Functional vagal paraganglioma developing 15 years after resection of a retroperitoneal paraganglioma.

The patient, a 40-year-old woman, was diagnosed as having a functional right vagal paraganglioma (PGL) 15 years after undergoing resection for a retroperitoneal PGL. 123I-MIBG scintigraphy showed no accumulation, but as the blood noradrenaline and urinary normetanephrine concentrations were elevated, the tumor was judged as being functional, and surgery was scheduled. The patient was started on doxazosin infusion and embolization of the tumor feeding vessel was performed before the surgery. Intraoperative examination showed that the tumor was contiguous with the vagal nerve, necessitating combined resection of the vagal nerve with the tumor. Postoperatively, the catecholamine levels returned to normal range. Histopathologically, the tumor was diagnosed as a moderately differentiated, intermediate-malignant-grade PGL, with a GAPP score of 4 to 6. No non-chromaffin tissue was observed in the tumor background, so that the functional vagal PGL was considered as a sporadic metachronous tumor rather than as a metastasis from the retroperitoneal PGL. More than half of head and neck paragangliomas (HNPGLs) are reported to arise in the carotid body, and about 5% from the vagal nerve. In addition, HNPGLs rarely produce catecholamines. Herein, we consider the relationship with the previously resected retroperitoneal PGL based on a review of the literature.

Post-intubation laryngeal injury after COVID-19 treatment causing dyspnea: A report of six cases.

Severe cases of COVID-19 often require orotracheal intubation (OTI) and mechanical ventilation, and post-intubation laryngeal injury (PI-LI) is one of the important complications of OTI. Some studies have claimed that the frequency of PI-LI may be higher in COVID-19 patients as compared with that in non-COVID-19 patients, because of the larger size of endotracheal tube used, the longer OTI time, use of prone positioning of the patients, etc. Herein, we describe six cases of PI-LI who presented with dyspnea after recovering from COVID-19. Five of the patients were male and the median OTI period was 9 days. All the patients showed abnormal endoscopic findings, including posterior glottic synechiae/stenosis or subglottic/posterior glottic granulomas. Four patients required surgical intervention, including tracheostomy, laryngomicrosurgery, or laterofixation of the vocal cord. Many post-COVID-19 patients experience persistent symptoms (post-COVID-19 syndrome), including dyspnea. Two of our patients with dyspnea had been treated by internists as cases of post-COVID-19 syndrome. Therefore, we wish to underscore the need for every healthcare professional to be aware of the possibility of PI-LI after OTI, especially during the ongoing COVID-19 pandemic. Otolaryngologists should undertake endoscopic assessment of the larynx in patients presenting with dyspnea after recovering from COVID-19.

Comprehensive Genomic Profiling Reveals Clinical Associations in Response to Immune Therapy in Head and Neck Cancer.

Comprehensive genomic profiling (CGP) provides information regarding cancer-related genetic aberrations. However, its clinical utility in recurrent/metastatic head and neck cancer (R/M HNC) remains unknown. Additionally, predictive biomarkers for immune checkpoint inhibitors (ICIs) should be fully elucidated because of their low response rate. Here, we analyzed the clinical utility of CGP and identified predictive biomarkers that respond to ICIs in R/M HNC. We evaluated over 1100 cases of HNC using the nationwide genetic clinical database established by the Center for Cancer Genomics and Advanced Therapeutics (C-CAT) and 54 cases in an institution-based study. The C-CAT database revealed that 23% of the cases were candidates for clinical trials, and 5% received biomarker-matched therapy, including NTRK fusion. Our institution-based study showed that 9% of SCC cases and 25% of salivary gland cancer cases received targeted agents. In SCC cases, the tumor mutational burden (TMB) high (≥10 Mut/Mb) group showed long-term survival (>2 years) in response to ICI therapy, whereas the PD-L1 combined positive score showed no significant difference in progression-free survival. In multivariate analysis, CCND1 amplification was associated with a lower response to ICIs. Our results indicate that CGP may be useful in identifying prognostic biomarkers for immunotherapy in patients with HNC.

Real-world treatment patterns and outcomes in Japanese patients with cervical esophageal cancer.

