Publications by authors named "Yasuhisa Hasegawa"

192 Publications

Gas Permeation Properties of High-Silica CHA-Type Zeolite Membrane.

Membranes (Basel) 2021 Mar 30;11(4). Epub 2021 Mar 30.

Research Institute of Chemical Process Technology, National Institute of Advanced Industrial Science and Technology, 4-2-1 Nigatake, Sendai 983-8551, Japan.

The polycrystalline CHA-type zeolite layer with Si/Al = 18 was formed on the porous α-AlO tube in this study, and the gas permeation properties were determined using single-component H, CO, N, CH, -CH, and SF at 303-473 K. The membrane showed permeation behavior, wherein the permeance reduced with the molecular size, attributed to the effect of molecular sieving. The separation performances were also determined using the equimolar mixtures of N-SF, CO-N, and CO-CH. As a result, the N/SF and CO/CH selectivities were as high as 710 and 240, respectively. However, the CO/N selectivity was only 25. These results propose that the high-silica CHA-type zeolite membrane is suitable for the separation of CO from CH by the effect of molecular sieving.
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http://dx.doi.org/10.3390/membranes11040249DOI Listing
March 2021

Pervaporative Dehydration of Organic Solvents Using High-Silica CHA-Type Zeolite Membrane.

Membranes (Basel) 2021 Mar 23;11(3). Epub 2021 Mar 23.

National Institute of Advanced Industrial Science and Technology (AIST), Research Institute of Chemical Process Technology, 4-2-1 Nigatake, Sendai 983-8551, Japan.

A high-silica chabazite (CHA) type zeolite membrane was prepared on the porous α-AlO support tube by the secondary growth of seed particles. The dehydration performances of the membrane were determined using methanol, ethanol, 2-propanol, acetone, acetic acid, methyl ethyl ketone (MEK), tetrahydrofuran (THF), -dimethylformamide (DMF), dimethyl sulfoxide (DMSO), and -methyl-2-pyrolidone (NMP) at 303-373 K. As a result, the dehydration performances of the membrane were categorized to following three types: (1) 2-propanol, acetone, THF, and MEK; (2) ethanol and acetic acid; and (3) methanol, DMF, and DMSO, and NMP. The adsorption isotherms of water, methanol, ethanol, and 2-propanol were determined to discuss the influences of the organic solvents on the permeation and separation performances of the membrane. For 2-propanol, acetone, MEK, and THF solutions, the high permeation fluxes and separation factors were obtained because of the preferential adsorption of water due to molecular sieving. In contrast, the permeation fluxes and separation factors were relatively low for methanol, DMF, and DMSO, and NMP solutions. The lower dehydration performance for the methanol solution was due to the adsorption of methanol. The permeation fluxes for ethanol and acetic acid solution were ca. 1 kg m h. The significantly low flux was attributed to the similar molecular diameter to the micropore size of CHA-type zeolite.
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http://dx.doi.org/10.3390/membranes11030229DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8005107PMC
March 2021

Serum CD109 levels reflect the node metastasis status in head and neck squamous cell carcinoma.

Cancer Med 2021 Feb 9;10(4):1335-1346. Epub 2021 Feb 9.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background: Various biomarkers are being developed for the early diagnosis of cancer and for predicting its prognosis. The aim of this study is to evaluate the diagnostic significance of serum CD109 in head and neck squamous cell carcinoma (HNSCC).

Methods: The serum CD109 levels in a total of 112 serum samples collected before and after surgery from 56 HNSCC patients were analyzed with an enzyme-linked immunosorbent assay (ELISA). The clinical factor that showed a statistically significant association with both the preoperative serum CD109 level, and the CD109 index: which was defined as the ratio of the preoperative serum CD109 level to the postoperative serum CD109 level, were assessed. The correlations between the serum CD109 levels and lymph node density (LND), pathological features such as lymphatic invasion, and serum SCC antigen levels were also assessed.

Results: The ELISA measurement revealed that preoperative serum CD109 levels were elevated in patients with node metastasis-positive and stage IV disease, in comparison to those with node metastasis-negative and Stage I+II+III disease, respectively. A multiple regression analysis indicated that serum CD109 level was significantly associated with the node metastasis status. A Spearman's rank correlation analysis also revealed a positive correlation between the preoperative serum CD109 level and LND. Furthermore, the probabilities of the overall and relapse-free survival were significantly lower in patients with a preoperative serum CD109 level of ≥38.0 ng/ml and a CD109 index of ≥1.6, respectively, than in others. There was no significant correlation between the serum CD109 and SCC antigen levels.

Conclusions: The serum CD109 levels were elevated in patients with advanced stage disease, reflecting the node metastasis status. CD109 in sera could be a novel prognostic marker for HNSCC involving lymph node metastasis.
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http://dx.doi.org/10.1002/cam4.3737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7926025PMC
February 2021

Usefulness of dual-energy computed tomography for oral cancer image.

Oral Radiol 2021 Jan 1. Epub 2021 Jan 1.

Department of Oral and Maxillofacial Surgery, Asahi University Hospital, 3-23 Hashimoto-cho, Gifu, 500-8523, Japan.

Objectives: We aimed to compare dual-energy computed tomography (DECT) virtual monochromatic imaging (VMI) and iodine density imaging (IDI) of oral cancers in terms of visual scoring and tumour volume estimation.

