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1.
Mol Clin Oncol ; 16(2): 34, 2022 Feb.
Article in English | MEDLINE | ID: mdl-34987803

ABSTRACT

Only one case of melanoma arising from melanin-producing medullary thyroid carcinoma (MTC) has been reported previously. In the present study, a second such case was reported and compared with the previous one. The patient was an 86-year-old male who presented with a right anterior neck mass. Ultrasound revealed a nodule measuring 49x48x40 mm in the right lobe of the thyroid. The levels of serum calcitonin (2,298 pg/ml) and carcinoembryonic antigen (CEA; 27.0 ng/ml) were markedly elevated. Aspiration cytology revealed suspected malignant anaplastic thyroid carcinoma and total thyroidectomy without neck nodal dissection was performed. On gross observation, the nodule was well encapsulated, soft, solid and black. Light microscopy indicated that the nodule was composed mainly of large, occasionally huge, pleomorphic cells with a solid or alveolar growth pattern. On immunohistochemistry, these cells were positive for melan-A and S-100 protein, and negative for thyroid transcription factor 1, calcitonin, chromogranin A and CEA. In the subcapsular area, melanin-producing MTC was intimately intermingled with the pleomorphic cells. No primary site of the melanoma was detectable in other organs. At three years after surgery, the patient died due to metastasis of the melanoma to the brain. The previously reported case had no detectable recurrence or distant metastasis up to 11 years after surgery. In comparison with that case, the present case had a similar morphology but the outcome was poorer. Thus, the prognosis of melanoma that transforms from MTC appears to remain uncertain.

2.
J Nippon Med Sch ; 89(3): 277-286, 2022 Jun 28.
Article in English | MEDLINE | ID: mdl-34526468

ABSTRACT

BACKGROUND: Endoscopic thyroidectomy offers excellent cosmetic outcomes but requires some time for surgeons to become proficient. We examined the learning curve for the first 100 patients treated by a single surgeon using a subclavian approach for video-assisted neck surgery (VANS). METHODS: We retrospectively studied the records of 100 patients (99 women, 1 man; mean age, 36.2 years) with either benign or malignant thyroid disease treated between 2016 and 2020. RESULTS: Preoperative diagnosis was papillary thyroid carcinoma (PTC) in 36 cases and other (non-PTC) in 64 cases. All patients underwent lobectomy, with additional unilateral central node dissection for patients with PTC. Mean operative time was 125 min for non-PTC cases and 129 min for PTC cases (p = 0.43); blood loss was 33.8 mL and 7.6 mL, respectively (p = 0.01). Recurrent laryngeal nerve paralysis (RNP) was observed in 12 patients (12%) and hemorrhage in 2 patients (2%). In a comparison of the first 30 cases and subsequent 70 cases, no significant differences in operative time or blood loss were evident, although tumor size was significantly greater among later non-PTC cases (32.4 mm vs. 39.5 mm, p = 0.039). RNP was significantly lower in later cases (26.7% vs. 5.7%, p = 0.003). Multivariate analysis revealed that tumor size was a significant risk factor for increased blood loss, and increased experience significantly correlated with a decrease in RNP. CONCLUSIONS: In VANS, satisfactory surgical proficiency was reached after treating 30 patients.


Subject(s)
Surgeons , Thyroid Neoplasms , Vocal Cord Paralysis , Adult , Female , Humans , Learning Curve , Male , Neck Dissection , Retrospective Studies , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroidectomy , Video-Assisted Surgery
3.
Front Endocrinol (Lausanne) ; 12: 703410, 2021.
Article in English | MEDLINE | ID: mdl-34858321

ABSTRACT

To the best of our knowledge, we report a case of MEN2A complicated by moyamoya syndrome. A 52-year-old woman presented with vertigo. Magnetic resonance angiography (MRA) revealed bilateral supraclinoid stenosis of the internal carotid artery and abnormal moyamoya-like vessels around the basal ganglia. She had a heterozygous variant of RNF213, which is the susceptibility gene for moyamoya disease. She had also previously received diagnoses of medullary thyroid carcinoma (MTC) at age 23 and left-sided pheochromocytoma (PHEO) at age 41. Genetic testing revealed heterozygosity for a mutation at codon 634 in exon 11 (TGC-TTC mutation; p.Cys634Phe) of the Ret gene. Intracranial vascular stenosis may have been caused by a genetic mutation of RNF213 and hypersecretion of catecholamines by MEN2A. Physicians should recognize that MEN2A can be present with moyamoya syndrome.


