Survival Outcomes of Complete Pulmonary Metastasectomy for Head and Neck Squamous Cell Carcinomas.

Purpose: Metastatic head and neck squamous cell carcinoma (HNSCC) is relatively poor; however, depending on the selected cases, pulmonary metastasectomy can be a practical therapeutic option. This study aimed to identify the outcomes of complete metastasectomy based on each primary site and to investigate unfavorable prognostic factors. Patients and Methods: We used the database from the Metastatic Lung Tumour Study Group of Japan. Between November 1980 and April 2017, 231 patients were deemed eligible. According to anatomy and the current epidemiology of HNSCC, the patients were divided into three groups: nasopharynx, oropharynx, and salivary gland (n = 40, Group 1), oral cavity, tongue, and paranasal sinuses (n = 69, Group 2), and larynx and hypopharynx (n = 122, Group 3). Results: The 5-year overall survival after complete pulmonary metastasectomy was 58.5%, 25.0%, and 46.9% in G1, 2, and 3, respectively (p < 0.01). Multivariate analyses revealed unfavourable prognostic factors to be G2, and pathological maximum diameter was >20 mm. Therefore, on dividing group 1 and 3 with or without diameter, the 5-year overall survival was significantly worse in HNSCC with a diameter >20 mm (n = 74) than that in the remnant (n = 88; 61.9% vs 35.5%; p < 0.01). Conclusion: According to the multi-institutional Japanese data, pulmonary metastasectomy from HNSCC indicates a potential survival benefit. Oral cavity, tongue, and paranasal sinuses cancer, and tumour size (>20 mm) were poor prognostic factors for pulmonary metastasectomy from head and neck cancer.

Effects of salicylate derivatives on localization of p.H723R allele product of SLC26A4.

OBJECTIVE: Pendrin is a transmembrane protein encoded by the SLC26A4 gene that functions in maintaining ion concentrations in the endolymph of the inner ear, most likely by acting as a chloride/bicarbonate transporter. Variants in the SLC26A4 gene are responsible for sensorineural hearing loss. Although pendrin localizes to the plasma membrane, we previously identified that 8 missense allele products of SLC26A4 were retained in the intracellular region and lost their anion exchange function. We also found that 10 mM salicylate induced the translocation of 4 out of 8 allele products from the intracellular region to the plasma membrane and restored their anion exchanger activity. However, since 10 mM salicylate exhibits cytotoxicity, the use of chemical compounds with less cell toxicity is needed. In the present study, therefore, salicylate derivatives were used as the chemical compounds and their effects on the p.H723R allele products of SLC26A4 were investigated. METHODS: HEK293 cells were transfected with the cDNA of p.H723R. Cell proliferation, viability and toxicity assays were performed to investigate the response and health of cells in culture after treatment with four types of salicylate derivatives, i.e., 2-hydroxybenzyl alcohol, 2,3-dihydroxybenzoic acid, 2'-hydroxyacetophenone and methyl salicylate. The effects of these salicylate derivatives on the localization of the p.H723R were investigated by immunofluorescence microscopy. RESULTS: The application of 10 mM salicylate showed an increase in cell toxicity and decrease in cell viability, leading to a significant decrease in cell proliferation. In contrast, the application of 1 mM salicylate derivatives did not show any significant increase in cell toxicity and decrease in cell viability, corresponding to a logarithmic increase in cell concentration with an increase in culture time. Immunofluorescence experiments showed that the p.H723R retained in the endoplasmic reticulum (ER). Among the salicylate derivatives applied, 2-hydroxybenzyl alcohol induced the translocation of p.H723R from the ER to the plasma membrane 3 h after its application. CONCLUSION: The results obtained showed that 2-hydroxybenzyl alcohol restored the localization of the p.H723R allele products of SLC26A4 from the ER to the plasma membrane at a concentration of 1 mM by 3 h after its administration with less cytotoxicity than 10 mM salicylate.

Comparison of Surgical Outcomes Between Invasive Mucinous and Non-Mucinous Lung Adenocarcinoma.

