Publications by authors named "Yasushi Fujimoto"

92 Publications

Skull Base Invasion Patterns of Malignant Head and Neck Tumors: A Neurosurgical Perspective.

J Neurol Surg B Skull Base 2021 Jul 8;82(Suppl 3):e120-e130. Epub 2020 Jan 8.

Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan.

 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.  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.  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.  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.
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http://dx.doi.org/10.1055/s-0039-3402034DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8289545PMC
July 2021

Sites of invasion of cancer of the external auditory canal predicting oncologic outcomes.

Head Neck 2021 Jul 9. Epub 2021 Jul 9.

Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Japan.

Background: This study aimed to reveal the influence of the invasion site of external auditory canal (EAC) cancer by analyzing the outcome of patients with advanced tumor.

Methods: A total of 111 patients with T4 EAC cancer were enrolled in this study. Of these patients, 79 underwent chemoradiotherapy and 32 underwent surgery under curative intent. Univariate and multivariate analyses and the Kaplan-Meier method were used to focus on the tumor invasion sites and overall survival of the patients.

Results: The 3-year overall survival rate of all patients was 55.0%. In multivariate analysis, the only significant invasion site for overall survival was the facial nerve, with the dura mater being the next most influential site. When Kaplan-Meier survival curve was calculated, facial nerve and dura mater were the significant factors resulting in poor patient outcomes.

Conclusion: The facial nerve and dura mater are crucial sites of EAC cancer for patient outcomes.
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http://dx.doi.org/10.1002/hed.26800DOI Listing
July 2021

Surgical Classification of Radical Temporal Bone Resection and Transcranial Tympanotomy: A Retrospective Study from the Neurosurgical Perspective.

World Neurosurg 2021 Jul 13;151:e192-e207. Epub 2021 Apr 13.

Department of Neurosurgery, Fukushima Medical University, Fukushima, Japan.

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.
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http://dx.doi.org/10.1016/j.wneu.2021.04.002DOI Listing
July 2021

Association of Matrix Metalloproteinase-2 mRNA Expression with Subtypes of Pediatric Cholesteatoma.

Biomed Res Int 2021 10;2021:6644897. Epub 2021 Mar 10.

Department of Otorhinolaryngology, Aichi Medical University School of Medicine, 1-1, Yazakokarimata, Nagakute, Aichi 480-1195, Japan.

Objective: Cholesteatoma is a clinically heterogeneous disease, with some patients showing spontaneous regression, while others experiencing an aggressive, lethal disease. Cholesteatoma in children can be divided into two types: congenital and acquired. Identifying good prognostic markers is needed to help select patients who will require immediate surgical intervention. Matrix metalloproteinase-2 (MMP2) was previously reported to play an important role in cholesteatoma progression, by promoting bone destruction and keratinocyte infiltration. Herein, we analyzed mRNA expression level in cholesteatoma using RNA-in situ hybridization in formalin-fixed, paraffin-embedded (FFPE) tissue samples.

Methods: Sixty patients with cholesteatoma under 15 years old, who underwent their primary surgery at Aichi Medical University's Otolaryngology Department, were analyzed for MMP2 expression level, using RNA-in situ hybridization.

Results: There were no significant differences in mRNA expression level between congenital cholesteatoma and acquired cholesteatomas. In congenital cholesteatoma, higher MMP2 signals were observed in the open type than in the closed type ( < 0.001). In acquired cholesteatoma, higher MMP2 signals were observed in the pars tensa than in the pars flaccida ( < 0.001). mRNA expression level was almost exclusively found in the fibroblasts or in the inflammatory cells in the stroma, but not in the epithelium.

Conclusion: Our study reveals that mRNA expression level is strongly associated with the subtypes of cholesteatoma. The findings suggest that the level of expression of mRNA may be related to the pathogenesis and aggressive features of cholesteatoma.
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http://dx.doi.org/10.1155/2021/6644897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972836PMC
May 2021

Oncolytic herpes simplex virus HF10 (canerpaturev) promotes accumulation of CD8 PD-1 tumor-infiltrating T cells in PD-L1-enriched tumor microenvironment.

Int J Cancer 2021 Jul 23;149(1):214-227. Epub 2021 Mar 23.

Cancer Immune Therapy Research Center, Graduate School of Medicine, Nagoya University, Nagoya, Japan.

Oncolytic viruses (OVs) remodel the tumor microenvironment by switching a "cold" tumor into a "hot" tumor with high CD8 T-cell infiltration. CD8 T-cell activity plays an essential role in the antitumor efficacy of OVs. However, the activity of T cells is impaired by the programmed cell death protein-1/programmed cell death-ligand 1 (PD-1/PD-L1) interaction. To date, it remains unclear why OVs alone have a significant antitumor activity even when PD-L1 expression persists on tumor or immune cells. In this study, we found that canerpaturev (C-REV) treatment significantly suppressed tumor growth, even though it induced a significant increase in PD-L1 expression in tumors in vivo as well as persistence of high PD-L1 expression on antigen-presenting cells (macrophage and dendritic cells [DCs]). Surprisingly, we observed that C-REV treatment increased the abundance of activated CD8 PD-1 tumor-infiltrating lymphocytes (TILs) in the tumor on both the injected and contralateral sides, although infiltration of CD8 PD-1 TILs into the tumor was observed in the control group. Moreover, the difference in PD-1 expression was observed only in tumors after treatment with C-REV, whereas most CD8 T cells in the spleen, tumor-draining lymph nodes and blood were PD-1-negative, and this did not change after C-REV treatment. In addition, changes in expression of T-cell immunoglobulin and mucin-domain containing-3 and T-cell immune-receptor with Ig and ITIM domains were not observed on CD8 TILs after C-REV treatment. Taken together, our findings may reveal mechanisms that allow OVs to trigger an antitumor immune response, irrespective of a PD-L1-enriched tumor microenvironment, by recruitment of CD8 PD-1 TILs.
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http://dx.doi.org/10.1002/ijc.33550DOI Listing
July 2021

Treatment outcomes of transoral robotic and non-robotic surgeries to treat oropharyngeal, hypopharyngeal, and supraglottic squamous cell carcinoma: A multi-center retrospective observational study in Japan.