Subject(s)
Adenosine Triphosphatases/genetics , Adrenal Gland Neoplasms/physiopathology , Carcinoma, Neuroendocrine/physiopathology , Moyamoya Disease/pathology , Multiple Endocrine Neoplasia Type 2a/complications , Mutation , Pheochromocytoma/physiopathology , Thyroid Neoplasms/physiopathology , Ubiquitin-Protein Ligases/genetics , Female , Humans , Male , Middle Aged , Moyamoya Disease/etiology , Moyamoya Disease/metabolism , Pedigree
4.
Molecules ; 26(9)2021 Apr 26.
Article in English | MEDLINE | ID: mdl-33925959

ABSTRACT

The direct and indirect bactericidal effects of dielectric barrier discharge (DBD) cold atmospheric-pressure microplasma in an air and plasma jet generated in an argon-oxygen gas mixture was investigated on Staphylococcus aureus and Cutibacterium acnes. An AC power supply was used to generate plasma at relatively low discharge voltages (0.9-2.4 kV) and frequency (27-30 kHz). Cultured bacteria were cultivated at a serial dilution of 10-5, then exposed to direct microplasma treatment and indirect treatment through plasma-activated water (PAW). The obtained results revealed that these methods of bacterial inactivation showed a 2 and 1 log reduction in the number of survived CFU/mL with direct treatment being the most effective means of treatment at just 3 min using air. UV-Vis spectroscopy confirmed that an increase in treatment time at 1.2% O2, 98.8% Ar caused a decrease in O2 concentration in the water as well as a decrease in absorbance of the peaks at 210 nm, which are attributed NO2- and NO3- concentration in the water, termed denitratification and denitritification in the treated water, respectively.


Subject(s)
Anti-Bacterial Agents/chemistry , Anti-Bacterial Agents/pharmacology , Atmospheric Pressure , Plasma Gases/chemistry , Plasma Gases/pharmacology , Microbial Sensitivity Tests , Ozone/analysis , Ozone/chemistry , Reactive Nitrogen Species/chemistry , Reactive Oxygen Species/chemistry , Staphylococcus aureus/drug effects , Sterilization/methods , Water/chemistry
6.
Surg Today ; 50(10): 1126-1137, 2020 Oct.
Article in English | MEDLINE | ID: mdl-31728730

ABSTRACT

PURPOSE: To describe and evaluate our video-assisted neck surgery (VANS) method for thyroid and parathyroid diseases. METHODS: We describe in detail the VANS method for enucleation, lobectomy, total (nearly total) thyroidectomy, and lymph node dissection for malignancy and Graves' disease. In collaboration with the Japan Society of Endoscopic Surgery (JSES), we evaluated several aspects of this method. The JSES evaluated the method for working-space formation and surgical complications, whereas we examined the learning curve of the surgeons, and the cosmetic satisfaction of the patients and the degree of numbness and pain they experienced. We also asked patients who underwent conventional surgery whether they would have selected VANS had it been available. RESULTS: The working space for 81.5% of the procedures in Japan was created using the gasless lifting method. The learning curve, considering both blood loss and operating time, decreased after 30 cases. Both factors improved for tumors smaller than 5 cm in diameter. Over 60% of the patients who underwent conventional surgery stated that they would have selected VANS, had it been available. Postoperative pain was worse after conventional surgery than after VANS, but neck numbness after VANS was more frequent than expected. CONCLUSIONS: The VANS method is a feasible, safe, and cost-effective procedure with clear cosmetic advantages over conventional surgery.


Subject(s)
Parathyroid Diseases/surgery , Thyroid Diseases/surgery , Thyroidectomy/methods , Video-Assisted Surgery/methods , Cost-Benefit Analysis , Feasibility Studies , Humans , Lymph Node Excision , Operating Rooms , Pain, Postoperative/etiology , Pain, Postoperative/prevention & control , Patient Satisfaction , Safety
7.
Oncol Lett ; 16(6): 7278-7286, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30546467

