Degranulation and expression of cytokines were modulated by diazinon in activated mast cells.

Diazinon is an organophosphorus (OP) insecticides used in agriculture, home gardening and indoor pest control in Japan. It can activate macrophages and induce pro-inflammatory responses and has been reported to cause airway hyper-reactivity, suggesting the possibility of asthma exacerbation from exposure to OP insecticides. Despite the correlation between insecticide use and the pathogenesis of allergic diseases, there have been no reports on the effects of diazinon on mast cell function. Therefore, in this study, we investigated the effects of diazinon on mast cell function in rat basophilic leukemia (RBL)-2H3 cells. Surprisingly, we found that diazinon inhibited mast cell activation, although the degree of inhibition varied with concentration. Diazinon induced reactive oxygen species (ROS) generation and HO-1 expression at a concentration of 150 µM without affecting cell viability. Diazinon inhibited A23187-mediated degranulation and Tnf and Il4 expression in RBL-2H3 cells but did not affect calcium influx. Suppression of degranulation by diazinon was reversed when the culture supernatant was removed. As a signaling event downstream of calcium influx, diazinon inhibited the phosphorylation of extracellular signal-regulated kinase (ERK) induced by A23187, whereas the phosphorylation of p38 had little effect. IgE cross-linking-mediated degranulation as well as the induction of Tnf and IL4 expression was significantly inhibited by diazinon, while diazinon had little effect on calcium influx. In conclusion, diazinon inhibited mast cell activation, including degranulation and cytokine expression. When evaluating the in vivo effects of diazinon, its potential to inhibit mast cell activation should be considered in the pathophysiology and development of allergic diseases in terms of basic and clinical aspects, respectively, although the effect of diazinon varies depending on the cell type.

Protocol for in vivo elimination of avian auditory hair cells, multiplexed mRNA detection, immunohistochemistry, and S-phase labeling.

The avian inner ear can naturally regenerate sensory hair cells and is therefore an ideal candidate for investigating mechanisms leading to hair cell regeneration and functional recovery. Here, we present a surgical protocol for eliminating auditory hair cells via sisomicin injection into the lateral semicircular canal. We describe steps for multiplex mRNA detection in chicken basilar papilla and utricle sections. We then detail procedures for integrating immunohistochemistry for concurrent mRNA and protein visualization, complemented by S-phase labeling with EdU. For complete details on the use and execution of this protocol, please refer to Benkafadar et al., Benkafadar et al., Sato et al., Janesick et al., Scheibinger et al.1,2,3,4,5.

BRAFV600E promotes anchorage-independent growth but inhibits anchorage-dependent growth in hTERT/Cdk4-Immortalized normal human bronchial epithelial cells.

Certain oncogenes, including mutant RAS and BRAF, induce a type of senescence known as oncogene-induced senescence (OIS) in normal cells in a cell-type-specific manner. OIS serves as a barrier to transformation by activated oncogenes. Our previous studies showed that mutant KRASV12 did not efficiently induce OIS in an hTERT/Cdk4-immortalized normal human bronchial epithelial cell line (HBEC3), but it did enhance both anchorage-dependent and anchorage-independent growth. In this study, we investigated whether mutant BRAF, a well-known inducer of OIS, could trigger OIS in HBEC3 cells. We also assessed the impact of mutant BRAF on the growth of HBEC3 cells, as no previous studies have examined this using a normal bronchial epithelial cell line model. We established an HBEC3 cell line, designated as HBEC3-BIN, that expresses mutant BRAFV600E in a doxycycline-regulated manner. Unlike our previous finding that KRASV12 upregulated both pERK and pAKT, mutant BRAFV600E upregulated pERK but not pAKT in HBEC3-BIN cells. Similar to KRASV12, BRAFV600E did not efficiently induce OIS. Interestingly, while BRAFV600E inhibited colony formation in anchorage-dependent conditions, it dramatically enhanced colony formation in anchorage-independent conditions in HBEC3-BIN. In HBEC3 cells without BRAFV600E or KRASV12 expression, p21 was only detected in the cytoplasm, and its localization was not altered by the expression of BRAFV600E or KRASV12. Next-generation sequencing analysis revealed an enrichment of gene sets known to be involved in carcinogenesis, including IL3/JAK/STAT3, IL2, STAT5, and the EMT pathway. Our results indicate that, unlike KRASV12, which promoted both, BRAFV600E enhances anchorage-independent growth but inhibits anchorage-dependent growth of HBEC3. This contrast may result from differences in activation signaling in the downstream pathways. Furthermore, HBEC3 cells appear to be inherently resistant to OIS, which may be partly due to the fact that p21 remains localized in the cytoplasm upon expression of BRAFV600E or KRASV12.