Auris Nasus Larynx 2021 Jun 22;48(3):502-510. Epub 2021 Feb 22.

Department of Otorhinolaryngology-Head and Neck Surgery, Yokohama City University, School of Medicine, Yokohama, Japan.

Objectives: The aim of this multicenter retrospective cohort study was to compare efficacy and subsequent postoperative treatment between transoral robotic surgery (TORS) and any non-robotic transoral surgery in Japanese patients with early oropharyngeal squamous cell carcinoma (OPSCC), hypopharyngeal SCC (HPSCC), or supraglottic SCC (SGSCC).

Materials And Methods: Clinical information and surgical outcomes were compared between patients with early-stage OPSCC, HPSCC, and SGSCC who underwent TORS (TORS cohort) and those who underwent non-robotic transoral surgery, including transoral videolaryngoscopic surgery (TOVS), endoscopic laryngopharyngeal surgery (ELPS), and transoral laser microsurgery (TLM) (non-robotic cohort). The data of the Head and Neck Cancer Registry of Japan (registry cohort) were used to validate the comparison. The main outcomes were the presence of positive margins under pathology and the requirement for postoperative therapy, including radiotherapy or chemoradiotherapy.

Results: Sixty-eight patients in the TORS cohort, 236 patients in the non-robotic cohort, and 1,228 patients in the registry cohort were eligible for this study. Patients in the TORS cohort were more likely to have oropharyngeal tumor disease and T2/3 disease than those in the other cohorts (P<0.001 and P=0.052, respectively). The TORS cohort had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.018), as well as fewer patients who underwent postoperative treatment, although the difference was not significant (P=0.069). In the subgroup analysis of patients with OPSCC, a total of 57 patients in the TORS cohort, 73 in the non-robotic cohort, and 171 in the registry cohort were eligible for the present study. Patients with OPSCC who underwent TORS were more likely to have lateral wall lesions than those in the other cohorts (P=0.003). The TORS cohort also had significantly fewer patients with positive surgical margins than the non-robotic cohort (P=0.026), and no patients in the TORS cohort underwent any postoperative treatment for OPSCC, although the difference was not significant (P=0.177).

Conclusions: Our results suggest that TORS leads to fewer positive surgical margins than non-robotic transoral surgeries. The clinical significance of TORS may be further validated through the results of all-case surveillance for patients who underwent TORS running in Japan in the future.
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http://dx.doi.org/10.1016/j.anl.2021.01.024DOI Listing
June 2021

Management of tracheostomy in COVID-19 patients: The Japanese experience.

Auris Nasus Larynx 2021 Jun 9;48(3):525-529. Epub 2021 Jan 9.

Department of Otolaryngology - Head and Neck Surgery, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, North 15 West 7, Sapporo 060-8638, Japan. Electronic address:

Objective: Involvement in the tracheostomy procedure for COVID-19 patients can lead to a feeling of fear in medical staff. To address concerns over infection, we gathered and analyzed experiences with tracheostomy in the COVID-19 patient population from all over Japan.

Methods: The data for health-care workers involved in tracheostomies for COVID-19-infected patients were gathered from academic medical centers or their affiliated hospitals from all over Japan.

Results: Tracheostomies have been performed in 35 COVID-19 patients with a total of 91 surgeons, 49 anesthesiologists, and 49 surgical staff members involved. Twenty-eight (80%) patients underwent surgery more than 22 days after the development of COVID-19-related symptoms (11: 22-28 days and 17: ≥29 days). Thirty (85.7%) patients underwent surgery ≥ 15 days after intubation (14: 15-21 days, 6: 22-28 days, and 10: ≥29 days). Among the total of 189 health-care workers involved in the tracheostomy procedures, 25 used a powered air-purifying respirator (PAPR) and 164 used a N95 mask and eye protection. As a result, no transmission to staff occurred during the 2 weeks of follow-up after surgery.

Conclusion: No one involved in tracheostomy procedures were found to have been infected with COVID-19 in this Japanese study. The reason is thought to be that the timing of the surgery was quite late after the infections, and the surgery was performed using appropriate PPE and surgical procedure. The indications for and timing of tracheostomy for severe COVID-19 patients should be decided through multidisciplinary discussion.
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http://dx.doi.org/10.1016/j.anl.2021.01.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7794599PMC
June 2021

Pathological evaluation of tumor grade for salivary adenoid cystic carcinoma: A proposal of an objective grading system.

Cancer Sci 2021 Mar 2;112(3):1184-1195. Epub 2021 Feb 2.

Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.

