A Case of Olfactory Neuroblastoma Developing Bilateral Retropharyngeal Lymph Node Metastasis 14-years After Skull Base Surgery.

Olfactory neuroblastoma (ONB) is an uncommon malignant tumor and is usually treated by a multidisciplinary approach includes surgery, radiotherapy, and chemotherapy. A 62 years-old male had a tumor in the nasal cavity and diagnosed as ONB with Kadish A stage. Anterior skull base surgery was performed as radical treatment. Since the surgical margin was negative, no postoperative radiotherapy was administered. 14 years after the surgery, bilateral otitis media with effusion (OME) was occurred, we found the recurrence tumor at bilateral retropharyngeal lymph node (RPLN) which surrounded the internal carotid arteries. Since these were unresectable, we planned chemoradiotherapy which was 70Gy of intensity modulated radiotherapy combined with two courses of carboplatin and etoposide. The tumor volume was reduced and bilateral OME were improved. He has been alive for 3 years after salvage treatment. Although ONB has a relatively good prognosis, it is known to often cause cervical lymph node metastasis. Grades III and IV of Hyams classification are considered high risk. This case, initial tumor was limited in the nasal cavity and its clinical classification was early stage, but Hyams classification was grade III. In reference to this case, considering that RPLN metastasis are difficult to radically resect at the salvage surgery, including this area in postoperative radiotherapy was considered an option.

Indocyanine green fluorescence visualizes landmark arteries for endoscopic sinus and skull base surgery.

OBJECTIVE: Landmark arteries during endoscopic sinus surgery are currently identified on the basis of anatomy, CT imaging and navigation, and Doppler flowmetry. However, the advantage of intraoperative fluorescence imaging during endoscopic sinus surgery has not been demonstrated. This study aimed to investigate whether Indocyanine Green (ICG) is useful for visualizing landmark arteries during endoscopic sinus and skull base surgery. METHODS: Eight patients who underwent endoscopic sinus and pituitary surgeries and consented to study participation were included. After planned procedures were performed as usual, landmark arteries were examined by ICG endoscope. Recorded video and preoperative CT images were analyzed for identification of five landmark arteries: anterior ethmoidal artery (AEA), posterior ethmoidal artery (PEA), internal carotid artery (ICA), sphenopalatine artery (SPA), and postnasal artery (PNA). Identification of arteries was evaluated three grades: identifiable, locatable, unrecognizable. RESULTS: Eight patients and eleven sides were evaluated. The ICG dose was 2.5 mg/body and a single shot was sufficient for evaluation. 100 % of AEA was identified (9/9 sides), 86 % of PNA (6/7 sides), 56 % of ICA (5/9 sides), and 25 % of PEA and SPA (2/8 sides). CONCLUSION: ICG could visualize landmark arteries, even thin arteries like AEA, during endoscopic sinus and skull base surgeries. Visualization was affected by thickness of bone or soft tissue above arteries, blood clots, sensitivity setting, and angle and distance of near-infrared light irradiation. ICG visualization of landmark arteries may help avoid vascular injuries during endoscopic sinus and skull base surgeries, particularly of AEA, PNA and ICA.

Oncological outcomes of concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil for locally advanced squamous cell carcinoma of the external auditory canal: A single-center study.

BACKGROUND: Squamous cell carcinoma of the external auditory canal (EACSCC) is a rare condition. However, a standard treatment has not yet been established. We retrospectively evaluated the efficacy, adverse events, and feasibility of TPF-CCRT (concomitant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil) in patients with advanced EACSCC. METHODS: Thirty-five consecutive patients with advanced EACSCC (T3, T4) initially treated with TPF-CCRT at Kobe University Hospital were included. T4 diseases with invasion of the brain, internal carotid artery, or internal jugular vein were classified as T4b, and those without these features were classified as T4a. RESULTS: Five-year overall survival rates for T3 and T4 were 100% and 64.2%, respectively. A significant difference was observed between T4a and T4b (82.4% vs. 30%, p = 0.007). Five-year progression-free survival rates of T3, T4a, and T4b were 100%, 68%, and 20% (p = 0.022), respectively. CONCLUSIONS: TPF-CCRT should be considered as a plausible treatment option for advanced EACSCC.

OK432 sclerotherapy for refractory chylous leakage after neck dissection.

Chylous leakage is a rare but serious postoperative complication of neck dissection (ND). Most chylous leakages are successfully treated either by drainage or ligation of the thoracic duct, but the resolution is occasionally prolonged. OK432 sclerotherapy is used to treat various refractory cystic diseases of the head and neck. Three patients were treated with OK432 sclerotherapy for refractory chylous leakage following ND. Case 1 involved a 77-year-old man with chylous leakage after a total laryngectomy and bilateral ND. Case 2 involved a 71-year-old woman who underwent total thyroidectomy and left ND for thyroid cancer. Case 3 involved a 61-year-old woman who underwent right ND for oropharyngeal cancer. In all patients, chylous leakage rapidly improved after OK432 injection without any complications. Our results suggest the efficacy of OK432 sclerotherapy in patients with refractory chylous leakage after ND.