Hair cell regeneration, reinnervation, and restoration of hearing thresholds in the avian hearing organ.

Hearing starts, at the cellular level, with mechanoelectrical transduction by sensory hair cells. Sound information is then transmitted via afferent synaptic connections with auditory neurons. Frequency information is encoded by the location of hair cells along the cochlear duct. Loss of hair cells, synapses, or auditory neurons leads to permanent hearing loss in mammals. Birds, in contrast, regenerate auditory hair cells and functionally recover from hearing loss. Here, we characterized regeneration and reinnervation in sisomicin-deafened chickens and found that afferent neurons contact regenerated hair cells at the tips of basal projections. In contrast to development, synaptic specializations are established at these locations distant from the hair cells' bodies. The protrusions then contracted as regenerated hair cells matured and became functional 2 weeks post-deafening. We found that auditory thresholds recovered after 4-5 weeks. We interpret the regeneration-specific synaptic reestablishment as a location-preserving process that might be needed to maintain tonotopic fidelity.

The oncogenic role of LGR6 overexpression induced by aberrant Wnt/ß-catenin signaling in lung cancer.

BACKGROUND: Molecular abnormalities in the Wnt/ß-catenin pathway confer malignant phenotypes in lung cancer. Previously, we identified the association of leucine-rich repeat-containing G protein-coupled receptor 6 (LGR6) with oncogenic Wnt signaling, and its downregulation upon ß-catenin knockdown in non-small cell lung cancer (NSCLC) cells carrying CTNNB1 mutations. The aim of this study was to explore the mechanisms underlying this association and the accompanying phenotypes. METHODS: LGR6 expression in lung cancer cell lines and surgical specimens was analyzed using quantitative RT-PCR and immunohistochemistry. Cell growth was assessed using colony formation assay. Additionally, mRNA sequencing was performed to compare the expression profiles of cells subjected to different treatments. RESULTS: LGR6 was overexpressed in small cell lung cancer (SCLC) and NSCLC cell lines, including the CTNNB1-mutated NSCLC cell lines HCC15 and A427. In both cell lines, LGR6 knockdown inhibited cell growth. LGR6 expression was upregulated in spheroids compared to adherent cultures of A427 cells, suggesting that LGR6 participates in the acquisition of cancer stem cell properties. Immunohistochemical analysis of lung cancer specimens revealed that the LGR6 protein was predominantly overexpressed in SCLCs, large cell neuroendocrine carcinomas, and lung adenocarcinomas, wherein LGR6 overexpression was associated with vascular invasion, the wild-type EGFR genotype, and an unfavorable prognosis. Integrated mRNA sequencing analysis of HCC15 and A427 cells with or without LGR6 knockdown revealed LGR6-related pathways and genes associated with cancer development and stemness properties. CONCLUSIONS: Our findings highlight the oncogenic roles of LGR6 overexpression induced by aberrant Wnt/ß-catenin signaling in lung cancer.

An essential signaling cascade for avian auditory hair cell regeneration.

