Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

Objective  Surgical indications for advanced-stage squamous cell carcinoma (SCC) of the external auditory canal (EAC) are highly dependent on the skull base surgery team. The aim of this study was to evaluate the surgical outcomes in patients with SCC of the EAC and to clarify the surgical indication of far advanced cases using the T4 subclassification. Methods  Patients with SCC of the EAC who underwent curative treatment from 2002 to 2021 at our hospital were retrospectively reviewed. Clinical and surgical results, including operative data, overall survival (OS), and disease-specific survival (DSS), were analyzed. To clarify the surgical indication for advanced-stage tumors, we proposed the T4 subclassification. Results  In the 46 patients included in the study, 8 patients had T1 tumors, 10 had T2 tumor, 5 had T3 tumors, and 23 had T4 tumors. The 5-year DSS with T1, T2, T3, and T4 tumors were 100, 85.7, 100, and 61.7%, respectively. No prognostic impacts for margin status were found between the 5-year OS and DSS ( p  = 0.23 and 0.13, respectively). Patients with far-advanced-stage (T4b) tumors were significantly associated with shorter DSS than those with early-stage (T1/T2) and advanced-stage (T3/T4a) tumors ( p  = 0.007 and 0.03, respectively). Conclusion  The present study focused on patients with SCC of the EAC at a university hospital over a period of 20 years, especially with skull base involvement, and a T4 subclassification was proposed. Complete tumor resection in an en bloc fashion could help achieve a good survival rate even in patients with locally advanced tumors.

DOI： 10.1055/a-1733-2585

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

This study evaluated the safety of laryngeal closure and post-surgical changes in swallowing function of patients with amyotrophic lateral sclerosis (ALS) and proposed an appropriate surgical strategy for patients with ALS. Clinical and surgical data of 26 consecutive patients with ALS who underwent laryngeal closure at Nagoya University Hospital in Japan between 2003 and 2020 were retrospectively analyzed. Changes in swallowing functions were evaluated before and approximately 1 month post-surgery using Neuromuscular Disease Swallowing Status Scale (NdSSS), and Functional Oral Intake Scale (FOIS). The median operation time was 126 min (range, 51-163 min), and the median intraoperative blood loss was 20 mL (range, 0-88 mL). Among the 26 ALS patients who underwent laryngeal closure, grade 1 (mild) complications occurred in three patients (12%); however, no severe complications were observed. After surgery, 25 patients (96%) maintained the swallowing function and only one patient (4%) had deteriorating NdSSS and FOIS scores. No patients were referred to our hospital due to severe aspiration pneumonia after the surgery. Two patients did not require a feeding tube after the surgery and returned to oral intake. Laryngeal closure may be a safe surgical procedure for preventing chronic aspiration and may also maintain swallowing function of patients with ALS. Further multicenter prospective studies using the gold standard videofluoroscopic swallowing examination are required to support our findings.

DOI： 10.1007/s00455-022-10454-0

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Language：English   Publishing type：Research paper (scientific journal)  

Endoscopic cricopharyngeal myotomy (ECPM) is a safe and minimally invasive technique that is used to treat patients whose esophageal inlet fails to open because of specific diseases, such as Wallenberg's syndrome and neuromuscular diseases. The present study described the performance of a new, safe and simple ECPM using a curved rigid laryngoscope, which is used for endoscopic laryngopharyngeal surgery for patients with dysphagia due to pharyngeal residue after swallowing. The patient was an 80-year-old woman with laryngeal palsy caused by lower cranial nerve palsy after cranial base schwannoma surgery. ECPM was performed with a curved rigid laryngoscope. The postoperative course was good; postoperative rehabilitation eliminated the residue after swallowing a thickened solution and mealtimes were shorter than before surgery. This procedure allows the hypopharynx to be widely expanded and it is possible to develop a wider surgical field than when using a direct laryngoscope. In addition, this procedure appears to be relatively easy to perform if the surgeon is familiar with the curved rigid laryngoscope technique.

DOI： 10.3892/mco.2023.2606

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(NPO)日本頭頸部外科学会  

頭頸部外科手術の基盤となる技術スキルに対する認識について多施設アンケート調査を行った。先行研究の7つのカテゴリーに分類されている60個の技術スキルを用いて,若手医師69名と熟達医15名の回答を比較した。若手医師は,熟達医よりも技術スキル全体を重要と評価しており(P=0.027),熟達医が重要視しているスキルだけでなく,全ての技術スキルに対して気を配っていることが示唆された。熟達医は,「カウンタートラクション」が全カテゴリー中最も難易度が高いと評価していたが,若手医師は自身のスキルに7カテゴリー中3番目に高い自信を持っていた。このような認識の乖離が,技術伝承のひとつの障壁になっている可能性がある。(著者抄録)

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：日本喉頭科学会  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2022&ichushi_jid=J02852&link_issn=&doc_id=20230111160002&doc_link_id=10.5426%2Flarynx.34.51&url=https%3A%2F%2Fdoi.org%2F10.5426%2Flarynx.34.51&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publishing type：Research paper (scientific journal)  

Clinical imaging performance using a fluorescent antibody was compared across three cancers to elucidate physical and biological factors contributing to differential translation of epidermal growth factor receptor (EGFR) expression to macroscopic fluorescence in tumors. Methods: Thirty-one patients with high-grade glioma (HGG, n = 5), head-and-neck squamous cell carcinoma (HNSCC, n = 23) or lung adenocarcinoma (LAC, n = 3) were systemically infused with 50 mg panitumumab-IRDye800, 1 - 3 days prior to surgery. Intraoperative open-field fluorescent images of the surgical field were acquired, where imaging device settings and operating room lighting conditions were tested on tissue-mimicking phantoms. Fluorescence contrast and margin size were measured on resected specimen surface. Antibody distribution and EGFR immunoreactivity were characterized in macroscopic and microscopic histological structures. Integrity of the blood-brain barrier (BBB) was examined via tight junction protein (claudin-5) expression with immunohistochemistry. Stepwise multivariate linear regression of biological variables was performed to identify independent predictors of panitumumab-IRDye800 concentration in tissue. Results: Optimally acquired at the lowest gain for tumor detection with ambient light, intraoperative fluorescence imaging enhanced tissue-size dependent tumor contrast by 5.2-fold, 3.4-fold and 1.4-fold in HGG, HNSCC and LAC, respectively. Tissue surface fluorescence target-to-background ratio correlated with margin size and identified 78 - 97% of at-risk resection margins ex vivo. In 4 µm-thick tissue sections, fluorescence detected tumor with 0.85 - 0.89 areas under the receiver operating characteristic curves. Preferential breakdown of BBB in HGG improved tumor specificity of intratumoral antibody distribution relative to that of EGFR (96% vs 80%) despite its reduced concentration (3.9 ng/mg tissue) compared to HNSCC (8.1 ng/mg) and LAC (6.3 ng/mg). Cellular EGFR expression, tumor cell density, plasma antibody concentration and delivery barrier were independently associated with local intratumoral panitumumab-IRDye800 concentration with 0.62 goodness-of-fit of prediction. Conclusion: In multi-cancer clinical imaging of receptor-ligand based molecular probe, plasma antibody concentration, delivery barrier, as well as intratumoral EGFR expression driven by cellular biomarker expression and tumor cell density, led to heterogeneous intratumoral antibody accumulation and spatial distribution while tumor size, resection margin, and intraoperative imaging settings substantially influenced macroscopic tumor contrast.

DOI： 10.2967/jnumed.121.263674

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Primary laryngeal cryptococcosis is an extremely rare infection and presents with non-specific symptoms such as hoarseness or sore throat, resulting in delayed diagnosis. Here, we report the patient of a 56-year-old female patient with primary laryngeal cryptococcosis, who was being treated with oral and inhaled steroids for rheumatoid arthritis and bronchial asthma. The patient suffered from prolonged hoarseness and sore throat, and endoscopic biopsy was performed several times under local anesthesia, demonstrating only inflammatory cell infiltration. Considering the possibility of laryngeal malignancy, a third biopsy was performed by endoscopic laryngomicrosurgery under general anesthesia. Intraoperative frozen section revealed non-neoplastic laryngeal mucosa with erosion and severe inflammatory cell infiltration. However, we could not confirm the definite diagnosis of the lesion in the intraoperative consultation. Postoperative histopathological examination revealed a small number of yeast-type fungi and a definitive diagnosis was established by special stains including Alcian blue stain. Finally, the patient was diagnosed as primary laryngeal cryptococcosis. Daily oral administration of fluconazole (400 mg/day) was performed for 6 months according to the treatment protocol for pulmonary cryptococcosis. The symptoms gradually improved, and endoscopy revealed no recurrence 6 months post-treatment. Clinicians should consider the possibility of laryngeal cryptococcosis when severe inflammation is found in the larynx and discuss the disease history and pathological results with pathologists more closely.

DOI： 10.18999/nagjms.84.4.900

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Language：English   Publishing type：Research paper (scientific journal)  

Rationale: In head and neck cancer, a major limitation of current intraoperative margin analysis is the ability to detect areas most likely to be positive based on specimen palpation, especially for larger specimens where sampling error limits detection of positive margins. This study aims to prospectively examine the clinical value of fluorescent molecular imaging to accurately identify "the sentinel margin," the point on a specimen where tumour lies closest to the resected edge in real-time during frozen section analysis. Methods: Eighteen patients with oral squamous cell carcinoma were enrolled into a prospective clinical trial and infused intravenously with 50mg of panitumumab-IRDye800CW 1-5 days prior to surgery. Resected specimens were imaged in a closed-field near-infrared optical imaging system in near-real time, and custom designed software was used to identify locations of highest fluorescence on deep and peripheral margins. The surgeon identified the sentinel margin blinded to optical specimen mapping, and then the regions of highest fluorescence were identified and marked for frozen analysis. Final pathology based on specimen reconstruction was used as reference standard. Results: Resected specimens were imaged in the operating room and fluorescence had a higher interobserver agreement with pathology (Cohen kappa value 0.96) than the surgeon (Cohen kappa values of 0.82) for the location of the closest margin. Plotting margin distance at the predicted sentinel margin location of each observer versus the actual closest margin distance at pathology demonstrated best correlation between fluorescence and pathology (R2 = 0.98), with surgeon (R2 = 0.75). Principal Conclusion: Fluorescence imaging can improve identification of the sentinel margin in head and neck cancer resections, holding promise for rapid identification of positive margins and improved oncological outcomes.

DOI： 10.2967/jnumed.121.262235

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Language：English   Publishing type：Research paper (scientific journal)  

Objective: To determine the efficacy of a surgical training model for fluorescence-guided cancer surgery and validate its utility to detect any residual tumors after tumor resection using electrocautery. Methods: We developed surgical training models containing indocyanine green (ICG) for near-infrared (NIR) fluorescence imaging using a root vegetable organic material (konjac). After the fluorescence assessment for the models, the surgical simulation for fluorescence-guided cancer surgery using electrocautery was performed. ICG-containing tumors were divided into two surgical groups: "Enucleation" (removal of the entire visible tumor) and "Complete resection" (removal of the tumor with an appropriate 5-mm surgical margin). Results: All 12 ICG-containing tumors were clearly visible from the normal view but not from the flipped view. The tumor resection time was significantly longer in the "Complete resection" group than in the "Enucleation" group (p < .001). The ICG-containing tumors showed a high tumor-to background ratio from the normal (average = 45.8) and flipped (average = 19.2) views, indicating that the models including ICG-containing tumors were useful for a surgical simulation in fluorescence-guided surgery. The average mean fluorescence intensity of the wound bed was significantly higher in the "Enucleation" group than in the "Complete resection" group (p < .01). No decrease in fluorescence signal was found in the wound bed even at 2 days postresection. Conclusion: Our surgical training model containing a fluorescent agent is safe, inexpensive, not harmful for humans, and easy to dispose after use. Our model would be beneficial for surgeons to learn NIR fluorescence imaging and to accelerate fluorescence-guided cancer surgery into clinical application.

DOI： 10.1002/lio2.858

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Previous studies showed that although the risk of thyroid dysfunction (thyroid immune-related adverse events [irAEs]) induced by anti-programmed cell death-1 antibodies (PD-1-Ab) was as low as 2-7% in patients negative for anti-thyroid-antibodies (ATAs) at baseline, it was much higher (30-50%) in patients positive for ATAs. However, whether a similar increase occurs with combination therapy using PD-1-Ab plus anti-cytotoxic T-lymphocyte antigen-4 antibody (CTLA-4-Ab) is unknown. METHODS: A total of 451 patients with malignancies treated with PD-1-Ab, CTLA-4-Ab, or a combination of PD-1-Ab plus CTLA-4-Ab (PD-1/CTLA-4-Abs) were evaluated for ATAs at baseline and for thyroid function every 6 weeks for 24 weeks after treatment initiation, and then observed until the last clinical visit. RESULTS: Of the 451 patients, 51 developed thyroid-irAEs after immunotherapy [41 of 416 (9.9%) treated with PD-1-Ab, 0 of 8 (0%) with CTLA-4-Ab, and 10 of 27 (37.0%) with PD-1/CTLA-4-Abs]. The cumulative incidence of thyroid-irAEs was significantly higher in patients who were positive versus negative for ATAs at baseline after both PD-1-Ab [28/87 (32.2%) vs. 13/329 (4.0%), p < 0.001] and PD-1/CTLA-4-Abs [6/10 (60.0%) vs. 4/17 (23.5%), p < 0.05] treatments. The risk of thyroid-irAEs induced by PD-1/CTLA-4Abs, which was significantly higher than that induced by PD-1-Ab, in patients negative for ATAs at baseline was not statistically different from that induced by PD-1-Ab in patients positive for ATAs at baseline. CONCLUSIONS: This study showed that the incidence of thyroid-irAEs was high and not negligible after PD-1/CTLA-4-Abs treatment even in patients negative for ATAs at baseline.