Ligation of the ethmoid arteries in superselective intra-arterial infusion of cisplatin for advanced maxillary sinus cancer fed by the ophthalmic artery.

BACKGROUND: Superselective cisplatin (CDDP) infusion via the external carotid artery system and concomitant radiotherapy (RADPLAT) provides favorable oncological and functional outcomes in patients with maxillary sinus cancer. However, targeted lesions are occasionally fed by the branch of the internal carotid artery. METHODS: In RADPLAT for maxillary sinus cancer partly fed by the ophthalmic artery, the ethmoid arteries were ligated in two patients without medial orbital wall involvement. In four patients with that, CDDP was administered via the ophthalmic artery. RESULTS: A complete response was obtained in all six patients. Locoregional recurrence was not observed in any cases. However, visual acuity was lost in four patients who received the ophthalmic artery infusion. CONCLUSIONS: Ligation of the ethmoid arteries is recommended in RADPLAT for maxillary sinus cancer with lesions fed by the ophthalmic artery. CDDP administered via the ophthalmic artery may be considered if a patient accepts the possibility of visual loss.

Expressions of NeuroD and GAP43 as diagnostic markers for olfactory neuroblastoma.

OBJECTIVE: Olfactory neuroblastoma (ONB) is often difficult to pathologically distinguish from other small round cell tumors (SRCTs) arising in the nasal cavities. Although there are several diagnostic markers used for differential diagnosis of ONB, these molecules are also expressed in various neuronal derived tumors. Here, we examined the expression of NeuroD, GAP43, and olfactory marker protein (OMP) in ONB and non-ONB SRCT to determine their utility in the differential diagnosis of ONB. METHODS: Twenty-six patients diagnosed with and treated for ONB at Kobe University Hospital between 1997 and 2017 with formalin-fixed, paraffin-embedded biopsy or surgical resection specimens were included. The expressions of NeuroD, GAP43, and OMP were immunohistochemically examined in these 26 ONB specimens and specimens from 13 SRCTs arising in the nasal cavities for reference. RESULTS: Among the 26 ONB samples, focal, patchy, and marked staining for NeuroD was observed in 4, 3, and 9 samples, respectively. Focal, patchy, and marked GAP43 staining was observed in 5, 3, and 11 samples, respectively. Consequently, marked positive staining for either NeuroD or GAP43 was observed in 54% (14/26) of ONBs. Among the 13 SRCTs, marked staining for NeuroD was observed in two small cell carcinomas, one undifferentiated carcinoma, and one neuroendocrine carcinoma, whereas marked positive staining for GAP43 was observed only in one undifferentiated carcinoma. No specimen in this study exhibited OMP staining. CONCLUSIONS: Our results suggest possible roles of GAP43 immunostaining in the differential diagnosis of ONB.

Efficacy of a High-definition Three-dimensional Exoscope in Simultaneous Transcranial and Endoscopic Endonasal Surgery: A Case Report.

Owing to recent advances in medical optical technology, a high-definition (4K) three-dimensional (3D) exoscope has been developed as an alternative tool to using conventional microscopes for microscopic surgery, and its efficacy for neurosurgery has been reported. We report a case who underwent simultaneous surgery aiming for en bloc resection of an anterior skull base malignancy with concurrent exoscopic transcranial and endoscopic endonasal approaches using a 4K 3D exoscope. The patient was a 76-year-old woman who underwent en bloc resection for an anterior skull base olfactory neuroblastoma 13 years ago. After confirming the recurrence of progressive olfactory neuroblastoma, tumor resection was again decided to be performed. As with the first procedure, surgery was performed in an en bloc manner, using both transcranial and endonasal approaches. Exoscope provided enough space above the surgical field to allow us to perform transcranial and endonasal surgeries simultaneously. Moreover, the surgeons could maintain a comfortable posture throughout the procedure, and total tumor removal was successfully achieved without any abnormal event. To our knowledge, this is the first report of the introduction of an exoscope aiming for en bloc resection of an anterior skull base malignancy while performing simultaneous surgery with both transcranial and endonasal approaches. We believe that the more cases are accumulated, the more efficacy of a 4K 3D exoscope will be elucidated.

Surgical treatment of bony nasal airway stenosis in a patient with adult Crouzon's syndrome.