Hearing loss is a chronic disease affecting millions of people worldwide, yet no restorative treatment options are available. Although non-mammalian species can regenerate their auditory sensory hair cells, mammals cannot. Birds retain facultative stem cells known as supporting cells that engage in proliferative regeneration when surrounding hair cells die. Here, we investigated gene expression changes in chicken supporting cells during auditory hair cell death. This identified a pathway involving the receptor F2RL1, HBEGF, EGFR, and ERK signaling. We propose a cascade starting with the proteolytic activation of F2RL1, followed by matrix-metalloprotease-mediated HBEGF shedding, and culminating in EGFR-mediated ERK signaling. Each component of this cascade is essential for supporting cell S-phase entry in vivo and is integral for hair cell regeneration. Furthermore, STAT3-phosphorylation converges with this signaling toward upregulation of transcription factors ATF3, FOSL2, and CREM. Our findings could provide a basis for designing treatments for hearing and balance disorders.

Pterygoid Muscle Necrosis Caused by Radiation and Intra-Arterial Cisplatin Infusion Chemotherapy (RADPLAT): A Case Report.

Introduction: Radiation and intra-arterial cisplatin infusion chemotherapy (RADPLAT) for advanced maxillary sinus cancer has accumulated evidence as a treatment with fewer complications and better 5-year survival rates. In this study, we report a case in which pterygoid muscle necrosis occurred 6 months following RADPLAT treatment for maxillary sinus cancer. Case Presentation: The 45-year-old woman had a long history of taking immunosuppressants against rheumatoid arthritis (RA) prior to treatment. Although achieving complete response (CR) to RADPLAT, the patient developed trismus (1 fingerbreadth or less) 6 months following treatment. Abscess formation and recurrence were suspected from the imaging findings; however, the biopsy with endoscopy indicated necrotic tissue. Currently, 18 months have passed without cancer recurrence. Although trismus temporarily improved with rehabilitation, the width of the mouth opening is currently a few millimeters, so the patient can only take liquid food. Conclusion: Pterygoid muscle necrosis should be recognized as a new major complication.

Silencing of GRHL2 induces epithelial­to­mesenchymal transition in lung cancer cell lines with different effects on proliferation and clonogenic growth.

Grainyhead-like 2 (GRHL2) is a transcription factor that suppresses epithelial-to-mesenchymal transition (EMT). It has been previously shown that GRHL2 can confer both oncogenic and tumor-suppressive roles in human cancers, including breast, pancreatic and colorectal cancers. However, its role in lung cancer remains elusive. In the present study, a meta-analysis of multiple gene expression datasets with clinical data revealed that GRHL2 expression was increased in lung cancer compared with that in the normal tissues. Copy number analysis of GRHL2, performed using datasets of whole exome sequencing involving 151 lung cancer cell lines, revealed frequent amplifications, suggesting that the increased GRHL2 expression may have resulted from gene amplification. A survival meta-analysis of GRHL2 using The Cancer Genome Atlas (TCGA) dataset showed no association of GRHL2 expression with overall survival. GRHL2 expression was found to be associated with EMT status in lung cancer in TCGA dataset and lung cancer cell lines. GRHL2 knockdown induced partial EMT in the hTERT/Cdk4-immortalized normal lung epithelial cell line HBEC4KT without affecting proliferation measured by CCK-8 assays. In addition, GRHL2 silencing caused three lung cancer cell lines, H1975, H2009 and H441, to undergo partial EMT. However, the proliferative effects differed significantly. GRHL2 silencing promoted proliferation but not colony formation in H1975 cells whilst suppressing colony formation without affecting proliferation in H2009 cells, but it did not affect proliferation in H441 cells. These results suggest cell type-dependent effects of GRHL2 knockdown. Downstream, GRHL2 silencing enhanced the phosphorylation of AKT and ERK, assessed by western blotting with phospho-specific antibodies, in HBEC4KT, H1975 and H2009 cell lines but not in the H441 cell line. By contrast, transient GRHL2 overexpression did not affect A549 cell proliferation, which lack detectable endogenous expression of the GRHL2 protein. However, GRHL2 overexpression did suppress E-cadherin expression in A549 cells. These results suggested that GRHL2 does not only function as a tumor suppressor of EMT but can also behave as an oncogene depending on the lung cancer cell-type context.