Materials And Methods: Nine patients diagnosed with oral cancer who underwent DECT VMI and IDI were enrolled. One radiation oncologist, one head and neck surgeon and nine oral surgeons evaluated image clarity and quality in each patient in terms of metal artefacts due to dental prosthesis, internal tumour structure, tumour-organ boundary and total quality of images for diagnosis. Tumour volume was estimated using VMI, IDI and magnetic resonance imaging (MRI).

Results: The mean score for image artefact was significantly higher for IDI than for VMI in three observers, the mean score for internal structure was significantly higher for IDI than for VMI in five, the mean score for tumour-organ boundary was significantly higher for IDI than for VMI in two and the mean score for total quality of images for diagnosis was significantly higher for IDI than for VMI in five. Standard deviation of estimated tumour volume was not significantly different between VMI and IDI, but that of MRI was significantly lowest in three images.

Conclusions: In DECT for oral cancer, IDI has a visual image superior to VMI; thus, we recommend the use of IDI.

Trial Registration: Clinical trial number: UMIN000038994.
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http://dx.doi.org/10.1007/s11282-020-00494-3DOI Listing
January 2021

Attempting to define sentinel node micrometastasis in oral squamous cell carcinoma.

Fukushima J Med Sci 2020 Dec 2;66(3):143-147. Epub 2020 Dec 2.

Department of Head and Neck Surgery and Otolaryngology, Asahi University Hospital.

Objective: The aim of this supplemental study of a sentinel node (SN) biopsy (SNB) trial for oral squamous cell carcinoma (OSCC) was to assess the effectiveness in identifying micrometastasis and determining whether elective neck dissection (END) is necessary.

Materials And Methods: Twenty-three patients with pathologically positive SNs were included. The sizes of the metastatic lesions in positive SNs (SMSNs) were classified and the rates of occult metastasis of non-SNs were compared.

Results: The patients were divided according to the SMSN:<0.2 mm (group A, n=3);0.2 mm to <2.0 mm (group B, n=7);and ≥2.0 mm (group C, n=13). The rates of occult metastasis in groups A, B, and C were 0% (0/3), 14% (1/7) and 23% (3/13), respectively.

Conclusion: Rare cancer cell distribution to nodes other than SNs was observed in the patients with SN metastatic lesions of at least smaller than 0.2 mm in size, suggesting the possibility of defining SN micrometastasis in N0 OSCC.
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http://dx.doi.org/10.5387/fms.2020-17DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7790463PMC
December 2020

Successful treatment of recurrent small cell carcinoma of urinary bladder with pembrolizumab.

IJU Case Rep 2020 Nov 5;3(6):252-256. Epub 2020 Aug 5.

Department of Urology National Hospital Organization Fukuyama Medical Center Hiroshima Japan.

Introduction: Small cell carcinoma of urinary bladder is rare and has an aggressive malignant behavior and poor prognosis. Advanced bladder cancers are treated with immune checkpoint inhibitors, however, its efficacy for small cell carcinoma of urinary bladder is unclear.

Case Presentation: A 54-year-old female, diagnosed with clinical stage T2N0M0 small cell carcinoma of urinary bladder, underwent radical cystectomy after three cycles of etoposide-cisplatin neoadjuvant chemotherapy. Despite the fact that pathological examination revealed no residual carcinoma in bladder in her cystectomy specimen, local recurrence of a 60-mm mass detected in the follow-up investigation 7.5 months later. This was completely treated by pembrolizumab without any adverse effects. Immunohistochemical staining revealed that the tumor had no programmed death ligand 1 expression but it showed CD8-positive T-lymphocyte infiltration into the tumor.

Conclusion: Immune checkpoint inhibitors might have curative potentials for treatment of small cell carcinoma of urinary bladder.
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http://dx.doi.org/10.1002/iju5.12208DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609171PMC
November 2020

[Outcomes of Laparoscopic Radical Prostatectomies by a Single Surgeon Alternating Operating Position].

Hinyokika Kiyo 2020 Aug;66(8):251-257

The Department of Urology, Sanyo Hospital.

The clinical outcome of laparoscopic radical prostatectomy (LRP) was retrospectively investigated taking into consideration the surgeon's position during the procedure. The study cohort included 184 consecutive patients who had undergone LRP performed by a single surgeon from February 2013 to July 2018. During the study period,the surgeon stood alternately on either the left or right side of the patient. The D'Amico risk classification was low,intermediate and high in 26 (14.1%),45 (24.5%) and 113 (61.4%) patients,respectively. Mean surgical duration was 203.5 minutes and mean estimated blood loss was 437.6 ml. Nerve sparing (NS) was implemented in 82 (44. 6%) patients. The mean period of having an indwelling urethral catheter was 5. 0 days. Perioperative Clavien-Dindo degree ≥IIIa complications occurred in three (1.6%) patients. Except for cases with presurgical hormonal treatment,surgical margins were positive in 41 (22.3%) patients,among whom 23 (17.4%) had pT2 disease. The 5-year biochemical recurrence-free survival rate was 81.4%,and 84.8% of patients regained urinary continence at 12 months after surgery. Where the surgeon stood during LRP was not associated with significant differences in any parameter. However,the margin positive rate was higher on the side away from where the surgeon stood than the side closer to the surgeon (70.7% vs 29.3%). In conclusion,the position of the surgeon during LRP does not influence the outcome.
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http://dx.doi.org/10.14989/ActaUrolJap_66_8_251DOI Listing
August 2020

Long term-follow-up multicenter feasibility study of ICG fluorescence-navigated sentinel node biopsy in oral cancer.

