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.

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.

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.

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.

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.

Effects of 2450 MHz electromagnetic fields with a wide range of SARs on methylcholanthrene-induced transformation in C3H10T1/2 cells.

This study examined whether 2450 MHz continuous wave high frequency electromagnetic fields (HFEMF) could induce cancer-like changes in mouse C3H10T1/2 cells, and whether HFEMF could initiate malignant or synergistic transformation. Transformed foci, Type II and Type III, were independently counted as the experiment endpoint. The cells were exposed to HFEMF alone at a wide range of specific absorption rates (SARs) of 5 to 200 W/kg for 2 h and/or were treated with a known initiating chemical, methylcholanthrene (MC) (2.5 microg/ml). No significant differences were observed in the malignant transformation (Type II + Type III) frequency between the controls and HFEMF with or without 12-O-tetradecanoylphorbol-13-acetate (TPA) (0.5 ng/ml), a tumor promoter that could enhance transformation frequency initiated by MC in multistage carcinogenesis. However, the transformation frequency for HFEMF at SAR of more than 100 W/kg with MC or MC plus TPA was increased compared with MC alone or MC plus TPA. On the other hand, the corresponding heat groups (heat alone, heat + MC, and heat + MC + TPA) did not increase transformation compared with each control level in C3H10T1/2 cells. This result suggests that 2450 MHz HFEMF could not contribute to the initiation stage of tumor formation, but it may contribute to the promotion stage at the extremely high SAR (100 W/kg).

Effect of high-frequency electromagnetic fields with a wide range of SARs on chromosomal aberrations in murine m5S cells.

To investigate the induction of chromosomal aberrations in mouse m5S cells after exposure to high-frequency electromagnetic fields (HFEMFs) at 2.45 GHz, cells were exposed for 2 h at average specific absorption rates (SARs) of 5, 10, 20, 50 and 100 W/kg with continuous wave-form (CW), or at a mean SAR of 100 W/kg (with a maximum of 900 W/kg) with pulse wave-form (PW). The effects of HFEMF exposure were compared with those in sham-exposed controls and with mitomycin C (MMC) or X-ray treatment as positive controls. We examined all structural, chromatid-type and chromosome-type changes after HFEMF exposures and treatments with MMC and X-rays. No significant differences were observed following exposure to HFEMFs at SARs from 5 to 100 W/kg CW and at a mean SAR of 100 W/kg PW (a maximum SAR of 900 W/kg) compared with sham-exposed controls, whereas treatments with MMC and X-rays increased the frequency of chromatid-type and chromosome-type aberrations. In summary, HFEMF exposures at 2.45 GHz for 2 h with up to 100 W/kg SAR CW and an average 100 W/kg PW (a maximum SAR of 900 W/kg) do not induce chromosomal aberrations in m5S cells. Furthermore, there was no difference between exposures to CW and PW HFEMFs.

Decrease in glucose-stimulated insulin secretion following exposure to magnetic fields.

We evaluated the effects of extremely low frequency magnetic field (ELFMF) on glucose-stimulated insulin secretion from HIT-T15 cells and investigated the mechanisms of these effects. We demonstrated that exposure to ELFMF at 5mT decreased glucose-stimulated insulin secretion by preventing the increases in cellular adenosine 5'-triphosphate/adenosine 5'-diphosphate, membrane depolarization, and cytosolic free calcium ion concentration. The glucose-induced upregulation of insulin mRNA expression was also attenuated by exposure to ELFMF, although cell viability was not affected. These findings demonstrate the potential of exposure to ELFMF for clinical use as a novel inhibitory method of insulin secretion.

ELF electromagnetic fields increase hydrogen peroxide (H2O2)-induced mutations in pTN89 plasmids.