Contrast-enhanced ultrasound imaging for monitoring the efficacy of near-infrared photoimmunotherapy.

BACKGROUND: Near-infrared photoimmunotherapy (NIR-PIT) is a promising cancer therapy combining NIR-light irradiation with an antibody and IR700DX, a light-sensitive substance, to destroy tumours. However, homogeneous irradiation is difficult because the light varies depending on the distance and tissue environment. Therefore, markers that indicate sufficient irradiation are necessary. Nanoparticles sized 10∼200 nm show enhanced permeation and retention within tumours, which is further enhanced via NIR-PIT (super enhanced permeability and retention, SUPR). We aimed to monitor the effectiveness of NIR-PIT by measuring SUPR. METHODS: A xenograft mouse tumour model was established by inoculating human cancer cells in both buttocks of Balb/C-nu/nu mice, and NIR-PIT was performed on only one side. To evaluate SUPR, fluorescent signal examination was performed using QD800-fluorescent nanoparticles and NIR-fluorescent poly (d,l-lactide-co-glycolic acid) (NIR-PLGA) microparticles. Harmonic signals were evaluated using micro-bubbles of the contrast agent Sonazoid and contrast-enhanced ultrasound (CEUS) imaging. The correlation between SUPR immediately after treatment and NIR-PIT effectiveness on the day after treatment was evaluated. FINDINGS: QD800 fluorescent signals persisted only in the treated tumours, and the intensity of remaining signals showed high positive correlation with the therapeutic effect. NIR-PLGA fluorescent signals and Sonazoid-derived harmonic signals remained for a longer time in the treated tumours than in the controls, and the kE value of the two-compartment model correlated with NIR-PIT effectiveness. INTERPRETATION: SUPR measurement using Sonazoid and CEUS imaging could be easily adapted for clinical use as a therapeutic image-based biomarker for monitoring and confirming of NIR-PIT efficacy. FUNDING: This research was supported by ARIM JAPAN of MEXT, the Program for Developing Next-generation Researchers (Japan Science and Technology Agency), KAKEN (18K15923, 21K07217) (JSPS), CREST (JPMJCR19H2, JST), and FOREST-Souhatsu (JST). Mochida Memorial Foundation for Medical and Pharmaceutical Research; Takeda Science Foundation; The Japan Health Foundation; and Princess Takamatsu Cancer Research Fund. Funders only provided financial support and had no role in the study design, data collection, data analysis, interpretation, and writing of the report.

Prognostic significance of the harmonized maximum standardized uptake value of 18F-FDG-PET/CT in patients with resectable oral tongue squamous cell carcinoma: a multicenter study.

OBJECTIVES: To investigate the usefulness of harmonized 18F-FDG-PET/CT parameters for predicting the postoperative recurrence and prognosis of oral tongue squamous cell carcinoma (OTSCC). METHODS: We retrospectively analyzed the cases of 107 OTSCC patients who underwent surgical resection at four institutions in Japan in 2010-2016 and evaluated the harmonized PET parameters of the maximum standardized uptake value (SUVmax), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) for the primary tumor as the pSUVmax, pMTV, and pTLG. For lymph node metastasis, we used harmonized PET parameters of nodal-SUVmax, nodal-total MTV (tMTV), and nodal-total TLG (tTLG). The associations between the harmonized PET parameters and the patients' relapse-free survival (RFS) and overall survival (OS) were evaluated by the Kaplan-Meier method and Cox proportional hazard regression analysis for model 1 (preoperative stage) and model 2 (preoperative + postoperative stages). RESULTS: The harmonized SUVmax values were significantly lower than those before harmonization (p=0.012). The pSUVmax was revealed as a significant preoperative risk factor for RFS and OS. Nodal-SUVmax, nodal-tMTV, and nodal-tTLG were significant preoperative risk factors for OS. The combination of pSUVmax + nodal-SUVmax significantly stratified the patients into a low-risk group (pSUVmax <3.97 + nodal-SUVmax <2.85 or ≥2.85) and a high-risk group (pSUVmax ≥3.97 + nodal-SUVmax <2.85 or pSUVmax ≥3.97 + nodal-SUVmax ≥2.85) for recurrence and prognosis (RFS: p=0.001; OS: p<0.001). CONCLUSIONS: The harmonized pSUVmax is a significant prognostic factor for the survival of OTSCC patients. The combination of pSUVmax and nodal-SUVmax identified OTSCC patients at high risk for recurrence and poor prognosis at the preoperative stage.