DOI： 10.1210/clinem/dgab829

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1080/23772484.2022.2033122

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Other Link： https://search.jamas.or.jp/default/link?pub_year=2021&ichushi_jid=J07551&link_issn=&doc_id=20211201440017&doc_link_id=10.3950%2Fjibiinkotokeibu.124.11_1543&url=https%3A%2F%2Fdoi.org%2F10.3950%2Fjibiinkotokeibu.124.11_1543&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: The clinical course of liver injury induced by immune checkpoint inhibitors (ICIs) varies among individuals, and there were few reports on the therapeutic effects of corticosteroids based on the patterns of liver injury. METHODS: We evaluated the characteristics and clinical course of immune-related liver injury in 1214 patients treated with ICIs for advanced malignancies except for hepatocellular carcinoma between August 2014 and May 2021. RESULTS: During the follow-up period (median, 252 days), 58 patients (4.8%) had an immune-related liver injury (≥ Grade 3). The liver-injury patterns were hepatocellular (n = 26, 44.8%), mixed (n = 11, 19.0%), or cholestatic (n = 21, 36.2%), and the median time to onset of liver injury was 39, 81, and 53 days, respectively; the hepatocellular pattern occurred earlier than the other types (p = 0.047). Corticosteroids were administered to 30 (51.7%) patients; while liver injury was improved in almost all patients with the hepatocellular pattern (n = 13/14, 92.9%), that failed to show improvement in over half of the patients with the non-hepatocellular patterns, and three patients with mixed patterns needed secondary immunosuppression with mycophenolate mofetil. Liver biopsies performed in 13 patients mainly showed lobular injury, endothelialitis, and spotty necrosis with infiltration of T cells positive for CD3 and CD8, but not CD4 or CD20. CONCLUSION: The incidence pattern and therapeutic response to corticosteroids in immune-related liver injury differ according to the injury type. Although corticosteroids were effective for the hepatocellular pattern, an additional strategy for refractory non-hepatocellular patterns is needed.

DOI： 10.1007/s12072-021-10238-y

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: To investigate the clinical features of ears with dilatation of the endolymphatic space in the ampulla of the posterior semicircular canal on magnetic resonance imaging. STUDY DESIGN: Retrospective study. SETTING: A university hospital. METHODS: This study included 1,842 ears from 934 patients who underwent 3-T magnetic resonance imaging with gadolinium to investigate the presence of endolymphatic hydrops. Age, sex distribution, hearing thresholds on pure-tone audiometry, and vestibular symptoms were compared between cases of unilateral and bilateral dilatation of the endolymphatic space in the ampulla of the posterior semicircular canal. RESULTS: Forty-eight ears (17 men and 14 women; mean age 49.9 yrs) showed dilatation of the endolymphatic space in the ampulla of the posterior semicircular canal. Age and the rate of chronic sensorineural hearing loss were significantly higher in the unilateral group (14 ears) than in the bilateral group (34 ears). The average hearing thresholds and rates of vestibular symptoms reported did not differ between unilateral and bilateral cases, but some patients showed positional nystagmus. CONCLUSIONS: Dilatation of the endolymphatic space in the ampulla was observed selectively in the posterior semicircular canal, though its pathogenesis was not clear. Such dilatation is not usually accompanied by vestibular endolymphatic hydrops, and it may be a cause of vertigo and dizziness.

DOI： 10.1097/MAO.0000000000003073

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: To review the authors' surgical experience with radical temporal bone resection (TBR) with an emphasis on the classification of skull base osteotomy and transcranial tympanotomy (TCT) that is required for middle ear transection. METHODS: We reviewed the records of 25 patients who underwent radical TBR at our facilities between 2011 and 2020. RESULTS: The osteotomy line of radical TBR was divided into 3 segments: anterior (A), medial (M), and posterior (P). Each segment was further classified as follows: A1, through the glenoid fossa (1 patient); A2, in front of the glenoid fossa (23 patients); A3, through the greater wing of the sphenoid bone (1 patient); M1, through the middle ear (16 patients); M2, through the inner ear (9 patients); P1, through the mastoid (9 patients); and P2, through the posterior cranial fossa (16 patients). The M segment was significantly associated with operation time and intraoperative blood loss. In all patients with M1 osteotomy, TCT was performed; TCT was classified into superior and far posterior approaches. A superior approach was performed in all 16 patients, whereas the far posterior approach was performed in only 7 patients with both M1 and P2 osteotomy. CONCLUSIONS: Our newly proposed osteotomy classification of radical TBR is suitable for minute but clinically important adjustment of the osteotomy line. TCT is an indispensable technique for M1 osteotomy; our newly proposed classification expands our understanding of TCT and how to incorporate this technique into radical TBR.

DOI： 10.1016/j.wneu.2021.04.002

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Language：English   Publishing type：Research paper (scientific journal)  

Objective  Craniofacial resection (CFR) and temporal bone resection (TBR) on malignant head and neck tumors (MHNTs) invading skull base require accurate and precise determination of the tumor invasion. We investigated tumor skull base invasion patterns and surgical results in CFR and TBR cases. Methods  We performed either CFR or TBR for 75 selected patients with the possibility of en bloc resection over the period between 2011 and 2018. The medical charts of the selected patients were reviewed. Results  Primary tumor onset site (TOS) groups were: (1) nasal cavity/ethmoid sinus, 20 cases; (2) orbit, 10 cases; (3) maxillary sinus, 28 cases; and (4) external ear/temporomandibular joint, 17 cases. Grades for tumor invasion depth (TID) included: (I) extracranial invasion and skull base bone invasion; (II) extradural invasion; or (III) intradural invasion. Patients in groups 1 and 2 had a significantly higher frequency of grade II and III invasions than patients in groups 3 and 4. The main invasion site was nasal cavity superior wall and ethmoid sinus superior wall for group 1 tumors, orbit superior wall, and lateral skull base sphenoid bone for group 2 and 3 tumors, and lateral skull base temporal bone for group 4 tumors. Positive resection margins represented a significant negative prognostic factor. TID and TOS did not affect skull base margin status. Conclusion  Skull base invasion of MHNTs exhibits certain fixed patterns in sites susceptible to invasion based on the TOS. The frequencies of extradural and intradural invasions differed, indicating the importance for accurate preoperative tumor evaluation.

DOI： 10.1055/s-0039-3402034

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: Tracheostomy is an important surgical procedure for coronavirus disease-2019 (COVID-19) patients who underwent prolonged tracheal intubation. Surgical indication of tracheostomy is greatly affected by the general condition of the patient, comorbidity, prognosis, hospital resources, and staff experience. Thus, the optimal timing of tracheostomy remains controversial. METHODS: We reviewed our early experience with COVID-19 patients who underwent tracheostomy at one tertiary hospital in Japan from February to September 2020 and analyzed the timing of tracheostomy, operative results, and occupational infection in healthcare workers (HCWs). RESULTS: Of 16 patients received tracheal intubation with confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, five patients (31%) received surgical tracheostomy in our hospital. The average consultation time for surgical tracheostomy was 7.4 days (range, 6 - 9 days) from the COVID-19 team to the otolaryngologist. The duration from tracheal intubation to tracheostomy ranged from 14 to 27 days (average, 20 days). The average time of tracheostomy was 27 min (range, 17 - 39 min), and post-wound bleeding occurred in only one patient. No significant differences in hemoglobin (Hb) levels were found between the pre- and postoperative periods (mean: 10.2 vs. 10.2 g/dl, p = 0.93). Similarly, no difference was found in white blood cell (WBC) count (mean: 12,200 vs. 9,900 cells /µl, p = 0.25). After the tracheostomy, there was no occupational infection among the HCWs who assisted the tracheostomy patients during the perioperative period. CONCLUSION: We proposed a modified weaning protocol and surgical indications of tracheostomy for COVID-19 patients and recommend that an optimal timing for tracheostomy in COVID-19 patients of 2 - 3 weeks after tracheal intubation, from our early experiences in Japan. An experienced multi-disciplinary tracheostomy team is essential to perform a safe tracheostomy in patients with COVID-19 and to minimize the risk of occupational infection in HCWs.

DOI： 10.1016/j.anl.2020.11.004

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1097/AS9.0000000000000059

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The presence of lymph node (LN) metastases is an essential prognostic indicator in patients with head and neck squamous cell carcinoma (HNSCC). This study assessed photoacoustic molecular imaging (PAMI) of the anti-epidermal growth factor receptor (EGFR) antibody (panitumumab) conjugated to a near-infrared fluorescent dye, IRDye800CW (panitumumab-IRDye800CW; pan800) for the identification of occult metastatic LNs in patients with HNSCC (n=7). After in vitro photoacoustic imaging characterization of pan800, PAMI was performed on excised neck specimens of patients infused with pan800 prior to surgery. Freshly obtained neck specimens were imaged with three-dimensional, multiwavelength spectroscopic PAMI (680, 686, 740, 800, 860, 924, and 958 nm wavelengths). Harvested LNs were then imaged with a closed-field near-infrared fluorescence imager and histologically examined by the pathologist to determine their metastatic status. A total of 53 LNs with a maximum diameter of 10 mm were analyzed with photoacoustic and fluorescence imaging, of which four were determined to be metastatic on final histopathology. Photoacoustic signal in the LNs corresponding to accumulated pan800 were spectrally unmixed using a linear least square error classification algorithm. Metastatic LNs had a five-fold higher average thresholded photoacoustic signal intensity corresponding to pan800 compared to benign LNs (2.50 ± 1.09 a.u. vs. 0.53 ± 0.32 a.u., p<0.001). Fluorescence imaging showed that metastatic LNs had a two-fold increase in fluorescence signal compared to benign LNs ex vivo (p<0.01, 0.068 ± 0.027 a.u. vs. 0.035 ± 0.018 a.u.) Moreover, the ratio of the average of the highest 10% photoacoustic signal intensity over total average, representative of degree of heterogeneity of pan800 signal in LNs, showed a significant difference between metastatic LNs vs. benign LNs (11.6 ± 13.4 vs. 1.8 ± 0.7, p<0.01) and an area under the receiver operating characteristic (ROC) curve of 0.96 (95% CI; 0.91-1.00). The data indicate that PAMI of IRDye800-labeled tumor-specific antibody may have the potential to identify occult LN metastasis perioperatively in HNSCC patients.

DOI： 10.2967/jnumed.120.245241

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Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: This study evaluated the effect of formalin fixation for near-infrared (NIR) fluorescence imaging of an antibody-dye complex (panitumumab-IRDye800CW) that was intravenously administered to patients with head and neck squamous cell carcinoma (HNSCC) scheduled to undergo surgery of curative intent. PROCEDURES: HNSCC patients were infused with 25 or 50 mg of panitumumab-IRDye800CW followed by surgery 1-5 days later. Following resection, primary tumor specimens were imaged in a closed-field fluorescence imaging device, before and after formalin fixation. The fluorescence images of formalin-fixed specimens were compared with images prior to formalin fixation. Regions of interest were drawn on the primary tumor and on the adjacent normal tissue on the fluorescence images. The mean fluorescence intensity (MFI) and tumor-to-background ratios (TBRs) of the fresh and formalin-fixed tissues were compared. RESULTS: Of the 30 enrolled patients, 20 tissue specimens were eligible for this study. Formalin fixation led to an average of 10 % shrinkage in tumor specimen size (p < 0.0001). Tumor MFI in formalin-fixed specimens was on average 10.9 % lower than that in the fresh specimens (p = 0.0002). However, no statistical difference was found between the TBRs of the fresh specimens and those of the formalin-fixed specimens (p = 0.85). CONCLUSIONS: Despite the 11 % decrease in MFI between fresh and formalin-fixed tissue specimens, the relative difference between tumor and normal tissue as measured in TBR remained unchanged. This data suggests that evaluation of formalin-fixed tissue for assessing the accuracy of fluorescence-guided surgery approaches could provide a valid, yet more flexible, alternative to fresh tissue analysis. TRIAL REGISTRATION: NCT02415881.

DOI： 10.1007/s11307-020-01553-1

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The aim of this study is to establish a unilateral tongue atrophy model by cutting the hypoglossal nerve and to evaluate the safety and feasibility of a fat injection of adipose-derived stem cells (ADSCs) to restore swallowing function. METHODS: A total of 12 rabbits were randomized to three groups; the ADSCs+fat group (n=4), the fat group (n=4) and the control group (n=4). All rabbits were treated with denervation of the left hypoglossal nerve and their conditions including body weight and food intake were checked during follow-up periods (8 weeks). At 4 weeks after the transection of the nerve, rabbits received the injection therapy into the denervated side of the tongue with 1.0mL fat tissue premixed with 0.5mL ADSCs in the ADSCs+fat group, 1.0mL fat tissue premixed with 0.5mL PBS in the fat group and 1.5mL PBS in the control group. Rabbits were euthanized 8 weeks post-treatment and resected tongues were collected, formalin-fixed and paraffin embedded. To evaluate the change of the intrinsic muscles of the tongue, muscle fibers around the treatment area was analyzed by evaluating 5 consecutive hematoxylin-eosin slides per rabbit. RESULTS: Food intake did not decrease upon nerve denervation, and none of the rabbits displayed adverse effect such as aspiration, surgical wound dehiscence or infection. No significant body weight changes were found between the three groups at 4 and 8 weeks after nerve transection (p>0.05). In the control group, the denervated side of tongue had significantly smaller muscle fiber areas and diameters compared to the non-denervated side (p<0.05). The ADSCs+fat group demonstrated a larger area of inferior longitudinal muscle fibers compared to the control and the fat groups (582±312µm2 vs. 405±220µm2 and 413±226µm2; p<0.05). A significant thicker lesser diameter of inferior longitudinal muscle fibers was found in the ADSCs+fat group compared to the control and the fat groups (24±8µm vs. 20±6µm and 20±7µm; p<0.05). CONCLUSION: The rabbit tongue atrophy model was found suitable for the assessment of muscle change after nerve transection. Fat injection therapy with ADSCs demonstrated great potential to prevent the muscle atrophy after denervation and to promote the muscle regeneration around the injection area.

DOI： 10.1016/j.anl.2020.08.003

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Language：English   Publishing type：Research paper (scientific journal)  

In the head and neck region, preoperative evaluation of the free flap volume is challenging. The current study validated preoperative three-dimensional (3D) virtual surgical simulation for soft tissue reconstruction by assessing flap volume and evaluated fat and muscle volume changes at follow-up in 13 head and neck cancer patients undergoing anterolateral craniofacial resection. Patients received 3D virtual surgical simulation, and the volume of the planned defects was estimated by surgical simulation. Following en bloc resection of the tumor, the defect in the skull base was covered using a rectus abdominis myocutaneous flap. Following surgery, computed tomography scans were acquired at day 1 and at 6 and 12 months. Virtual planned defect was on average 227 ml (range, 154–315) and was 10% smaller than the actual flap volume in patients without skin involvement of the tumor. Between day 1 and 12 months post-surgery, the volume of fat and muscle tissue in the free flap dropped by 9% and 58%, respectively. Our results indicate that 3D virtual surgical simulation provides essential information in determining the accurate volume of the required free flap for surgical defect repair and may thus help improve surgical planning and functional and esthetic outcome.