Three pathological grading systems advocated by Perzin/Szanto, Spiro, and van Weert are currently used for adenoid cystic carcinoma (AdCC). In these systems, the amount or presence of the solid tumor component in AdCC specimens is an important index. However, the "solid tumor component" has not been well defined. Salivary AdCC cases (N = 195) were collected after a central pathology review. We introduced a novel criterion for solid tumor component, minAmax (minor axis maximum). The largest solid tumor nest in each AdCC case was histologically screened, the maximum oval fitting the solid nest was estimated, and the length of the minor axis of the oval (minAmax) was measured. The prognostic cutoff for the minAmax was determined using training and validation cohorts. All cases were evaluated for the four grading systems, and their prognostic impact and interobserver variability were examined. The cutoff value for the minAmax was set at 0.20 mm. Multivariate prognostic analyses showed the minAmax and van Weert systems to be independent prognostic tools for overall, disease-free, and distant metastasis-free survival while the Perzin/Szanto and Spiro systems were selected for overall survival but not for disease-free or distant metastasis-free survival. The highest hazard ratio for overall survival (11.9) was obtained with the minAmax system. The reproducibility of the minAmax system (kappa coefficient of 0.81) was scored as very good while those of the other three systems were scored as moderate. In conclusion, the minAmax is a simple, objective, and highly reproducible grading system useful for prognostic stratification for salivary AdCC.
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http://dx.doi.org/10.1111/cas.14790DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7935776PMC
March 2021

Multi-institutional Survey of Squamous Cell Carcinoma of the External Auditory Canal in Japan.

Laryngoscope 2021 03 30;131(3):E870-E874. Epub 2020 Jul 30.

Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Japan.

Objectives: This study aimed to evaluate the efficacy of chemoradiotherapy (CRT) for patients with advanced cancer of the external auditory canal (EAC) by analyzing the outcome of the patients.

Methods: This is a multi-institutional retrospective survey, and we reviewed the medical records of the subjects. A total of 181 patients with tumor (T)3 or T4 tumor in 17 institutions were enrolled. Further analysis was performed for 74 patients who underwent CRT under curative intent.

Results: Overall 5-year survival rates of the patients who underwent CRT (n = 74) were 54.6%. Those of the patients who underwent CRT with modified TPF (docetaxel, cisplatin [CDDP], and 5-fluorouracil) regimen (n = 50) and CRT with CDDP regimens (n = 24) were 64.4% and 36.7%, respectively. Significant differences were observed between these two groups.

Conclusion: Given the tendency that head and neck surgeons prefer CRT for advanced larger cancer of the EAC, CRT for advanced EAC cancer using the modified TPF regimen showed good clinical outcomes.

Level Of Evidence: 4 Laryngoscope, 131:E870-E874, 2021.
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http://dx.doi.org/10.1002/lary.28936DOI Listing
March 2021

Prospective Evaluation of Health-Related Quality of Life in Patients Undergoing Anterolateral Craniofacial Resection with Orbital Exenteration.

J Neurol Surg B Skull Base 2020 Oct 24;81(5):585-593. Epub 2019 Jul 24.

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

 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.  Present study is a prospective, observational study.  The study took place at the hospital department.  Twenty-six consecutive patients were selected who underwent AL-CFR with OE at our hospital between 2005 and 2015.  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.  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.  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.
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http://dx.doi.org/10.1055/s-0039-1694010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7591358PMC
October 2020

Pathological and Virological Studies of p16-Positive Oropharyngeal Carcinoma with a Good Response to Neoadjuvant Chemotherapy.

Microorganisms 2020 Sep 29;8(10). Epub 2020 Sep 29.

Department of Otolaryngology, Aichi Medical University, Nagakute, Aichi 480-1195, Japan.

Human papillomavirus (HPV)-related, p16-positive oropharyngeal carcinoma is considered to be sensitive to anticancer drugs, and the standard treatment is therefore chemoradiotherapy, rather than surgery, especially for aggressive disease. However, with this higher sensitivity, chemotherapy alone may achieve a pathological complete response (CR), making radiation therapy unnecessary. A 46-year-old man with p16-positive squamous cell carcinoma (SCC) of the lateral oropharynx (palatine tonsil) underwent neoadjuvant chemotherapy. This achieved clinically significant tumor shrinkage and therefore surgery was performed for subsequent definitive treatment. Clinical and CT findings indicated a good effect of neoadjuvant chemotherapy on the tumor. A biopsy prior to chemotherapy revealed SCC, which demonstrated p16 immunoreactivity and positive signals for high-risk HPV by RNA in situ hybridization. The post-chemotherapy surgical specimen showed pathological CR and no p16 positive cells nor positive signals for high-risk HPV those were detected in the pre-chemotherapy specimen. There are some reports of chemotherapy alone achieving pathological CR in cases of p16-positive oropharyngeal carcinoma, but none have included high-risk HPV RNA findings. This is the first report of the disappearance of cancer cells as well as p16 staining and a positive signal for high-risk HPV. Achieving pathological CR confirmed by immunohistochemistry and high-risk HPV RNA in situ hybridization in a solid tumor with chemotherapy alone suggests that chemotherapy may have both an antitumor effect and an antiviral effect. Forgoing subsequent radiotherapy and undergoing surgery might be unnecessary and follow-up instead might be sufficient in such cases. Into the future, in an optimal tailored treatment approach, the option of neoadjuvant chemotherapy should be considered for management of p16-positive oropharyngeal carcinoma. Other options such as tumor immunotherapy are also expected to be effective.
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http://dx.doi.org/10.3390/microorganisms8101497DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7600755PMC
September 2020

Questionnaire survey on nurses and speech therapists regarding dysphagia rehabilitation in Japan.