Mol Clin Oncol 2020 Oct 12;13(4):41. Epub 2020 Aug 12.

Department of Otolaryngology-Head and Neck Surgery, Kyorin University School of Medicine, Tokyo 181-8611, Japan.

In the current study, the utility of sentinel node (SN) identification using indocyanine green (ICG) was investigated for oral cancers in the clinical N0 stage. The current study was a prospective, multicentre, phase II clinical trial that was conducted in Japan. A total of 18 patients were included. Before surgery, the patients underwent lymphoscintigraphy to map the SNs. During surgery, radioactive isotope (RI) mapping was used to detect the SNs, and ICG was subsequently injected. ICG mapping of the SNs was then performed through the skin. The primary tumour was resected, and a neck flap was elevated for neck dissection, followed by SN biopsy (SNB) using RI or ICG mapping. With the RI method, a total of 63 SNs were detected. Among these SNs, 8 (12.7%) were positive for metastasis, including those with isolated tumour cells (ITCs). The median number of SNs per patient identified by SNB was 4. With the ICG method, a total of 67 SNs were detected. Among these SNs, 7 (10.4%) were positive for metastasis, including those with ITCs. The median number of SNs per patient identified by SNB was 4 (range, 1-6). The 5-year overall survival (OS) of all patients was 83.3%, and the 5-year disease-free survival (DFS) of all patients was 76.7%. The neck compression technique is a simple method that can be used to facilitate surgical procedures of ICG fluorescence navigated SNB for head and neck cancer.
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http://dx.doi.org/10.3892/mco.2020.2111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7439131PMC
October 2020

Impact of the systemic immune-inflammation index for the prediction of prognosis and modification of the risk model in patients with metastatic renal cell carcinoma treated with first-line tyrosine kinase inhibitors.

Can Urol Assoc J 2020 Nov;14(11):E582-E587

Department of Urology, Hiroshima General Hospital, Hatsukaichi, Japan.

Introduction: International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) criteria are the most representative risk model for patients with metastatic renal cell carcinoma (mRCC). However, the intermediate-risk group of IMDC criteria is thought to include patients with different prognoses because many of the patients are classified into the intermediate-risk group. In this study, we investigated the impact of systemic immune-inflammation index (SII), which is calculated based on neutrophil count, platelet count, and lymphocyte count, on predicting the prognosis in patients with mRCC, and its usefulness for re-classification of patients with a more sophisticated risk model.

Methods: From January 2008 to January 2018, 179 mRCC patients with a pretreatment and SII were retrospectively investigated. All patients were classified into either a high-SII group or a low-SII group based on the cutoff value of a SII at 730, as reported in previous studies; the overall survival (OS) rates in each group were compared.

Results: The median age was 65 years old. Males and females comprised 145 and 34 cases, respectively. The categories of favorable-, intermediate-, and poor-risk groups in the IMDC model were assessed in 39, 102, and 38 cases, respectively. The median observation period was 24 months. The low-SII and high-SII groups consisted of 73 and 106 cases, respectively. The 50% OS in the high-SII group was 21.4 months, which was significantly worse than that in the low-SII group (49.7 months; p<0.0001). Multivariate analysis showed that a high SII was an independent predictive factor for a worse OS. Next, we constructed a modified IMDC risk model that included the SII instead of a neutrophil count and a platelet count. By using this modified IMDC model, all cases were re-classified into four groups of 33, 52, 81, and 13 cases with 50% OS of 88.8, 45.9, 29.4, and 4.8 months, respectively.

Conclusions: The SII is useful for establishing a more sophisticated prognostic model that can stratify mRCC patients into four groups with different prognoses.
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http://dx.doi.org/10.5489/cuaj.6413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673821PMC
November 2020

Improved prognosis for elderly patients with metastatic renal cell carcinoma in the era of targeted therapy.

Mol Clin Oncol 2020 Jun 24;12(6):557-564. Epub 2020 Mar 24.

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

The present study investigated the outcomes of targeted therapy for elderly patients with metastatic renal cell carcinoma (mRCC). A total of 277 patients with mRCC who were treated with tyrosine kinase inhibitor as a first-line therapy from January 2008 to May 2018 were retrospectively investigated by reviewing clinicopathological data. Patients 75 years or older were classified into the older-aged group (n=55) while all others were classified into the younger-aged group (n=222). The preoperative clinicopathological characteristics and the overall survival (OS) rate for these two groups were subsequently compared. The median age in the older- and younger-aged groups was 78 and 63 years (P<0.0001), respectively. A total of 7, 42 and 6 cases in the older-aged group and 46, 118 and 58 cases in the younger-aged group were classified into favorable, intermediate, and poor risk groups, respectively. The rate of patients with cardiovascular diseases (29.1%) and malignant diseases other than RCC (20.0%) was significantly higher in the older-aged group compared with the younger-aged group (6.8%; P<0.0001 and 7.2%; P=0.0042, respectively). There was a significant improvement in the OS rate for patients beginning targeted therapy after 2011 compared with those starting therapy prior to 2010. The 50% OS rate in patients starting targeted therapy before 2010 and after 2011 was, respectively, 17.1 and 38.6 months for the older-aged group (P=0.0066), while there was no significant difference for the younger-aged group (P=0.1441; 50% OS; 35.9 vs. 30.5 months). The results of the present study indicated that the prognosis for older patients has improved since the introduction of targeted therapy.
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http://dx.doi.org/10.3892/mco.2020.2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7179395PMC
June 2020

Visual Feedback Control of a Rat Ankle Angle Using a Wirelessly Powered Two-Channel Neurostimulator.