BACKGROUND: Cervical esophageal cancer (CEC) carries a poor prognosis; however, due to its low incidence, optimal treatment for CEC remains to be established. The purpose of this study was to clarify the current status of treatment of CEC in Japan and obtain evidence for establishing the appropriate treatment method. PATIENTS AND METHODS: We asked specialist training facilities accredited by the Japanese Broncho-Esophageal Society to register data on CEC cases that received curative treatment from January 2009 to December 2014, and conducted a retrospective review of the clinical data of 302 cases registered from 27 facilities. RESULTS: In regard to the initial therapy, of the 302 patients, 33 had undergone endoscopic resection, 41 had undergone surgery, 67 had received induction chemotherapy (IC), and 143 had received chemoradiotherapy (CRT). There were no significant differences in the 5-year overall survival rates among the patient groups that had received surgery, IC or CRT as the initial treatment; advanced stage and recurrent nerve invasion were identified as independent poor prognostic factors. Among the patients who had received IC or CRT as laryngeal-preserving surgery was not indicated at the time of the initial diagnosis, the functional laryngeal preservation rate at the end of the observation period was 34.8%. CONCLUSION: Even in patients with advanced CEC, there is the possibility of preserving the larynx by adopting IC or CRT. However, if the laryngeal function cannot be preserved, there is a risk of complications from aspiration pneumonia, so that the choice of treatment should be made carefully.

Superior mediastinal paraganglioma initially suspected of being a mediastinal thyroid goiter.

Paraganglioma is a rare tumor arising from paraganglia. Few reports have described paragangliomas in the superior mediastinum. We report a case of superior mediastinal paraganglioma treated in our department. A 28-year-old woman visited our department because of suspected mediastinal tumor during a medical checkup. Contrast-enhanced CT showed a 39 × 35 × 65-mm tumor with a well-defined border extending from the lower pole of the left thyroid gland to the superior mediastinum. Laboratory tests showed no evidence of catecholamine overproduction. Mediastinal thyroid goiter was the most suspected preoperative diagnosis. We decided to perform a transcervical excision for both diagnosis and treatment. The tumor was easily detached from the lower pole of the left thyroid gland and was not continuous. The tumor capsule was brittle and bled easily. The operating time was 3 h and 11 min, and the amount of bleeding was 571 mL. The pathological diagnosis was paraganglioma. Paragangliomas are characterized by abundant blood flow and are likely to result in a high intraoperative bleeding volume. In addition, if the tumor is functional, circulatory abnormalities can occur during the perioperative period. Accurate preoperative diagnoses are important, and the possibility that paragangliomas can develop in the superior mediastinum should be considered.

Evaluation of synchronous multiple primary superficial laryngo-pharyngeal cancers that were treated by endoscopic laryngo-pharyngeal surgery.

OBJECTIVE: ndoscopic laryngopharyngeal surgery (ELPS) is a useful surgery for superficial cancers of the head and neck region, but it has not yet been well evaluated for synchronous multiple primary cancers (multiple primaries). The purpose of this study was to clarify the safety and usefulness of ELPS for patients with multiple superficial primary cancers in the head and neck region. METHODS: rom December 2009 to December 2016, 145patients with superficial head and neck cancers underwent ELPS. The patients were divided into two groups; a group consisting of patients with a single primary cancer (single primary) and another group consisting of patients with synchronous multiple primaries, and the incidences of postoperative complications and lymph node metastasis were retrospectively compared between the two groups. RESULTS: f the 145 patients, 107 had a single primary cancer and 38 had multiple primaries. There was no significant difference in the age, sex, or rate of intraepithelial cancer between the two groups. Postoperative complications included dysphagia in 6 (5.6%) patients with a single primary and 2 (5.3%) patients with multiple primaries. One patient with multiple primaries required gastrostomy because of aspiration pneumonia. In addition, the following complications were also observed. Laryngeal paralysis occurred in 2 (1.9%) patients with a single primary, and 1 (2.6%) patient with multiple primaries; tracheostomy because of postoperative bleeding in 1 (0.9%) patient with a single primary; infection occurred in 2 (5.3%) patients with multiple primaries. Postoperative lymph node metastasis was found in 7 (6.5%) patients with a single primary and 6 (15.8%) patients with multiple primaries. Lymphatic invasion of the primary cancer was noted in 3 (2.8%) patients with a single primary and 5 (13.2%) patients with multiple primaries, being significantly higher in the latter group. CONCLUSION: ELPS is also a safe surgery for patients with multiple primaries. However, the incidence of lymphatic invasion of the primary cancer was significantly higher in patients with multiple primaries.