Auris Nasus Larynx 2021 Apr 25;48(2):241-247. Epub 2020 Aug 25.

Department of Otolaryngology and Head and Neck Surgery, Tohoku University Graduate School of Medicine, 1-1 Seiryo-machi, Aoba-ku, Sendai 980-8574, Japan.

Objective: Current interventions of dysphagia are not generalizable, and treatments are commonly used in combination. We conducted a questionnaire survey on nurses and speech therapists regarding dysphagia rehabilitation to understand the current situation in Japan.

Methods: The questionnaire was sent to 616 certified nurses in dysphasia nursing and 254 certified speech-language-hearing therapists for dysphagia. Based on "Summaries of training methods in 2014" by JSDR, 24 local indirect exercises, 11 general indirect exercises, and 13 direct exercises were selected. The Likert scale "How do you feel about each method" was used as follows: A; Frequency, B; Ease, C; Adherence, D; Effectiveness (1-5))?".

Results: Two hundred fifty (40%) nurses and 145 (57%) speech-language-hearing therapists (ST) responded to the questionnaire. The direct exercise was associated with a significantly high score in every question. In indirect exercises, "Cervical range of motion exercise," "Orofacial myofunctional exercise," "Lip closure exercise." "Ice massage of pharynx" and "Huffing" were used relatively frequently. "Balloon dilatation therapy" and "Tube exercise" was associated with a relatively high discrepancy for two questions. Frequency" and the sum of "Ease," "Adherence," and "Effectiveness." was significantly correlated for local indirect exercises (r2 = 0.928, P < 0.01), general indirect exercises (r2 = 0.987, P < 0.01), and direct exercises (r2 = 0.996, P < 0.01) (Fig. 5).

Conclusion: This study examined the current situation of dysphagia rehabilitation in Japan. Our results aid to increase understanding and selection of rehabilitative treatments for dysphagia patients in Japan.
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http://dx.doi.org/10.1016/j.anl.2020.08.004DOI Listing
April 2021

Safety and feasibility of fat injection therapy with adipose-derived stem cells in a rabbit hypoglossal nerve paralysis model: A pilot study.

Auris Nasus Larynx 2021 Apr 20;48(2):274-280. Epub 2020 Aug 20.

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550, Japan.

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±312µm vs. 405±220µm and 413±226µm; 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.
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http://dx.doi.org/10.1016/j.anl.2020.08.003DOI Listing
April 2021

Society of swallowing and dysphagia of Japan: Position statement on dysphagia management during the COVID-19 outbreak.

Auris Nasus Larynx 2020 Oct 23;47(5):715-726. Epub 2020 Jul 23.

Department of Otolaryngology, Tokyo Metropolitan Health and Hospitals Corporation Ebara Hospital, Tokyo, Japan; Department of Speech and Hearing Sciences, International University of Health and Welfare, and the Voice and Swallowing Center, Fukuoka Sanno Hospital, Fukuoka, Japan.

On April 14, the Society of Swallowing and Dysphagia of Japan (SSDJ) proposed its position statement on dysphagia treatment considering the ongoing spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The main routes of transmission of SARS-CoV-2 are physical contact with infected persons and exposure to respiratory droplets. In cases of infection, the nasal cavity and nasopharynx have the highest viral load in the body. Swallowing occurs in the oral cavity and pharynx, which correspond to the sites of viral proliferation. In addition, the possibility of infection by aerosol transmission is also concerning. Dysphagia treatment includes a broad range of clinical assessments and examinations, dysphagia rehabilitation, oral care, nursing care, and surgical treatments. Any of these can lead to the production of droplets and aerosols, as well as contact with viral particles. In terms of proper infection control measures, all healthcare professionals involved in dysphagia treatment must be fully briefed and must appropriately implement all measures. In addition, most patients with dysphagia should be considered to be at a higher risk for severe illness from COVID-19 because they are elderly and have complications including heart diseases, diabetes, respiratory diseases, and cerebrovascular diseases. This statement establishes three regional categories according to the status of SARS-CoV-2 infection. Accordingly, the SSDJ proposes specific infection countermeasures that should be implemented considering 1) the current status of SARS-CoV-2 infection in the region, 2) the patient status of SARS-CoV-2 infection, and 3) whether the examinations or procedures conducted correspond to aerosol-generating procedures, depending on the status of dysphagia treatment. This statement is arranged into separate sections providing information and advice in consideration of the COVID-19 outbreak, including "terminology", "clinical swallowing assessment and examination", "swallowing therapy", "oral care", "surgical procedure for dysphagia", "tracheotomy care", and "nursing care". In areas where SARS-CoV-2 infection is widespread, sufficient personal protective equipment should be used when performing aerosol generation procedures. The current set of statements on dysphagia management in the COVID-19 outbreak is not an evidence-based clinical practice guideline, but a guide for all healthcare workers involved in the treatment of dysphagia during the COVID-19 epidemic to prevent SARS-CoV-2 infection.
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http://dx.doi.org/10.1016/j.anl.2020.07.009DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7377736PMC
October 2020

Optimization of therapeutic strategy for p16-positive oropharyngeal squamous cell carcinoma: Multi-institutional observational study based on the national Head and Neck Cancer Registry of Japan.