Sensors (Basel) 2020 Apr 14;20(8). Epub 2020 Apr 14.

Department of Hand Surgery, Nagoya University, Nagoya 4668550, Japan.

Peripheral nerve disconnections cause severe muscle atrophy and consequently, paralysis of limbs. Reinnervation of denervated muscle by transplanting motor neurons and applying Functional Electrical Stimulation (FES) onto peripheral nerves is an important procedure for preventing irreversible degeneration of muscle tissues. After the reinnervation of denervated muscles, multiple peripheral nerves should be stimulated independently to control joint motion and reconstruct functional movements of limbs by the FES. In this study, a wirelessly powered two-channel neurostimulator was developed with the purpose of applying selective FES to two peripheral nerves-the peroneal nerve and the tibial nerve in a rat. The neurostimulator was designed in such a way that power could be supplied wirelessly, from a transmitter coil to a receiver coil. The receiver coil was connected, in turn, to the peroneal and tibial nerves in the rat. The receiver circuit had a low pass filter to allow detection of the frequency of the transmitter signal. The stimulation of the nerves was switched according to the frequency of the transmitter signal. Dorsal/plantar flexion of the rat ankle joint was selectively induced by the developed neurostimulator. The rat ankle joint angle was controlled by changing the stimulation electrode and the stimulation current, based on the Proportional Integral (PI) control method using a visual feedback control system. This study was aimed at controlling the leg motion by stimulating the peripheral nerves using the neurostimulator.
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http://dx.doi.org/10.3390/s20082210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7218912PMC
April 2020

Head-Mounted Display-Based Microscopic Imaging System with Customizable Field Size and Viewpoint.

Sensors (Basel) 2020 Apr 1;20(7). Epub 2020 Apr 1.

Department of Micro-Nano Mechanical Science and Engineering, Nagoya University, Furo-cho 1, Chikusa Word, Nagoya 464-8603, Japan.

In recent years, the use of microinjections has increased in life science and biotechnology fields; specific examples include artificial insemination and gene manipulation. Microinjections are mainly performed based on visual information; thus, the operator needs high-level skill because of the narrowness of the visual field. Additionally, microinjections are performed as the operator views a microscopic image on a display; the position of the display requires the operator to maintain an awkward posture throughout the procedure. In this study, we developed a microscopic image display apparatus for microinjections based on a view-expansive microscope. The prototype of the view-expansive microscope has problems related to the variations in brightness and focal blur that accompany changes in the optical path length and amount of reflected light. Therefore, we propose the use of a variable-focus device to expand the visual field and thus circumvent the above-mentioned problems. We evaluated the observable area of the system using this variable-focus device. We confirmed that the observable area is 261.4 and 13.9 times larger than that of a normal microscope and conventional view-expansive microscopic system, respectively. Finally, observations of mouse embryos were carried out by using the developed system. We confirmed that the microscopic images can be displayed on a head-mounted display in real time with the desired point and field sizes.
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http://dx.doi.org/10.3390/s20071967DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7181164PMC
April 2020

Magnetic self-assembly of toroidal hepatic microstructures for micro-tissue fabrication.

Biomed Mater 2020 07 9;15(5):055001. Epub 2020 Jul 9.

Department of Micro-Nano Mechanical Science and Engineering, Nagoya University, Nagoya, Japan.

In this study, we developed a procedure for assembling hepatic microstructures into tube shapes using magnetic self-assembly for in vitro 3D micro-tissue fabrication. To this end, biocompatible hydrogels, which have a toroidal shape, were made using the micro-patterned electrodeposition method. Ferrite particles were used to coat the fabricated toroidal hydrogel microcapsules using a poly-L-lysine membrane. The microcapsules were then magnetized with a 3 T magnetic field, and assembled using a magnetic self-assembly process. During electrodeposition, hepatic cells were trapped inside the microcapsules, and they were cultured to construct tissue-like structures. The magnetized toroidal microstructures then automatically assembled to form tube structures. Shaking was used to enhance the assembly process, and the shaking speed was experimentally optimized to achieve the high-speed assembly of longer tube structures. The flow velocity inside the dish during shaking was measured by particle image velocimetry. Hepatic functions were evaluated to check for side-effects of the magnetized ferrite particles on the microstructures. Collectively, our findings indicated that the developed method can achieve the high-speed assembly of a large number of microstructures to form tissue-like hepatic structures.
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http://dx.doi.org/10.1088/1748-605X/ab8487DOI Listing
July 2020

On-Chip Fabrication of Cell-Attached Microstructures using Photo-Cross-Linkable Biodegradable Hydrogel.

J Funct Biomater 2020 Mar 15;11(1). Epub 2020 Mar 15.

Department of Mechatronics Engineering, Meijo University, Nagoya 4688502, Japan.