The Usefulness of Total Laryngectomy in Sarcopenic Patients With Hypopharyngeal and Laryngeal Cancer.

BACKGROUND/AIM: Sarcopenia has an adverse effect on postoperative complications and prognoses in head and neck cancer. This study focused on hypopharyngeal and laryngeal cancer patients with sarcopenia and analyzed the body composition following treatment when the larynx was preserved and when total laryngectomy was performed to examine the usefulness of laryngectomy. PATIENTS AND METHODS: We retrospectively reviewed 88 primary hypopharyngeal and laryngeal cancer patients aged 65 years or older with cT2N0M0 or higher who visited our department. RESULTS: There were no significant differences in the 3-year overall survival rate and the 1-year local control rate between the laryngeal preservation group and laryngectomy group. The average change one year following treatment in the laryngeal preservation group, when compared to prior to treatment, was a significant decrease in the body weight (BW) of -0.035, skeletal muscle mass (SMM) of -0.030, skeletal muscle mass index (SMI) of -0.026, body mass index (BMI) of -0.034, and grip strength (GS) of -0.066. The average change one year following treatment in the laryngectomy group, compared with prior to treatment, was an increase in BW of +0.028, SMM of +0.026, SMI of +0.008, BMI of +0.032, and GS of +0.026. Although no changes in serum biochemical testing after treatment were observed in the laryngeal preservation group, albumin, transferrin, and transthyretin all exhibited significant improvement or a tendency toward improvement in the laryngectomy group. The patients with sarcopenia before treatment in the laryngeal preservation group had a significantly higher incidence of aspiration pneumonia. CONCLUSION: The presence or absence of sarcopenia before starting treatment is considered to be an index for selecting total laryngectomy.

Leukocyte Depletion and Size-Based Enrichment of Circulating Tumor Cells Using a Pressure-Sensing Microfiltration Device.

Considering the challenges in isolating circulating tumor cells (CTCs) pertaining to cellular stress and purity, we report the application of a blood microfiltration device as an optimal approach for noninvasive liquid biopsy to target CTCs. We experimentally analyzed the filtration behavior of the microfilter using pressure sensing to separate tumor cells from leukocytes in whole blood. This approach achieved an average recovery of >96% of the spiked tumor cells and depletion of >99% of total leukocytes. Furthermore, we carried out genomic profiling of the CTCs using the blood microfiltration device. The method was also applied in a clinical setting; DNA amplification was performed using a small number of microfiltered CTCs and epidermal growth factor receptor mutations were successfully detected to characterize the efficacy of molecularly targeted drugs against lung cancer. Overall, the proposed method can provide a tool for evaluating efficient filtration pressure to concentrate CTCs from whole blood.

Decrease in cholesterol in the cell membrane is essential for Nrf2 activation by quercetin.