BACKGROUND: Invasive mucinous adenocarcinoma (IMA) is a rare subtype of invasive lung adenocarcinoma. However, the clinical course and prognostic outcomes following IMA resection, particularly postoperative recurrence, remain unclear. METHODS: We pathologically reevaluated 1362 lung adenocarcinoma resections performed at our institution, categorizing cases into the IMA group (72 cases) and non-IMA group (1290 cases). The IMA group was further classified into pneumonia and nodular types based on preoperative computed tomography. RESULTS: Overall, the IMA group had lower carcinoembryonic antigen levels (3 vs 8 ng/mL; P < .01), fewer lymph node metastasis (4% vs 24%; P < .01), and more KRAS mutations (56% vs 7%; P < .01) than the non-IMA group. Although postoperative recurrence rates did not differ between both groups (32% vs 27%; P = 0.35), lung recurrence occurred more frequently in the IMA group (83% vs 17%; P < .01). Propensity score-matched pair analysis showed that the IMA group had fewer lymph node metastasis (3% vs 35%; P < .01), more KRAS mutations (56% vs 9%; P < .01), and higher intrapulmonary recurrence rate (84% vs 31%; P < .01) than the non-IMA group. The 5-year overall survival rates did not differ between both groups (74% vs 81%; P = 0.26). However, among patients with intrapulmonary recurrence, those in the IMA group had significantly worse prognosis than those in the non-IMA group (35% vs 77%; P < .01). CONCLUSIONS: Intrapulmonary recurrence, which induced significantly worse prognosis, was more likely to occur in the IMA than non-IMA group.

An endobronchial recurrence of resected lung adenocarcinoma.

We report a rare case of endobronchial metastasis arising from peripheral lung adenocarcinoma 12 months after its complete resection. A 69-year old man underwent left upper lobectomy and lymph node dissection. A year after surgery, a bronchial nodule was identified at the left main bronchus through a computed tomography study. A bronchoscope examination showed that the bronchial nodule in the cartilage was located apart from the stump of the upper bronchus. Thus, bronchoscopic resection was performed. The pathological diagnosis was papillary adenocarcinoma, which was identical to the pathology of the previously resected lung cancer. Endobronchial metastasis from the primary lung cancer was confirmed. The present case highlights that clinicians should pay more attention to this rare recurrence pattern of lung cancer.

Uniquely Modified Robotic-Assisted Thoracic Surgery With Good Intrathoracic Visual Field.

Although the use of robot-assisted thoracoscopic surgery is increasing rapidly, it allows only a limited visual field on the head side because the system's camera port is usually placed in the eighth or ninth intercostal space. Because the visual field on the intrathoracic head side is critical during lung cancer surgery, such as when peeling off the first branches of the pulmonary artery (right truncus superior artery or left upper ventral lobe branch), a poor visual field could be fatal. We therefore devised a new port arrangement, the "Hamamatsu method," which ensures a good visual field.

Long-term exposure to a 40-GHz electromagnetic field does not affect genotoxicity or heat shock protein expression in HCE-T or SRA01/04 cells.

Millimeter waves are used in various fields, and the risks of this wavelength range for human health must be carefully evaluated. In this study, we investigated the effects of millimeter waves on genotoxicity and heat shock protein expression in human corneal epithelial (HCE-T) and human lens epithelial (SRA01/04) cells. We exposed the cells to 40-GHz millimeter waves at 1 mW/cm2 for 24 h. We observed no statistically significant increase in the micronucleus (MN) frequency or the level of DNA strand breaks in cells exposed to 40-GHz millimeter waves relative to sham-exposed and incubator controls. Heat shock protein (Hsp) expression also exhibited no statistically significant response to the 40-GHz exposure. These results indicate that exposure to 40 GHz millimeter waves under these conditions has little or no effect on MN formation, DNA strand breaks, or Hsp expression in HCE-T or SRA01/04 cells.