DOI： 10.1016/j.ijom.2020.07.025

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The rate of positive margins in head and neck cancers has remained stagnant over the past three decades and is consistently associated with poor overall survival. This suggests that significant improvements must be made intraoperatively to ensure negative margins. We discuss the important role of fluorescence imaging to guide surgical oncology in head and neck cancer. This review includes a general overview of the principles of fluorescence, available fluorophores used for fluorescence imaging, and specific clinical applications of fluorescence-guided surgery, as well as challenges and future directions in head and neck surgical oncology. Laryngoscope, 131:529-534, 2021.

DOI： 10.1002/lary.28822

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PURPOSE: The development of molecularly targeted tracers is likely to improve the accuracy of diagnostic, screening, and therapeutic tools. Despite the many therapeutic antibodies that are FDA-approved with known toxicity, only a limited number of antibody-dye conjugates have been introduced to the clinic. Thorough evaluation of the safety, stability, and pharmacokinetics of antibody conjugates in the clinical setting compared with their parental components could accelerate the clinical approval of antibodies as agents for molecular imaging. Here we investigate the safety and stability of a near-infrared fluorescent dye (IRDye800CW) conjugated panitumumab, an approved therapeutic antibody, and report on the product stability, pharmacokinetics, adverse events, and QTc interval changes in patients. PROCEDURES: Panitumumab-IRDye800CW was made under good manufacturing practice (GMP) conditions in a single batch on March 26, 2014, and then evaluated over 4.5 years at 0, 3, and 6 months, and then at 6-month intervals thereafter. We conducted early phase trials in head and neck, lung, pancreas, and brain cancers with panitumumab-IRDye800CW. Eighty-one patients scheduled to undergo standard-of-care surgery were infused with doses between 0.06 to 2.83 mg/kg of antibody. Patient ECGs, blood samples, and adverse events were collected over 30-day post-infusion for analysis. RESULTS: Eighty-one patients underwent infusion of the study drug at a range of doses. Six patients (7.4 %) experienced an adverse event that was considered potentially related to the drug. The most common event was a prolonged QTc interval which occurred in three patients (3.7 %). Panitumumab-IRDye800CW had two OOS results at 42 and 54 months while meeting all other stability testing criteria. CONCLUSIONS: Panitumumab-IRDye800CW was safe and stable to administer over a 54-month window with a low rate of adverse events (7.4 %) which is consistent with the rate associated with panitumumab alone. This data supports re-purposing therapeutic antibodies as diagnostic imaging agents with limited preclinical toxicology studies.

DOI： 10.1007/s11307-020-01536-2

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BACKGROUND: High signals in the inner ear of idiopathic sudden sensorineural hearing loss (ISSNHL) on magnetic resonance imaging (MRI) have been reported, but no quantitative evaluation has yet been done. OBJECTIVES: To evaluate hearing outcomes and cochlear signal intensities on 3-T heavily T2-weighted three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging (hT2W-3D-FLAIR) in patients with ISSNHL. MATERIALS AND METHODS: Twenty-nine patients with ISSNHL were included. Patients underwent hT2W-3D-FLAIR with intravenous gadolinium injection and pure tone audiometry (PTA) at initial visits and 3 months later. Signal intensity ratios (SIRs) were measured in the basal or apical-middle turns of the affected cochlea. A statistical analysis of relationships between SIRs and the average hearing levels (HLs) at low (125, 250, and 500 Hz) and high (2, 4, and 8 kHz) tone frequencies was performed. RESULTS: Hearing improvements at high-tone frequencies in ears with HLs ≥60 dB were significantly worse in those with high SIRs at the basal turns on pre-contrast images. Similarly, hearing improvements at low-tone frequencies in ears with HLs ≥60 dB were significantly worse in those with high SIRs at the apical-middle turns on post-contrast images. CONCLUSIONS AND SIGNIFICANCE: High SIRs on hT2W-3D-FLAIR indicate cochlear disturbances with severe ISSNHL and could provide lesion-specific prognostic information.

DOI： 10.1080/00016489.2020.1827159

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Rationale: First-line therapy for high-grade gliomas (HGGs) includes maximal safe surgical resection. The extent of resection predicts overall survival, but current neuroimaging approaches lack tumor specificity. The epidermal growth factor receptor (EGFR) is a highly expressed HGG biomarker. We evaluated the safety and feasibility of an anti-EGFR antibody, panitumuab-IRDye800, at subtherapeutic doses as an imaging agent for HGG. Methods: Eleven patients with contrast-enhancing HGGs were systemically infused with panitumumab-IRDye800 at a low (50 mg) or high (100 mg) dose 1-5 days before surgery. Near-infrared fluorescence imaging was performed intraoperatively and ex vivo, to identify the optimal tumor-to-background ratio by comparing mean fluorescence intensities of tumor and histologically uninvolved tissue. Fluorescence was correlated with preoperative T1 contrast, tumor size, EGFR expression and other biomarkers. Results: No adverse events were attributed to panitumumab-IRDye800. Tumor fragments as small as 5 mg could be detected ex vivo and detection threshold was dose dependent. In tissue sections, panitumumab-IRDye800 was highly sensitive (95%) and specific (96%) for pathology confirmed tumor containing tissue. Cellular delivery of panitumumab-IRDye800 was correlated to EGFR overexpression and compromised blood-brain barrier in HGG, while normal brain tissue showed minimal fluorescence. Intraoperative fluorescence improved optical contrast in tumor tissue within and beyond the T1 contrast-enhancing margin, with contrast-to-noise ratios of 9.5 ± 2.1 and 3.6 ± 1.1, respectively. Conclusions: Panitumumab-IRDye800 provided excellent tumor contrast and was safe at both doses. Smaller fragments of tumor could be detected at the 100 mg dose and thus more suitable for intraoperative imaging.

DOI： 10.7150/thno.60582

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Rationale: Sentinel lymph node biopsy (SLNB) is a well-established minimally invasive staging procedure that maps the spread of tumour metastases from their primary site to the regional lymphatics. Currently, the procedure requires the local peri-tumoural injection of radiolabelled and/or optical agents, and is therefore operator dependent, disruptive to surgical workflow and restricted largely to a small subset of malignancies that can be readily accessed externally for local tracer injection. The present study set out to determine whether intravenous (IV) infusion of a tumor-targeted tracer could identify sentinel and metastatic lymph nodes (LNs) in order to overcome these limitations. Methods: We examined 27 patients with oral squamous cell carcinoma (OSCC), 18 of whom were clinically node negative (cN0). Patients were infused intravenously with 50mg of Panitumumab-IRDye800CW prior to surgical resection of their primary tumour with neck dissection and/or SLNB. Lymphadenectomy specimens underwent fluorescence molecular imaging to evaluate tracer distribution to LNs. Results: A total of 960 LNs were analysed, of which 34 (3.5%) contained metastatic disease. Panitumumab-IRDye800CW preferentially localized to metastatic and sentinel LNs as evidenced by a higher fluorescent signal relative to other lymph nodes. The median MFI of metastatic LNs was significantly higher than the median MFI of benign LNs (0.06 versus 0.02, p < 0.05). Furthermore, selecting the highest five fluorescence intensity LNs from individual specimens resulted in 100% sensitivity, 85.8% specificity and 100% negative predictive value (NPV) for the detection of occult metastases and 100% accuracy for clinically staging the neck. In the cN+ cohort, assessment of the highest 5 fluorescence LNs per patient had 87.5% sensitivity, 93.2% specificity and 99.1% NPV for the detection of metastatic nodes. Conclusion: When intravenously infused, a tumour-targeted tracer localized to sentinel and metastatic lymph nodes. Further validation of an IV tumor-targeted tracer delivery approach for SLNB could dramatically change the practice of SLNB, allowing its application to other malignancies where the primary tumour is not accessible for local tracer injection.

DOI： 10.7150/thno.55389

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PubMed

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OBJECTIVE: Endoscopic resection of sinonasal squamous cell carcinoma has become the standard of care, but challenges remain in obtaining clear resection margins. The current study evaluated the feasibility of endoscopic fluorescence-guided surgery (FGS) to improve surgical resection in a human sinus surgical model. METHODS: A fluorescence endoscope optimized for near-infrared (NIR) fluorescence detection was evaluated in a phantom study. Various endoscope diameters (4 and 10 mm) and viewing angles (0, 30, and 45 degrees) were evaluated to determine the sensitivity of the system for IRDye800CW detection at various working distances (1-5 cm). Endoscopic FGS was then validated in a three-dimensional human sinus surgical model to which squamous cell tumors derived from mice were inserted. Mice had received intravenous panitumumab-IRDye800CW and upon fluorescence-guided tumor resection, mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were calculated in in situ and ex vivo settings. RESULTS: A significantly higher fluorescence intensity was found when using the 10-mm diameter endoscope compared to the 4mm diameter endoscope (P < .001). No significant difference in MFI was found among the viewing angles of the 4-mm diameter endoscope. Using the human sinus model, the highest MFI and TBR were obtained at a 1-cm working distance compared to longer working distances. CONCLUSION: We demonstrate that clinically acceptable TBRs were obtained with several working distances to discriminate tumor tissue from adjacent normal tissue in a human sinus model, and that endoscopic FGS may have great potential in identifying residual tumor tissue regions during surgery. Laryngoscope, 2019.

DOI： 10.1002/lary.28483

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Poor tissue penetration remains a major challenge for antibody-based therapeutics of solid tumors, but proper dosing can improve the tissue penetration and thus therapeutic efficacy of these biologics. Due to dose-limiting toxicity of the small molecule payload, antibody-drug conjugates (ADCs) are administered at a much lower dose than their parent antibodies, which further reduces tissue penetration. We conducted an early-phase clinical trial (NCT02415881) and previously reported the safety of an antibody-dye conjugate (panitumumab-IRDye800CW) as primary outcome. Here, we report a retrospective exploratory analysis of the trial to evaluate whether co-administration of an unconjugated antibody could improve the intratumoral distribution of the antibody-dye conjugate in patients. By measuring the multiscale distribution of the antibody-dye conjugate, this study demonstrates improved microscopic antibody distribution without increasing uptake (toxicity) in healthy tissue when co-administered with the parent antibody, supporting further clinical investigation of the co-administration dosing strategy to improve the tumor penetration of ADCs.

DOI： 10.1038/s41467-020-19498-y

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BACKGROUND: High signal intensity in the endolymphatic duct (ED) is occasionally observed on magnetic resonance imaging (MRI) in ears that have otological disorders. OBJECTIVE: The signal intensity (SI) in the ED on post-contrast MRI was investigated in subjects with various otological disorders, and the meaning of high SI in the ED was evaluated. MATERIAL AND METHODS: 392 patients with otological disorders and 21 controls without otological symptoms underwent 3 T MRI. The SIs of the ED and the cerebellum were measured, the SI ratio (SIR) was calculated, and ears with SIR ≥4 were identified. RESULTS: A high SIR was identified in the ED of 3.7% of ears affected by definite Meniere's disease (dMD), 100% of ears affected by large vestibular aqueduct syndrome (LVAS), and 7.1% of ears with no otological symptoms. On the whole, a significant relationship was found between the existence of vestibular or cochlear EH and the SIR in the ED. CONCLUSION: The MRI finding of high SI in the ED may indicate the mechanism of inner ear disturbances in ears with otological disorders, especially in those with LVAS, and it may suggest an underlying disorder in some ears in which otological symptoms are not apparent.

DOI： 10.1080/00016489.2020.1781927

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Objective  This study was aimed to evaluate health-related quality of life in patients undergoing anterolateral craniofacial resection (AL-CFR) with orbital exenteration (OE) for malignant skull base tumors and to investigate the effects of early psychiatric intervention. Design  Present study is a prospective, observational study. Setting  The study took place at the hospital department. Participants  Twenty-six consecutive patients were selected who underwent AL-CFR with OE at our hospital between 2005 and 2015. Main Outcome Measures  Health-related quality of life was assessed preoperatively and 3, 6, 12, and 24 months after surgery using the Hospital Anxiety and Depression Scale (HADS) and medical outcomes study 8-items Short Form health survey (SF-8). In all cases, psychiatric intervention was organized by the consultation liaison psychiatry team preoperatively and postoperatively. Results  Ten (38.0%) of the 26 patients died and 16 (62.0%) were alive and disease-free at the end of the study. The 3-year overall and disease-free survival rates were 64.9% and 53.3%, respectively. Twenty-one patients (80.8%) developed psychiatric complications after surgery and needed treatment with psychotropic medication. Before surgery, 28% of patients had HADS scores ≥8 for anxiety and 20% had scores ≥8 for depression. Seven of the eight items in the SF-8 were significantly lower than those for the general Japanese population. However, scores for all the SF-8 items gradually improved during postoperative follow-up, reaching approximately 50 points, which is the national standard value, at 2 years after surgery. Conclusions  Craniofacial resection with OE was feasible and well tolerated in patients with malignant skull base tumors who received early psychiatric intervention to decrease the considerable psychological impact of this procedure.

DOI： 10.1055/s-0039-1694010

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本耳鼻咽喉科学会  

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Complete surgical resection remains the primary curative option for pancreatic ductal adenocarcinoma, with positive margins in 30-70% of patients. In this study, we aimed to evaluate the use of intraoperative tumour-specific imaging to enhance a surgeon's ability to detect visually occult cancer in real time. METHODS: In this single-centre, open-label, single-arm study, done in the USA, we enrolled patients who had clinically suspicious or biopsy-confirmed pancreatic ductal adenocarcinomas and were scheduled for curative surgery. Eligible patients were 19 years of age or older with a life expectancy of more than 12 weeks and a Karnofsky performance status of at least 70% or an Eastern Cooperative Oncology Group or Zubrod level of one or lower, who were scheduled to undergo curative surgery. Patients were sequentially enrolled into each dosing group and 2-5 days before surgery, patients were intravenously infused with 100 mg of unlabelled panitumumab followed by 25 mg, 50 mg, or 75 mg of the near-infrared fluorescently labelled antibody (panitumumab-IRDye800CW). The primary endpoint was to determine the optimal dose of panitumumab-IRDye800CW in identifying pancreatic ductal adenocarcinomas as measured by tumour-to-background ratio in all patients. The tumour-to-background ratio was defined as the fluorescence signal of the tumour divided by the fluorescence signal of the surrounding healthy tissue. The dose-finding part of this study has been completed. This study is registered with ClinicalTrials.gov, NCT03384238. FINDINGS: Between April, 2018, and July, 2019, 16 patients were screened for enrolment onto the study. Of the 16 screened patients, two (12%) patients withdrew from the study and three (19%) were not eligible; 11 (69%) patients completed the trial, all of whom were clinically diagnosed with pancreatic ductal adenocarcinoma. The mean tumour-to-background ratio of primary tumours was 3·0 (SD 0·5) in the 25 mg group, 4·0 (SD 0·6) in the 50 mg group, and 3·7 (SD 0·4) in the 75 mg group; the optimal dose was identified as 50 mg. Intraoperatively, near-infrared fluorescence imaging provided enhanced visualisation of the primary tumours, metastatic lymph nodes, and small (<2 mm) peritoneal metastasis. Intravenous administration of panitumumab-IRDye800CW at the doses of 25 mg, 50 mg, and 75 mg did not result in any grade 3 or higher adverse events. There were no serious adverse events attributed to panitumumab-IRDye800CW, although four possibly related adverse events (grade 1 and 2) were reported in four patients. INTERPRETATION: To our knowledge, this study presents the first clinical use of panitumumab-IRDye800CW for detecting pancreatic ductal adenocarcinomas and shows that panitumumab-IRDye800CW is safe and feasible to use during pancreatic cancer surgery. Tumour-specific intraoperative imaging might have added value for treatment of patients with pancreatic ductal adenocarcinomas through improved patient selection and enhanced visualisation of surgical margins, metastatic lymph nodes, and distant metastasis. FUNDING: National Institutes of Health and the Netherlands Organization for Scientific Research.