ABSTRACT

Thyroid carcinoma (TC) has characteristic genetic alterations, including point mutations in proto-oncogenes and chromosomal rearrangements that vary by histologic subtype. Recent developments in next-generation sequencing (NGS) technology enable simultaneous analysis of cancer-associated genes of interest, thus improving diagnostic accuracy and allowing precise personalized treatment for human cancer. A total of 50 patients who underwent thyroidectomy between 2014 and 2016 at Hokuto Hospital were enrolled. Total DNA was extracted from formalin-fixed, paraffin-embedded tissue sections and quantified. Targeted regions of 24 cancer-associated genes were amplified by PCR, barcoded and sequenced using an Illumina MiSeq platform. Subjects included 30 patients with papillary carcinoma (PC), two with PC tall cell variant (TVPC), two with PC follicular variant (FVPC), eight with follicular carcinoma, seven with poorly differentiated carcinoma (PDC), and one with anaplastic carcinoma (AC). The BRAF V600E mutation was present in 25 of 30 (83%) patients with PC, 2 of 2 (100%) patients with TVPC, 6 of 7 (86%) patients of PDC, and one patient with AC. PIK3CA mutations were present in 3 of 30 (delPV104P, A1046T and C420R; 10%) patients with PC and 1 of 7 (H1047R; 14%) patients with PDC. The TP53 mutation was present in 1 of 30 (R306*; 3.3%) patients with PC and 1 of 7 (Q152*; 14%) patients with PDC. The NRAS mutation was present in 1 of 2 (Q61K, 50%) patients with FVPC. Statistical analysis showed that patients without the BRAF V600E mutation had advanced pathologic T and N stages compared with those with the mutation (P=0.047 and P=0.019, respectively). The BRAF V600E mutation was not correlated with overall and disease-free survival in patients with PC. A patient with PC with a mutation in EGFR (K852Q) and the PIK3CA mutation had an aggressive course with multiple bone and lung metastases. Detection of mutations in cancer-associated genes using NGS could enhance the understanding of the clinical behavior of TC.

8.
J Nippon Med Sch ; 85(3): 178-182, 2018.
Article in English | MEDLINE | ID: mdl-30135345

ABSTRACT

BACKGROUND: Multiple endocrine neoplasia type 2B (MEN2B) is an extremely rare syndrome mainly caused by RET918 germline mutations. MEN2B typically causes medullary thyroid carcinoma (MTC), pheochromocytoma, and unique physical characteristics including mucosal neuroma, distinctive facial appearance, and Marfanoid habitus. Most patients have abdominal symptoms such as bloating, intermittent constipation, and diarrhea. MTC is the most important determinant of mortality in patients with MEN2B. Establishing the diagnosis of MEN2B at a curative stage of MTC is crucial. CASE PRESENTATION: We have encountered four patients with MEN2B. Two were hereditary cases from the same family, and two were considered de novo cases with phenotypically normal parents. Mean age at diagnosis was 25.5 years (range, 13-39 years). Although all patients had shown mucosal neuroma on the lips and tongue, in addition to gastrointestinal symptoms from infancy, diagnoses were made from symptomatic MTC even for the hereditary patients (our index case was a 14-year-old girl, whose mother was subsequently diagnosed with advanced MTC). Genetic tests for RET mutations revealed the M918T mutation in all patients. Two patients developed pheochromocytoma, two died from distant metastases of MTC, and two received treatment for multiple metastases of MTC (one with vandetanib). CONCLUSIONS: In our patients with MEN2B, prophylactic or early thyroidectomy could not be performed. The characteristic phenotype associated with MEN2B is almost always seen prior to detection of MTC or pheochromocytoma. Knowledge about the non-endocrine manifestations of MEN2B needs to be shared among pediatricians and gastroenterologists.


Subject(s)
Multiple Endocrine Neoplasia Type 2b/diagnosis , Multiple Endocrine Neoplasia Type 2b/pathology , Physical Appearance, Body , Adolescent , Adrenal Gland Neoplasms , Adult , Female , Humans , Lip/pathology , Male , Multiple Endocrine Neoplasia Type 2b/genetics , Multiple Endocrine Neoplasia Type 2b/physiopathology , Mutation , Neuroma , Phenotype , Pheochromocytoma , Proto-Oncogene Proteins c-ret/genetics , Thyroid Neoplasms , Tongue/pathology
9.
Biointerphases ; 12(2): 02B402, 2017 05 04.
Article in English | MEDLINE | ID: mdl-28476092

ABSTRACT

A study of the transdermal delivery of Cyclosporine A by atmospheric plasma irradiation was realized on the epidermal layer of the Hairless Yucatan micropig. Drug flux and the amount of drug penetrated through the skin were determined by a Franz cell diffusion experiment. After treatment of the skin by atmospheric plasma jet or microplasma dielectric barrier discharge, an increase in the permeability of the skin was observed. The authors did not observe drug penetration for samples that were not treated with plasma. There was no significant difference between treatments of skin by plasma jet or microplasma dielectric barrier discharge. Drug flux increased to its maximal value up to 3 h after the drug application, and then it decreased. This phenomenon could indicate a temporal effect of plasma on skin. A pharmacokinetic two-compartment model was developed to estimate the possibility of using plasma drug delivery of Cyclosporine A in medical praxis. Our model showed that it is possible to use this technique if a suitable treatment area and concentration of applied drug are chosen.


