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1.
Endocr J ; 71(4): 357-362, 2024 Apr 30.
Article in English | MEDLINE | ID: mdl-38246643

ABSTRACT

In papillary thyroid carcinoma (PTC) patients with mediastinal lymph nodes (LN) and lung metastases, adding preoperative computed tomography (CT) to ultrasound is useful for planning surgery. We identified risk factors (RFs) for mediastinal lymph node metastasis (MLNM) and lung metastasis in PTC patients. Frequencies of MLNM and lung metastases were compared in 478 patients. Relative risk (RR) was calculated based on RFs. MLNM and lung metastases were detected in 1.2% and 3.3% of patients, respectively. cT3-4, cN1, central LN metastasis, and lateral LN metastasis were RFs for MLNM in all patients (p < 0.05, p < 0.05, p < 0.05, p < 0.01) and older patients (age: ≥55 years) (p < 0.01, p < 0.05, p < 0.05, p < 0.05). cT3-4, cN1, gross extrathyroidal extension, central LN metastasis, and lateral LN metastasis were RFs for lung metastasis in all patients (p < 0.01, p < 0.05, p < 0.01, p < 0.01, p < 0.01, respectively). cN1 and gross extrathyroidal extension, central LN metastasis, and lateral LN metastasis were RFs in older patients (p < 0.01, p < 0.01, p < 0.05, p < 0.01), while lateral LN metastasis was an RF for lung metastasis in those of <55 years of age (younger patients) (p < 0.05). No MLNM was observed in cT1-2cN0 PTC patients, who accounted for 50.5% of patients included in the MLNM analysis. No lung metastasis was present in cT1-2cN0 PTC patients, who accounted for 50.5% of the patients included in the lung metastasis analysis. PTC patients with cT3-4 and cN1 have an increased risk of MLNM and lung metastasis. RFs differed between older and younger patients. Preoperative neck and chest CT are not necessary for PTC patients with ultrasound-diagnosed as cT1-2cN0.


Subject(s)
Lung Neoplasms , Lymphatic Metastasis , Thyroid Cancer, Papillary , Thyroid Neoplasms , Tomography, X-Ray Computed , Humans , Middle Aged , Male , Female , Lung Neoplasms/pathology , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/secondary , Lymphatic Metastasis/diagnostic imaging , Adult , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/diagnostic imaging , Thyroid Cancer, Papillary/secondary , Risk Factors , Thyroid Neoplasms/pathology , Thyroid Neoplasms/diagnostic imaging , Aged , Mediastinum/diagnostic imaging , Lymph Nodes/pathology , Lymph Nodes/diagnostic imaging , Young Adult , Preoperative Care , Adolescent , Retrospective Studies , Thyroidectomy
2.
World J Surg ; 47(10): 2464-2473, 2023 10.
Article in English | MEDLINE | ID: mdl-37266697

ABSTRACT

BACKGROUND: The management of intermediate-risk group of papillary thyroid cancer (PTC) is still vague, particularly regarding whether or not total thyroidectomy, postoperative radioactive iodine ablation (RAI-a), and postoperative TSH suppression are mandatory. METHODS: This retrospective study evaluated 680 PTC patients from 2010 to 2017, who were classified into the three risk groups as low, intermediate, and high-risk groups according to the criteria of the Japanese Association of Endocrine Surgeons (JAES) 2010 and underwent surgery according to the JAES guidelines. We retrospectively collected patient data for analyses of disease-free survivals in the intermediate-risk group patients. RESULTS: We performed surgery on 680 PTC patients from 2010 to 2017. Of them, 297 were classified as the intermediate-risk group. DFS was not statistically significantly different in patients with/without total thyroidectomy and postoperative TSH suppression therapy. For RAI-a, DFS (95% confidence interval) at 3, 5, and 8 years were 93.2% (84.6 ~ 97.2), 81.6% (68,3 ~ 90.2), and 70.7% (51.4 ~ 84.6) in patients with postoperative RAI-a and 100%, 100%, and 100% in patients without postoperative RAI-a after total thyroidectomy, respectively. DFS of patients without RAI-a was superior to those with RAI-a (P < 0.0004). Multivariable analysis by stepwise selection method revealed that postoperative RAI-a was a risk factor with a hazard ratio of 5.69. (95% CI 1.998-16.21) (P = 0.001131). CONCLUSIONS: Our study did not show the efficacy of RAI-a in patients with intermediate-risk PTC. This study implies that judging the efficacy of adjuvant therapy such as RAI or TSh suppression in intermediate-risk patients is difficult.