DOI： 10.1016/S2468-1253(20)30088-1

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.rmed.2020.106024

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PubMed

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本頭頸部癌学会  

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: The efficacy of antibody-based therapeutics depends on successful drug delivery into solid tumors; therefore, there is a clinical need to measure intratumoral antibody distribution. This study aims to develop and validate an imaging and computation platform to directly quantify and predict antibody delivery into human head and neck cancers in a clinical study. EXPERIMENTAL DESIGN: Twenty-four patients received systemic infusion of a near-infrared fluorescence-labeled therapeutic antibody followed by surgical tumor resection. A computational platform was developed to quantify the extent of heterogeneity of intratumoral antibody distribution. Both univariate and multivariate regression analyses were used to select the most predictive tumor biological factors for antibody delivery. Quantitative image features from the pretreatment MRI were extracted and correlated with fluorescence imaging of antibody delivery. RESULTS: This study not only confirmed heterogeneous intratumoral antibody distribution in-line with many preclinical reports, but also quantified the extent of interpatient, intertumor, and intratumor heterogeneity of antibody delivery. This study demonstrated the strong predictive value of tumor size for intratumoral antibody accumulation and its significant impact on antibody distribution in both primary tumor and lymph node metastasis. Furthermore, this study established the feasibility of using contrast-enhanced MRI to predict antibody delivery. CONCLUSIONS: This study provides a clinically translatable platform to measure antibody delivery into solid tumors and yields valuable insight into clinically relevant antibody tumor penetration, with implications in the selection of patients amenable to antibody therapy and the design of more effective dosing strategies.

DOI： 10.1158/1078-0432.CCR-19-3717

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OBJECTIVE: The ongoing pandemic coronavirus disease-2019 (COVID-19) infection causes severe respiratory dysfunction and has become an emergent issue for worldwide healthcare. Since COVID-19 spreads through contact and droplet infection routes, careful attention to infection control and surgical management is important to prevent cross-contamination of patients and medical staff. Tracheostomy is an effective method to treat severe respiratory dysfunction with prolonged respiratory management and should be performed as a high-risk procedure METHOD: The anesthetic and surgical considerations in this case involved difficult goals of the patient safety and the management of infection among health care workers. Our surgical procedure was developed based on the previous experiences of severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV). RESULTS: We described the management procedures for tracheostomy in a patient with COVID-19, including the anesthesia preparation, surgical procedures, required medical supplies (a N95 mask or powered air purifying respirator, goggles, face shield, cap, double gloves, and a water-resistant disposable gown), and appropriate consultation with an infection prevention team. CONCLUSION: Appropriate contact, airborne precautions, and sufficient use of muscle relaxants are essential for performing tracheostomy in a patient with COVID-19.

DOI： 10.1016/j.anl.2020.04.002

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OBJECTIVE: Basic surgical skills such as knot-tying and suturing are important for all otolaryngologists, regardless of subspecialty. The present study was undertaken in order to assess basic surgical techniques such as knot-tying and suturing required for novice otolaryngology residents with taking the variety of subspecialties into consideration, and evaluate the impact of a proficiency-based training curriculum based on these techniques. METHODS: A prospective study was performed for developing of proficiency-based knot-tying and suturing curriculum for otolaryngology residents in the third post-graduate year (PGY-3). The proficiency-based training curriculum was developed based on the tasks selected by RAND/UCLA method with expert panel, which is an iterative and anonymous survey used to establish consensus among participants. Expert panelists were selected from various divisions to reflect variety of their subspecialties. PGY-3 residents trained with the developed curriculum that included proctored pre-test, self-training to proficiency, and proctored post-test. Visual analogue scale (VAS) of trainees' overall competence in the operating room was self-assessed by each resident, before and after completing the training curriculum. RESULTS: Nine PGY-3 residents were enrolled as trainees. Eleven experts chosen as panelists had various subspecialty, including 2 from otology, 2 from rhinology, 2 from laryngology, 2 from head and neck surgery, and 3 from general otolaryngology. Seven tasks were selected from RAND/UCLA method and used to develop the curriculum. Trainee scores at pre-test were significantly lower than expert scores for all 7 tasks (p < 0.01) and each coefficient of variation of trainee score was larger than that of expert score (p < 0.05), supporting construct validity. The mean of composite scores between pre-test and post-test had statistical significance (68.6 ± 11.6 vs 95.9 ± 3.6, p < 0.01), documenting substantial improvement after training. Self-assessment VAS was also improved pre- to post-training (1.2 ± 0.9 vs 4.5 ± 1.4, p < 0.01). A follow-up questionnaire showed that trainees felt the educational curriculum to be beneficial. CONCLUSION: In the present study, seven basic technical skills were selected using the RAND/UCLA method and used to create a proficiency-based training curriculum. Our results indicate that this curriculum significantly improves proficiency of basic surgical skills of junior otolaryngology residents.

DOI： 10.1016/j.anl.2019.11.005

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: To identify the optimal dosing strategy for fluorescence-guided surgery in patients with head and neck squamous cell carcinoma, we conducted a dose-ranging study evaluating the anti-epidermal growth factor receptor (EGFR) therapeutic antibody, panitumumab, that was fluorescently labeled with the near-infrared dye IRDye800CW. PROCEDURES: Patients (n = 24) received either 0.5 or 1.0 mg/kg panitumumab-IRDye800CW in the weight-based dosing group or 25 or 50 mg panitumumab-IRDye800CW in the fixed dosing group. Following surgery, whole primary specimens were imaged in a closed-field device and the mean fluorescence intensity (MFI) and tumor-to-background ratio (TBR) were assessed. Clinical variables, including dose, time of infusion-to-surgery, age, unlabeled dose, gender, primary tumor site, and tumor size, were analyzed to evaluate the factors affecting the fluorescence intensity in order to identify the optimal dose for intraoperative fluorescence imaging. RESULTS: A total of 24 primary tumor specimens were imaged and analyzed in this study. Although no correlations between TBR and dose of panitumumab-IRDye800CW were found, there were moderate-strong correlations between the primary tumor MFI and panitumumab-IRDye800CW dose for fixed dose (mg) (R2 = 0.42) and for dose/weight (mg/kg) (R2 = 0.54). Results indicated that the optimal MFI was at approximately 50 mg for fixed dose and 0.75 mg/kg for dose/weight. No significant differences were found for the primary tumor MFI and TBRs between the weight-based dosing and the fixed dosing groups. MFIs significantly increased when the infusion-to-surgery window was reduced to within 2 days (vs. 3 days or more, p < 0.05). CONCLUSIONS: Antibody-based imaging for surgical resection is under investigation in multiple clinical trials. Our data suggests that a fixed dose of 50 mg is an appropriate diagnostic dose for successful surgical fluorescence imaging.

DOI： 10.1007/s11307-019-01358-x

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Objective: Complete surgical resection is the standard of care for treatment of oral cancer although the positive margin rate remains 15-30%. Tissue sampling from the resected specimen and from the wound bed for frozen section analysis (FSA) remains the mainstay for intraoperative margin assessment but is subject to sampling error and can require the processing of multiple samples. We sought to understand if an ex vivo imaging strategy using a tumor-targeted fluorescently labeled antibody could accurately identify the closest peripheral margin on the mucosal surface of resected tumor specimen, so that this "sentinel margin" could be used to guide pathological sampling. Materials and Methods: Twenty-nine patients with oral squamous cell carcinoma scheduled for surgical resection were consented for the study and received systemic administration of a tumor-targeted fluorescently labeled antibody (Panitumumab IRDye800CW). After surgical resection, the tumor specimen was imaged using a closed-field fluorescent imaging device. Relevant pathological data was available for five patients on retrospective review. For each of these five patients, two regions of highest fluorescence intensity at the peripheral margin and one region of lowest fluorescence intensity were identified, and results were correlated with histology to determine if the region of highest fluorescence intensity along the mucosal margin (i.e., the sentinel margin) was truly the closest margin. Results: Imaging acquisition of the mucosal surface of the specimen immediately after surgery took 30 s. In all of the specimens, the region of highest fluorescence at the specimen edge had a significantly smaller margin distance than other sampled regions. The average margin distance at the closest, "sentinel," margin was 3.2 mm compared to a margin distance of 8.0 mm at other regions (p < 0.0001). Conclusions: This proof-of-concept study suggests that, when combined with routine FSA, ex vivo fluorescent specimen imaging can be used to identify the closest surgical margin on the specimen. This approach may reduce sampling error of intraoperative evaluation, which should ultimately improve the ability of the surgeon to identify the sentinel margin. This rapid sentinel margin identification improves the surgeon's orientation to areas most likely to be positive in the surgical wound bed and may expedite pathology workflow.

DOI： 10.3389/fonc.2019.01476

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Despite the rapid growth of fluorescence imaging, accurate sampling of tissue sections remains challenging. Development of novel technologies to improve intraoperative assessment of tissue is needed. METHODS: A novel contact probe-based fluorescence dosimeter device, optimized for IRDye800CW quantification, was developed. After evaluation of the device in a phantom setup, its clinical value was defined ex vivo in patients with head and neck squamous cell carcinoma who received panitumumab-IRDye800CW. RESULTS: Ten patients were enrolled with a total of 216 data points obtained. Final histopathology showed tumor in 119 spots and normal tissue in 97 spots. Fluorescence-to-excitation ratios in tumor tissue were more than three times higher than those in normal tissue. The area under the curve was 0.86 (95% CI: 0.81-0.91) for tumor detection. CONCLUSIONS: Fluorescence-guided tissue preselection using a fluorescence dosimeter could have substantial impact on tissue sampling for frozen section analysis and potentially reduce sampling errors.

DOI： 10.1002/hed.25964

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OBJECTIVE: The purpose of this study was to evaluate the usefulness of ultrasound (US) volume measurement of the cervical lymph nodes for diagnosing nodal metastasis in patients with head and neck cancer using a node-by-node comparison. METHODS: Thirty-four consecutive patients with head and neck cancer from one tertiary university hospital were prospectively enrolled from 2012 to 2017. Patients with histologically proven squamous cell primary tumors in the head and neck region scheduled to undergo a therapeutic neck dissection were eligible. For each patient, 1-4 target lymph nodes were selected from the planned neck dissection levels. Lymph nodes with thickness >20 mm or in a cluster were excluded. Node-by-node comparisons between the pre-operative US assessment, the post-operative actual measurements and histopathological results were performed for all target lymph nodes. Quantitative measurements, such as three diameters, ratios of the three diameters and volume were analyzed in this study. Lymph node volume was calculated using the ellipsoid formula. RESULTS: Patients comprised 28 men and 6 women with a mean age of 60.0 years (range, 29-80 years) at the time of surgery. In total, 67 target lymph nodes were analyzed in this study and the thickness ranged from 3.9 to 20.0 mm (mean 8.0 mm). There was a strong correlation between the US volume and post-operative actual volume (ρ = 0.87, p < 0.01). The US volume measured 2156 ± 2156 mm3 for the tumor positive nodes, which was significantly greater than the US volume of 512 ± 315 mm3 for tumor negative nodes (p < 0.01). Significant differences between tumor positive and tumor negative nodes were found in five variables (volume, thickness, major axis, minor axis and ratio of minor axis to thickness) for total lymph nodes. To identify predictors of lymph node metastasis, ROC curves of the US variables of target lymph nodes were compared, of which 4 variables were considered acceptable for predicting the lymph node metastasis: volume (AUC 0.86), thickness (AUC 0.86), major axis (AUC 0.79), and minor axis (AUC 0.79) for total lymph nodes. The optimal cut-off level for US volume in total lymph nodes was found to be 1242 mm3, whereby a 62% sensitivity and 98% specificity was reached (likelihood ratio: 25.2). CONCLUSION: Pre-operative ultrasonic volume measurement of the cervical lymph nodes was useful for early detection of cervical nodal metastasis in head and neck cancer.

DOI： 10.1016/j.anl.2019.02.003

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: In head and neck cancer, surgical resection using primarily visual and tactile feedback is considered the gold standard for solid tumors. Due to high numbers of tumor-involved surgical margins, which are directly correlated to poor clinical outcomes, intraoperative optical imaging trials have rapidly proliferated over the past 5 years. However, few studies report on intraoperative in situ imaging data that could support surgical resection. To demonstrate the clinical application of in situ surgical imaging, we report on the imaging data that are directly (ie in real-time) available to the surgeon. STUDY DESIGN: Fluorescence intensities and tumor-to-background ratios (TBRs) were determined from the intraoperative imaging data-the view as seen by the surgeon during tumor resection-of 20 patients, and correlated to patient and tumor characteristics including age, sex, tumor site, tumor size, histologic differentiation, and epidermal growth factor receptor (EGFR) expression. Furthermore, different lighting conditions in regard to surgical workflow were evaluated. RESULTS: Under these circumstances, intraoperative TBRs of the primary tumors averaged 2.2 ± 0.4 (range 1.5 to 2.9). Age, sex, tumor site, and tumor size did not have a significant effect on open-field intraoperative molecular imaging of the primary tumors (p > 0.05). In addition, variation in EGFR expression levels or the presence of ambient light did not seem to alter TBRs. CONCLUSIONS: We present the results of successful in situ intraoperative imaging of primary tumors alongside the optimal conditions with respect to both molecular image acquisition and surgical workflow. This study illuminates the potentials of open-field molecular imaging to assist the surgeon in achieving successful cancer removal.