Crouzon's syndrome is associated with the respiratory impairment of the upper airway due to mid-facial hypoplasia. We managed an adult Crouzon patient who wanted us to treat his choanal and nasopharyngeal stenosis for obstructive sleep apnea relief and tracheostomy tube extubation. We drilled out the abnormal maxillary bone and created a new nasal passage to the pharynx. Epithelialization of the new nasal cavity was completed within a month, and the patient was able to breathe through the nose and his sense of smell improved somewhat after the surgery. Although the apnea-hypopnea index had decreased, sleep apnea remained.

Recurrent erysipelas led to diagnosis of hereditary hemorrhagic telangiectasia.

Hereditary hemorrhagic telangiectasia (HHT) is a risk of infection, such as by brain abscess associated with pulmonary arteriovenous malformations. However, association between HHT and recurrent erysipelas is not well described. HHT can cause vessel malformations in organs, leading to various serious outcomes. Prophylactic treatment is effective, but many people with HHT are undiagnosed. HHT is not described as a risk factor for soft tissue infection, but may increase the risk of serious infections requiring hospitalization. Our 72-year-old female patient was admitted for recurrent erysipelas. Pulmonary nodules indicated pulmonary arteriovenous fistula on chest computed tomography. By recognizing this combination, although seemingly unrelated problems, we could diagnose HHT and the patient could receive adequate treatment to prevent life-threatening events. The recurrent erysipelas was likely associated with HHT. Recurrent erysipelas is an important presentation which may facilitate early diagnosis of HHT.

Blowing time ratio and high-resolution manometry to evaluate swallowing function of patients with oral and oropharyngeal cancer.

OBJECTIVE: The blowing time ratio, which is the ratio of the blowing time when the nostrils are open and closed, is significantly correlated with velopharyngeal pressure, not only during speech but also during swallowing. This study aimed to further evaluate the usefulness of the blowing time ratio as a screening tool to evaluate the swallowing pressure of patients treated for oral and oropharyngeal cancers using high-resolution manometery (HRM). METHODS: Ten patients treated for oral or oropharyngeal cancer were recruited for this study. Swallowing pressures at the velopharynx, oropharynx, and upper esophageal sphincter (UES) were measured using HRM. Their correlations with the blowing time ratio were analyzed. RESULTS: The blowing time ratio was significantly correlated with the swallowing pressures of the oropharynx (CC = 0.815, p = 0.004) and the velopharynx (CC = 0.657, p = 0.039), but not of the UES. CONCLUSIONS: The present results further support our previous finding that the blowing time ratio is a useful screening tool to evaluate velopharyngeal and oropharyngeal swallowing pressures in patients treated for oral and oropharyngeal cancer.

Validation of epistaxis severity score for hereditary hemorrhagic telangiectasia in Japan.

OBJECTIVE: This study aimed to assess the health-related QoL (HR-QoL) of patients with hereditary hemorrhagic telangiectasia (HHT), with emphasis on the role/social aspects, and validate the Japanese version of the epistaxis severity score (ESS) in these patients. METHODS: The Japanese version of the ESS was created through forward and reverse translation, and consultation with the original author. A validation analysis was performed by comparing ESS severity with the invasiveness of previous treatments for epistaxis and assessing the correlation between the ESS and HR-QoL. Medical history forms, ESS questionnaires, and the Medical Outcomes Study Short Form 36 (SF-36) were distributed to participants with HHT in August 2020. The relation between the ESS and summary scores of SF-36 was assessed by performing analysis of variance and Spearman's correlation. RESULTS: In total, 73 participants were included in this study. The average ESS was 5.02; there were mild (32.9%), moderate (45.2%), and severe (21.9%) epistaxis groups. Patients with higher ESS received a significantly more invasive treatment (Fisher's exact test, p < 0.05). The ESS was also negatively correlated with the physical component score (PCS) (r = -0.489, p < 0.001). Comorbid liver and gastrointestinal arteriovenous malformations significantly reduced the PCS (p < 0.05). Multiple regression analysis revealed that the ESS was a significant variable (p < 0.01). The role/social component score was significantly lower in the severe ESS group than in the mild or moderate group. CONCLUSION: The Japanese version of the ESS was considered valid and may be useful as an outcome measure of future HHT-associated epistaxis trials in Japan.

Left non-recurrent inferior laryngeal nerve in a patient with right-sided aortic arch and aberrant left subclavian artery.

Non-recurrent inferior laryngeal nerve (NRILN) is rare but one of the important anatomical variations in thyroid and parathyroid surgery. Almost all cases were observed on the right side with aberrant right subclavian artery and left NRILN have been reported in only five cases so far. Here, we reported a 38 year-old Japanese male with left NRILN accompanying adenomatous goiter. He was referred to our hospital for the surgical treatment of left thyroid goiter. Preoperative computed tomography revealed right-sided aortic arch and aberrant left subclavian artery with no signs of complete situs inversus viscerum, suggesting possible left NRLN. Left hemithyroidectomy was performed using nerve monitoring system. Intraoperatively, left recurrent laryngeal nerve was not identified along tracheoesophageal groove, but directly originated from vagal nerve and was running horizontally to larynx. Mobility of vocal cords were not impaired and postoperative course was uneventful. During thyroid surgery for the patients with right-sided aortic arch, meticulous care should be taken using nerve monitoring system to avoid nerve injury.