Subject(s)
Cyclosporine/pharmacology , Cyclosporine/pharmacokinetics , Plasma Gases , Skin Absorption/drug effects , Skin/metabolism , Administration, Cutaneous , Animals , Swine , Swine, Miniature
10.
Endocr J ; 63(7): 597-602, 2016 Jul 30.
Article in English | MEDLINE | ID: mdl-27210070

ABSTRACT

Differentiated thyroid carcinoma (DTC) is generally indolent in nature and, even though it metastasizes to distant organs, the prognosis is normally excellent. In contrast, the overall survival (OS) of patients with radioactive iodine (RAI)-refractory and progressive metastases is dire, because no effective therapies have been available to control the metastatic lesions. However, recently, administration of tyrosine-kinase inhibitors (TKIs) has become a new line of therapy for RAI-refractory and progressive metastases. Previous studies have reported significant improvement regarding the progression-free survival rates of patients with metastatic lesions. However, TKIs cause various severe adverse events (AEs) that damage patients' quality of life and can even be life-threatening. Additionally, metastatic lesions may progress significantly after stopping TKI therapy. Therefore, it is difficult to determine who is a candidate for TKI therapy, as well as how and when physicians start and stop the therapy. The present review, created by Committee of pharmacological therapy for thyroid cancer of the Japanese Society of Thyroid Surgery (JSTS) and the Japan Association of Endocrine Surgeons (JAES) describes how to appropriately use TKIs by describing what we do and do not know about treatment using TKIs.


Subject(s)
Adenocarcinoma/drug therapy , Iodine Radioisotopes/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Thyroid Neoplasms/drug therapy , Adenocarcinoma/pathology , Adenocarcinoma/radiotherapy , Chemotherapy, Adjuvant , Disease Progression , Humans , Neoplasm Metastasis , Neoplasm Recurrence, Local , Protein-Tyrosine Kinases/antagonists & inhibitors , Thyroid Neoplasms/pathology , Thyroid Neoplasms/radiotherapy , Treatment Failure
11.
Endocr J ; 62(12): 1067-75, 2015.
Article in English | MEDLINE | ID: mdl-26424174

ABSTRACT

In general, juvenile differentiated thyroid carcinoma (DTC) demonstrate indolent characteristics and favorable prognosis are observed in comparison with many other carcinomas. However, recurrence is frequent, necessitating additional treatment, including radioactive iodine (RAI) therapy. In this report, the probability of recurrence, prognostic factors, treatment, and outcomes in both juvenile- and adult-onset DTC were analyzed and compared. At our institution, a total of 1552 DTC patients underwent thyroidectomy and/or lymph node dissection. The patients included 23 in their teens, 118 in their twenties, and 1412 in their thirties or older. The risk factors for distant metastases for DTC were male gender, follicular carcinoma, size of the PTC primary tumor, cervical lymph node metastases from PTC, and the presence of more than two distant metastatic foci. Patients with the highest risk underwent RAI ablation in line with institutional guidelines. Although the overall outcome in our juvenile patients was excellent, during follow-up, 4 (17.4%) of the 23 patients developed recurrent disease: 91.3% achieved complete remission, 4.35% partial remission, and 4.35% stable disease, with no disease-related deaths. Among the 118 patients in their twenties to thirties, 1 (0.8%) experienced progressive disease and disease-related death. A younger age at diagnosis and less radical primary surgery without subsequent RAI ablation are factors strongly predictive of distant metastases in patients with juvenile-onset DTC. To reduce the rate of relapse and improve surveillance for recurrent disease, total thyroidectomy followed by RAI appears to be the most beneficial initial treatment for patients with high- and intermediate-risk juvenile DTC.