Cancer 2020 09 10;126(18):4177-4187. Epub 2020 Jul 10.

University Hospital Medical Information Network, Tokyo, Japan.

Background: Although the American Joint Committee on Cancer TNM classification has been amended to include human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (OPSCC) as an independent entity, to the authors' knowledge the optimized de-escalating treatment modality has not been established to date.

Methods: The authors conducted a retrospective, nationwide, observational study in patients with HPV-related OPSCC who were treated from 2011 to 2014 in Japan to determine the best treatment modality.

Results: A total of 688 patients who were newly diagnosed with HPV-related OPSCC who were treated with curative intent at 35 institutions and had coherent clinical information and follow-up data available were included in the current study. In patients with T1-T2N0 disease (79 patients), both the 3-year recurrence-free survival and overall survival (OS) rates were 100% in the group treated with radiotherapy (RT) as well as the group receiving concurrent chemoradiotherapy (CCRT). The 3-year OS rates were 94.4% (for patients with T1N0 disease) and 92.9% (for patients with T2N0 disease) among the patients treated with upfront surgery. In patients with stage I to stage II HPV-related OPSCC, the 5-year recurrence-free survival and OS rates were 91.4% and 92%, respectively, in the patients treated with CCRT with relatively high-dose cisplatin (≥160 mg/m ; 114 patients) and 74.3% and 69.5%, respectively, in the patients treated with low-dose cisplatin (<160 mg/m ; 17 patients).

Conclusions: Despite it being a retrospective observational trial with a lack of information regarding toxicity and morbidity, the results of the current study demonstrated that patients with T1-T2N0 HPV-related OPSCC could be treated with RT alone because of the equivalent outcomes of RT and CCRT, and patients with stage I to stage II HPV-related OPSCC other than those with T1-T2N0 disease could be treated with CCRT with cisplatin at a dose of ≥160 mg/m .
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http://dx.doi.org/10.1002/cncr.33062DOI Listing
September 2020

The impact of clinicopathological factors on clinical outcomes in patients with salivary gland adenoid cystic carcinoma: a multi-institutional analysis in Japan.

Int J Clin Oncol 2020 Oct 1;25(10):1774-1785. Epub 2020 Jul 1.

Department of Pathology and Molecular Diagnostics, Nagoya City University Graduate School of Medical Sciences, 1-Kawasumi, Mizuho-ku, Nagoya, 467-8601, Japan.

Background: Owing to the low incidence of adenoid cystic carcinoma (AdCC), reliable survival estimates and prognostic factors remained unclarified.

Methods: In this multi-institutional retrospective analysis, we collected 192 AdCC cases, and investigated the impact of clinicopathological factors on clinical outcomes of the patients. All AdCC cases were of salivary gland origin and were surgically treated with curative intent. Diagnoses of AdCC were validated by a central pathology review by expert pathologists.

Results: The 5-year overall survival (OS) and disease-free survival (DFS) rates were 92.5 and 50.0%, respectively. Treatment failure occurred in 89 patients (46%) with the distant failures in 65 (34%). Multivariate analysis indicated that pN2 and a pathologically positive surgical margin were independent prognostic factors for both OS and DFS. Histological grade III was an independent prognostic factor for OS. A primary site in the submandibular gland, pT3/4, pN1, and histological grade II were independent prognostic factors for DFS. Postoperative radiation therapy (PORT) improved the locoregional control (LRC) rate. Prophylactic neck dissection was not associated with a better OS or better LRC among patients with cN0. Facial nerve dissection did not improve clinical outcomes in parotid AdCC cases without facial nerve palsy.

Conclusions: A higher TN classification, a pathologically positive surgical margin, and a higher histological grade were associated with a lower OS. PORT improved LRC rates but neck dissection failed to improve clinical outcomes in patients with cN0. As the distant metastasis was frequent, effective systemic therapy is imperative to improve the survival of AdCC patients.
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http://dx.doi.org/10.1007/s10147-020-01731-9DOI Listing
October 2020

Pituitary dysfunction induced by immune checkpoint inhibitors is associated with better overall survival in both malignant melanoma and non-small cell lung carcinoma: a prospective study.

J Immunother Cancer 2020 07;8(2)

Department of Endocrinology and Diabetes, Nagoya University Graduate School of Medicine, Nagoya, Japan

Background: Several immune-related adverse events (irAEs) are reported to be associated with therapeutic efficacy of immune checkpoint inhibitors, yet whether pituitary dysfunction, a life-threatening irAE, affects overall survival (OS) in patients with malignancies is unclear. This prospective study examined the association of pituitary dysfunction (pituitary-irAE) with OS of patients with non-small cell lung carcinoma (NSCLC) or malignant melanoma (MM).

Methods: A total of 174 patients (NSCLC, 108; MM, 66) treated with ipilimumab, nivolumab, pembrolizumab, or atezolizumab at Nagoya University Hospital were evaluated for OS and the development of pituitary-irAE. Kaplan-Meier curves of OS as a function of the development of pituitary-irAE were produced with the log-rank test as a primary endpoint.

