Patients received lusutrombopag at 3 mg for up to 7 days. Safety and efficacy assessments were collected from two clinical studies and the post-marketing surveillance; pharmacokinetic data were collected from the phase 1/2 study. RESULTS: Mean Cmax and AUC0-τ were lower in Child-Pugh class C patients than Child-Pugh class A and B; individual patients' Cmax and AUC0-τ values overlapped among Child-Pugh classes. In lusutrombopag patients who did not receive platelet transfusion (n = 4 in phase 1/2, n = 1 in phase 3, n = 24 in post-marketing surveillance), the median (range) maximum platelet count was 88.5 × 109/L (54-105 × 109/L), 80 × 109/L, and 91 × 109/L (41-186 × 109/L; n = 23), respectively. There were no treatment-related adverse events or treatment-related serious adverse events. One patient from the phase 1/2 study had a non-serious portal vein thrombosis, which was not considered treatment-related. CONCLUSIONS: The analysis presented in this study suggests that lusutrombopag increases platelet counts in Child-Pugh class C patients and is safe and well tolerated in this patient population. TRIAL REGISTRATION: L-PLUS 2: NCT02389621 (Clinicaltrials.gov). Phase 1/2: JapicCTI-163289 (Japan Pharmaceutical Information Center [JAPIC]). Post-marketing surveillance: JapicCTI-163432 (JAPIC).

Relationship between baseline clinical characteristics and efficacy of lusutrombopag in thrombocytopenic patients with chronic liver disease: post hoc analysis of two placebo-controlled phase 3 trials.

OBJECTIVE: Lusutrombopag is a thrombopoietin receptor agonist approved to treat thrombocytopenia in patients with chronic liver disease (CLD). This post hoc analysis of the Japanese L-PLUS 1 and global L-PLUS 2 trials aimed to clarify factors related to platelet count increase after lusutrombopag treatment. METHODS: In L-PLUS 1, Pearson's correlation coefficients were used to evaluate correlations between platelet count and spleen index, thrombopoietin concentration, white blood cell (WBC) counts, and red blood cell counts (intent-to-treat [ITT] population). Associations between platelet count increase after lusutrombopag treatment and each parameter were assessed by regression analysis and mixed-effect model for repeated measures (MMRM). Associations between time-dependent changes in platelet count increase and each parameter were also examined in the L-PLUS 2 lusutrombopag ITT population by MMRM. RESULTS: In L-PLUS 1, the baseline platelet count was correlated with pretreatment spleen index (r = -0.23, 95% confidence interval [CI] -0.41 to -0.03) and WBC count (r = 0.26, 95% CI 0.06 to 0.43). No selected parameters were associated with the maximum platelet count increase from baseline. Patients with WBC counts below the normal range showed smaller platelet count increases after lusutrombopag treatment than patients with WBC counts within the normal range (p = .0028). In L-PLUS 2 (p = .0533), findings were similar and confirmed by larger pooled data of L-PLUS 1/L-PLUS 2 (p = .0021). CONCLUSIONS: This post hoc analysis revealed a possible association between baseline WBC count and platelet count increase after lusutrombopag treatment. WBC count could be a relevant factor for lusutrombopag efficacy.

Nasogastric Tube Syndrome: A Severe Complication of Nasointestinal Ileus Tube.

Nasogastric tube syndrome (NGTS) induced by a nasointestinal ileus tube is an uncommon but potentially life-threatening complication. NGTS often becomes serious and progresses to acute upper airway obstruction caused by bilateral vocal cord paralysis or laryngeal infection. Early detection and proper treatment of NGTS are necessary. We describe the case of a 78-year-old patient with this syndrome induced by a nasointestinal ileus tube. At administration, ileus was suspected based on physical examination and thoracoabdominal X-ray findings. A nasointestinal ileus tube was placed through the left nasal cavity. Three days after tube placement, hoarseness and wheezing were found during nutrition support team rounds. Upper airway obstruction was suspected and evaluated immediately with flexible laryngoscopy by an otolaryngologist. The nasointestinal ileus tube was removed. The symptoms decreased with prompt proper management. Immediate removal of the tube and early recognition of symptoms are the first steps in the treatment for this syndrome, in addition to the initiation of steroid, proton pump inhibitor, and antibiotic therapy. The cause of NGTS is thought to be continuous pressure on the hypopharynx and cervical esophagus. NGTS should be considered in patients with either nasogastric or nasointestinal ileus tubes. Early diagnosis and proper management of NGTS are important.