Effects of Exposure to 5.8 GHz Electromagnetic Field on Micronucleus Formation, DNA Strand Breaks, and Heat Shock Protein Expressions in Cells Derived From Human Eye.

In the near future, electrification will be introduced to heavy-duty vehicles and passenger cars. However, the wireless power transfer (WPT) requires high energy levels, and the suitability of various types of WPT systems must be assessed. This paper describes a method for solving technical and safety issues associated with this technology. We exposed human corneal epithelial (HCE-T) cells derived from the human eye to 5.8-GHz electromagnetic fields for 24 h. We observed no statistically significant increase in micronucleus (MN) frequency in cells exposed to a 5.8-GHz field at 1 mW/cm2 (the general public level in ICNIRP) relative to sham-exposed or incubator controls. Similarly, the DNA strand breaks, and the expression of heat shock protein (Hsp) Hsp27, Hsp70, and Hsp 90α exhibited no statistically significant effects as a result of exposure. These results indicate that the exposure to 5.8-GHz electromagnetic fields at 1 mW/cm2 for 24 h has little or no effect on micronucleus formation, DNA strand breaks, and Hsp expression in human eye cells.

Recovery kinetics of micronucleus formation by fractionated X-ray irradiation in various types of human cells.

High-dose ionizing radiation is sufficient for breaking DNA strands, leading to cell death and mutations. By contrast, the effects of fractionated ionizing radiation on human-derived cells remain unclear. To better understand the genotoxic effects of fractionated ionizing radiation, as well as the cellular recovery rate, we investigated the frequency of micronucleus (MN) formation in various types of human cells. We irradiated cells with fractionated X-ray doses of 2 Gy at a rate of 0.0635 Gy/min, separated into two to eight smaller doses. After irradiation, we investigated the frequency of MN formation. In addition, we investigated the rate of decrease in MN frequency after irradiation with 1 or 2 Gy X-rays at various recovery periods. Fractionated irradiation decreased MN frequency in a dose-dependent manner. When the total dose of X-rays was the same, the MN frequencies were lower after fractionated X-ray irradiation than acute irradiation in every cell type examined. The rate of MN decrease was faster in KMST-6 cells, which were derived from a human embryo, than in the other cells. The rate of MN decrease was higher in cells exposed to fractionated X-rays than in those exposed to acute irradiation. Recovery rates were very similar among cell lines, except in KMST-6 cells, which recovered more rapidly than other cell types.

[Suppressive Effects of Extract of Cedar Wood on Heat-induced Expression of Cellular Heat Shock Protein].

In recent years, highly antimicrobial properties of cedar heartwood essential oil against the wood-rotting fungi and pathogenic fungi have been reported in several papers. Antimicrobial properties against oral bacteria by hinokitiol contained in Thujopsis have been also extensively studied. The relation of naturally derived components and human immune system has been studied in some previous papers. In the present study, we focused on Japanese cedar, which has the widest artificial afforestation site in the country among various tree species. Extract oil was obtained from mixture of sapwood and heartwood of about 40-year cedar grown in Oguni, Kumamoto, Japan. We examined the influence of extract components from Japanese cedar woods on the expression of heat shock protein 70 (Hsp70) during heating, and on the micronucleus formation induced by the treatment of bleomycin as a DNA damaging agent. Cell lines used in this study were human fetal glial cells (SVGp12) and human glioma cells (MO54). Remarkable suppression of the Hsp70 expression induced by heating at 43°C was detected by the treatment of cedar extract in both SVGp12 and MO54 cells. We also found that cedar extract had an inhibitory tendency to reduce the micronucleus formation induced by bleomycin. From these results, the extract components from Japanese cedar woods would have an inhibitory effect of the stress response as a suppression of the heat-induced Hsp70 expression, and might have a reductive effect on carcinogenicity.

Effect of low-dose X-ray irradiation on micronucleus formation in human embryo, newborn and child cells.