We developed a procedure for fabricating movable biological cell structures using biodegradable materials on a microfluidic chip. A photo-cross-linkable biodegradable hydrogel gelatin methacrylate (GelMA) was used to fabricate arbitrary microstructure shapes under a microscope using patterned ultraviolet light. The GelMA microstructures were movable inside the microfluidic channel after applying a hydrophobic coating material. The fabricated microstructures were self-assembled inside the microfluidic chip using our method of fluid forcing. The synthesis procedure of GelMA was optimized by changing the dialysis temperature, which kept the GelMA at a suitable pH for cell culture. RLC-18 rat liver cells (Riken BioResource Research Center, Tsukuba, Japan) were cultured inside the GelMA and on the GelMA microstructures to check cell growth. The cells were then stretched for 1 day in the cell culture and grew well on the GelMA microstructures. However, they did not grow well inside the GelMA microstructures. The GelMA microstructures were partially dissolved after 4 days of cell culture because of their biodegradability after the cells were placed on the microstructures. The results indicated that the proposed procedure used to fabricate cell structures using GelMA can be used as a building block to assemble three-dimensional tissue-like cell structures in vitro inside microfluidic devices.
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http://dx.doi.org/10.3390/jfb11010018DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7151615PMC
March 2020

Prognostic value of lymph node density for major salivary gland carcinoma without clinical lymph node metastasis.

Am J Otolaryngol 2020 Jan - Feb;41(1):102304. Epub 2019 Oct 5.

Department of Head and Neck Surgery, Asahi University Hospital, Gifu, Japan. Electronic address:

Background And Objective: This study aimed to investigate whether lymph node density (LND) was correlated with overall survival (OS) in major salivary gland carcinoma without clinical lymph node metastasis.

Methods: Sixty patients who were diagnosed with major salivary gland carcinoma without clinical lymph node metastasis were enrolled. Of these, 50 patients underwent neck dissection. LND was defined as the ratio of the number of positive lymph nodes to the total number of resected lymph nodes.

Results: An LND of ≥0.1 was significantly associated with a short OS (p < 0.05). Multivariate analysis with adjustment for pathological N classification and positive surgical margin showed that an LND of ≥0.1 is a predictor of OS.

Conclusion: Results demonstrated that lymph node density functions as a predictor of outcomes for major salivary gland carcinoma without clinical lymph node metastasis.
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http://dx.doi.org/10.1016/j.amjoto.2019.102304DOI Listing
April 2020

Minimally invasive surgery for laryngopharyngeal cancer: Multicenter feasibility study of a combination strategy involving transoral surgery and real-time indocyanine green fluorescence-navigated sentinel node navigation surgery.

Head Neck 2020 02 31;42(2):254-261. Epub 2019 Oct 31.

Department of Head and Neck Surgery and Otolaryngology, Asahi University Hospital, Gifu, Japan.

Background: Sentinel node navigation surgery using indocyanine green (ICG-SNNS) can be performed in the operation room. The combination of minimally invasive transoral surgery (TOS) with ICG-SNNS can provide functional preservation options for both primary lesions and lymph node (LN) metastasis. This multicenter feasibility study of this strategy was conducted in Japan.

Methods: Patients with clinical T1 or T2, N0 oropharyngeal, hypopharyngeal, or supraglottic cancer were enrolled. The identification rate of sentinel nodes, delayed cervical LN metastasis in 2 years, and survival rate were assessed.

Results: Twenty-two patients (10 oropharynx, 8 hypopharynx, 4 supraglottic cancer) were enrolled. The identification rate was 100%. One case had delayed nodal metastasis. The accuracy was 95.5%, sensitivity was 75%, and specificity was 100%. The 5-year disease-specific survival was 100%, overall survival was 72.3%, and disease-free survival was 60.5%.

Conclusions: The combination of TOS with ICG-SNNS is feasible as a minimally invasive strategy and has favorable oncological outcomes.
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http://dx.doi.org/10.1002/hed.25993DOI Listing
February 2020

C-reactive protein can be used to predict the therapeutic effects of nivolumab in patients with metastatic renal cell carcinoma.

Int J Urol 2019 11 31;26(11):1076-1077. Epub 2019 Jul 31.

Department of Urology, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.

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http://dx.doi.org/10.1111/iju.14084DOI Listing
November 2019

Epithelioid hemangioendothelioma of the parotid gland: a case report.

Int Cancer Conf J 2019 Jan 29;8(1):39-42. Epub 2018 Nov 29.

1Department of Head and Neck surgery, Aichi Cancer Center Hospital, 1-1, Kanokoden, Chikusa-ku, Nagoya, Aichi 464-8681 Japan.

We present the case of a patient with epithelioid hemangioendothelioma of the parotid gland. A 70-year-old female developed swelling and pain in the lower part of the left ear 18 months previously and had visited a local hospital. Fine-needle aspiration cytology revealed no definitive diagnosis, but incisional biopsy under local anesthesia suggested epithelioid hemangioendothelioma. She was then transferred to our hospital, where she underwent total extirpation of the left parotid gland, left cervical lymph node dissection, and postoperative radiation therapy. However, she died from distant metastases 13 months after surgery. No previous study has reported any case of distant metastasis or death due to epithelioid hemangioendothelioma of the parotid gland. To the best of our knowledge, this is the first case report on distant metastasis and death due to the development of parotid gland cancer.
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http://dx.doi.org/10.1007/s13691-018-0351-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6498246PMC
January 2019

Efficient Epstein-Barr Virus Progeny Production Mediated by Cancer-Derived LMP1 and Virally-Encoded microRNAs.

Microorganisms 2019 Apr 30;7(5). Epub 2019 Apr 30.

Division of Microbiology, Faculty of Medicine, Tohoku Medical and Pharmaceutical University, Sendai 983-8536, Japan.