Subject(s)
Neoplasm Metastasis/radiotherapy , Thyroid Neoplasms/radiotherapy , Adenocarcinoma, Follicular/pathology , Adenocarcinoma, Follicular/radiotherapy , Adenocarcinoma, Follicular/surgery , Adolescent , Adult , Age Factors , Aged , Carcinoma/pathology , Carcinoma/radiotherapy , Carcinoma/surgery , Carcinoma, Papillary , Female , Humans , Iodine Radioisotopes/therapeutic use , Lymph Node Excision , Lymphatic Metastasis , Male , Middle Aged , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/prevention & control , Prognosis , Remission Induction , Risk Factors , Sex Factors , Thyroid Cancer, Papillary , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroidectomy , Young Adult
12.
Biointerphases ; 10(2): 029517, 2015 Jun 06.
Article in English | MEDLINE | ID: mdl-25947391

ABSTRACT

Application of atmospheric plasma could be used for wound healing, skin rejuvenation, and wrinkle treatment. The authors explored the feasibility of atmospheric microplasma irradiation (AMI) for enhancement of percutaneous absorption of drugs as an alternative to hypodermic needles. Pig skin was used as a biological sample exposed to AMI and analyzed by attenuated total reflection-Fourier transform infrared spectroscopy. A tape-stripping test (an evaluation method for skin-barrier performance) was also conducted to compare with AMI. Transepidermal water loss was also measured and compared with and without AMI. Results showed that surface modification of the stratum corneum (outermost skin layer) was observed upon AMI. Small pores on sample skin were observed with plasma jet irradiation due to the collision of charged particles. Percutaneous absorption was confirmed without damage upon microplasma irradiation. Our data suggested that dye pathways through skin samples could be related to the dynamic behavior of intercellular lipid bilayers, suggesting that AMI could enhance percutaneous absorption.


Subject(s)
Administration, Cutaneous , Atmosphere , Drug Delivery Systems/methods , Pharmaceutical Preparations/administration & dosage , Plasma Gases , Skin/radiation effects , Animals , Dehydration , Female , Permeability/radiation effects , Skin/chemistry , Spectroscopy, Fourier Transform Infrared , Sus scrofa
13.
World J Surg ; 39(7): 1728-35, 2015 Jul.
Article in English | MEDLINE | ID: mdl-25743484

ABSTRACT

BACKGROUND: Diffuse sclerosing variant (DSV) of papillary thyroid carcinoma (PTC) is a rare variant more common among younger patients. MATERIALS AND METHODS: Excluding patients with microcarcinoma, 5848 patients with PTC underwent initial surgery between 1995 and 2011. Twenty-two patients (0.4 %) were histologically diagnosed with DSV, of whom 20 (91 %) were <45 years old. We compared clinicopathologic characteristics and outcomes between patients with DSV and those with classical PTC <45 years old. Univariate analysis by the Kaplan-Meier method in relation to cause-specific survival (CSS) and disease-free survival (DFS) rates was performed with regard to the following variables: sex; anti-thyroglobulin antibody (TgAb) positivity; presence of distant metastasis; pathological lymph node metastasis; extra-thyroidal invasion; and pathological variant (classical vs. DSV). RESULTS: The 20 patients with DSV <45 years old comprised 18 females and 2 males. Frequencies of TgAb, pN1b, and local recurrence were higher in the DSV group than in the classical PTC group. Ten-year CSS and DFS rates for PTC patients <45 years old were 99.7 and 88.6 % in the classical PTC group and 100 and 60.5 % in the DSV group. CSS rate did not differ between groups, but DFS rate was significantly lower in the DSV group than in the classical PTC group (p < 0.0001, log-rank test). Multivariate analysis identified DSV group and pN1b as prognostic factors for recurrence in young PTC patients. CONCLUSIONS: Most DSV patients were young and had a background of chronic thyroiditis. Outcomes for DSV were very good, but recurrence was more common than in classical PTC.


Subject(s)
Carcinoma, Papillary/pathology , Carcinoma/pathology , Thyroid Neoplasms/pathology , Adolescent , Adult , Carcinoma/complications , Carcinoma/surgery , Carcinoma, Papillary/complications , Carcinoma, Papillary/surgery , Child , Female , Hashimoto Disease/complications , Humans , Lymphatic Metastasis , Male , Neoplasm Metastasis , Neoplasm Recurrence, Local , Thyroglobulin/analysis , Thyroid Cancer, Papillary , Thyroid Neoplasms/complications , Thyroid Neoplasms/surgery , Young Adult
14.
Oncol Rep ; 33(4): 2052-60, 2015 Apr.
Article in English | MEDLINE | ID: mdl-25632963