Quercetin is a flavonoid with various cytoprotective effects. We previously reported that quercetin exerts anti-allergic, anti-oxidative, and anti-fibrotic activities via the induction of heme oxygenase (HO)-1. However, the mechanisms by which quercetin induces HO-1 to exhibit cytoprotective effects are poorly understood. We focused on its action on the cell membrane, which is the first part of the cell to interact with the extracellular environment. The cell membrane contains lipid rafts and caveolae, which play important roles in cellular signaling. A recent study showed that nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating anti-oxidative enzymes including HO-1, interacts with caveolin-1 (Cav-1), a component of caveolae, to regulate cellular anti-oxidative capacity. In this study, we investigated the changes in the cell membrane that leads to the induction of HO-1 by quercetin. Quercetin decreased the amount of cholesterol in the raft fractions, which in turn promoted the induction of HO-1. It also changed the composition of the lipid rafts and decreased and increased the expression of Cav-1 in the raft and non-raft fractions, respectively. Nrf2, which was localized in the cell membrane under resting conditions, was translocated along with Cav-1 to the nucleus after exposure to quercetin. These findings indicate for the first time that the HO-1-dependent cytoprotective effects of quercetin are mediated by the structural changes in lipid rafts brought about by decreasing the amount of cholesterol in the cell membrane, which thereby results in the translocation of the Cav-1-Nrf2 complex to the nucleus and induces the expression of HO-1.

High-performance glass filters for capturing and culturing circulating tumor cells and cancer-associated fibroblasts.

Various liquid biopsy methods have been developed for the non-invasive and early detection of diseases. In particular, the detection of circulating tumor cells (CTCs) and cancer-associated fibroblasts (CAFs) in blood has been receiving a great deal of attention. We have been developing systems and materials to facilitate such liquid biopsies. In this study, we further developed glass filters (with various patterns of holes, pitches, and non-adhesive coating) that can capture CTCs, but not white blood cells. We optimized the glass filters to capture CTCs, and demonstrated that they could be used to detect CTCs from lung cancer patients. We also used the optimized glass filters for detecting CAFs. Additionally, we further developed a system for visualizing the captured cells on the glass filters. Finally, we demonstrated that we could directly culture the captured cells on the glass filters. Based on these results, our high-performance glass filters appear to be useful for capturing and culturing CTCs and CAFs for further examinations.

Recent Advances in Localized Immunomodulation Technology: Application of NIR-PIT toward Clinical Control of the Local Immune System.

Current immunotherapies aim to modulate the balance among different immune cell populations, thereby controlling immune reactions. However, they often cause immune overactivation or over-suppression, which makes them difficult to control. Thus, it would be ideal to manipulate immune cells at a local site without disturbing homeostasis elsewhere in the body. Recent technological developments have enabled the selective targeting of cells and tissues in the body. Photo-targeted specific cell therapy has recently emerged among these. Near-infrared photoimmunotherapy (NIR-PIT) has surfaced as a new modality for cancer treatment, which combines antibodies and a photoabsorber, IR700DX. NIR-PIT is in testing as an international phase III clinical trial for locoregional recurrent head and neck squamous cell carcinoma (HNSCC) patients (LUZERA-301, NCT03769506), with a fast-track designation by the United States Food and Drug Administration (US-FDA). In Japan, NIR-PIT for patients with recurrent head and neck cancer was conditionally approved in 2020. Although NIR-PIT is commonly used for cancer therapy, it could also be exploited to locally eliminate certain immune cells with antibodies for a specific immune cell marker. This strategy can be utilized for anti-allergic therapy. Herein, we discuss the recent technological advances in local immunomodulation technology. We introduce immunomodulation technology with NIR-PIT and demonstrate an example of the knockdown of regulatory T cells (Tregs) to enhance local anti-tumor immune reactions.

Genetic variants of cancer­associated genes analyzed using next­generation sequencing in small sporadic vestibular schwannomas.

Vestibular schwannoma (VS) is the most common tumor of the cerebellopontine angle. Despite the increasing diagnosis of sporadic VS over the past decade, the use of traditional microsurgeries to treat VS has decreased. This is likely a result of the adoption of serial imaging as the most common initial evaluation and treatment strategy, especially for small-sized VS. However, the pathobiology of VSs remains unclear, and elucidating the genetic information of tumor tissue may reveal novel insights. The present study performed a comprehensive genomic analysis of all exons in the key tumor suppressor and oncogenes from 10 small (<15 mm) sporadic VS samples. The evaluations identified NF2, SYNE1, IRS2, APC, CIC, SDHC, BRAF, NUMA1, EXT2, HRAS, BCL11B, MAGI1, RNF123, NLRP1, ASXL1, ADAMTS20, TAF1L, XPC, DDB2 and ETS1 as mutated genes. The current study could not draw any new conclusions about the relationship between VS-related hearing loss and gene mutations; however, it did reveal that NF2 was the most frequently mutated gene in small sporadic VS.