Epstein-Barr virus (EBV) genomes, particularly their latent genes, are heterogeneous among strains. The heterogeneity of EBV-encoded latent membrane protein 1 (LMP1) raises the question of whether there are functional differences between LMP1 expressed by cancer-associated EBV and that by non-cancerous strains. Here, we used bacterial artificial chromosome (BAC)-cloned EBV genomes retaining all virally encoded microRNA (miRNA) genes to investigate the functions of cancer-derived LMP1 in the context of the EBV genome. HEK293 cells were stably transfected with EBV-BAC clone DNAs encoding either nasopharyngeal carcinoma (NPC)-derived CAO-LMP1 (LMP1) or LMP1 from a prototype B95-8 strain of EBV (LMP1). When an EBV-BAC clone DNA encoding LMP1 was stably transfected into HEK293 cells, it generated many more stable transformants than the control clone encoding LMP1. Furthermore, stably transfected HEK293 cells exhibited highly efficient production of progeny virus. Importantly, deletion of the clustered viral miRNA genes compromised the ability to produce progeny viruses. These results indicate that cancer-derived LMP1 and viral miRNAs together are necessary for efficient production of progeny virus, and that the resulting increase in efficiency contributes to EBV-mediated epithelial carcinogenesis.
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http://dx.doi.org/10.3390/microorganisms7050119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6560388PMC
April 2019

Durable response to the ALK inhibitor alectinib in inflammatory myofibroblastic tumor of the head and neck with a novel SQSTM1-ALK fusion: a case report.

Invest New Drugs 2019 08 21;37(4):791-795. Epub 2019 Feb 21.

Department of Clinical Oncology, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya, Aichi, 464-8681, Japan.

An inflammatory myofibroblastic tumor (IMT) is a rare mesenchymal neoplasm that typically develops in the lungs and seldom in the head and neck region. It is often related to the anaplastic lymphoma kinase (ALK) fusion gene. Crizotinib, a first-generation ALK inhibitor, has been shown to have a notable response in patients with ALK-positive IMT. Here, we report the first case of a 46-year-old man with IMT harboring a novel SQSTM1-ALK fusion gene who demonstrated marked response to alectinib. The patient presented a right neck mass (5-cm diameter) that progressively enlarged and expanded to the upper mediastinum. ALK-rearranged IMT was diagnosed after complete tumor resection. Spindle cells displayed diffuse cytoplasmic staining for ALK on immunohistochemistry. A fluorescence in situ hybridization analysis revealed the translocation of a part of the ALK gene locus at chromosome 2p23. FoundationOne CDx™ assay identified an SQSTM1-ALK gene fusion. After a year, right cervical, subclavian, and mediastinal lymph node metastases, considered unresectable, developed. Notably, the patient exhibited a marked response to alectinib treatment and has sustained for 17 months following systemic therapy initiation without significant adverse events. This report highlights the possibility of alectinib being a reasonable option for advanced IMT with the SQSTM1-ALK fusion.
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http://dx.doi.org/10.1007/s10637-019-00742-2DOI Listing
August 2019

Treatment package time predicts cancer-specific survival and distant metastasis in laryngeal cancer.

Oncol Lett 2019 Jan 5;17(1):1384-1390. Epub 2018 Nov 5.

Department of Radiation Oncology, Aichi Cancer Center Hospital, Nagoya, Aichi 464-8681, Japan.

We investigated whether treatment package time was significantly associated with survival outcomes of resectable locally-advanced laryngeal squamous cell carcinoma in patients who consecutively underwent various treatments, including surgery alone and salvage surgery for residual tumor. A total of 100 patients with clinical T3-T4 resectable laryngeal squamous cell carcinoma were enrolled in this study. The treatment package time was calculated in days between the start of any treatment and the end of all treatments, including postoperative radiotherapy and salvage surgery for residual tumors. Using a log-rank test, a treatment package time of ≥68 days showed significantly shorter cancer-specific (P=0.0013) and distant metastasis-free survival (P=0.0017), compared with a treatment package time of <68 days. Multivariate survival analyses of two Cox's hazards proportional models was conducted. In both model-1, which adjusted for cT3/cT4, cN0-1/cN2-3 and total laryngectomy/non-total laryngectomy, and model-2, which adjusted for cT3/cT4, cN0-1/cN2-3 and induction therapy/non-induction therapy, the cancer-specific survival and distant metastasis-free survival, according to treatment package time, were significantly longer with <68 days compared with ≥68 days (P<0.01). The present study demonstrated that a prolonged treatment package time is a prognostic factor for shorter cancer-specific and distant metastasis-free survival after various treatments for resectable locally-advanced laryngeal cancer.
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http://dx.doi.org/10.3892/ol.2018.9664DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6313000PMC
January 2019

The high-sensitivity modified Glasgow prognostic score is superior to the modified Glasgow prognostic score as a prognostic predictor for head and neck cancer.

Oncotarget 2018 Dec 11;9(97):37008-37016. Epub 2018 Dec 11.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Aichi, Japan.

Background: There is increasing evidence that the inflammatory indices of modified Glasgow prognostic score (mGPS) and high-sensitivity mGPS (HS-mGPS) play important roles in predicting the survival in many cancer; however, evidence supporting such an association in head and neck cancer (HNC) is scarce.

Materials And Methods: We evaluated the impact of the mGPS and HS-mGPS on the overall survival (OS) in 129 patients with HNC treated at Aichi Cancer Center Central Hospital from 2012-2013. The mGPS was calculated as follows: mGPS of 0, C-reactive protein (CRP) ≤1.0 mg/dl; 1, CRP >1.0 mg/dl; 2, CRP>1.0 mg/dl and albumin <3.5 mg/dl. Regarding the HS-mGPS, the CRP threshold level was set as 0.3 mg/dl. Hazard ratios (HRs) and 95% confidence intervals (95% CIs) were estimated by Cox proportional hazard models after adjusting for potential confounders.