We have examined the mutational effects of hydrogen peroxide (H(2)O(2)) in the presence and absence of an extremely low-frequency magnetic field (ELFMF), using pTN89 plasmids. Mutations were detected in the supF gene carried by these plasmids in Escherichia coli. The plasmids were either treated with H(2)O(2) (1microM) alone at 37 degrees C for 4h, or were exposed to an ELFMF (60Hz, 5millitesla (mT)) simultaneously with H(2)O(2) treatment. The mutation frequency was 2.28 x 10(-4) for H(2)O(2) treatment alone, and 5.81 x 10(-4) for ELFMF exposure with H(2)O(2) treatment. We did not observe any mutations using treatment with ELFMF exposure alone. This indicates that the ELFMF may potentiate H(2)O(2)-induced mutation. Sequence analysis of the supF mutant plasmids revealed that base substitutions, G: C-->A :T transitions and G:C-->T:A transversions were dominant in both treatment groups, and there was no difference in the mutation spectrum or the hotspots between the groups. Therefore, ELFMFs may interact and potentiate the damage induced by H(2)O(2), resulting in an increase in the number of mutations.

Effects of high frequency electromagnetic fields on micronucleus formation in CHO-K1 cells.

To investigate the effects of high frequency electromagnetic fields (HFEMFs), we assessed the frequency of micronucleus (MN) formation induced by chromosomal breakage or inhibition of spindles during cell division in Chinese hamster ovary (CHO)-K1 cells, using the cytokinesis block micronucleus method. The MN frequency in cells in the inner, middle and outer wells of an annular culture plate was determined for the following four conditions: (1) CHO-K1 cells were exposed to a HFEMF for 18 h at average specific absorption rates (SARs) of 13, 39 and 50 W/kg with input power 7.8 W, and were compared with a sham-exposed control; (2) the cells were also exposed to a HFEMF at SARs of 78 and 100 W/kg with input power 13 W, and were compared with a sham-exposed control; (3) the cells were treated with bleomycin alone or with bleomycin followed by exposure to a HFEMF for 18 h at SARs of 25, 78 and 100 W/kg, and were compared with a bleomycin-treated positive control. The cells treated with bleomycin alone were compared with sham-exposed controls; and (4) As a high temperature control, CHO-K1 cells were incubated at 39 degrees C for 18 h. In study (1), the MN frequency of cells exposed to a HFEMF at a SAR of up to 50 W/kg was not different to that in sham-exposed cells. In study (2), there were statistically significant increases in the MN frequencies of cells in the middle and outer wells of the annular culture plate caused by exposure to a HFEMF at 100 and 78 W/kg, respectively. In study (3), the MN frequencies of cells in the middle (100 W/kg) and outer wells (78 W/kg) of the annular culture plate were statistically higher than that caused by bleomycin-treatment alone. In study (4), there was a statistically significant increase of MN frequency in the cells treated by heat at 39 degrees C. These results indicate that cells exposed to a HFEMF at a SAR of 78 W/kg and higher form MN more frequently than sham-exposed cells, while exposure to a HFEMF at up to 50 W/kg does not induce MN formation. In addition, a HFEMF at a SAR of 78 W/kg and higher may potentiate MN formation induced by bleomycin-treatment.

In vitro oocyte culture and somatic cell nuclear transfer used to produce a live-born cloned goat.

The use of an in vitro culture system was examined for production of somatic cells suitable for nuclear transfer in the goat. Goat cumulus-oocyte complexes were incubated in tissue culture medium TCM-199 supplemented with 10% fetal bovine serum (FBS) for 20 h. In vitro matured (IVM) oocytes were enucleated and used as karyoplast recipients. Donor cells obtained from the anterior pituitary of an adult male were introduced into the perivitelline space of enucleated IVM oocytes and fused by an electrical pulse. Reconstituted oocytes were cultured in chemically defined medium for 9 days. Two hundred and twenty-eight oocytes (70%) were fused with donor cells. After in vitro culture, seven somatic cell nuclear transfer (SCNT) oocytes (3%) developed to the blastocyst stage. SCNT embryos were transferred to the oviducts of recipient females (four 8-cell embryos per female) or uterine horn (two blastocysts per female). One male clone (NT1) was produced at day 153 from an SCNT blastocyst and died 16 days after birth. This study demonstrates that nuclear transferred goat oocytes produced using an in vitro culture system could develop to term and that donor anterior pituitary cells have the developmental potential to produce term offspring. In this study, it suggested that the artificial control of endocrine system in domestic animal might become possible by the genetic modification to anterior pituitary cells.