DOI： 10.1016/j.jamcollsurg.2019.09.007

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Identification of lymph node (LN) metastasis is essential for staging of solid tumors, and as a result, surgeons focus on harvesting significant numbers of LNs during ablative procedures for pathological evaluation. Isolating those LNs most likely to harbor metastatic disease can allow for a more rigorous evaluation of fewer LNs. Here we evaluate the impact of a systemically injected, near-infrared fluorescently-labeled, tumor-targeting contrast agent, panitumumab-IRDye800CW, to facilitate the identification of metastatic LNs in the ex vivo setting for head and neck cancer patients. Molecular imaging demonstrates a significantly higher mean fluorescence signal in metastatic LNs compared to benign LNs in head and neck cancer patients undergoing an elective neck dissection. Molecular imaging to preselect at-risk LNs may thus allow a more rigorous examination of LNs and subsequently lead to improved prognostication than regular neck dissection.

DOI： 10.1038/s41467-019-13076-7

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVEAlthough sphenoidotomy is more commonly performed via the transnasal approach than via the transcranial approach, transcranial sphenoidotomy (TCS) remains indispensable for en bloc resection of locally advanced sinonasal malignant tumors (SNMTs) extending to the skull base. TCS also enables transsphenoidal transposition of the temporoparietal galeal flap (TPGF) to compensate for the lack of vascularized reconstructive tissue after endoscopic transnasal skull base surgery. The objective of this study was to review the authors' surgical experience using TCS with an emphasis on the surgical anatomy of the sphenoid sinus and on the purpose of TCS. Relevant anatomy is further illustrated through cadaveric dissection and photo documentation.METHODSThe authors reviewed the records of 50 patients who underwent TCS at the Nagoya University Hospital, Fukushima Medical University Hospital, or Aichi Medical University Hospital over the course of 7 years (between January 2011 and November 2017). The authors also performed cadaveric dissection in 2 adult cadaveric skull base specimens.RESULTSOf the 50 patients included in this study, 44 underwent craniofacial resection (CFR) for en bloc resection of SNMTs involving the anterior and/or lateral skull base, and 6 underwent transsphenoidal transposition of the TPGF flap. The authors categorized the TCS procedures according to the portion of the sphenoid sinus wall involved (i.e., superior, lateral, and superolateral). Superior sphenoidotomy was used in patients requiring anterior CFR. Lateral sphenoidotomy was further divided into 2 subtypes, with type 1 procedures performed for the transsphenoidal transpositioning of the TPGF, and type 2 procedures used in patients requiring lateral CFR. Superolateral sphenoidotomy was used in anterolateral CFR.CONCLUSIONSTCS still represents a useful tool in the armamentarium of neurosurgeons treating central skull base lesions. The newly proposed surgical classification facilitates a profound understanding of TCS and how to incorporate this technique into clinical practice.

DOI： 10.3171/2018.6.JNS181013

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PubMed

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OBJECTIVE: High-grade dysplasia is associated with a risk of malignant transformation, and it is necessary to distinguish from normal epithelium or low-grade dysplasia, especially in the intraoperative setting. We hypothesize that an anti-epidermal growth factor receptor (EGFR) contrast agent can be used to differentiate high-grade dysplasia from low-grade dysplasia and normal epithelium. MATERIALS AND METHODS: Patients with biopsy proven head and neck squamous cell carcinoma (HNSCC) were enrolled in a clinical trial using systemically injected fluorescently labeled anti-EGFR antibody (panitumumab-IRDye800CW) (NCT02415881). Paraffin embedded tumor specimens from 11 patients were evaluated by fluorescence histopathology. Hematoxylin and eosin (H&E) slides were reviewed by a board-certified pathologist, and regions of invasive squamous cell carcinoma, high-grade dysplasia and low-grade dysplasia were delineated. EGFR expression was assessed for each patient by way of immunohistochemistry. RESULTS: 11 patients were included in the study with a total of 219 areas on tissue sections analyzed; 68 normal epithelium, 53 low-grade dysplasia, 48 high-grade dysplasia, and 50 malignant regions. The signal-to-background ratio (SBR) increased proportionally with increasing grade of dysplasia; normal epithelium (1.5 ± 0.1), low-grade dysplasia (1.8 ± 0.1), high-grade dysplasia: (2.3 ± 0.2). High-grade dysplasia had a significantly higher SBR when compared to normal or low-grade dysplasia (p < 0.05). Fluorescence histopathology positively correlated with EGFR expression by immunohistochemistry, which also increased proportionally with increasing degree of dysplasia. CONCLUSION: Molecular imaging with an anti-EGFR agent can successfully discriminate high-grade dysplastic lesions from low-grade dysplasia and normal epithelium.

DOI： 10.1016/j.oraloncology.2019.08.008

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Asthma often coexists with chronic rhinosinusitis (CRS). Recent studies revealed that sinus inflammation in asthmatic patients was related to eosinophilic inflammation. However, the relationship between the severity of CRS and four different sputum inflammatory phenotypes as defined by the proportion of eosinophils and neutrophils is unknown. The aim of this study was to examine the impact of the severity of CRS on lower airway and systemic inflammation in asthmatic patients. METHODS: We enrolled 57 adult asthmatic patients who underwent sinus computed tomography (CT). The severity of CRS was evaluated by the Lund-Mackay score (LMS). The induced sputum inflammatory phenotype was defined by eosinophils (≥/<2%) and neutrophils (≥/<60%). Peripheral blood mononuclear cells (PBMC) were collected to examine cytokine productions. RESULTS: The median LMS of subjects was 6 (interquartile range, 0-11.5). The sputum inflammatory cell phenotype was categorized as paucicellular (n = 14), neutrophilic (n = 11), eosinophilic (n = 20), or mixed (n = 12). LMS was positively correlated with the percentage of blood eosinophils, sputum eosinophils, and mean fluorescence intensity (MFI) of IL-5 on CD4+ T cells. In the severe CRS group (LMS, 12-24), the number of mixed cellular phenotypes was higher than that in the group without CRS (LMS, 0-4) and mild-to-moderate CRS group (LMS, 5-11). CONCLUSIONS: In asthmatic patients with severe CRS, the proportion of the mixed cellular inflammatory phenotype was increased as well as eosinophilic inflammation.

DOI： 10.1016/j.alit.2019.05.004

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

PURPOSE: Despite major advancements in surgical oncology, the positive margin rate for primary head and neck cancer resection remains around 15%-30%. In particular, the deep surface margin is the most challenging to adequately assess. Inadequate margins are directly correlated to poor survival, and as such, mitigation of these rates is critical to improve patient outcomes. We have developed an ex vivo imaging strategy that utilizes fluorescence intensity peaks (relative to background signal) of an injected anti-EGFR antibody conjugated to a fluorescent probe to locate potential close or positive margins on the deep surface of the resected tumor specimen. EXPERIMENTAL DESIGN: Twelve patients with head and neck cancer scheduled for surgery received systemic administration of a tumor-specific contrast-agent (panitumumab-IRDye800CW). After surgical resection, the tumor specimen was imaged using a fluorescence imager. The three highest fluorescence intensity-peaks on the deep surface of the specimen were isolated and correlated to histology to determine the margin distance at these regions. RESULTS: Relative fluorescence peak intensities identified the closest margin on the deep surface of the specimen within 2.5 minutes. The highest intensity peak consistently (100%) detected the closest margin to the tumor. The difference in tumor margin distance between the first and second highest fluorescence intensity peak averaged 2.1 ± 1.4 mm. The tumor-margin difference between the second and third highest peak averaged 1.6 ± 0.6 mm. CONCLUSIONS: Fluorescence intensity peaks can identify the region on the specimen where tumor is closest to specimen's edge on the deep surface. This technique could have broad applications in obtaining adequate margins in oncological surgery.

DOI： 10.1158/1078-0432.CCR-19-0319

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PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Although surgical resection has been the primary treatment modality of solid tumors for decades, surgeons still rely on visual cues and palpation to delineate healthy from cancerous tissue. This may contribute to the high rate (up to 30%) of positive margins in head and neck cancer resections. Margin status in these patients is the most important prognostic factor for overall survival. In addition, second primary lesions may be present at the time of surgery. Although often unnoticed by the medical team, these lesions can have significant survival ramifications. We hypothesize that real-time fluorescence imaging can enhance intraoperative decision making by aiding the surgeon in detecting close or positive margins and visualizing unanticipated regions of primary disease. The purpose of this study was to assess the clinical utility of real-time fluorescence imaging for intraoperative decision making. Methods: Head and neck cancer patients (n = 14) scheduled for curative resection were enrolled in a clinical trial evaluating panitumumab-IRDye800CW for surgical guidance (NCT02415881). Open-field fluorescence imaging was performed throughout the surgical procedure. The fluorescence signal was quantified as signal-to-background ratios to characterize the fluorescence contrast of regions of interest relative to background. Results: Fluorescence imaging was able to improve surgical decision making in 3 cases (21.4%): identification of a close margin (n = 1) and unanticipated regions of primary disease (n = 2). Conclusion: This study demonstrates the clinical applications of fluorescence imaging on intraoperative decision making. This information is required for designing phase III clinical trials using this technique. Furthermore, this study is the first to demonstrate this application for intraoperative decision making during resection of primary tumors.

DOI： 10.2967/jnumed.118.222810

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Language：English   Publishing type：Research paper (scientific journal)  

Majority of head and neck cancer (HNC) patients are male, and more than 85% of patients with HNC have the habit of smoking and drinking. Due to the specific demographic characteristics, HNC patients are anticipated to have specific coping styles, affecting psychological distress, survival, and quality of life. We explored the subscales of the Mental Adjustment to Cancer (MAC) Scale in male patients with HNC, and then examined the correlation between revised subscales of the MAC scale and anxiety/depression. Participants were 150 male inpatients with HNC, and their demographic and medical data were obtained. Coping style was assessed by MAC scale. Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale. Out of 40 items in the original MAC scale, 19 items were excluded by factor analysis, and the remaining 21 items were divided into three factors: Negative Adjustment, Positive Adjustment, and Abandonment. Negative and Positive Adjustments were similar to the copings of mixed gender patients with heterogeneous cancers, and Abandonment was a new subscale specific to male patients with HNC. This subscale had a weak positive correlation with anxiety and depression. Male HNC patients revealed a specific coping style of Abandonment, related with psychological distress. We believe that an understanding of the Abandonment coping style revealed in our study will improve the psychological support offered to male patients with HNC.

DOI： 10.18999/nagjms.81.2.249

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1016/j.jaci.2018.12.579

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OBJECTIVE: Surgical resection remains the primary treatment for the majority of solid tumors. Despite efforts to obtain wide margins, close or positive surgical margins (<5 mm) are found in 15-30% of head and neck cancer patients. Obtaining negative margins requires immediate, intraoperative feedback of margin status. To this end, we propose optical specimen mapping of resected tumor specimens immediately after removal. MATERIALS AND METHODS: A first-in-human pilot study was performed in patients (n = 8) after infusion of fluorescently labeled antibody, panitumumab-IRDye800 to allow surgical mapping of the tumor specimen. Patients underwent standard of care surgical resection for head and neck squamous cell carcinoma (HNSCC). Optical specimen mapping was performed on the primary tumor specimen and correlated with pathological findings after tissue processing. RESULTS: Optical mapping of the specimen had a 95% sensitivity and 89% specificity to detect cancer within 5 mm (n = 160) of the cut surface. To detect tumor within 2 mm of the specimen surface, the sensitivity of optical specimen mapping was 100%. The maximal observed penetration depth of panitumumab-IRDye800 through human tissue in our study was 6.3 mm. CONCLUSION: Optical specimen mapping is a highly sensitive and specific method for evaluation of margins within <5 mm of the tumor mass in HNSCC specimens. This technology has potentially broad applications for ensuring adequate tumor resection and negative margins in head and neck cancers.

DOI： 10.1016/j.oraloncology.2018.11.012

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES: The pathology of sudden sensorineural hearing loss, which is known as sudden deafness (SD), remains unknown. The purpose of this study was to investigate the association between mitochondrial uncoupling protein 2 (UCP2) polymorphism and SD risk. MATERIALS AND METHODS: We compared 83 patients suffering from SD and 2048 controls who participated in the Longitudinal Study of Aging at the National Institute for Longevity Sciences. Multiple logistic regression was used to calculate the odds ratios (ORs) for SD with a polymorphism of the UCP2 (rs660339) gene. RESULTS: Under the additive model of inheritance, UCP2 polymorphisms showed significant association with a SD risk. The OR was 1.468 (95% confidence interval, 1.056-2.040) with an adjustment for any past history, such as diabetes, dyslipidemia, or hypertension, and for age and sex. CONCLUSION: Our results imply that the UCP2 (rs660339) polymorphism has a significant association with the risk of developing SD.

DOI： 10.5152/iao.2018.5442

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Background: The recommended treatment strategies for early glottic carcinoma with intent of larynx preservation are
primarily radiotherapy. However, the outcomes of radiotherapy for bulky T1 or T2 glottic carcinoma are unsatisfactory.
We designed a protocol consisting of concurrent chemoradiotherapy using S-1 as the radiosensitizer. We have performed
this protocol in patients with favorable T2 lesions and demonstrated its efficacy and safety. In contrast, we have
treated non-bulky T1 glottic carcinomas with 2.25 Gy per fraction, for a total of 25-28 fractions, starting in 2011 to
improve efficacy and shorten the treatment period. Since this treatment strategy was implemented for T1 disease, no
local failure has occurred to date, and it appears to be almost as safe as radiotherapy using 2.0 Gy per fraction. With
the aim of improving the local control rate and shortening the treatment period primarily for favorable T2 disease, we
changed the dose of radiation in our protocol from 2.0 Gy to 2.25 Gy per fraction, for a total of 25 fractions (from 30
fractions). The present study aims to evaluate the efficacy and safety of this new protocol. Methods: This study will
be conducted as a clinical, prospective, single-armed, non-randomized trial. Patients are to receive S-1 (55.3 mg /m2
/day, once daily) and radiotherapy (2.25 Gy per fraction, for a total of 25 fractions). S-1 and radiotherapy are started
on the same day that radiotherapy is performed, 3-6 hours after oral administration of S-1. The primary study aim is
the 3-year local control rate. The secondary study aims are overall survival, voice-preservation survival, disease-free
survival, complete response rate, completion rate, and toxicity. Result and conclusion: This is the first single-center,
non-randomized, prospective study of concurrent chemoradiotherapy with S-1 and hypofractionated radiotherapy to
be conducted. The trial will evaluate the efficacy and safety of our protocol.