Results: Pituitary-irAE was observed in 16 patients (4 (3.7%) with NSCLC, 12 (18.2%) with MM) having two different disease types: hypophysitis with deficiency of multiple anterior pituitary hormones accompanied by pituitary enlargement, and isolated adrenocorticotropic hormone (ACTH) deficiency without pituitary enlargement. Among these patients, 6 developed pituitary-irAE while being treated with ipilimumab (6/25 patients (24.0%) treated with ipilimumab) and 10 developed pituitary-irAE during treatment with nivolumab or pembrolizumab (10/167 (6.0%)). All 16 patients had ACTH deficiency and were treated with physiological doses of hydrocortisone. The development of pituitary-irAE was associated with better OS in patients with NSCLC (not reached vs 441 (95% CI not calculated) days, p<0.05) and MM (885 (95% CI 434 to 1336) vs 298 (95% CI 84 to 512) days, p<0.05).

Conclusions: In our study cohort, the incidence of pituitary-irAE was higher than previously reported and the development of pituitary-irAE predicted better prognosis for both NSCLC and MM when patients were treated with physiological doses of hydrocortisone.

Clinical Trials Registration: UMIN000019024.
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http://dx.doi.org/10.1136/jitc-2020-000779DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7328763PMC
July 2020

Anesthetic and surgical management of tracheostomy in a patient with COVID-19.

Auris Nasus Larynx 2020 Jun 18;47(3):472-476. Epub 2020 Apr 18.

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 466-8550 Japan.

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.
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http://dx.doi.org/10.1016/j.anl.2020.04.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165273PMC
June 2020

Erratum: Increased Defect Size is Associated with Increased Complication Rate after Free Tissue Transfer for Midanterior Skull-Base Reconstruction.

J Neurol Surg B Skull Base 2020 Apr 10;81(2):e1. Epub 2019 Jun 10.

Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

[This corrects the article DOI: 10.1055/s-0038-1676777.].
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http://dx.doi.org/10.1055/s-0039-1692394DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082163PMC
April 2020

Increased Defect Size is Associated with Increased Complication Rate after Free Tissue Transfer for Midanterior Skull-Base Reconstruction.

J Neurol Surg B Skull Base 2020 Apr 26;81(2):121-127. Epub 2019 Feb 26.

Department of Plastic and Reconstructive Surgery, Nagoya University Graduate School of Medicine, Nagoya, Japan.

 Complications after skull-base reconstruction are often problematic. We consider that local factors, for example, localization of defect areas are possible risk factors. This study aimed to investigate our case series of skull-base reconstructions in our institution and to identify local risk factors that predispose to wound complications.  This study is presented as a retrospective study.  Research work was took place at Nagoya University Hospital.  Forty-eight patients who had undergone reconstruction after midanterior skull-base resection between January 2004 and December 2015 were included in this study. Defects apart from the skull-base were categorized into nasal and paranasal cavity (N), orbit (O), palate (P), and facial skin (S). Postoperative local complications including cerebrospinal fluid (CSF) leakage, local infection, wound dehiscence (fistula in face or palate), and flap necrosis (partial or total) were investigated.  Main outcome measures were postoperative complications in patients with each defect.  Apart from the skull-base, defects included 28 ONP (58.3%), 10 ONPS (20.8%), 3 ON (6.3%), 3 ONS (6.3%), 1 NP (2.1%), and 1 OS (2.1%). Comparison based on numbers of resected regions revealed that a significantly higher complication rate was seen in patients with four resected regions than in those with three regions (90.0% vs. 45.2%,  < 0.05).  There was a trend suggesting that more resected regions corresponded to a greater risk of complications in midanterior skull-base reconstruction. Reconstructive surgeons need to carefully consider the reconstruction of such complicated defects.
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http://dx.doi.org/10.1055/s-0038-1676777DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7082168PMC
April 2020

Real world data of liver injury induced by immune checkpoint inhibitors in Japanese patients with advanced malignancies.

J Gastroenterol 2020 Jun 2;55(6):653-661. Epub 2020 Mar 2.

Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, 466-8550, Japan.

Background: Liver injury induced by immune checkpoint inhibitors (ICIs) is an immune-related adverse event (irAE) whose incidence has increased with the broader use of ICIs in clinical practice. However, the incidental risk factors of immune-related liver injury are unknown. We investigated the clinical characteristics of immune-related liver injury.

Methods: A total of 546 patients treated with ICIs for advanced malignancies between September 2014 and February 2019 were included retrospectively. Factors associated with immune-related liver injury were determined.

Results: Immune-related liver injury (≥ Grade 3) occurred in 29 (5.3%) patients (Grade 3, n = 20; Grade 4, n = 8; Grade 5, n = 1) during the follow-up period (median 153 days). The patterns of liver injuries were hepatocellular, n = 6 (20.7%); cholestatic, n = 17 (58.6%); and mixed, n = 6 (20.7%). The median period between the initial administration of ICIs and the incidence of irAEs was 52 days. Of 29 patients with immune-related liver injury (≥ Grade 3), four showed immune-related cholangitis with non-obstructive dilation of the bile ducts. Factors that were significantly associated with the incidence of immune-related liver injury in multivariate analysis were use of ipilimumab, anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) agent [hazard ratio [HR] 4.22, 95% confidence interval (CI) 1.65-10.80, P = 0.003], and fever over 38 °C within 24 h of initial ICI administration (HR 6.21, 95% CI 2.68-14.40, P < 0.001).

Conclusions: We found that the use of ipilimumab and the presence of fever within 24 h of initial ICI administration were predictive factors for immune-related liver injury.
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http://dx.doi.org/10.1007/s00535-020-01677-9DOI Listing
June 2020

Anti-thyroid antibodies and thyroid echo pattern at baseline as risk factors for thyroid dysfunction induced by anti-programmed cell death-1 antibodies: a prospective study.

