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Purpose This study assessed the efficacy of upfront neck dissection (ND) versus concurrent chemoradiotherapy (CRT) in patients diagnosed with T1–3N3 hypopharyngeal carcinoma (HPC).Methods This retrospective study enrolled patients with T1–3N3 HPC who had undergone upfront ND followed by CRT (upfront group) or only CRT (CRT group). Local control rate, neck control rate, metastasis-free rate, disease-free survival, disease-specific survival, and overall survival were compared between the upfront and CRT groups. Univariate and multivariate analyses using Cox proportional hazards models were performed to identify the survival-related clinical and systemic factors.Results Forty-eight patients were enrolled in this study, with 18 in upfront group and 30 in CRT group. The groups differed significantly in terms of neck control rate (p = 0.000121) and disease-free survival (p = 0.0256). The upfront CRT group showed a significantly better overall survival (OS) than that of the unresectable CRT group (p = 0.046). Among the various factors, node status, body mass index, and platelet-to-lymphocyte ratio were significantly associated with OS in a univariate analysis.Conclusion Upfront ND can be recommended for T1–3N3 HPC, provided resectability is feasible.

Inhalation therapy can effectively treat chronic obstructive pulmonary disease (COPD), but the physical factors determining the appropriate aerosol delivery into the targeted airways remain unclear. The problem is nontrivial because pulmonary structures differ among individual patients with COPD and depend on the severity of the disease. In an in silico evaluation, the present study investigates the differences in particle transport and deposition in the airways of three patients with different degrees of COPD. Specific pulmonary airway models were reconstructed based on the computed tomography data of three patients with a different degree of COPD severity. The transport and deposition of inhaled particles in the airways were evaluated in a computational fluid dynamics simulation and a Lagrangian multiphase model. The sizes of the inhaled particles (1.0, 2.5, 5.5, 8.5, and 10.0 μm) were representative of drug particles delivered from inhalation devices, including dry powder inhalers (DPIs). The deposition behaviors of the inhaled particles strongly depended on the individual geometrical structure of the airways. The largest inhaled particles (10.0 μm) were most strongly affected by inertia and were deposited mostly in the oropharynx; consequently, they were rare in the bronchi. In contrast, the smallest inhaled particles (1.0 μm) were effectively delivered distally with the airflow. The spatial distributions and amounts of deposited particles in the airways obviously differed among the three COPD patients. Small particles are preferred as they can penetrate the inner lung regions. The results can assist the design and development of powder formulations and DPIs for patients with various severities of COPD.

Objectives With the advent of new optical technologies, early pharyngolaryngeal cancerous lesions can be better visualized. Although the conventional transnasal approach offers great views of the hypopharynx and larynx, the visualization of the oropharynx and palatine tonsils is limited. Through the transoral insertion of a flexible video-laryngoscope, direct views of the oropharynx and oral cavity can be obtained. Thus, transoral examination may contribute to primary detection of cancers of unknown primary (CUP). Methods Eighty-five CUP patients from Tokai University were included retrospectively in this study, from 2006 to 2017. Starting in 2010, we employed the transoral examination in addition to our conventional method. The primary detection rates were compared before and after 2010. Oropharyngeal primaries were further analyzed for tumor subsite and p16 status. Results The overall primary detection rate did not improve with the addition of transoral examination. However, greater numbers of oropharyngeal primaries were detected. The oropharyngeal lesions detected by transoral examination were mainly p16 positive, located on the palatine tonsil. Conclusion Transoral examination is a noninvasive, easy method to adopt in an outpatient setting, and a promising technique to improve tumor detection in this era of human papillomavirus-associated head and neck cancers. Level of evidence 3.

Malignant lymphomas of the paranasal sinuses, which have a minimal tendency for invasion but considerable necrosis, may be misdiagnosed as an inflammatory disease, based on MRI and clinical findings. In cases where a thorough physical examination does not rule out a malignant lymphoma, an endoscopic biopsy should be immediately considered.

In December 2019, pembrolizumab was approved in Japan for the treatment of head and neck cancer with recurrence or distant metastasis, making it a new option for first-line treatment. However, there are still many unanswered questions about Overall survival (OS), Progression free survival (PFS), adverse events including immune-related adverse events (irAEs), and biomarkers.The aim of this study was to retrospectively review first-line treatment of head and neck cancer with recurrence or distant metastasis treated with pembrolizumab and to determine whether Combined positive score (CPS) is still useful as a biomarker in the clinical practice.We retrospectively reviewed clinical records of 20 patients who received pembrolizumab as first-line treatment for head and neck cancer with recurrence or distant metastasis between December 2019 and March 2021.Age ranged from 45 to 83 years (median 66 years), 17 male patients and 3 female patients. The response rate was 40%, and the disease control rate was 60%. OS and PFS in patients with CPS1 were significantly worse than those with CPS ≤ 1 (CPS-positive patients). The OS and PFS of patients with CPS1 were s ignificantly worse than those of p atients with 1= CPS (CPS-positive p atients), and there was no significant difference between the group with CPS between 1 and 20 and the group with CPS over 20. And we experiences several CR cases with high CPS.CPS is a useful biomarker for pembrolizumab.There are no reported cases of CR after two courses of pembrolizumab in head and neck cancer. There are no reports of pembrolizumab in patients with head and neck cancer in Japan.