PURPOSE: It is well known that a high-dose of ionizing radiation is sufficient to break DNA strands, which leads to elevated genotoxic risks; however, the risks associated with low doses of ionizing radiation remain unclear. In addition, there is little data about the effect of low-dose ionizing radiation on human-derived embryo, newborn and child cells. We investigated the frequency of micronucleus (MN) formation in these cells to understand the genotoxic effects of ionizing radiation. MATERIALS AND METHODS: We irradiated the cells with X-rays from 0.02-2 Gy at a rate of 0.0635 Gy/min. After irradiation, we investigated the effect of low-dose X-ray irradiation on cellular viability and frequency of MN formation. RESULTS: Increases in MN formation were largely dose-dependent; however, there were no differences between controls and doses lower than 0.2 Gy, except in KMST-6 human transformed embryo cells. CONCLUSION: We could not detect an obvious effect of low-dose X-ray irradiation at doses lower than 0.1 Gy. The embryonic cells were more sensitive to X-ray irradiation than newborn and child cells. The threshold for X-ray-induced MN formation appears to be in the range of 0.05-0.1 Gy in cultured human embryo, newborn and child cells.

Twenty Four-Hour Exposure to a 0.12 THz Electromagnetic Field Does Not Affect the Genotoxicity, Morphological Changes, or Expression of Heat Shock Protein in HCE-T Cells.

To investigate the cellular effects of terahertz (THz) exposure, human corneal epithelial (HCE-T) cells derived from human eye were exposed to 0.12 THz radiation at 5 mW/cm² for 24 h, then the genotoxicity, morphological changes, and heat shock protein (Hsp) expression of the cells were examined. There was no statistically significant increase in the micronucleus (MN) frequency of cells exposed to 0.12 THz radiation compared with sham-exposed controls and incubator controls, whereas the MN frequency of cells treated with bleomycin for 1 h (positive control) did increase significantly. Similarly, there were no significant morphological changes in cells exposed to 0.12 THz radiation compared to sham-exposed controls and incubator controls, and Hsp expression (Hsp27, Hsp70, and Hsp90α) was also not significantly different between the three treatments. These results indicate that exposure to 0.12 THz radiation using the present conditions appears to have no or very little effect on MN formation, morphological changes, and Hsp expression in cells derived from human eye.

Effects of Long-Term Exposure to 60 GHz Millimeter-Wavelength Radiation on the Genotoxicity and Heat Shock Protein (Hsp) Expression of Cells Derived from Human Eye.

Human corneal epithelial (HCE-T) and human lens epithelial (SRA01/04) cells derived from the human eye were exposed to 60 gigahertz (GHz) millimeter-wavelength radiation for 24 h. There was no statistically significant increase in the micronucleus (MN) frequency in cells exposed to 60 GHz millimeter-wavelength radiation at 1 mW/cm² compared with sham-exposed controls and incubator controls. The MN frequency of cells treated with bleomycin for 1 h provided positive controls. The comet assay, used to detect DNA strand breaks, and heat shock protein (Hsp) expression also showed no statistically significant effects of exposure. These results indicate that exposure to millimeter-wavelength radiation has no effect on genotoxicity in human eye cells.

Mediastinal mature teratoma with complete gastrointestinal and bronchial walls.

An extremely rare case of anterior mediastinal mature teratoma with almost complete gastrointestinal and bronchial walls is described. A 65-year-old woman presented with left precordial pain. Chest computed tomography showed a huge anterior mediastinal tumor, 15 cm × 21 cm, occupying the left thoracic cavity. Post-resection histopathological examination confirmed the diagnosis of mature teratoma and demonstrated almost complete gastrointestinal and bronchial walls. Although mature teratomas of the ovary and sacrococcygeal area are known to rarely contain organoid structures with various degrees of differentiation, this is the first case of an anterior mediastinal mature teratoma that contained well-developed organoid structures.

ALK-rearranged squamous cell carcinoma of the lung.