Clinical Characteristics and Predictors Related to the Progression of Multinodular Goiter Causing Tracheal Compression and Deviation: A Report of Two Cases and Review of the Literature.

We describe the clinical course of two patients who developed tracheal compression and deviation by multinodular goiter (MNG). Case 1: A 66-year-old woman presented with thyroid swelling. Five years after the initial admission, she was diagnosed with hyperthyroidism by Graves' disease and increased bilateral thyroid lobes compressing the trachea. Thyroglobulin was elevated from 210 to 472 ng/mL. Case 2: A 52-year-old woman presented with thyroid swelling. Five years after the initial admission, the increased right lobe deviated the trachea and compressed the right recurrent laryngeal nerve. Thyroglobulin was elevated from 122 to 392 ng/mL. Two cases and literature review indicated that MNG with >50 mm, solid components, and extension to the mediastinum or paralarynx were risk factors of tracheal compression and deviation. Monitoring thyroglobulin elevation can help predict the clinical course.

Primary Closure With Posteriorly Based Lateral Tongue Flap Reconstruction After Transoral Videolaryngoscopic Surgery for Tonsil Cancer.

INTRODUCTION: Transoral surgery for head and neck cancer provides excellent oncologic outcomes while preserving speech and swallowing function. When neck dissection and resection of oropharynx are performed concomitantly, there is a risk of creating a communication defect or developing a pharyngocutaneous fistula. To prevent pharyngocutaneous fistula, we performed the reconstruction using a posteriorly based lateral tongue flap for communication defect. PATIENT: A 72-year-old male with oropharyngeal cancer (tonsil cancer) T2N1M0 underwent concomitant transoral videolaryngoscopic surgery and neck dissection. The lateral wall of the oropharynx was resected with the pharynx constrictor muscle and parapharyngeal fat due to infiltration of the parapharyngeal space by the tonsil cancer. The posteriorly based lateral tongue flap was used to close the perforation. There was no leakage to the neck postoperatively. The patient had no problem with phonation or oral intake and remained free of disease at 12 months after treatment. CONCLUSION: For a small defect confined to the oropharyngeal lateral wall, the posteriorly based lateral tongue flap should be considered as a useful option for reconstruction of the oropharynx without impairment of posterior function.

Use of Cervical Ultrasonography in Globus Sensation Investigation: A Retrospective Cohort Study.

BACKGROUND: A globus sensation is one of the most common complaints in otolaryngological practice. Patients with no associated abnormalities detected during the usual examinations performed in ENT clinics, are being diagnosed with globus sensation. Cervical ultrasonography is usually not performed in ENT clinics; however, it is useful in screening diseases of the subcutaneous tissue/organs, whose detection is not possible with the routine ENT examinations. The purpose of our study was to elucidate whether cervical ultrasound examination identifies abnormalities in patients with globus sensation. METHODS: A single-centre retrospective cohort study. Cervical ultrasonographic examinations were performed on patients with globus sensation at the Department of Otolaryngology, Head and Neck Surgery of Tottori university hospital, a tertiary care centre, from January 2013 to September 2017. The subjects were 74 patients who complained of globus sensation with no abnormality in general otolaryngological examination including laryngoscopy. RESULTS: Ultrasonography detected structural abnormalities in 60.8% of the patients with globus sensation: thyroid disorders in 41 patients, including: 35 patients with thyroid nodules, 4 patients with Hashimoto's disease, 1 patient with Grave's disease, and 1 patient with subacute thyroiditis; Sjögren syndrome in 2 patients; and cervical lipoma in 1 patient. Furthermore, 2 patients with thyroid disorders had concomitant esophageal cancer. CONCLUSION: Cervical ultrasonography identified thyroid disorders in patients with globus sensation, despite the normal ENT status. Therefore, it would be appropriate to adopt cervical ultrasonography as a routine examination at ENT clinics for patients with globus sensation.