This study aimed to determine the prognostic value of inflammatory and nutritional biomarkers of immune checkpoint inhibitor (ICI) therapy for recurrent or metastatic squamous cell carcinoma of the head and neck (RMHNSCC) and to identify the most useful factor for prognosis assessment. We retrospectively reviewed the medical records of patients with RMHNSCC who received ICI therapy. The response rate for ICI therapy and the relationship between inflammatory and nutritional biomarkers and overall survival were examined. The included biomarkers did not correlate with an objective response rate but were associated with a disease control rate. Univariate analysis showed significant correlations between the serum albumin level, C-reactive protein level, platelet to lymphocyte ratio, neutrophil to lymphocyte ratio, lymphocyte to monocyte ratio (LMR), systemic immune-inflammation index, and controlling the nutritional status score and overall survival; multivariate analysis showed that LMR was significantly correlated with overall survival. LMR was the most important biomarker according to the machine learning model. This study suggests that LMR may be the most useful biomarker for predicting the prognosis of ICI treatment for RMHNSCC.

Gardner syndrome (GS) with odontogenic sinusitis is rare but should be suspected in patients with multiple osteomas of the skull and facial bones, excess teeth, impacted teeth, and odontomas. Early diagnosis of GS and treatment for familial adenomatous polyposis may improve prognosis.

Since the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, morphological abnormalities in lepidopteran insects, such as shrinkage and/or aberration of wings, have been reported. Butterflies experimentally exposed to radiocesium also show such abnormalities. However, because of a lack of data on absorbed dose and dose-effect relationship, it is unclear whether these abnormalities are caused directly by radiation. We conducted a low dose-rate exposure experiment in silkworms reared from egg to fully developed larvae on a

Severe peripheral nerve injury, which does not promise natural healing, inevitably requires clinical treatment. Here, we demonstrated the facilitation effect of peripheral nerve regeneration using a cytokine cocktail secreted by skeletal muscle-derived stem cells (Sk-MSCs). Mouse sciatic nerve was transected with a 6 mm gap and bridged collagen tube, and the culture supernatant of Sk-MSCs with 20% adult mouse serum (AMS)/Iscove’s modified Dulbecco’s medium (IMDM) was administered into the tube immediately after the operation, followed by an injection once a week for six weeks through the skin to the surrounding tube of the cytokine (CT) group. Similarly, 20% AMS/IMDM without cytokines was administered to the non-cytokine control (NT) group. Tension recovery in the plantar flexor muscles via electrical stimulation at the upper portion of the damaged nerve site, as well as the numerical recovery of axons and myelinated fibers at the damaged site, were evaluated as an index of nerve regeneration. Specific cytokines secreted by Sk-MSCs were compared with damaged sciatic nerve-derived cytokines. Six weeks after operation, significantly higher tension output and numerical recovery of the axon and myelinated fibers were consistently observed in the CT group, showing that the present cytokine cocktail may be a useful nerve regeneration acceleration agent. We also determined 17 candidate factors, which are likely included in the cocktail.

A 42-year-old woman presented to our clinic with tongue pain and dysarthria. She had a smoking history of 22 pack-years and no history of alcohol consumption. A deep ulcer at the left side of the tongue and induration across the whole tongue were observed. The bilateral cervical lymph nodes were palpable. A biopsy from the ulcer revealed squamous cell carcinoma. PET/CT showed sternal bone metastasis resulting in the final diagnosis of left-sided oral tongue cancer (cT4aN2cM1). Systemic chemotherapy treatment involving 6 courses of the EXTREME regimen followed by weekly cetuximab administration was indicated.After the first two courses, diminished tongue pain and improved dysarthria were observed; complete response was obtained after 6 courses. Re-examination of the biopsy specimen showed that the tumor was p16 positive. The p16 protein is a surrogate marker for HPV, but in this case HPV in-situ hybridization was negative. Locoregional or distant failure were not observed during the 5-year follow-up period.The treatment regimen unexpectedly proved successful. It may be beneficial to examine p16 expression in oral tongue cancer to identify patients that are more likely to benefit from the EXTREME treatment regimen.