The fusion gene echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) is identified in approximately 5% of non-small-cell lung cancer patients. A rare case of ALK-positive squamous cell carcinoma of the lung is reported. A 60-year-old man, an ex-smoker with a 720-packs-per-year tobacco smoking history, presented with a mass lesion in the upper lobe of the left lung on chest computed tomography. Transbronchial biopsy of the mass confirmed a diagnosis of lung squamous cell carcinoma, and it was proven to have ALK rearrangement by fluorescent in situ hybridization. The patient underwent left upper lobectomy. Hematoxylin and eosin staining of the surgical specimen demonstrated the typical morphology of pure squamous cell carcinoma. The patient has been advised to attend regular check-ups for postoperative recurrence. ALK testing and subsequent ALK-targeted treatment can be a possible option in cases of postoperative recurrence.

Effect of a 2.45-GHz radiofrequency electromagnetic field on neutrophil chemotaxis and phagocytosis in differentiated human HL-60 cells.

The potential public health risks of radiofrequency (RF) fields have been discussed at length, especially with the use of mobile phones spreading extensively throughout the world. In order to investigate the properties of RF fields, we examined the effect of 2.45-GHz RF fields at the specific absorption rate (SAR) of 2 and 10 W/kg for 4 and 24 h on neutrophil chemotaxis and phagocytosis in differentiated human HL-60 cells. Neutrophil chemotaxis was not affected by RF-field exposure, and subsequent phagocytosis was not affected either compared with that under sham exposure conditions. These studies demonstrated an initial immune response in the human body exposed to 2.45-GHz RF fields at the SAR of 2 W/kg, which is the maximum value recommended by the International Commission for Non-Ionizing Radiation Protection (ICNIRP) guidelines. The results of our experiments for RF-field exposure at an SAR under 10 W/kg showed very little or no effects on either chemotaxis or phagocytosis in neutrophil-like human HL-60 cells.

Effect of an intermediate-frequency magnetic field of 23 kHz at 2 mT on chemotaxis and phagocytosis in neutrophil-like differentiated human HL-60 cells.

Public concerns about potential health risks of intermediate-frequency (IF) electromagnetic fields are increasing, especially as the use of induction-heating cooktops has spread extensively in Japan and Europe. In order to investigate the properties of IF electromagnetic fields, we examined the effect of exposure to a 23-kHz IF magnetic field of 2 mT for 2, 3, or 4 h on neutrophil chemotaxis and phagocytosis using differentiated human HL-60 cells. Compared with sham exposure, exposure to the IF magnetic field had no effect on neutrophil chemotaxis or phagocytosis. Previous studies demonstrated that exposure to a 23-kHz IF magnetic field of 2 mT (about 74-times the maximum value recommended by the International Commission for Nonionizing Radiation Protection guidelines) may affect the first-line immune responses in humans. To our knowledge, this is the first study to evaluate the effects of IF magnetic fields on cellular immune responses. We found that exposure to an IF magnetic field of 2 mT has minimal if any effect on either the chemotaxis or phagocytic activity of neutrophil-like human HL-60 cells.

Attention deficits in Japanese multiple sclerosis patients with minor brain lesion loads.

BACKGROUND: To investigate whether Japanese multiple sclerosis (MS) patients with minor brain lesion loads have attention deficits and brain atrophy, and to correlate their circumstance. METHOD: Twenty-one Japanese patients with relapsing-remitting MS were included in this study. Attention deficits were evaluated using Clinical Assessment for Attention (CAT) standardized according to age groups. Lesion load in the brain was assessed by tallying the total volume of plaques visible on brain magnetic resonance imaging (MRI). The width of the third ventricle and the bicaudate ratio were measured. RESULTS: The completion time for the visual cancellation tasks and/or the reaction times for the continuous performance test were prolonged in 14 patients (66.7%). The accuracy of responses was preserved throughout the CAT. Deviation from the normal value was not exaggerated based on the increasing difficulty of the task. The total volume of plaques on brain MRI was small. The width of the third ventricle was significantly increased in patients with MS when compared to controls, but was not correlated with the low performance on the CAT. CONCLUSIONS: Japanese MS patients with minor brain lesion loads frequently had attention deficits characterized by slowness of automatic information processing, but controlled processing that requires working memory demands was spared.