ABSTRACT

Malignant pleural mesothelioma (MPM) is a highly aggressive tumor that has a poor prognosis, limited treatment options, and a worldwide incidence that is expected to increase in the next decade. We evaluated Wnt7A expression in 50 surgically resected tumor specimens using quantitative PCR. The expression values, were assessed by clinicopathological factors and K-M and Cox's regression with OS. The mean level of Wnt7A expression had a significant correlation with International Mesothelioma Interest Group (IMIG) stage (P<0.034), gender, smoking history and ethnicity, respectively (P=0.020, P=0.014, P=0.039). In the univariate analysis, low Wnt7A expression was a significant negative factor for overall survival (P=0.043, HR=2.30). However, multivariate Cox's regression revealed no significant factors for overall survival (low Wnt7A: P=0.051, HR=2.283; non-epithelioid subtype: P=0.050, HR=2.898). In patients with epithelioid tumors, those with low Wnt7A expression had significantly worse prognosis (P=0.019, HR=2.98). In patients with epithelioid tumors, females had significantly better prognosis than males (P=0.035). In patients who did not have neoadjuvant chemotherapy, prognosis was significantly more favorable for patients with high Wnt7A expression than for those with low Wnt7A expression (P=0.031). Among the patients with low Wnt7A-expressing tumors, those who received neoadjuvant chemotherapy had better prognosis than those who did not (P=0.024). The results of our study suggest that Wnt7A expression is a putative prognostic factor and a predictor of chemosensitivity.


Subject(s)
Biomarkers, Tumor/genetics , Lung Neoplasms/diagnosis , Lung Neoplasms/genetics , Mesothelioma/diagnosis , Mesothelioma/genetics , Pleural Neoplasms/diagnosis , Pleural Neoplasms/genetics , Wnt Proteins/genetics , Aged , Aged, 80 and over , Female , Humans , Male , Mesothelioma, Malignant , Middle Aged , Prognosis
15.
Odontology ; 103(2): 194-202, 2015 May.
Article in English | MEDLINE | ID: mdl-24916282

ABSTRACT

The purpose of this research was to clarify the effects of microplasma irradiation on human gingival fibroblasts (HGF). Microplasma irradiation exposure for all HGF samples was limited to 30 s at an irradiation distance of 10 mm with a gas flow of 10 L/min. Three experimental groups were used: a 0 V control group (Control); a 650 V (low) microplasma irradiation group (LV); and a 975 V (high) irradiation group (HV). The following cellular characteristics were evaluated in order to analyze the effects of microplasma treatment; morphology, cell count, DNA content, metabolic activity, cell migration, fibroblast growth factor ß (FGF-2) production, type I collagen secretion, and cytotoxic analysis. Cell count, DNA content and FGF-2 production have all been linked to wound healing and, interestingly, both the LV and HV groups showed significant (P < 0.05) increases in these categories at 72 h after irradiation when compared to the control group. Cytotoxic effects were measured by determining the levels of lactate dehydrogenase, cell death, and DNA damage in HGF cells. In these analyses, the HV and LV groups were not statistically different when compared with the control group at 72 h post-irradiation. These findings suggest that microplasma irradiation activated HGF with no clear cell-damaging effects.


Subject(s)
Fibroblasts/radiation effects , Gingiva/cytology , Plasma Gases/pharmacology , Cell Movement/radiation effects , Cell Proliferation/radiation effects , Cells, Cultured , Enzyme-Linked Immunosorbent Assay , Fibroblast Growth Factors/metabolism , Humans , Wound Healing/radiation effects
16.
J Nippon Med Sch ; 81(4): 211-20, 2014.
Article in English | MEDLINE | ID: mdl-25186575