Chemical burns of the paranasal sinus are rare; therefore, assessment methods for treatment of and prognoses for the exposure site are unknown. We experienced a case in which a hydrochloric acid burn of the paranasal sinuses caused irreversible tissue damage. Computed tomography is useful for identifying the exposure site and assessing tissue damage over time. Identification of the exposure site and proactive washing are recommended for patients with chemical burns of the paranasal sinuses. Laryngoscope, 131:E2490-E2493, 2021.

The correlation between genomic mutations (or the overexpression of abnormal proteins) and prognosis in temporal bone squamous cell carcinoma (TBSCC) is not clear. We investigated the overexpression of EGFR and p53 as a pathological biomarker for predicting the clinical course of patients with TBSCC.We performed a retrospective review of 22 TBSCC cases treated in Tokai University Hospital between January 2005 and October 2016. We assessed the overexpression of EGFR and p53 in TBSCC patients through immunohistochemical staining. We also evaluated the association between the overexpression of these proteins and clinicopathological variables, including survival outcomes.The primary lesion in all patients was the external auditory canal. Nine (40.9%) patients were EGFR positive, and 9 (40.9%) were p53 positive. The 5-year overall survival rate for EGFR-positive patients (55.6%) was significantly lower (p = 0.043) than that of the EGFR-negative patients (92.3%).EGFR overexpression in TBSCC patients may be a prognostic biomarker.

Since the Fukushima Dai-ichi Nuclear Power Plant (FDNPP) accident, morphological abnormalities in lepidopteran insects, such as shrinkage and/or aberration of wings, have been reported. Butterflies experimentally exposed to radiocesium also show such abnormalities. However, because of a lack of data on absorbed dose and dose–effect relationship, it is unclear whether these abnormalities are caused directly by radiation. We conducted a low dose-rate exposure experiment in silkworms reared from egg to fully developed larvae on a 137CsCl-supplemented artificial diet and estimated the absorbed dose to evaluate morphological abnormalities in pupal wings. We used 137CsCl at 1.3 × 103 Bq/g fresh weight to simulate 137Cs contamination around the FDNPP. Absorbed doses were estimated using a glass rod dosimeter and Monte Carlo particle transport simulation code PHITS. Average external absorbed doses were approximately 0.24 (on diet) and 0.016 mGy/day (near diet); the average internal absorbed dose was approximately 0.82 mGy/day. Pupal wing structure is sensitive to radiation exposure. However, no significant differences were observed in the wing-to-whole body ratio of pupae between the 137CsCl-exposure and control groups. These results suggest that silkworms are insensitive to low dose-rate exposure due to chronic ingestion of high 137Cs at a high concentration.

Background Several reports have suggested that selected patients with human papillomavirus-related oropharyngeal cancer can be managed with surgery alone. We retrospectively reviewed tonsillar cancer cases to analyze treatment de-intensification after transoral resection. Methods Eighteen patients with tonsillar cancer who had undergone transoral resection were included. The patients' characteristics, p16 status, adverse features, clinical course, overall survival, and relapse-free survival according to p16 status were retrospectively examined. Results Four lesions showed positive surgical margins and one lesion showed close surgical margin; these patients were treated with postoperative irradiation. Seven p16-positive patients had multiple node metastases and two had extracapsular spread. No p16-positive patients agreed to postoperative irradiation, and recurrence within the surgical field was not observed. The five-year overall and relapse-free survival rates were 89% and 74%, respectively. The five-year relapse-free survival rates of p16-positive and p16-negative patients were 81% and 50%, respectively (p = .075). Conclusions Postoperative irradiation for cervical lymph node metastases might be avoidable in selected patients with human papillomavirus-related tonsillar cancer. Level of Evidence 4.

This report describes a cooperative step climbing strategy using an electric wheelchair and autonomous robot. The robot, which was developed by our research group, has a wheeled travel mechanism and dual manipulators. The wheelchair is a commercially available model modified with added sensors, circuits, and batteries. When the wheelchair and robot encounter a step, the robot grasps the wheelchair and they help each other to ascend the step. In the step climbing process, the wheelchair front wheels are lifted using the difference between the wheelchair and robot velocities, and the front wheels are placed on the step. To make the rear wheels of the wheelchair climb the step, the robot upper arms push against the back of the wheelchair, which is like the motion of man pushing a wheelchair up the step. Similarly, the robot front and rear wheels climb the step using assistance from the wheelchair. We developed an automatic control system that realizes the cooperative step climbing of the wheelchair and robot and also simplifies the operation of both vehicles. An experiment was conducted to demonstrate that the wheelchair and robot can successfully maneuver up a step.