Br J Cancer 2020 03 3;122(6):771-777. Epub 2020 Feb 3.

Department of Clinical Oncology and Chemotherapy, Nagoya University Hospital, Nagoya, Japan.

Background: Anti-programmed cell death-1 (PD-1) antibodies can cause thyroid dysfunction. However, no predictive biomarkers enabling stratification of thyroid dysfunction risk have been identified.

Methods: A total of 209 patients treated with an anti-PD-1 antibody were evaluated for anti-thyroid antibodies at baseline and prospectively for thyroid function every 6 weeks for 24 weeks after treatment initiation, and then observed until the visits stopped. Thyroid ultrasonography was performed if the patient was positive for anti-thyroid antibodies at baseline.

Results: Of the 209 patients, 19 (9.1%) developed thyroid dysfunction (destructive thyroiditis or hypothyroidism). The cumulative incidence of thyroid dysfunction was significantly higher in patients who were positive vs. negative for anti-thyroid antibodies (15/44 [34.1%] vs. 4/165 [2.4%], p < 0.001). Forty-two patients positive for anti-thyroid antibodies at baseline were divided into two groups according to the presence of an irregular echo pattern. The cumulative incidence of thyroid dysfunction was significantly higher in those with an irregular vs. a regular echo pattern (13/23 [56.5%] vs. 1/19 [5.3%], p = 0.001). None of the patients developed thyroid dysfunction after the initial 24-week period.

Conclusions: The risk of thyroid dysfunction induced by anti-PD-1 antibodies can be predicted by evaluation of anti-thyroid antibodies and the thyroid echo pattern at baseline.

Trial Registration: UMIN000019024.
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http://dx.doi.org/10.1038/s41416-020-0736-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078193PMC
March 2020

Central pathology review of salivary gland adenoid cystic carcinoma.

Head Neck 2020 08 23;42(8):1721-1727. Epub 2020 Jan 23.

Department of Pathology and Molecular Diagnostics, Graduate School of Medical Sciences, Nagoya City University, Nagoya, Japan.

Background: To assess the role of a central pathology review in the diagnosis of salivary gland adenoid cystic carcinoma (AdCC).

Methods: Surgically resected salivary gland tumors diagnosed as AdCC (n = 219) in 15 reference hospitals in Japan were subjected to a retrospective pathological re-evaluation.

Results: After the review, the AdCC diagnosis was revised in 21/219 cases (9.6%). The six benign tumors (2.7%) comprised five basal cell adenomas and one pleomorphic adenoma, and among these six patients, three received postoperative radiotherapy. The remaining 15 malignant tumors (6.8%) comprised nine basal cell adenocarcinomas and six other carcinomas. All revised basal cell adenoma/adenocarcinoma cases were of rare cribriform variants.

Conclusions: A significant proportion of AdCC pathology reports were revised after the central pathology review. It should be emphasized that the greatest attention should be paid in differentiating AdCC from cribriform variant basal cell adenoma/adenocarcinoma, which is very rare in salivary gland tumors.
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http://dx.doi.org/10.1002/hed.26081DOI Listing
August 2020

Third Epidemiological Analysis of Nasopharyngeal Carcinoma in the Central Region of Japan from 2006 to 2015.

Cancers (Basel) 2019 Aug 15;11(8). Epub 2019 Aug 15.

Department of Otorhinolaryngology Head and Neck Surgery Graduate School of Medical Science University of Fukui, Fukui 910-1193, Japan.

The present study aimed to clarify the incidence and clinical outcomes of nasopharyngeal carcinoma (NPC) in the Chubu region of Japan from 2006 to 2015, compared with previous reports. A retrospective analysis was conducted based on medical records from 40 hospitals located in the Chubu region in the central Japanese main island, with a population of around 22.66 million individuals. This study was designed in line with to two previous clinical studies into NPC conducted in the same area of Japan. We recruited NPC patients diagnosed in hospitals across this area over a 10-year period (2006-2015) using a questionnaire about sex, age, primary site, clinical symptoms, pathology, Union for International Cancer Control (UICC) staging, serological exam, treatment, and survival. A total of 620 NPC patients were identified. The age-standardized incidence of NPC from 2006 to 2015 was 0.27 per 100,000 individuals per year. There were no significant differences between this study and the previous two studies conducted in the same area of Japan. The five-year overall survival rate for all patients was 75.9%, while those for patients with stages I, II, III, and IVA were 97%, 91%, 79%, and 68%, respectively. The age-standardized annual incidence of NPC in the present study was 0.27 per 100,000 individuals per year, which was relatively low and stable. The five-year overall survival rate for all NPC patients was significantly improved in this decade compared with previous studies. The smoking rates in male and female NPC patients were 64.5% and 18.8%, respectively, thereby suggesting the involvement of smoking in the incidence of NPC.
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http://dx.doi.org/10.3390/cancers11081180DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6721521PMC
August 2019

Exploration of coping styles in male patients with head and neck cancer: a prospective cohort study.

Nagoya J Med Sci 2019 May;81(2):249-258

Department of Psychiatry, Nagoya University Graduate School of Medicine, Nagoya, Japan.