DOI： 10.22034/APJCP.2018.19.5.1195

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Advances in the diagnosis and treatment of patients with maxillary sinus carcinoma have improved patient prognosis. This study investigated changes in demographic and clinical characteristics, treatment methods, and outcomes of patients with maxillary sinus carcinomas during three different 10-year periods spanning 60 years at our university hospital. Of the 233 patients with maxillary sinus carcinomas managed at Nagoya University Hospital, 135 were treated between 1951 and 1960 (first period), 35 between 1981 and 1990 (second period), and 63 between 2003 and 2012 (third period). Patient age, sex, TN classifications, treatment methods, and survival rates were compared among patients treated during these time periods. Of the 135, 35, and 63 patients with maxillary sinus carcinomas treated during these time periods, 86 (63.7%), 21 (51.4%), and 48 (76.2%), respectively, were men; 14 (10.4%), six (17.1%), and 14 (22.2%), respectively, were aged ≥70 years; and 135 (100%), 28 (80.0%), and 43 (68.3%), respectively, were treated surgically. The 5-year overall survival rates in patients treated during the first, second, and third periods were 29.7%, 44.3%, and 57.5%, respectively. These findings indicated that advances in the diagnosis and treatment of patients with maxillary sinus carcinoma, including computed tomography and craniofacial resection, have contributed to improvements in patient survival rates.

DOI： 10.18999/nagjms.80.1.91

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Language：English   Publishing type：Research paper (scientific journal)  

Lingual node metastasis from early-stage squamous cell carcinoma of the tongue is uncommon and difficult to detect. We present a case of a lingual lymph node metastasis from an early tongue cancer. Sonography demonstrated a small nonpalpable lingual node on the floor of the mouth. The patient underwent complete surgical resection and had no evidence of recurrence 5 years later. © 2017 Wiley Periodicals, Inc. J Clin Ultrasound 46:69-72, 2018.

DOI： 10.1002/jcu.22486

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Publishing type：Research paper (scientific journal)  

© 2018 Society of Practical Otolaryngology. All rights reserved. An ectopic hamartomatous thymoma (EHT) is an extremely rare benign soft tumor most commonly occurring in the lower neck region, that can be difficult to differentiate (preoperatively) from malignant tumors. We report a case of EHT of the neck diagnosed in a 42-year-old man. The patient presented with a 10-year history of a tumor in the lower neck region that had rapidly increased in size over the previous 3 years. Fine-needle aspiration biopsy findings suggested lipoma. As the clinical findings and CT/MRI images indicated the possibility of a malignant tumor, an open biopsy was performed. The biopsy revealed EHT and resection of the tumor was performed. Although there were slight adhesions between the tumor and mediastinum, the tumor had not invaded the thymus or thyroid, and could be successfully resected. Histopathological examination of the tumor revealed the characteristic features of EHT, including spindle cells, epithelial cells, and fat tissue mixed. The postoperative course was uneventful, and there was no evidence of recurrence during the 18-month follow up period. When encountering lesions in the lower neck, it is important to consider EHT in the differential diagnosis.

DOI： 10.5631/jibirin.111.645

Scopus

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Objective: To perform a quantitative computed tomography (CT) assessment of short- and long-term outcomes of autologous fat injection augmentation in patients with unilateral vocal fold paralysis. Study Design: Retrospective case series. Methods: Twelve patients who had undergone autologous fat injection augmentation for unilateral vocal fold paralysis in our hospital between 2011 and 2015 were enrolled in this study. The autologous fat for injection was acquired from periumbilical subcutaneous tissue and was injected orally using a special-purpose laryngeal injection needle. To evaluate the injected fat at the follow-up assessments, CT was performed at several times after surgery in clinical practice. All thin-section CT images were transferred to a workstation, and the volume of the injected fat was calculated. Results: Patients comprised 6 men and 6 women with a mean age at the time of surgery of 62.9 years (range, 46-82 years). The actual injected fat volume was 1.1-2.5 ml (mean, 1.6 ml). In seven patients assessed by CT two days after surgery, the average residual rate of the injected fat was 63.9%. The mean residual rates of the injected fat were 30.0% at 3 months, 33.7% at 6 months, 29.2% at 12 months, and 32.0% at 24 months. Conclusions: Although the injected fat volume decreased within the first three months and the residual rate of the injected fat was 30.0% at three months after injection, the residual fat volume remained at the same level for 24 months after injection. Level of Evidence: 4.

DOI： 10.1002/lio2.125

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The purpose of this study was to evaluate the clinical outcomes of radiotherapy for patients with T1/T2 glottic carcinoma. Patients with T1/T2 glottic carcinoma histopathologically diagnosed with squamous cell carcinoma and treated at our hospital between 2007 and 2015 were analyzed retrospectively. Our strategy for T1/T2 glottic carcinoma was as follows: radiotherapy alone with 2.25 Gy per fraction to a total of 25-28 fractions for patients with non-bulky T1 glottic carcinoma; concurrent chemoradiotherapy with oral S-1 and radiotherapy with 2 Gy per fraction to a total of 30 fractions for patients with T1 bulky/T2 favorable glottic carcinoma; or chemoradiotherapy with high-dose cisplatin and radiotherapy with 2 Gy per fraction to a total of 35 fractions for T2 unfavorable glottic carcinoma. Forty-eight patients were eligible. The median follow-up period among surviving patients was 38 months (range, 11-107). The disease was T1a in 23%, T1b in 13%, and T2 in 65% of patients. The 3-year local control rate in all patients, T1a, T1b, and T2 was 96.7%, 100%, 100%, and 96.0%, respectively. Of the 46 patients, one with T2 glottic carcinoma developed recurrent disease at the primary site, and one with T2 glottic carcinoma had lymph node recurrences in the neck. Acute Grade 3 dermatitis occurred in 8 (17%) patients and late Grade 2 hypothyroidism occurred in 2 (4%) patients. This retrospective study shows that our optimized treatment strategy of radiotherapy depending on the stage of early glottic carcinoma is not only effective but also well-tolerated.

DOI： 10.18999/nagjms.79.3.331

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Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/hed.24653

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

DOI： 10.1002/hed.24653

Language：English   Publishing type：Research paper (scientific journal)   Publisher：Cambridge University Press  

Objectives: To verify the effectiveness and safety of the addition of adipose-derived regenerative cells to autologous fat injection therapy. Methods: Unilateral vocal fold paralysis models were made by cutting the right recurrent laryngeal nerve in two pigs. At day 30, 0.5 ml adipose-derived regenerative cells mixed with 1 ml autologous fat was injected into the right vocal fold of one pig, with the other receiving 0.5 ml Ringer's solution mixed with 1 ml autologous fat. At day 120, fibrescopy, laser Doppler flowmeter, computed tomography, vocal function evaluation and histological assessment were conducted. Results: Although histological assessment revealed atrophy of the thyroarytenoid muscle fibre in both pigs, there was remarkable hypertrophy of the thyroarytenoid muscle fibre in the area surrounding the adipose-derived regenerative cells injection site. Conclusion: The addition of a high concentration of adipose-derived regenerative cells to autologous fat injection therapy has the potential to improve the treatment outcome for unilateral vocal fold paralysis.

DOI： 10.1017/S0022215116008707

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PubMed

Language：English   Publishing type：Research paper (scientific journal)   Publisher：John Wiley and Sons Inc.  

Historically, total pharyngolaryngectomy with total esophagectomy has been the standard radical surgical treatment for synchronous cancer of the thoracoabdominal esophagus and pharyngolaryngeal region, and for cancer of the cervical esophagus that has invaded as far as the thoracic esophagus. Although definitive chemoradiotherapy that enables preservation of the larynx has often been the first choice of treatment for cancers involving the cervical esophagus, total pharyngolaryngectomy with total esophagectomy is required as a salvage therapy for cases involving failure of complete remission or locoregional recurrence after chemoradiotherapy. However, salvage esophageal surgery after definitive high-dose chemoradiotherapy is generally associated with high morbidity and mortality. The aim of this study was to examine the short-term outcome of salvage total pharyngolaryngectomy with total esophagectomy. From 2001 to 2014, nine patients underwent salvage total pharyngolaryngectomy with total esophagectomy at the Department of Gastroenterological Surgery, Nagoya University. The mortality and morbidity rates were high at 22% and 89%, respectively. Four patients (44%) developed tracheal necrosis, which in two patients eventually led to lethal hemorrhage. Salvage total pharyngolaryngectomy with total esophagectomy is an uncommon and highly demanding surgical procedure that should be carefully planned and conducted in selected centers of excellence. Measures must be taken to preserve the tracheal blood supply, thus avoiding fatal complications.

DOI： 10.1111/dote.12362

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Language：English   Publishing type：Research paper (scientific journal)  

BACKGROUND: Although we have seen tremendous advancement in microsurgery over the last 2 decades and free tissue transfer has become standard for head and neck reconstruction, surgeons still struggle to prevent postoperative complications. We examined the relationship between body mass index (BMI) and postoperative complications in patients undergoing rectus abdominis free flap transfer after anterolateral craniofacial resection. METHODS: This was a retrospective review of reconstructive surgery using rectus abdominis musculocutaneous free flap in patients with locally advanced maxillary sinus carcinoma from 2003 to 2014 (n = 35, 27 men and 8 women; average age, 60.9 ± 7.8 years). All patients underwent craniofacial reconstruction after anterior and middle cranial fossa skull base resection and maxillectomy (class IV, subtype a) with palatal resection. Patients were categorized based on sex, BMI, and other parameters. RESULTS: Recipient-site infection occurred in 11 patients (31.4%), cerebrospinal fluid leakage in 6 (17.1%), partial flap necrosis in 2 (5.7%), total flap necrosis in 1 (2.9%), and facial fistula in 4 (11.4%). Women showed partial flap necrosis significantly more frequently (P = 0.047), probably owing to poor vascular supply of the subcutaneous fat layer. Patients with low BMI (<20 kg/m(2)) showed recipient-site infection (P = 0.02) and facial fistula (P = 0.01) significantly more frequently owing to insufficient tissue volume and poor vascular supply. CONCLUSION: Postoperative recipient-site infection and facial fistula occurred mainly in low-BMI patients. Surgeons should take care to achieve sufficient donor tissue on low-BMI patients. Using a prosthetic obturator in low-BMI patients for craniofacial reconstruction can be a good alternative option to reduce postoperative complications due to insufficient donor tissue volume.

DOI： 10.1097/GOX.0000000000000645

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Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVE: The objective of this study was to clarify the outcomes of craniofacial resection for locally advanced maxillary sinus carcinoma classified as T4 and to present methods for managing cases involving the skull base. STUDY DESIGN: Case series with chart review. SETTING: Tertiary university hospital. SUBJECTS AND METHODS: We performed anterolateral craniofacial resection in en bloc fashion for locally advanced maxillary sinus carcinoma at stage T4. Participants comprised 40 patients with T4 maxillary sinus carcinoma treated between 1992 and 2011. Surgical outcomes were analyzed retrospectively. RESULTS: Forty patients with stage T4a (n = 26) or stage T4b (n = 14) were included in this study. Five-year overall and disease-free survival rates for the 40 patients with T4 maxillary sinus carcinoma were 62.7% and 52.6%, respectively. Cavernous sinus involvement correlated significantly with worse prognosis (P = .012). In 35 cases without cavernous sinus involvement, previous treatment (P = .017) and positive margins (P = .019) correlated significantly with worse prognosis, and 5-year overall and disease-free survival rates were 72.4% and 55.3%, respectively. CONCLUSION: This study only included cases of locally advanced maxillary sinus carcinoma classified as T4. Considering the advanced stage, our study suggests relatively favorable outcomes and the importance of managing the cavernous sinus in en bloc resections of malignant skull base tumors. Craniofacial resection in en bloc fashion achieved good survival rates.

DOI： 10.1177/0194599815586770

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Authorship：Lead author   Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

CONCLUSION: This study revealed that endolymphatic hydrops (EH) reduced in some cases with Ménière's disease (MD) treated conservatively. It appears that the EH reduction was associated with improvement of the clinical symptoms. OBJECTIVES: The relationship between the degree of EH and clinical symptoms is not clear at present. The purpose of the present study was to investigate the time course of the relationship in patients with MD treated conservatively. PATIENTS: Twelve patients with MD treated conservatively for more than 1 year in a university hospital. METHODS: Twenty ears of 12 patients with MD treated conservatively were evaluated. The presence or absence of vertigo, tinnitus and ear fullness was confirmed when magnetic resonance imaging (MRI) was performed. Using a 3 T MRI scanner, three-dimensional fluid-attenuated inversion recovery (3D-FLAIR) MRI was performed 2 or 3 times 24 hours after intra-tympanic gadolinium injection or 4 hours after intravenous gadolinium injection. RESULTS: In the three ears in which the symptoms alleviated, EH was reduced in two ears, but EH was reduced in only one of 17 ears in which the symptoms did not alleviate. The Fisher exact test revealed that EH reduction occurred more frequently in ears with alleviation of the symptoms (p < 0.05).

DOI： 10.3109/00016489.2015.1015607

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本マイクロサージャリー学会  

Language：English   Publishing type：Research paper (scientific journal)  

The objective of the study was to evaluate the association between changes in laryngeal sensation and initiation of swallowing reflex or swallowing function before and after (chemo)radiotherapy. A prospective study was conducted in a tertiary referral university hospital. Thirteen patients who received (chemo)radiotherapy for treatment of laryngeal or hypopharyngeal cancer were included. Laryngeal sensation was evaluated at the tip of the epiglottis before and 1, 3 months, and 1 year after (chemo)radiotherapy. Videofluoroscopy was performed at the same time. Quantitative determinations included changes in laryngeal sensation, computed analysis of pharyngeal delay time, the distance and velocity of hyoid bone movement during the phase of hyoid excursion, and pharyngeal residue rate (the proportion of the bolus that was left as residue in the pharynx at the first swallow). Laryngeal sensation significantly deteriorated 1 month after (chemo)radiotherapy, but there was a tendency to return to pretreatment levels 1 year after treatment. Neither pharyngeal delay time nor displacement of the hyoid bone changed significantly before and after (chemo)radiotherapy. In addition, there was no significant difference in the mean velocity of hyoid bone movement and the amount of stasis in the pharynx at the first swallow before and after (chemo)radiotherapy. After (chemo)radiotherapy, laryngeal sensation deteriorated. But, in this study, videofluoroscopy showed that swallowing reflex and function were maintained.