A Novel Concept for Surgical Management of a Traumatic Comminuted Cricoid Fracture.

The cricoid plays 2 key roles: phonation and maintenance of the airway frame, both of which are lost in cases of comminuted cricoid fractures. The management of these 2 functions becomes a challenge in planning surgical treatment. We report the treatment course in a case of traumatic comminuted cricoid fracture that was resolved with good airway and phonatory functions. A 25-year-old man fell down the stairs and complained of respiratory discomfort and hoarseness of voice. A computed tomography scan showed comminuted cricoid fracture; therefore, surgery was performed to restore the patient's airway and phonation functions. We found that the airway was maintained by the anterior part and that the phonation depended on the posterior part of the cricoid. This novel concept helped clarify the treatment goal in this case of comminuted cricoid fractures. Furthermore, it is important that the anterior part of the cricoid is reconstructed with sufficient internal diameter, while the posterior part of the cricoid is reconstructed in the correct position.

Sequential Evaluation of Swallowing Function During Chemoradiotherapy for Head and Neck Cancer.

BACKGROUND: Many studies have addressed chronic dysphagia resulting from chemoradiotherapy for head and neck cancer (HNC) because of its severity, but changes in the swallowing function during chemoradiotherapy has been rarely reported. This study aimed to elucidate the changes in the swallowing function during chemoradiotherapy for HNC. METHODS: From April 2018 to July 2020, 20 patients who underwent definitive or postoperative chemoradiotherapy at our hospital for head and neck squamous cell carcinoma were evaluated by flexible endoscopy with the Hyodo scoring system for swallowing, the Penetration-Aspiration Scale (PAS), and the Functional Outcomes Swallowing Scale (FOSS). RESULTS: Assessments at the start of treatment, at 40 Gy, and at the end of treatment yielded these mean values: Hyodo score-0.39, 1.22, and 2.56; PAS-1.00, 1.05, and 1.5; FOSS-0.2, 0.55, and 1.1, respectively. The Dunn multiple comparison test was used for analysis to determine significance (P < 0.05). The Hyodo score and FOSS were significantly increased at the end of treatment versus initial evaluation; however, score was maintained at a tolerable level for oral intake. PAS did not show a significant increase. CONCLUSION: In conclusion, changes in the swallowing function during chemoradiotherapy for HNC were mild, and swallowing function was maintained at a tolerable level for oral intake.

Application of an Immobilization Device for the Modified Killian's Method.

BACKGROUND: The hypopharynx is a closed space that is difficult to observe. The modified Killian's (MK) method was introduced to obtain wider exposure. However, this method requires keeping the head forward during the examination. Postural maintenance might be problematic. To use the MK method safely for a thorough endoscopic examination, we introduced a new body immobilization device. The aim of this study was to evaluate the effectiveness of this body immobilization device. METHODS: Twenty-five patients underwent transnasal laryngoscopy using the MK method with the immobilization device. This device consists of a board to place the chest and a shaft. We classified hypopharynx visualization using a 5-point scale, in various combinations of head torsion, Valsalva maneuver, and MK position. Furthermore, we classified the feasibility of the MK method for 54 patients. Age, BMI, and performance status were evaluated by MK position feasibility class. RESULTS: The MK method with the body immobilization device was completed in all patients. It was significantly associated with higher hypopharyngeal visibility score. BMI and performance status were significantly associated with MK method feasibility. There were no significant differences in hypopharynx visualization scores with versus without this device for the patients that could maintain the MK position on their own. CONCLUSION: For patients with poor nutrition or poor ability to perform activities of daily living, it was difficult to maintain the MK position. Thus, this immobilization device might be useful to complete the MK method and provide accurate detection of hypopharyngeal lesions in these patients.