COVID-19 presenting as acute epiglottitis: A case report and literature review.

Coronavirus disease 2019 (COVID-19) occasionally causes acute laryngitis, requiring emergency treatment. Understanding the characteristic laryngeal findings can help diagnose COVID-19 earlier, prevent worsening infection, and properly manage airway obstruction. Herein, we report the case of a 44-year-old male with acute epiglottitis likely caused by COVID-19. On presentation, chest computed tomography (CT) showed no signs of pneumonia. However, the larynx had extensive necrotic-like erosive lesions resembling those of tuberculous laryngitis. COVID-19 was diagnosed by reverse-transcription polymerase chain reaction, and secondary bacterial superinfections were suspected after blood testing. The symptoms improved after administration of antibiotics (sulbactam sodium/ampicillin sodium), steroids (dexamethasone), and favipiravir. The patient developed a high fever on the sixth day of hospitalization, and pneumonia was identified on CT. Various culture tests, including tuberculosis, were negative. Thus, remdesivir was administered for COVID-19-induced pneumonia. The patient gradually recovered, was transferred to another hospital, and was discharged on the 35th day of hospitalization. Six previous case reports of COVID-19-induced acute epiglottitis suggested that acute epiglottitis preceded the onset of pneumonia. The laryngeal findings from this report may be useful for diagnosing COVID-19 that does not cause pneumonia and for bringing attention to pneumonia after a COVID-19 diagnosis.

Three Cases of Hematoma in the Retropharyngeal Space.

OBJECTIVES: Hematoma in the retropharyngeal space (RPS) is a life-threatening condition that leads to rapid airway obstruction. However, the indication for airway management remains unclear. Additionally, the requirement for surgical hematoma evacuation remains undetermined. Therefore, we attempt to suggest some criteria for the management of hematoma in such cases. METHODS: We report three cases of hematoma in the RPS wherein one patient was treated without surgery and the other two underwent tracheotomy followed by hematoma evacuation. RESULTS: We found that airway management should be based on whether the glottis could be visible on laryngoscopy and dyspnea severity. The degree of hematoma, swelling, subcutaneous bleeding in the anterior neck, and emotional stability should also be considered. Proper management during the acute phase may allow for conservative treatments. Hematomas extending below the tracheal bifurcation may help ease upper airway obstruction due to pressure distribution, allowing for conservative treatment. When hematomas are surgically evacuated, tracheotomy should be performed simultaneously. Our report suggests that mediastinal hematoma evacuation could be avoided. CONCLUSION: We should determine a therapeutic strategy for hematoma in RPS based on glottis visualization, patient's condition, and extent of hematoma growth under careful observation.

Near-Infrared Photoimmunotherapy for Thoracic Cancers: A Translational Perspective.

The conventional treatment of thoracic tumors includes surgery, anticancer drugs, radiation, and cancer immunotherapy. Light therapy for thoracic tumors has long been used as an alternative; conventional light therapy also called photodynamic therapy (PDT) has been used mainly for early-stage lung cancer. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a completely different concept from conventional PDT, has been developed and approved in Japan for the treatment of recurrent and previously treated head and neck cancer because of its specificity and effectiveness. NIR-PIT can apply to any target by changing to different antigens. In recent years, it has become clear that various specific and promising targets are highly expressed in thoracic tumors. In combination with these various specific targets, NIR-PIT is expected to be an ideal therapeutic approach for thoracic tumors. Additionally, techniques are being developed to further develop NIR-PIT for clinical practice. In this review, NIR-PIT is introduced, and its potential therapeutic applications for thoracic cancers are described.