DOI： 10.1007/s00405-013-2775-7

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Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

An inflammatory pseudotumor is a rare benign disease presenting with non-specific chronic inflammation, and reported occurrences involving the skull base are relatively rare. A 65-year-old man became aware of pain around the right temporomandibular joint and mild trismus, and palsies of the cranial nerves III, IV, V, and VI were observed. A biopsy was performed under general anesthesia with an infratemporal fossa approach, and he was diagnosed with inflammatory pseudotumor of the infratemporal fossa. There was a rapid improvement in symptoms after the start of steroid administration, and 29 months after the initial consultation, the patient remained under strict observation. The 3 criteria in our department for confirming progression of the disease are (1) clinical symptoms, (2) C-reactive protein levels in blood tests, and (3) contrast effect of the tumor on magnetic resonance imaging. This is a rare case report to demonstrate the inflammatory pseudotumor of the infratemporal fossa leading to orbital apex syndrome.

DOI： 10.1097/SCS.0000000000000789

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Language：English   Publishing type：Research paper (scientific journal)  

Lymph node metastasis is a major prognostic factor in parotid carcinoma, however, the pre-operative diagnosis of occult nodal metastasis is difficult in clinical N0 (cN0) parotid cancer patients. In addition, the indication of neck dissection in T1-3 cN0 patients is controversial. The current study investigated 17 patients with clinical T1-3 cN0 parotid cancer, and analyzed the correlation between patient symptoms/findings and pathological N status/tumor histological grade. In the statistical analysis, pain was found to significantly correlate with neck metastasis. Furthermore, cN0-staged patients without pain exhibited no neck metastasis. However, no significant correlation was identified between patient symptoms or findings and histological grade. These results indicate the possibility that selective neck dissection can be omitted for T1-3 cN0-staged patients without pain.

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.3892/ol.2014.2137

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Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publishing type：Research paper (scientific journal)   Publisher：Japan Society for Head and Neck Cancer  

We reviewed 47 patients who underwent cervical esophageal reconstruction using a free jejunal flap transfer between July 2001 and December 2011. There were 40 males and 7 females with an average age of 64.3. Fifteen patients had radiotherapy preoperatively, and 24 patients postoperatively. The patients who underwent preoperative radiotherapy tended to suffer postoperative complications including surgical site infection and leakage, whereas those who underwent postoperative radiotherapy tended to suffer contracture at the anastomosed site between the free jejunal flap and the esophagus. We consider that free jejunal flap transfer in patients with cervical esophageal cancer is a safe procedure.

DOI： 10.5981/jjhnc.40.1

Scopus

Language：English   Publishing type：Research paper (scientific journal)  

OBJECTIVES/HYPOTHESIS: Endothelin-1 is a potent vasoconstrictor peptide that is widely distributed throughout the mammalian body including the spiral modiolar artery, vestibule, and cochlea. This study aimed to investigate the association between the Lys198Asn (G/T) polymorphism (rs5370) of the endothelin-1 gene and sudden sensorineural hearing loss (SSNHL). STUDY DESIGN: Case-control study. METHODS: Seventy-two SSNHL patients (mean age, 58.3 ± 14.0 years) were compared with 2,159 controls included in a community-based study of aging. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL. In subgroup analysis, patients with SSNHL who visited to the hospital within the first month of onset were selected to assess audiometric features according to genotype. Pure-tone averages at 250, 500, 1,000, 2,000, and 4,000 Hz were calculated in the affected ear. RESULTS: Under the recessive genetic model, after adjustment for age, sex, histories of hypertension, dyslipidemia and diabetes, the crude and adjusted ORs for SSNHL risk were 2.209 (95% confidence interval [CI]: 1.140-4.281) and 2.173 (95% CI: 1.086-4.348), respectively. No significant ORs were observed under the additive and dominant models. The severity of SSNHL differed significantly between genotypes. The mean pure-tone averages at the initial visit were 78.6, 66.4, and 57.8 dB for the GG, GT, and TT genotypes, respectively (P = .034). CONCLUSIONS: Our study indicates that the recessive genotype was significantly associated with increased SSNHL risk; however, the severity was lower in these individuals than it was in those with the wild-type genotype. Endothelin-1 may be implicated in SSNHL.

DOI： 10.1002/lary.24298

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The etiologies of idiopathic sudden sensorineural hearing loss (SSNHL) and Ménière's disease remain unclear. Recently, accumulating evidence has demonstrated that free radicals are related to the pathology of inner ear disease. Because genetic factors may contribute partly to the etiologies of SSNHL and Ménière's disease, we investigated the association between genetic polymorphisms located in genes related to the free-radical process and susceptibility to SSNHL and Ménière's disease. We compared 83 patients affected by SSNHL and 83 patients affected by Ménière's disease with 2048 adults (for SSNHL) and 1946 adults (for Ménière's disease) who participated in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Multiple logistic regression was used to calculate odds ratios (ORs) for SSNHL and Ménière's disease in individuals with polymorphisms in the genes: methionine synthase (MTR
rs1805087)
methionine-synthase reductase (MTRR
rs1801394)
nitric oxide synthase 3 (NOS3
rs1799983)
caveolin 1 (Cav1
rs3840634)
melatonin receptor 1B (MTNR1B
rs1387153)
NAD(P)H oxidase p22(phox) subunit (NADH/NADPHp22phox
rs4673)
and mitochondria 5178 (MT5178
rs28357984). The NOS3 polymorphism was significantly associated with a risk of SSNHL
in addition, the OR for the NOS3 polymorphism and SSNHL risk was 2.108 (CI, 1.343-3.309) with adjustment for age and sex. The Cav1 polymorphism was significantly associated with a risk of Ménière's disease
moreover, the OR for the Cav1 polymorphism and Ménière's disease risk was 1.849 (CI, 1.033-3.310) with adjustment for age and sex. In conclusion, the NOS3 and Cav1 polymorphisms were significantly associated with the risk of SSNHL and Ménière's disease, respectively. © 2013 Informa UK, Ltd.

DOI： 10.3109/10715762.2013.793319

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Folate metabolism is essential for cellular functioning. Despite extensive research on the roles of folate-metabolism-related gene polymorphisms in the pathophysiology of many diseases, such as cardiovascular disease, cancers, and sudden sensorineural hearing loss, little is known about their association with Ménière's disease (MD). The aim of this study was to investigate the effect of methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) on the risk of MD in a Japanese population. We examined the C677T and A1298C (rs1801133 and rs1801131) polymorphisms in the MTHFR gene and compared them between 1946 adults (986 men and 960 women) participating in the National Institute for Longevity Sciences Longitudinal Study of Aging and 86 cases of MD. A multiple logistic regression was performed to obtain odds ratios (ORs) for the risk of MD regarding the MTHFR polymorphisms before (model 1) and after (model 2) adjustment for age and sex factors. The OR of MTHFR C677T for the risk of MD was 0.669 (95% confidence interval [CI], 0.479-0.934) in model 1 and 0.680 (95% CI, 0.484-0.954) in model 2. In contrast, the OR of MTHFR A1298C for the risk of MD was 1.503 (95% CI, 1.064-2.123) in model 1 and 1.505 (95% CI, 1.045-2.167) in model 2. Our results imply that the MTHFR C677T and A1298C polymorphisms are associated with the risk of MD.

DOI： 10.3109/01677063.2013.770510

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

AIMS: The etiologies of Ménière's disease and idiopathic sudden sensorineural hearing loss (SSNHL) remain unclear. The homeostasis of the water and blood circulation in the inner ear is essential for maintaining its hearing and equilibrium functions, and aquaporins and estrogen are involved in the fluid or ion balance in the inner ear. We investigated the associations between genetic polymorphisms in aquaporin 4 (AQP4, rs2075575), aquaporin 5 (AQP5, rs3736309), and estrogen receptor α (ERα1, rs2234693; ERα2, rs9340799) and susceptibility to Ménière's disease or SSNHL. MAIN METHODS: We compared 86 patients affected by Ménière's disease, 85 patients affected by SSNHL, and 2136 adults who were participants in a comprehensive longitudinal study of aging. KEY FINDINGS: With the AQP5 polymorphism, the odds ratio for Ménière's disease was 0.676 (95% confidence interval: 0.477-0.957) after adjustment for age and sex, when an additive genetic model was used. The AQP5 polymorphism entailed no significant risk of SSNHL and the polymorphisms of AQP4, ERα1, and ERα2 entailed no significant risk of Ménière's disease or SSNHL in the additive genetic model, regardless of adjustments for age and sex. SIGNIFICANCE: Our study suggests that the variant G allele of AQP5 polymorphism rs3736309 reduces the risk of Ménière's disease.

DOI： 10.1016/j.lfs.2013.01.019

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

The etiologies of idiopathic sudden sensorineural hearing loss (SSNHL) and Ménière's disease remain unclear. Recently, accumulating evidence has demonstrated that oxidative stress is related to the pathology of inner ear disease. Because genetic factors may contribute partly to the etiologies of SSNHL and Ménière's disease, we investigated the associations between genetic polymorphisms located in oxidative stress response genes and susceptibility to SSNHL and Ménière's disease. We compared 84 patients affected by SSNHL, 82 patients affected by Ménière's disease, and 2107 adults (1056 men and 1051 women; mean age, 59.2 years; range, 40-79 years) who participated in the National Institute for Longevity Sciences, Longitudinal Study of Aging. Multiple logistic regression was used to calculate odds ratios for SSNHL and Ménière's disease in individuals with polymorphisms in the genes glutathione peroxidase 1 (GPX1) (Pro198Leu, rs1050450), paraoxonase 1 (PON1) (Gln192Arg, rs662; and Met55Leu, rs854560), PON2 (Ser311Cys, rs7493), and superoxide dismutase 2 (SOD2) (Val16Ala, rs4880), with adjustment for age and gender. No significant differences in the distribution of the genotypes at these polymorphisms were observed among individuals with SSNHL and Ménière's disease and controls. No significant risk for SSNHL and Ménière's disease was observed in the additive genetic model, regardless of moderating variables. The C allele of SOD2 (rs4880) was more frequent in Ménière's disease cases with a hearing level over 50 dB compared with cases with a hearing level below 50 dB, suggesting that this polymorphism is associated with progression of a hearing loss in Ménière's disease. In conclusion, no significant associations between the polymorphisms of GPX1, PON1, PON2, and SOD2 and risk of SSNHL and Ménière's disease were observed in this Japanese case-control study.

DOI： 10.1089/dna.2012.1631

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Although the etiology of idiopathic sudden sensorineural hearing loss (SSNHL) remains unclear, the pathologically increased permeability of blood vessels, elucidated by gadolinium-enhanced magnetic resonance imaging (MRI), suggests the involvement of inflammation. Because SSNHL is considered a multifactorial disease, possibly caused by interactions between genetic factors and environmental factors, the authors investigated the associations of polymorphisms of inflammatory mediator genes with susceptibility to SSNHL. The authors compared 72 patients affected by SSNHL and 2010 adults (1010 men and 1000 women; mean age 59.2 years; range 40-79) who participated in the National Institute for Longevity Sciences Longitudinal Study of Aging. Multiple logistic regression was used to obtain odds ratios (ORs) for SSNHL in subjects with polymorphisms in the genes IL-6 C - 572G, IL-4R G1902A, IL-10 A - 592C, TNFα C - 863A, TNFRSF1B G593A, VEGF C936T, VEGF C - 2578A, and VEGF G - 1154A, with adjustment for age, gender, and any history of hypertension, diabetes, or dyslipidemia. The per-allele OR for the risk of SSNHL in subjects bearing IL-6 C - 572G was 1.480 (95% confidence interval [CI], 1.037-2.111) in model 1 (no adjustment), 1.463 (CI, 1.022-2.094) in model 2 (adjusted for age and gender), and 1.460 (CI, 1.016-2.097) in model 3 (adjusted for age, gender, and a history of hypertension, diabetes, or dyslipidemia). Under the dominant model of inheritance, the ORs were 1.734 (CI, 1.080-2.783) in model 1, 1.690 (CI, 1.050-2.721) in model 2, and 1.669 (CI, 1.035-2.692) in model 3. The remaining seven polymorphisms failed to show any associations with the risk of SSNHL. These data need to be confirmed on larger series of patients. In conclusion, the IL-6 C - 572G polymorphism is associated with a risk of SSNHL. Because permeability of blood vessels in the inner ear is frequently increased in patients with SSNHL, inflammation of the inner ear might be involved.

DOI： 10.3109/01677063.2011.652266

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Language：English   Publishing type：Research paper (scientific journal)  

Sudden sensorineural hearing loss (SSNHL) is one of the most common diseases encountered by otolaryngologists; however, the etiology is unclear. The aim of this study was to assess the association between SSNHL and polymorphism of complement factor H (CFH) Y402H, which is implicated in age-related macular degeneration. We conducted a case-control study, in which the cases were 72 SSNHL patients and the controls were 2161 residents selected randomly from the resident register. The odds ratio (OR) for SSNHL risk was determined using the additive-genetic model of CFH Y402H polymorphism. The OR for SSNHL risk was 1.788 (95% confidence interval [CI]: 1.008-3.172) with no adjustments and 1.820 (CI: 1.025-3.232) after adjusting for age and sex. Of the three lifestyle-related diseases hypertension, dyslipidemia, and diabetes, only diabetes was significantly associated with SSNHL risk. We classified both the controls and SSNHL patients into those with or without diabetes, and the OR for SSNHL risk was 6.326 (CI: 1.885-21.225) in diabetic subjects and 1.214 (CI: 0.581-2.538) in nondiabetic subjects. We conclude that CFH Y402H polymorphism and SSNHL risk are significantly related, and that diabetic CFH Y402H minor allele carriers may be susceptible to SSNHL.

DOI： 10.1016/j.gene.2012.02.027

Web of Science

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

Sudden sensorineural hearing loss (SSNHL) and Ménière's disease are the most common inner ear diseases in which the causes are unknown. As recent magnetic resonance imaging has demonstrated disruption of the blood-labyrinth barrier in these inner ear diseases, inflammatory reaction associated with increased permeability of the blood vessels may be involved. The genotypes of interleukin 1A (IL1A) (-889C/T
rs1800587) and interleukin 1B (IL1B) (-511C/T
rs16944) were determined using an allele-specific primer-polymerase chain reaction method in 72 patients with SSNHL, 68 patients with Ménière's disease, and 2202 control subjects living almost in the same area as the patients. A significantly higher prevalence of the IL1A-889T allele was observed in SSNHL and Ménière's disease compared with controls, although no significant difference in distribution of IL1B-511C/T genotypes was observed between the patients and controls. Adjusted odd ratios for SSNHL and Ménière's disease risks in the -889TT genotypes were 25.89 (95% confidence interval (CI) 12.19-54.98) and 18.20 (95% CI 7.80-42.46), respectively, after age and gender were taken as moderator variables. Our results suggested that IL1A is closely associated with susceptibility of SSNHL and Ménière's disease. © 2011 Blackwell Publishing Ltd.