Exposure to extremely low frequency magnetic fields affects insulin-secreting cells.

To evaluate the effects of extremely low frequency magnetic field (ELFMF) on beta-cell survival and function, we cultured a hamster-derived insulin-secreting cell line (HIT-T15), which exhibits responsiveness to glucose in a semi-physiological range, under exposure to sham and ELFMF conditions, and assessed cell survival and function. We used our previously developed ELFMF exposure unit (a sinusoidal magnetic field at a frequency of 60 Hz, 5 mT) to culture cells under exposure to ELFMF conditions. We found that exposure to ELFMF for 5 days in the absence of glucose increased cell number, exposure for 2 days in the absence of glucose and for 5 days with 100 mg/dl glucose increased the insulin secretion to the culture medium, and exposure for 2 and 5 days with 40 and 100 mg/dl glucose increased intracellular insulin concentration in HIT-T15 cells. The increase in cell number under apoptotic culture conditions by exposure to ELFMF could lead to new therapeutic concepts in the treatment of diabetes. The ELFMF-induced increase in intracellular insulin concentration could be utilized to develop culture conditions to enhance intracellular insulin concentration in insulin-secreting cells that would be useful for cell transplantation to cure diabetes mellitus.

Extremely low frequency (ELF) magnetic fields enhance chemically induced formation of apurinic/apyrimidinic (AP) sites in A172 cells.

PURPOSE: To detect the effects of extremely low frequency (ELF) magnetic fields, the number of apurinic/apyrimidinic (AP) sites in human glioma A172 cells was measured following exposure to ELF magnetic fields. MATERIALS AND METHODS: The cells were exposed to an ELF magnetic field alone, to genotoxic agents (methyl methane sulfonate (MMS) and hydrogen peroxide (H2O2)) alone, or to an ELF magnetic field with the genotoxic agents. After exposure, DNA was extracted, and the number of AP sites was measured. RESULTS: There was no difference in the number of AP sites between cells exposed to an ELF magnetic field and sham controls. With MMS or H2O2 alone, the number of AP sites increased with longer treatment times. Exposure to an ELF magnetic field in combination with the genotoxic agents increased AP-site levels compared with the genotoxic agents alone. CONCLUSIONS: Our results suggest that the number of AP sites induced by MMS or H2O2 is enhanced by exposure to ELF magnetic fields at 5 millitesla (mT). This may occur because such exposure can enhance the activity or lengthen the lifetime of radical pairs.

Effects of 2.45 GHz electromagnetic fields with a wide range of SARs on bacterial and HPRT gene mutations.

Present day use of mobile phones is ubiquitous. This causes some concern for human health due to exposure to high-frequency electromagnetic fields (HFEMF) from mobile phones. Consequently, we have examined the effects of 2.45 GHz electromagnetic fields on bacterial mutations and the hypoxanthine-guanine phosphoribosyl transferase (HPRT) gene mutations. Using the Ames test, bacteria were exposed to HFEMF for 30 min at specific absorption rates (SARs) from 5 to 200 W/kg. In all strains, there was no significant difference in the frequency of revertant colonies between sham exposure and HFEMF-exposed groups. In examination of mutations of the HPRT gene, Chinese hamster ovary (CHO)-K1 cells were exposed to HFEMF for 2 h at SARs from 5 to 200 W/kg. We detected a combination effect of simultaneous exposure to HFEMF and bleomycin at the respective SARs. A statistically significant difference was observed between the cells exposed to HFEMF at the SAR of 200 W/kg. Cells treated with the combination of HFEMF at SARs from 50 to 200 W/kg and bleomycin exhibited increased HPRT mutations. As the exposure to HFEMF induced an increase in temperature, these increases of mutation frequency may be a result of activation of bleomycin by heat. We consider that the increase of mutation frequency may be due to a thermal effect.