ABSTRACT

INTRODUCTION: An important mechanism by which trastuzumab inhibits the growth of human epidermal growth factor receptor 2 (HER2)-positive breast cancer cells is the activation of a host tumor response via antibody-dependent cell-mediated cytotoxicity (ADCC). Although paclitaxel has a synergistic effect in combination with trastuzumab, whether ADCC is enhanced by paclitaxel is not known. In the present study we examined whether adding paclitaxel to trastuzumab enhances ADCC and also investigated the kinetics of effector cells in ADCC. MATERIALS AND METHODS: The subjects were 20 patients with HER2-positive breast cancer: 9 received the combination of trastuzumab (4 mg/kg as a loading dose and 2 mg/kg weekly) and paclitaxel (80 mg/m(2) weekly) and 19 received monotherapy with trastuzumab. In blood samples (mononuclear cells) obtained before and 10 minutes after administration of chemotherapy, ADCC and the number of effector cells, including natural killer (NK) cells, monocytes, and CD64+ cells, were compared in each case. The ADCC was analyzed with a (51)Cr releasing assay using the SK-BR-3 cell line, and the fractions of NK cells (both CD16+ [FcγRIII] and CD56+) and CD64+ (FcγRI) cells were analyzed with flow cytometry. RESULTS: The mean ADCC level increased 20% after trastuzumab monotherapy and 126% (p<0.05) after combination therapy with trastuzumab and paclitaxel. All 9 patients receiving combination therapy had increased ADCC levels. The number of NK cells increased 51% after trastuzumab monotherapy and 112% (p<0.05) after combination therapy. No significant changes were found in monocytes (39% increase) or CD64+ cells (53% increase) after trastuzumab monotherapy, but monocytes decreased 40% (p<0.05) and CD64+ cells decreased 24% after combination therapy. CONCLUSIONS: Adding paclitaxel to trastuzumab significantly enhances ADCC, with levels twice as great as with trastuzumab monotherapy, through a rapid recruitment of NK cells. This finding suggests that the combination of trastuzumab and paclitaxel has a stronger-than-expected synergistic effect in HER2-positive breast cancer.


Subject(s)
Antibodies, Monoclonal, Humanized/pharmacology , Antibody-Dependent Cell Cytotoxicity/drug effects , Breast Neoplasms/drug therapy , Breast Neoplasms/immunology , Killer Cells, Natural/drug effects , Killer Cells, Natural/immunology , Paclitaxel/pharmacology , Receptor, ErbB-2/metabolism , Antibodies, Monoclonal, Humanized/therapeutic use , Antineoplastic Combined Chemotherapy Protocols/pharmacology , Antineoplastic Combined Chemotherapy Protocols/therapeutic use , Breast Neoplasms/metabolism , Breast Neoplasms/pathology , Female , Humans , Lymphocyte Count , Monocytes/drug effects , Paclitaxel/therapeutic use , Trastuzumab
17.
J Nippon Med Sch ; 81(3): 139-47, 2014.
Article in English | MEDLINE | ID: mdl-24998960

ABSTRACT

BACKGROUND: Patients with de novo stage IV and relapsed breast cancer are often treated with the same strategy. However, survival differences have recently been reported between the disease types. PURPOSE: The aim of this study was to compare outcomes between de novo stage IV disease and relapsed disease and to discuss any differences in prognostic factors between them. PATIENTS AND METHODS: The subjects were 79 patients with de novo stage IV disease and 213 patients with relapsed disease treated at the Tokyo Metropolitan Cancer and Infectious Diseases Center, Komagome Hospital, from October 2001 through November 2010. The Kaplan-Meier method was used to estimate overall survival (OS), and the Cox proportional hazards model was used to examine the association between metastatic disease and OS. RESULTS: The median follow-up period was 32 months for de novo stage IV disease and 34 months for relapsed disease. The median OS was 46 months and 43 months, respectively. No significant differences were evident. Identified prognostic factors were performance status and liver metastasis for de novo stage IV disease, and performance status, hormone receptor status, solitary bone metastasis, and disease-free interval for relapsed disease. CONCLUSION: No differences in outcome were found between de novo stage IV disease and relapsed disease. However, their prognostic factors differed substantially and suggest that different treatment strategies may be warranted for metastatic disease in each type of breast cancer.


Subject(s)
Breast Neoplasms/drug therapy , Breast Neoplasms/pathology , Neoplasm Recurrence, Local , Outcome Assessment, Health Care/methods , Adult , Aged , Aged, 80 and over , Breast Neoplasms/metabolism , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Middle Aged , Multivariate Analysis , Neoplasm Staging , Prognosis , Proportional Hazards Models , Receptor, ErbB-2/metabolism , Receptors, Estrogen/metabolism , Receptors, Progesterone/metabolism , Young Adult
18.
J Nippon Med Sch ; 81(2): 64-9, 2014.
Article in English | MEDLINE | ID: mdl-24805091

ABSTRACT

Familial medullary thyroid carcinoma (FMTC) is an autosomal dominant inherited disease that has highly characteristic clinical features, including medullary thyroid carcinoma (MTC). Mutation of the RET proto-oncogene is known to be responsible for development of FMTC and for multiple endocrine neoplasia types 2A and 2B. Hirschsprung's disease is the most common form of structural intestinal obstructive disease in human newborns. Hirschsprung's disease is defined by the absence of neural crest-derived enteric ganglia along a variable length of the bowel that invariably involves the rectoanal junction. Co-segregation of FMTC and Hirschsprung's disease is uncommon; nevertheless, in 3 generations of 1 family, we observed 5 patients with FMTC, 2 patients with Hirschsprung's disease, and 1 patient with characteristics of both FMTC and Hirschsprung's disease. Moreover, a Cys620Ser mutation in RET was identified in 4 of the 8 patients. This mutation had both activating and inactivating effects on the RET (REarranged during Transfection) protein. There were individual differences in the penetrance of Hirschsprung's disease due to the RET mutation, but the penetrance of MTC was uniform and high. Genetic testing is important for making decisions about treatment and follow-up in families of this kind.