DOI： 10.1111/j.1744-313X.2011.01004.x

Web of Science

Scopus

PubMed

Language：English   Publishing type：Research paper (scientific journal)  

CONCLUSION: Visualization of endolymphatic hydrops became possible after intravenous gadolinium (Gd) injection in patients with Ménière's disease. OBJECTIVE: To visualize endolymphatic hydrops after intravenous Gd injection. METHODS: Gd (gadoteridol; 0.2 mmol/kg) was injected intravenously in three patients with unilateral Ménière's disease. We performed three-dimensional fluid attenuated inversion recovery (3D-FLAIR) and three-dimensional real inversion recovery (3D-real IR) magnetic resonance imaging (MRI) 4 h after the injection using a 3-Tesla MRI unit. We used a 32-channel array coil to obtain a high signal-to-noise ratio. RESULTS: Endolymphatic hydrops was observed in the ears of patients with Ménière's disease. However, Gd concentration in the perilymph was lower compared with that obtained after intratympanic Gd injection.

DOI： 10.1080/00016480903143986

PubMed

Publishing type：Research paper (scientific journal)  

DOI： 10.3109/00016480903143986

Web of Science

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

J-GLOBAL

Language：Japanese   Publisher：The Society of Practical Otolaryngology  

Dermoid cysts are rare lesions of the head and neck that usually present with few symptoms. Complete resection is the mainstay of treatment for dermoid cysts, however, airway management after surgery is essential, especially in children. We report the case of sublingual dermoid cyst arising from the floor of the mouth in a 6-year-old female child. CT/MRI images demonstrated a 50×40×30 mm cystic mass in the sublingual space. Fine-needle aspiration was performed under ultrasound guidance, and the findings were suggestive of a dermoid cyst in the floor of mouth. The cyst was surgically removed via a transoral approach. After the surgery, the patient was returned to the intensive care unit under tracheal intubation for safe airway management. After some days, she was extubated and the postoperative course was good. There was no evidence of recurrence during the 6-month follow up period. When encountering sublingual dermoid cysts arising from the floor of the mouth in a pediatric case, it is important to consider not only the appropriate surgical procedure, but also about postoperative airway management, even during the preoperative period.

DOI： 10.5631/jibirin.115.277

CiNii Books

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

CiNii Books

Language：Japanese   Publisher：The Society of Practical Otolaryngology  

Fluorouracil (5-FU) is one of key therapeutic drugs for many solid tumors, including head and neck cancer. Pneumatosis intestinalis and portal venous gas, while being rare adverse effects of 5-FU administration, could prove fatal. Hyperammonemia is also one of the serious adverse effects of 5-FU. Herein, we report the case of a patient with hypopharyngeal cancer who developed both portal venous gas and hyperammonemia during 5-FU chemotherapy.

A 79-year-old man with a few months’ history of difficulty in swallowing was referred to our hospital. Upper gastrointestinal endoscopy and tissue biopsy revealed squamous cell carcinoma and the patient was diagnosed as having locally advanced hypopharyngeal cancer, cT4aN0M0. He was initiated on neoadjuvant chemotherapy with carboplatin (CBDCA) and 5-FU on day 1. On the day 3, he presented with consciousness disturbance and Kussmaul breathing. Upper gastrointestinal endoscopy revealed pneumatosis intestinalis under the gastric mucosa and abdominal computed tomography revealed portal venous gas. At the same time, blood test revealed hyperammonemia. As we considered these events to be serious adverse effects of 5-FU, we discontinued the 5-FU infusion and started the patient on treatment with antibiotics and a proton-pump inhibitor. The general condition of the patient gradually improved under careful observation, and the patient eventually showed complete recovery. In clinical settings, it is important to have a high index of suspicion for serious adverse effects of 5-FU, such as pneumatosis intestinalis, portal venous gas, and hyperammonemia.

DOI： 10.5631/jibirin.115.333

CiNii Books

Language：Japanese   Publisher：THE JAPAN LARYNGOLOGICAL ASSOCIATION  

Patients with head and neck cancer who undergo total laryngectomy often suffer from significant communication disorders due to permanent aphonia. While various substitutes for voice loss, including an electronic artificial larynx, tracheoesophageal shunt, esophageal speech, and written communication, have been currently employed to communicate against aphonia, few methods have used the voice of a preoperative patient. “Coestation^®” is a smartphone application that synthesizes patients’ voice and is now clinically applied to patients with amyotrophic lateral sclerosis (ALS). To verify whether this application has the potential to become a new substitute voice, we launched a clinical investigation for patients with head and neck cancer who were scheduled to undergo total laryngectomy. We preoperatively performed a voice synthesis using the smartphone application in two patients and postoperatively requested them to use an electronic artificial larynx and the synthesized voice. The patients stated that the synthesized voice was more similar to their original voice than the artificial larynx and were very satisfied about its voice quality. Based on these preliminary results, we plan to enroll more patients to assess the general usefulness of the synthesized voice as a new substitute voice.

DOI： 10.5426/larynx.33.230

Language：Japanese   Publisher：Japanese Society of Otorhinolaryngology-Head and Neck Surgery  

DOI： 10.3950/jibiinkotokeibu.124.11_1543

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

顔面神経を温存した耳下腺癌手術症例の、術後の顔面神経麻痺の推移と予後の関係を検討した報告は少ない。当科の耳下腺癌の治療方針は、術前から顔面神経麻痺がある場合は神経合併切除と一期的再建、麻痺がない場合は組織型にかかわらず原則温存としている。過去15年間の顔面神経を温存した耳下腺癌手術症例31例について検討した。観察期間中央値は60ヵ月、全摘24例、葉切除が7例であった。手術直後の顔面神経麻痺スコアは平均24点、中央値は27点であった。術後顔面神経麻痺の推移は、一過性に完全麻痺の症例もあったが、最終的に平均39.5点まで回復した。回復期間は多くの症例が術後6ヵ月までに回復した。治療成績は、5年全生存率・5年無病生存率・局所制御率それぞれ96.0%・89.5%・93.5%と良好な結果であった。術前顔面神経麻痺のない耳下腺癌症例は、病理型に関わらず神経を温存しても治療成績は担保されると考える。(著者抄録)

Authorship：Corresponding author   Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科頭頸部外科学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publisher：THE JAPAN LARYNGOLOGICAL ASSOCIATION  

DOI： 10.5426/larynx.30.55

Other Link： https://search.jamas.or.jp/link/ui/2019193307

Language：Japanese   Publisher：(一社)日本頭蓋顎顔面外科学会  

Language：Japanese   Publisher：耳鼻と臨床会  

眼咽頭筋ジストロフィー(oculopharyngeal muscular dystrophy:OPMD)に伴う高度の声帯萎縮による嗄声に対し、甲状軟骨形成術I型(TPI)とIII型(TPIII)を併用し(TPI+III)、音声の改善を得た。症例は68歳、男性。X-10年OPMDと診断され、X-7年嚥下障害に対して右輪状咽頭筋切除術を行い、いったん嚥下機能は改善した。その後も嗄声が進行し、複数回の右声帯内脂肪注入術や右声帯内アテロコラーゲン注入術を行うも音声改善は乏しかった。嚥下機能も次第に悪化し、嚥下機能改善手術の必要性も再度検討されたが本人希望はあくまで音声改善であり、X年10月局所麻酔下にTPI+IIIを施行した。術後両側声帯の内方移動が得られ、声門閉鎖不全は残存したが、他覚的な音声検査所見の改善を一部認めた。TPIIIの甲状軟骨縦切除が行われた右側の声帯の内方移動が左側に比べて良好であった。高度声帯萎縮に対する音声外科的治療としてTPI+IIIが有用と考えられた。(著者抄録)

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00581&link_issn=&doc_id=20181102070005&doc_link_id=10.11334%2Fjibi.64.5_189&url=https%3A%2F%2Fdoi.org%2F10.11334%2Fjibi.64.5_189&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

症例は42歳男性で、前頸部腫脹を主訴とした。10年前より放置していた左鎖骨上の腫瘤が徐々に増大し、近医造影MRIではT1強調画像、T2強調画像ともに内部不均一で高信号を呈する境界明瞭な腫瘤性病変を認めた。紹介受診時には胸腺腫が疑われたが、筋力低下や眼瞼下垂、貧血は認めず、抗アセチルコリンレセプター抗体、甲状腺ホルモンはともに正常であり、細胞診は脂肪腫疑いとの診断であった。画像検査で悪性腫瘍を否定できなかったため切開生検を行い、異所性過誤腫性胸腺腫の診断で腫瘍摘出術を行った。病理組織学的所見では脂肪細胞、紡錘形細胞、扁平上皮細胞を認め、免疫学的染色で紡錘形細胞がAE1/AE3、SMAに陽性を示したことから異所性過誤腫性胸腺腫の診断に至った。術後1年6ヵ月経過時点で再発は認めていない。頸部下方の腫瘍を認めた場合には鑑別診断として本疾患を念頭に置くことの重要性が示唆された。

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J00580&link_issn=&doc_id=20180906240010&doc_link_id=10.5631%2Fjibirin.111.645&url=https%3A%2F%2Fdoi.org%2F10.5631%2Fjibirin.111.645&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_2.gif

Language：Japanese   Publisher：(NPO)日本頭頸部外科学会  

頭頸部がん診療は、長時間の手術や緊急手術なども多く、妊娠・出産を考える女性医師にとってはハードルが高い分野でもある。筆者は妊娠出産を経験し2児の母として、現在頭頸部がん診療を専門としてフルタイム勤務をしている。当院では複数主治医担当医制度を導入し、カンファレンスにて症例を共有しチーム全体が患者全員を把握している。主治医として担当した手術時間を産前(2007〜2010年)、産後(2012〜2015年)に分け比較検討した。総手術件数は産前390件、産後278件であり、再建手術は21%(80件)から11%(31件)に減少し、4時間以内の手術の割合が69%(269件)から82%(228件)と増加した。ロールモデルもモチベーションを維持する大切なものである。周りの上司や同僚への感謝の気持ちの大切さを感じており、他の医師への負担の軽減なくしては継続的な取り組みはできないと考える。(著者抄録)

DOI： 10.5106/jjshns.27.161

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J04210&link_issn=&doc_id=20171120550005&doc_link_id=10.5106%2Fjjshns.27.161&url=https%3A%2F%2Fdoi.org%2F10.5106%2Fjjshns.27.161&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Language：Japanese   Publisher：日本内分泌外科学会・日本甲状腺外科学会  

Language：Japanese   Publisher：耳鼻咽喉科臨床学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：The Japan Broncho-esophagological Society  

DOI： 10.2468/jbes.68.166

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2017&ichushi_jid=J01054&link_issn=&doc_id=20170509420041&doc_link_id=%2Fea4broes%2F2017%2F006802%2F050%2F0166-0166%26dl%3D2&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fea4broes%2F2017%2F006802%2F050%2F0166-0166%26dl%3D2&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_5.gif

Language：Japanese   Publisher：(公社)日本超音波医学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publisher：The Society of Practical Otolaryngology  

DOI： 10.5631/jibirin.109.830

Language：Japanese   Publisher：(NPO)日本乳腺甲状腺超音波医学会  

Language：Japanese   Publisher：(一社)日本小児血液・がん学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(公社)日本超音波医学会  

Language：Japanese   Publisher：(NPO)日本乳腺甲状腺超音波医学会  

Language：Japanese   Publisher：(NPO)日本乳腺甲状腺超音波医学会  

Language：Japanese   Publisher：(NPO)日本乳腺甲状腺超音波医学会  

Language：Japanese   Publisher：(NPO)日本気管食道科学会  

Language：Japanese   Publisher：耳鼻咽喉科展望会  

DOI： 10.11453/orltokyo.58.6_341

Language：Japanese   Publisher：日本嚥下医学会  

Language：Japanese   Publisher：日本嚥下医学会  

Language：Japanese   Publisher：(一社)日本耳科学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(NPO)日本気管食道科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publisher：(一社)日本耳科学会  

Language：Japanese   Publisher：(一社)日本癌治療学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(公社)日本超音波医学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publisher：(一社)日本癌治療学会  

Language：Japanese   Publisher：(一社)日本癌治療学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(NPO)日本気管食道科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publisher：日本音声言語医学会  

Language：Japanese   Publisher：JIBI TO RINSHO KAI  

[OBJECTIVE] There are limited data regarding outcome analysis in patients who have undergone craniofacial resection of T4 squamours cell carcinoma of maxillary sinus. The purpose of this study was to evaluate the survival rate of patients with maxillary cancers invading the infratemporal fossa who underwent anterolateral skull base resection. [METHODS] At Nagoya University Hospital, 126 patients underwent craniofacial resection during 21-year period. Among them, 34 patients underwent anterolateral cranial base resections for T4 maxillary squamous cell carcinoma ; 21 cases were stage T4a and 13 tumors were in stage T4b according the UICC (7th edition) classification, and 4 cases were with Cavernous sinus resection. The median follow-up time was 38.7 months (range 12 to 158). [RESULTS] The 5-year survival rate was 60.3% (T4a : 75.1%, T4b : 51.3%), and the relapse-free survival rates was 43.7% (T4a : 46.8%, T4b : 39.9%) at 5 years, respectively. Univariate analysis showed that surgical margin and recurrent disease had a significant effect on the five-year overall survival and disease-free survival. [Conclusion] Anterolateral skull base resection is an effective treatment for T4 maxillary cancer. Patients with positive surgical margins show a poorer prognosis. The mortality and the morbidity is acceptable without cavernous sinus resection.

DOI： 10.11334/jibi.58.s57

Language：Japanese   Publisher：(NPO)日本緩和医療学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(一社)日本頭頸部癌学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publisher：(一社)日本耳科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publisher：(一社)日本耳鼻咽喉科学会  

Language：Japanese   Publisher：(一社)日本耳科学会  

Author：Other 

喉頭を摘出した方が、自分の声を取り戻すために、人工喉頭の発達のその将来について述べた。名大病院での、新たな代替発声についての臨床試験についての内容が紹介されている。