Background Induction chemotherapy (IC) in locally advanced squamous cell carcinoma of the head and neck (LA‐SCCHN) often compromises compliance with subsequent chemoradiotherapy (CRT), which negatively affects outcomes. Here, we assessed the combination of paclitaxel (PTX), carboplatin (CBDCA), and cetuximab (Cmab) as IC for unresectable LA‐SCCHN. Methods Induction chemotherapy consisted of weekly CBDCA area under the plasma concentration‐time curve = 1.5, PTX 80 mg/m2 and Cmab with an initial dose of 400 mg/m2 followed by 250 mg/m2 for 8 weeks. Following IC, CDDP (20 mg/m2, 4 days × 3 cycles) and concurrent radiotherapy (70 Gy/35 fr) were started. Primary endpoint was the proportion of CRT completion (%CRT completion). PCE was planned to be deemed effective if the Bayesian posterior probability (PP), defined as the probability that %CRT completion was larger than the threshold value of 65%, exceeded 84%. Results Thirty‐five patients were enrolled. Cases were hypopharynx/oropharynx/larynx in 17/17/1 patients, all at Stage IV. Of 35 patients, 34 (97%) completed IC and 32 received CRT and met the criteria of full analysis set (FAS). In FAS, the %CRT completion was 96.9%, and PP was 99.9%, exceeding the prespecified boundary of 84%. Mean cumulative dose and relative to dose intensity of CDDP in CRT was 232.5 mg/m2 and 100%, respectively. Response rate was 88.6% by IC and 93.8% in the CRT phase. Three year overall survival was 83.5%. Main grade 3 toxicities included neutropenia (11.4%) and skin rash (5.7%) during IC; and oral mucositis (31.3%) and neutropenia (12.5%) during CRT. No grade 4 toxicity or treatment‐related death was seen. Conclusions PCE as IC was feasible, with promising efficacy and no effect on compliance with subsequent CRT in unresectable LA‐SCCHN., The combination of PCE as induction chemotherapy was feasible and had no effect on compliance with subsequent chemoradiotherapy (CRT) with CDDP, and provided encouraging efficacy in high‐risk unresectable locally advanced squamous cell carcinoma of the head and neck (LA‐SCCHN). The regimen is a favorable alternative to TPF for LA‐SCCHN patients who required more aggressive treatment, herein sequential CRT.

This report describes an automatic control system that allows an assistive robot pushing a wheelchair to climb steps. The robot is equipped with a wheeled mechanism and dual manipulators. The wheelchair is a commercially available model that has been equipped with sensors, circuits, and batteries. The robot and wheelchair are connected when the vehicles climb a step. In that operation, the front wheels of the wheelchair are lifted and placed on the step using the velocity differences between the wheelchair and the robot. Next, when the rear wheels of the wheelchair ascend the step, the robot imitates the upper arm motions of a human pushing against his/her chest that commonly occurs when maneuvering a wheelchair up a step. Similarly, the front wheels of the robot are lifted and placed on the step using the velocity differences between the vehicles and the robot’s front wheels. After that, with the assistance of the wheelchair, the other wheels of the robot climb onto the step. In an effort to ensure safety, we also performed a theoretical analysis to determine the most suitable distance for lifting the front wheels of the robot when approaching and climbing a step. Our newly developed cooperative step-climbing system makes it possible to eliminate the complicated operations that were required by previous methods and can also prevent collisions between the wheelchair’s front wheels and the step, thus drastically improving the convenience of the operation. The test subject riding the wheelchair was an able-bodied male, and the experiment conducted to evaluate our system was performed on a 120 mm step height that had a friction coefficient of 0.72. This setup was sufficient for demonstrating the overall effectiveness of our system.

Poly (ethylene terephthalate) (PET) is available worldwide and has a broad range of applications. However, its basic properties as a scintillation material that is undoped with fluorescent guest molecules are not completely known. Here, we optically characterise undoped PET for use in radiation detection. Light absorption is primarily below 350 nm, with an emission maximum at 385 nm. An effective refractive index, determined from the emission spectrum and the wavelength dependence of the refractive index, is 1.62, which is greater than that for the sodium D line ( N D = 1.57). The density of PET is 1.33 g/cm 3 , and its stopping power for 1-MeV electrons is 1.72 MeV cm 2 /g. Distinct peaks generated by alpha particles from 210 Pb and 241 Am radioactive sources appear in PET light-yield distributions. The PET response to 5-6-MeV alpha particles is approximately one-eighth that for electrons. These results demonstrate that undoped PET has special attributes for alpha particle detection. This knowledge will enable better performance of radiation equipment based on PET and its blends with other aromatic ring polymers.