Results: The prognosis of HNC worsened significantly as both the mGPS and HS-mGPS increased in a univariate analysis. After adjusting for covariates, the HS-mGPS was significantly associated with the OS (adjusted HR for HS-mGPS of 2 compared to an HS-mGPS of 0 [HR] 3.14 [95% CI: 1.23-8.07], P < 0.001), while the mGPS was suggested to be associated with the survival (HR 2.37 [95% CI:0.89-6.33], P = 0.145). Even after stratification by clinical covariates, these associations persisted.

Conclusion: We conclude that the HS-mGPS is useful as an independent prognostic factor in HNC.
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http://dx.doi.org/10.18632/oncotarget.26438DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6319335PMC
December 2018

Primary Tumor Size Predicts Distant Metastasis of Mucosal Malignant Melanoma in Head and Neck.

Anticancer Res 2018 Nov;38(11):6485-6490

Department of Head and Neck Surgery, Asahi University, Gifu, Japan.

Background/aim: To investigate the possible association between primary tumor size and overall survival and/or distant metastasis-free survival of patients with mucosal malignant melanoma of the head and neck.

Patients And Methods: A total of 25 patients that have had primary tumor resection were enrolled in this study. Primary tumor size was assessed as the maximum size of the primary tumor in pathological and surgical reports.

Results: Patients with a primary tumor size of ≥43 mm showed a significant association with shorter overall survival (p=0.007) and distant metastasis-free survival (p=0.005) by the log-rank test. Multivariate survival analyses of two Cox's hazards proportional models showed that, in model1, pT4a-4b (p=0.01) and primary tumor size ≥43 mm (p=0.03) were significantly associated with shorter overall survival, and primary tumor size ≥43 mm (p=0.02) was significantly associated with shorter distant metastasis-free survival. In model2, pStage IVA-IVB (p=0.02) and primary tumor size ≥43 mm (p=0.03) were significantly associated with shorter overall survival, and primary tumor size ≥43 mm (p=0.02) was significantly associated with shorter distant metastasis-free survival.

Conclusion: Large tumor size (≥43 mm) is a predictor of shorter overall survival and distant metastasis-free survival after primary tumor resection of mucosal malignant melanoma of the head and neck.
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http://dx.doi.org/10.21873/anticanres.13012DOI Listing
November 2018

Clinical impact of cachexia in unresectable locally advanced head and neck cancer: supplementary analysis of a phase II trial (JCOG0706-S2).

Jpn J Clin Oncol 2019 Jan;49(1):37-41

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

Objectives: To evaluate the clinical impact of cachexia, defined by the combination of albumin and C-reactive protein levels, in patients with unresectable locally advanced head and neck squamous cell carcinomas who received chemoradiotherapy in a phase II trial of JCOG0706.

Methods: Forty-five patients received radiation for a total of 70 Gy/35fr concurrently with S-1 and cisplatin. The present analysis was conducted in 44 patients with available data. The association between treatment efficacy and cachexia was investigated. Pretreatment cachexia was defined as a serum albumin level of less than 3.5 mg/dl and C-reactive protein level of more than 0.5 mg/dl.

Results: Among the 44 patients, 5 patients had cachexia. On comparison with the cachexic and non-cachexic patients, the percentage of clinical complete remission (20% vs 72%), time to treatment failure at 3 years, (20% vs 53%) and proportion of treatment completion (20% vs 79%) were statistically worse in the cachexic patients, while overall survival, progression-free survival and local progression-free survival at 3 years tended to be worse in cachexic patients.

Conclusions: This supplementary analysis from a prospective study suggests that a pretreatment status of cancer cachexia is a prognostic factor for treatment outcomes and compliance in patients with locally advanced head and neck squamous cell carcinomas treated with chemoradiotherapy, and a candidate stratification factor in future prospective trials in this population.
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http://dx.doi.org/10.1093/jjco/hyy145DOI Listing
January 2019

Superficial Esophageal Cancer in a Fanconi Anemia Patient That Was Treated Successfully by Endoscopic Submucosal Resection.

Intern Med 2019 Feb 17;58(4):529-533. Epub 2018 Oct 17.

Department of Endoscopy, Aichi Cancer Center Hospital, Japan.

Fanconi anemia (FA) is a disorder of chromosomal fragility characterized by progression to aplastic anemia, myelodysplastic syndrome, and leukemia. FA patients are also predisposed to solid cancers. A case of FA in an adult patient who developed tongue and superficial esophageal cancers following hematopoietic stem cell transplantation is reported. This case was considered significant because it is the first reported case of superficial esophageal cancer in an FA patient that was treated successfully by endoscopic submucosal resection.
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http://dx.doi.org/10.2169/internalmedicine.1434-18DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6421153PMC
February 2019

Peak of Standardized Uptake Value in Oral Cancer Predicts Survival Adjusting for Pathological Stage.

In Vivo 2018 Sep-Oct;32(5):1193-1198

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Japan.

Background/aim: To predict survival outcomes of different patients with the same stage of disease is difficult. The possible correlation between F-fluorodeoxyglucose (F-FDG) uptake parameters and survival outcomes was investigated in oral squamous cell carcinoma patients by multivariate analysis adjusted for the pathological stage according to the 8th edition of the tumor-node-metastasis (TNM) classification of the Union for International Cancer Contro.