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: , and . and were similar to the copings of mixed gender patients with heterogeneous cancers, and 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 , related with psychological distress. We believe that an understanding of the coping style revealed in our study will improve the psychological support offered to male patients with HNC.
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http://dx.doi.org/10.18999/nagjms.81.2.249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6556458PMC
May 2019

Diagnosis of cervical lymph node metastases in head and neck cancer with ultrasonic measurement of lymph node volume.

Auris Nasus Larynx 2019 Dec 8;46(6):889-895. Epub 2019 Mar 8.

Department of Otorhinolaryngology, Nagoya University Graduate School of Medicine, Nagoya, Japan.

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 mm for the tumor positive nodes, which was significantly greater than the US volume of 512 ± 315 mm 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 mm, 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.
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http://dx.doi.org/10.1016/j.anl.2019.02.003DOI Listing
December 2019

Surgical management around the paratracheal area of hypopharyngeal cancer.

Jpn J Clin Oncol 2019 May;49(5):452-457

Department of Head and Neck Surgery, National Cancer Center Hospital East, Kashiwa, Japan.

Objective: We aimed to clarify the suitable surgical management around the paratracheal area of patients who undergo total pharyngolaryngectomy based on the pathological results of hypopharyngeal cancer.

Methods: The study was conducted under a multicenter, retrospective observational design in Japan. We analyzed histopathological paratracheal lymph node metastasis and thyroid invasion, and recurrence around the paratracheal area for 184 patients who underwent initial surgery among 280 participants.

Results: There were significant differences in the frequency of metastasis to paratracheal lymph nodes as cN advances (P = 0.0344) and cT advances (P = 0.00028). By subsite, the paratracheal lymph node metastasis ratio was 22/130 patients (16.9%) in piriform sinus (PS), 8/32 (25.0%) in PW, 5/22 (22.7%) in PC and 10/17 (58.8%) in cervical esophagus (Ce+). The ratio of cases with bilateral paratracheal metastasis tended to be higher in cN2c, posterior wall (PW) and postcricoid (PC). Invasion to the thyroid was histopathologically confirmed in 16/184 patients (8.7%). Invasion from the primary lesion was in 15 patients.

Conclusion: This study indicates that it is better for patients with advanced hypopharyngeal cancer at minimum undergo ipsilateral paratracheal lymph node dissection. Tumor subsite of PW, PC or cN2c disease or disease extending to the Ce+ should be treated with bilateral paratracheal neck dissection. In order to more reliably perform paratracheal dissection, there is also an option to resect the thyroid lobe in the range of dissection. Preservation of the thyroid gland can be considered if invasion into the thyroid gland has been clearly ruled out.
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http://dx.doi.org/10.1093/jjco/hyz019DOI Listing
May 2019

Incidence of Multiple Paternity and Inbreeding in High-Density Brown Bear Populations on the Shiretoko Peninsula, Hokkaido, Japan.

J Hered 2019 05;110(3):321-331

The Laboratory of Wildlife Biology and Medicine, Department of Environmental Veterinary Science, Graduate School of Veterinary Medicine, Hokkaido University, Hokkaido, Japan.

Understanding the breeding ecology of a species is essential for the appropriate conservation and management of wildlife. In brown bears, females occasionally copulate with multiple males in one breeding season, which may lead to multiple paternity in a single litter. In contrast, inbreeding, a potential factor in the reduction of genetic diversity, may occur, particularly in threatened populations. However, few studies have reported the frequency of these phenomena in brown bear populations. Here, we investigated the incidence of multiple paternity and inbreeding in a high-density brown bear population on the Shiretoko Peninsula in Hokkaido, Japan. A total of 837 individuals collected from 1998 to 2017 were genotyped at 21 microsatellite loci, and parentage analysis was performed. Out of 70-82 litters with ≥2 offspring, 14.6-17.1% of litters were sired by multiple males. This was comparable to the rate reported in a Scandinavian population, although population density and litter size, factors that potentially affect the incidence of multiple paternity, differed between the 2 populations. Out of 222 mother-father mating pairs, 6 litters (2.7%) resulted from matings between fathers and daughters. Additionally, 1 (0.5%) and 4 (1.8%) cases of mating between maternal half-siblings and between paternal half-siblings, respectively, were observed; however, no cases of mating between mothers and sons or between full siblings were observed. Our results suggest that male-biased natal dispersal effectively limits mating between closely related individuals (aside from fathers and daughters) in brown bears.
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http://dx.doi.org/10.1093/jhered/esz002DOI Listing
May 2019

Role of transcranial sphenoidotomy in skull base surgery: classification of surgical techniques based on the surgical anatomy of the sphenoid sinus.

J Neurosurg 2018 Nov 1:1-10. Epub 2018 Nov 1.

2Department of Neurosurgery, Fukushima Medical University, Fukushima; and.

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.
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http://dx.doi.org/10.3171/2018.6.JNS181013DOI Listing
November 2018

Study Protocol: Prospective Study of Concurrent Chemoradiotherapy with S-1 and Hypofractionated Radiotherapy for Outpatients with Early Glottic Squamous Cell Carcinomas

Asian Pac J Cancer Prev 2018 May 26;19(5):1195-1199. Epub 2018 May 26.

Department of Radiology, Nagoya University Graduate School of Medicine 65 Tsurumai-cho, Shouwa-ku, Nagoya 4668550, Aichi, Japan. Email:

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.
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http://dx.doi.org/10.22034/APJCP.2018.19.5.1195DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6031847PMC
May 2018
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