Subject(s)
Carcinoma, Medullary/genetics , Hirschsprung Disease/genetics , Thyroid Neoplasms/genetics , Adult , Carcinoma, Medullary/complications , Family , Female , Hirschsprung Disease/complications , Humans , Male , Middle Aged , Pedigree , Proto-Oncogene Mas , Proto-Oncogene Proteins c-ret/genetics , Thyroid Neoplasms/complications
19.
J Nippon Med Sch ; 81(2): 84-93, 2014.
Article in English | MEDLINE | ID: mdl-24805094

ABSTRACT

BACKGROUND: When performing parathyroid or thyroid surgery, surgeons must distinguish parathyroid tissue from the surrounding thyroid tissue, to preserve healthy parathyroid tissue while excising diseased thyroid tissue or to completely remove pathological parathyroid lesions. Here, we explored the feasibility of labeling the parathyroid glands for easy identification by administering 5-aminolevulinic acid (5-ALA) orally to patients undergoing endocrine neck surgery, because 5-ALA accumulates in the parathyroid and has a fluorescent metabolite, protoporphyrin IX. METHODS: Twenty-nine patients about to undergo endocrine (parathyroid or thyroid gland) neck surgery were orally given 5-ALA, a nontoxic substance that occurs naturally in the human body and has no known major side effects. During surgery, we used blue light to excite protoporphyrin IX, the fluorescent metabolite of 5-ALA, and viewed the resulting bright red fluorescence through an optical filter. RESULTS: In the majority of the patients, the parathyroid glands were defined by a clear fluorescence. In 23 patients with pathological parathyroid tissue, the fluorescence enabled us to identify and completely remove diseased parathyroid tissue. In 3 patients with thyroid disease, we were able to easily remove diseased thyroid tissue, and an accidentally removed parathyroid gland was autotransplanted during surgery. CONCLUSIONS: In all but a few cases, 5-ALA clearly labeled parathyroid tissue, allowing for its clean removal or preservation according to the purpose of the surgery. This simple, benign technique is extremely useful for identifying parathyroid tissue, whether pathological or normal, during endocrine neck surgery.


Subject(s)
Aminolevulinic Acid , Neck/surgery , Protoporphyrins , Adult , Aged , Female , Humans , Male , Middle Aged , Parathyroid Glands/surgery , Parathyroidectomy , Thoracic Surgery, Video-Assisted , Thyroid Gland/surgery , Thyroidectomy
20.
Gen Thorac Cardiovasc Surg ; 62(4): 248-51, 2014 Apr.
Article in English | MEDLINE | ID: mdl-23475297

ABSTRACT

Intramuscular myxomas are benign soft-tissue tumors that often develop in the thigh. A 66-year-old woman was referred with an abnormal shadow on chest roentgenogram. The tumor was well defined and smooth and originated from the second intercostal space. Positron emission tomography showed no accumulation of 18F-fluorodeoxyglucose in the tumor. The patient attended the outpatient department for follow-up care. Because the mass grew slightly after 52 months, the patient underwent complete removal by video-assisted thoracoscopic surgery. On histopathological examination, the tumor was diagnosed as an intramuscular myxoma in the chest wall. The patient has had no recurrence 3 years after surgery. A case of intramuscular myxoma in the chest wall, completely resected by video-assisted thoracoscopic surgery, is reported. A well-defined, smooth, homogeneous mass in the chest wall may therefore be intramuscular myxoma.


Subject(s)
Intercostal Muscles/pathology , Muscle Neoplasms/pathology , Myxoma/pathology , Thoracic Surgery, Video-Assisted/methods , Thoracic Wall/pathology , Aged , Diagnosis, Differential , Female , Fluorodeoxyglucose F18 , Humans , Muscle Neoplasms/diagnostic imaging , Muscle Neoplasms/surgery , Myxoma/diagnostic imaging , Myxoma/surgery , Neoplasm Recurrence, Local , Positron-Emission Tomography
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