Patients And Methods: F-FDG-uptake parameters of 28 patients were assessed by positron emission tomography with computed tomography (PET/CT).

Results: A peak of standardized uptake value of primary tumor (p-SUVpeak) of ≥14.1 was significantly correlated with shorter overall survival by univariate and multivariate analyses adjusted for the pathological TNM stage. A p-SUVpeak of ≥14.1 was significantly associated with shorter local recurrence-free survival and disease-free survival.

Conclusion: A higher p-SUVpeak on pretreatment F-FDG-PET/CT is a prognostic parameter of identifying lower survival outcomes.
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http://dx.doi.org/10.21873/invivo.11363DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6199585PMC
December 2018

Sinonasal squamous cell carcinoma and EGFR mutations: a molecular footprint of a benign lesion.

Histopathology 2018 Dec 23;73(6):953-962. Epub 2018 Oct 23.

Department of Pathology and Molecular Diagnostics, Aichi Cancer Center Hospital, Nagoya, Japan.

Aims: Molecular targeted therapy against EGFR kinase domain mutations has been successfully established for lung cancer. These mutations have now also been reported in head and neck tumours, particularly in inverted sinonasal papillomas (ISPs). The aim of this study was to clarify the spectrum of EGFR mutations in head and neck squamous cell carcinomas and papillomas.

Methods And Results: We examined EGFR mutations in 288 head and neck squamous cell carcinomas and 58 head and neck papillomas or polyps. EGFR mutations were detected in 24 (30%) of 80 sinonasal squamous cell carcinomas (SNSCCs) and in 19 (90%) of 21 ISPs. Notably, 15 (88%) of 17 SNSCCs that developed along with ISPs harboured EGFR mutations in both components, whereas EGFR mutations were detected in nine (14%) of 63 SNSCCs without any papilloma component. Analysis to detect other known driver oncogene mutations - KRAS, BRAF and HER2 - was also performed; none of these mutations was detected in SNSCCs. The other 208 non-sinonasal carcinomas and 37 non-ISP head and neck papillomas or polyps did not harbour EGFR mutations.

Conclusions: Taken together with the specific involvement of EGFR mutations in ISP, a molecular benign lesion trail suggests that 26 (33%) of 80 SNSCCs developed in association with an ISP. SNSCCs with EGFR mutations may be biologically distinct among head and neck cancers.
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http://dx.doi.org/10.1111/his.13732DOI Listing
December 2018

Association between Uncoupling Protein 2 Gene Ala55val Polymorphism and Sudden Sensorineural Hearing Loss.

J Int Adv Otol 2018 Aug;14(2):166-169

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

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.
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http://dx.doi.org/10.5152/iao.2018.5442DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354460PMC
August 2018

Generation of Human-Like Movement from Symbolized Information.

Front Neurorobot 2018 17;12:43. Epub 2018 Jul 17.

Intelligent Behavior Control Unit (BTCC), Brain Science Institute (BSI), RIKEN, Nagoya, Japan.

An important function missing from current robotic systems is a human-like method for creating behavior from symbolized information. This function could be used to assess the extent to which robotic behavior is human-like because it distinguishes human motion from that of human-made machines created using currently available techniques. The purpose of this research is to clarify the mechanisms that generate automatic motor commands to achieve symbolized behavior. We design a controller with a learning method called tacit learning, which considers system-environment interactions, and a transfer method called mechanical resonance mode, which transfers the control signals into a mechanical resonance mode space (MRM-space). We conduct simulations and experiments that involve standing balance control against disturbances with a two-degree-of-freedom inverted pendulum and bipedal walking control with humanoid robots. In the simulations and experiments on standing balance control, the pendulum can become upright after a disturbance by adjusting a few signals in MRM-space with tacit learning. In the simulations and experiments on bipedal walking control, the robots realize a wide variety of walking by manually adjusting a few signals in MRM-space. The results show that transferring the signals to an appropriate control space is the key process for reducing the complexity of the signals from the environment and achieving diverse behavior.
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http://dx.doi.org/10.3389/fnbot.2018.00043DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6056751PMC
July 2018

Pathological tumor volume predicts survival outcomes in oral squamous cell carcinoma.

Oncol Lett 2018 Aug 12;16(2):2471-2477. Epub 2018 Jun 12.

Department of Head and Neck Surgery, Aichi Cancer Center Hospital, Nagoya, Aichi 464-8681, Japan.

The present study examined whether the pathological tumor volume (PTV) was correlated with the survival outcomes in patients with oral squamous cell carcinoma (SCC) and clinical lymph node metastasis. Forty-seven patients who underwent radical surgery without preoperative treatment were enrolled. The PTV of the primary tumor, which was surgically resected without preoperative treatment, was calculated based on the diameters in three dimensions. A survival analysis was performed using a Cox proportional hazards model. A PTV of ≥18 cm was significantly correlated with shorter overall survival (P<0.01) and local recurrence-free survival (P<0.01) in a univariate analysis. A multivariate analysis with adjustment for the pathological stage (stage I-II/III-IV), primary site (tongue/others) and positive surgical margin and/or extracapsular extension (absent/present) showed that a PTV of ≥18 cm was significantly correlated with shorter overall survival (P<0.01) and local recurrence-free survival (P<0.01). The present findings suggested that PTV in oral SCC provides a prognostic parameter that may predict shorter or longer overall and local recurrence-free survival.
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http://dx.doi.org/10.3892/ol.2018.8951DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6036551PMC
August 2018