Indications for and extent of elective neck dissection for lymph node metastasis from external auditory canal carcinoma.

OBJECTIVES: We aim to clarify the frequency of lymph node metastasis of external auditory canal (EAC) carcinoma, including susceptible locations, adequate extent of elective neck dissection, and the relationship between the tumor infiltration site and lymph node metastasis. PATIENTS AND METHODS: From 2003 to 2018, 63 patients with EAC carcinoma at Tokyo Medical and Dental University Hospital were enrolled in this study. The T and N stages, locations of clinically positive lymph nodes, prognoses, and anatomic site of tumor infiltration were analyzed after treatment. RESULTS: Clinically positive lymph node metastasis (cN+) was detected in 18 patients (28.6%), consisting of T1, T2, T3, and T4 disease in 1 (6%), 2 (22%), 8 (38%), and 7 (41%) patients, respectively. The metastatic locations were at level II in 10 patients, parotid gland nodes in 7, preauricular nodes in 5, level Ib in 3, level Va in 3, level III in 1, and superficial cervical nodes in 1. Neck recurrence was determined in two of 45 patients with clinically negative lymph nodes (cN0), with the metastatic locations being levels II, Ib, and III. Among 18 cN+ cases, neck recurrence was noted in 2 of 9 patients who underwent neck dissection. Neck lesions were found to be manageable in all five patients who underwent docetaxel, cisplatin, 5-fluorouracil, and radiation therapy (TPF-RT). No relationship was noted between the tumor infiltration site and lymph node metastasis among T3/4 canrcinoma patients. CONCLUSIONS: Elective neck dissection could be indicated only in T3/4 patients with free flap reconstruction. Levels Ib to III are considered appropriate for elective neck dissection in cN0 cases. Levels Ib to III and Va indicated favorable sites, even in cases with metastasis in the parotid gland or preauricular area. Furthermore, TPF-RT could be a useful option even in cN+ cases.

[Combined Anterior Craniofacial Resection for Locally Advanced Ethmoid Carcinomas].

OBJECTIVE: Carcinoma of the ethmoid sinus is very rare, and treatment for locally advanced tumors remains as a formidable challenge to the clinician. We reviewed cases of ethmoid carcinoma in which anterior craniofacial resection had been undertaken and evaluated the safety and validity of the operative methods. METHODS: We retrospectively reviewed 13 patients with ethmoid carcinoma who underwent combined anterior craniofacial resection. We evaluated the surgical procedures, complications, outcomes, local recurrence, and the survival rate. RESULTS: Coronal incision and anterior craniotomy were performed in all cases. Four out of 13 cases underwent ipsilateral orbital exenteration due to involvement of the orbital contents. There were no potentially fatal complications, except for two cases of epidural abscesses which were successfully cured. Positive surgical margins were observed in 6 patients, and they received postoperative radiotherapy and/or chemotherapy. Local recurrences occurred in 4 cases, and 3 died at 9, 11, and 49 months after the surgery. Distant metastasis was not observed during the observation period. The overall 5-year survival rate was 75.2% (Kaplan-Meier method). CONCLUSION: These tumors were safely removed without severe complications and postoperative mortality. Combined anterior craniofacial resection is an effective and safe option for treatment of locally advanced ethmoid carcinomas after various preoperative treatments.

The approaches and outcomes of skull base surgery for pediatric sarcoma after initial therapy.