Frontal sinusitis associated with orbital decompression for Graves' orbitopathy.

Orbital decompression (OD) for Graves' orbitopathy usually includes removal of orbital medial wall. While OD occasionally cause or worsen chronic sinusitis because of the obstructed sinus drainage by prolapsed orbital fat, to date few reports have been published on the management or prevention of sinusitis associated with OD. Here, we present two patients (three sides) with newly developed and one patient (one side) with worsening obstructive frontal sinusitis following OD. These three patients had OD including the removal of the superior attachment of uncinated process to lamina papyracea. Endoscopic modified Lothrop procedure (EMLP) was useful to relieve symptoms and keep an enough access to frontal sinuses for all cases. We also performed EMLP for another two patients (four sides) with pre-existing sinusitis before OD. Worsening of sinusitis could be avoided by EMLP before OD. EMLP was useful approach for both treatment and prevention of sinusitis related to OD. The superior attachment site of uncinated process and the pattern of frontal sinus drainage might predict the occurrence of obstructive frontal sinusitis following OD.

Three-year prospective study on olfaction of patients with Parkinson's disease.

OBJECTIVE: We conducted a 3-year prospective study on olfaction of patients with Parkinson's disease (PD) in order to examine the severity and frequency of smell disorder in PD using odor identification test, Open Essence (OE) and to verify the validity of olfactory tests as a predictor of cognitive symptom onset of PD. PATIENTS AND METHODS: We conducted a prospective study by performing an annual examination over a 3-year period. For 56 cases diagnosed with PD by the Department of Neurology at our hospital, OE and Jet Stream Olfactometry (JSO) were performed to assess the olfactory function, and Mini-Mental-State Examination (MMSE) was conducted to measure cognitive impairment. RESULTS: At the beginning, 56 cases were examined, of which 42 remained to be followed up for 3 years. Based on the results of baseline, we found a correlation between OE and the average cognitive thresholds of JSO, but did not find any correlation between OE and MMSE. OE (median 4.0→4.0) and the average cognitive thresholds of JSO (median 2.2→1.6)　decreased after 3 years, and MMSE (median 29→29) also declined, but not significantly. At the 3rd year, 6 cases with MMSE score of 23 or less were identified as suspected dementia and 36 cases with more than 24 points were defined as an invariant group. In order to distinguish these two groups, OE scores of baselines were evaluated with a combination of 12 odors. Sensitivity 1.0 and specificity 0.722 were obtained and the sensitivity+specificity value (1.722) was the highest when the number of correct answers was 4 or less using an odor combination of lumber, menthol, Japanese orange, gas for household use, Hinoki cypress and condensed milk. CONCLUSION: When the number of correct answers of 6 odors (lumber, menthol, Japanese orange, gas for household use, Hinoki cypress and condensed milk) is 4 or less in patients with PD, there is a possibility that MMSE declines in 3 years.

Characteristics of Smell Identification Test in Patients With Parkinson Disease.

OBJECTIVES: Parkinson disease (PD) is frequently associated with olfactory disorder at early stage, which is caused by deposition of Lewy bodies emerging from the olfactory bulb to higher olfactory centers. Early detection of olfactory disorder in the patients with PD may lead to the early diagnosis and treatment for this refractory disease. METHODS: Visual analog scale (VAS), Jet Stream Olfactometry, and Japanese smell identification test, Open Essence (OE), were carried out on 39 patients with PD. Thirty-one patients with postviral olfactory disorder (PVOD), which was caused by the olfactory mucosal dysfunction, were also enrolled in this study as control. RESULTS: There were no significant differences in detection thresholds (2.2 vs. 1.4, P=0.13), recognition thresholds (3.9 vs. 3.5, P=0.39) and OE (4.8 vs. 4.2, P=0.47) between PVOD and PD, while VAS scores of PVOD and PD were significantly different (2.0 and 6.2, P<0.01). In OE, significant differences were observed in the accuracy rates of menthol (68% vs. 44%, P=0.04) and Indian ink (42% vs. 15%, P=0.01) between PVOD and PD. Of particular interest, patients with PVOD tended to select "no detectable," while patients with PD tended to select wrong alternative other than "no smell detected." CONCLUSION: Discrepancy between VAS and OE, and high selected rates of wrong alternative other than "undetectable" in OE might be significant signs of olfactory dysfunction associated with PD.