OBJECTIVE: Surgical removal of the residual pediatric sarcoma after initial therapy is common; however, that in the skull base area still presents a formidable challenge. We reviewed the approaches and outcomes of skull base surgery for pediatric sarcoma. METHODS: Thirteen patients with pediatric sarcoma who received skull base surgery were reviewed retrospectively. Tumor sites, surgical approach, complications, regional recurrence after surgery, and survival rate were analyzed. RESULTS: The residual tumor sites were the infratemporal fossa (8), nasal cavity and paranasal sinus (4) and orbit with anterior skull base invasion (1). Coronal skin incision (1), that with preauricular skin incision (7) and facial dismasking flap (5) were applied to patients as the skin preparation. Following skin preparations, anterior skull base surgery with frontal craniotomy (3), infratemporal fossa approach with temporal craniotomy (5), and anterior-lateral skull base with front-temporal craniotomy (1) were performed. Tumors were removed with a sufficient surgical field in all patients. Facial nerve palsy (9), facial deformity (4), orbital complications (diplopia, decreased visual acuity, narrowing of visual field) (2) and occlusal imbalance (1) occurred. However, facial palsy, diplopia and occlusal imbalance subsided gradually. Local recurrence occurred in 6 cases and distant metastasis was observed in 4 cases. The overall 5-years survival rate was 51.9% (Kaplan-Meier method). CONCLUSION: These tumors were safely removed with minimum morbidity. Skull base surgery is recommended to remove residual pediatric sarcoma after the initial treatment.

Secondary hyperbaric oxygen therapy for idiopathic sudden sensorineural hearing loss in the subacute and chronic phases.

This study investigated the efficacy of hyperbaric oxygen therapy (HBOT) as a secondary treatment for patients with idiopathic sudden sensorineural hearing loss (ISSNHL) in the subacute and chronic phases. Forty-eight ISSNHL patients (HBOT group) who had received primary conventional treatment within 4 weeks after onset and underwent HBOT between 4 and 20 weeks post-onset were retrospectively compared with 44 ISSNHL patients (control group) with primary conventional treatment alone. Mean hearing gain was slight, with gains of 5.2 +/- 8.9 dB in the HBOT group and 2.0 +/- 7.6 dB in the control group. However, no significant difference was recognized between the two groups. In the HBOT group, no significant difference was observed in hearing gain among patients with HBOT initial time at 4-7, 8-11, 12-15 or 16-20 weeks after onset. Meanwhile, hearing gain was significantly higher in patients with profound hearing loss than in the other patients. We conclude that the effectiveness of secondary HBOT for ISSNHL patients in either subacute or chronic phase remains unproven, and thus, the decision administer HBOT should be made with caution.

Hereditary hearing loss and deafness genes in Japan.

Hearing loss (HL) is the most common sensory impairment occurring at birth in developed countries. Epidemiological data show that more than one child in 1000 is born with HL, while more than 50% of prelingual HL cases are found to be hereditary. Approximately 70% of hereditary HL is nonsyndromic and subdivided to autosomal dominant (20%), autosomal recessive (75%), X-linked HL (1%), and maternally-inherited HL associated with the mitochondrial DNA mutation. More than 10 deafness genes have been reported to be responsible for nonsyndromic hereditary HL in Japan. Among them, the most prevalent causative genes, GJB2 and the mitochondrial DNA 12SrRNA are introduced. In addition, this study also refers to the specific genes responsible for the unique audiogram, mainly WFS1. Finally, the genes related to the enlargement of vestibular aqueduct of inner ear abnormality, SLC26A4, EYA1 and SIX1 are discussed. The clinical and genetic findings associated with these disorders including the results of a recent study are reviewed.

Cardiac metastasis of tongue cancer may cause sudden death.

OBJECTIVE: To identify cardiac metastases in a patient with a squamous cell carcinoma of the tongue and to clarify the relationship between cardiac metastases and sudden death. STUDY DESIGN: Autopsy and retrospective chart review for a patient. METHODS: We studied a Japanese patient who suddenly died after the operation and radiation therapy, despite an absence of thanatoid symptoms. We performed a subsequent autopsy. RESULTS: The patient had four metastatic lesions in the heart, one of which was in the septum and infiltrated the region around the conducting system of the heart. CONCLUSION: Cardiac metastasis of tongue cancer may cause sudden death.