Subject(s)
Carcinoma, Papillary , Iodine , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/surgery , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Retrospective Studies , Iodine Radioisotopes , East Asian People , Carcinoma, Papillary/surgery , Carcinoma, Papillary/pathology , Risk Factors , Thyroidectomy , Thyrotropin
3.
Surg Case Rep ; 8(1): 218, 2022 Dec 08.
Article in English | MEDLINE | ID: mdl-36480061

ABSTRACT

BACKGROUND: Distant metastasis is extremely rare for papillary thyroid microcarcinoma (PTMC) without lymph node metastasis or extrathyroidal extension, for which active surveillance (AS) is indicated. The evaluation of distant metastases in low-risk PTMC is controversial. A case of PTMC in which AS would have been performed if chest CT and lung surgery had not been performed is reported. CASE PRESENTATION: The patient was a 71-year-old woman undergoing follow-up in the Department of Thoracic Surgery at our hospital for multiple frosted glass shadows in both lung fields for one and a half years. To make a definitive diagnosis, thoracoscopic right middle lobectomy and left upper partial lobectomy were performed 4 and 6 months earlier, respectively. In both resected specimens, lung adenocarcinoma and small metastasis of papillary thyroid carcinoma (PTC) were found. The patient was transferred to our department for a thorough examination for PTC. Ultrasonography was performed to search for the primary lesion, and it showed an irregular hypoechoic mass of 4 mm and 6 mm in the middle of the right lobe of the thyroid gland. The patient was diagnosed with PTC. Its clinical stage was T1a (m) N0 M1 (stage IVC). Total thyroidectomy and prophylactic central node dissection were performed. The pathological diagnosis was PTC (typical type) pT1a (m) N0. Postoperatively, she received radioactive iodine therapy. CONCLUSIONS: We experienced an extremely rare case and struggled to determine a treatment plan. We might be aware that lung metastases could develop in low-risk PTMC.

4.
World J Surg Oncol ; 20(1): 394, 2022 Dec 12.
Article in English | MEDLINE | ID: mdl-36510206

ABSTRACT

INTRODUCTION: Non-total thyroidectomy (non-TTx) is a widely accepted operative procedure for low-risk papillary thyroid carcinoma (PTC). PTC patients preoperatively diagnosed with unifocal disease are often revealed as having multifocal foci by microscopy. The present study determined whether or not patients with clinically unifocal, but pathologically multifocal non-high-risk PTC treated with non-TTx have an increased risk of a poor prognosis compared to those with pathologically unifocal PTC. MATERIALS AND METHODS: PTC patients diagnosed as unifocal preoperatively who underwent non-TTx were multifocal in 61 and unifocal in 266 patients microscopically. Oncologic event rates were compared between pathologically multifocal and unifocal PTC patients. RESULTS: Pathological multifocality was associated with positive clinical lymph node metastasis (cN1) (odds ratio [OR] 4.01, 95% confidence interval [CI]: 1.91-8.04) and positive pathological lymph node metastasis (pN1) in > 5 nodes (OR 3.68, 95% CI: 1.60-8.49). No patients died from PTC. There was no significant difference in the disease-free survival rate, remnant thyroid disease-free survival rate, lymph node disease-free survival rate, or distant disease-free survival rate between the two groups. Recurrence in pathologically multifocal PTC patients was locoregional in all cases and able to be salvaged by reoperation. Cox proportional hazard model analyses showed no significant difference in recurrence rates with regard to pathological multifocality and cN or number of pNs. CONCLUSION: The prognosis of PTC with pathological multifocality treated by non-TTx was not inferior to that of unifocal PTC. Immediate completion thyroidectomy is not necessary when microscopic foci are proven.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Humans , Thyroid Cancer, Papillary/surgery , Lymphatic Metastasis , Retrospective Studies , Carcinoma, Papillary/pathology , Thyroid Neoplasms/pathology , Thyroidectomy , Prognosis , Risk Factors , Neoplasm Recurrence, Local/surgery , Neoplasm Recurrence, Local/pathology
5.
Surg Case Rep ; 7(1): 188, 2021 Aug 19.
Article in English | MEDLINE | ID: mdl-34410532

ABSTRACT

BACKGROUND: Metastasis to the breast is rare. We herein report a patient with metastatic medullary thyroid carcinoma to the breast for whom measuring the calcitonin level was an important clue to the correct diagnosis. CASE PRESENTATION: A 54-year-old woman visited our hospital for the treatment of recurrent metastatic medullary thyroid carcinoma due to multiple endocrine neoplasia 2A and breast cancer. Positron emission tomography performed before the operation for metastatic medullary thyroid carcinoma recurrence in the neck showed the accumulation of 18F-fluorodeoxyglucose in the bilateral breast at sites other than the disease in the neck. Ultrasonography revealed multiple tumors in both breasts. A core needle biopsy of three breast tumors was performed. Microscopically, the tumor cells showed solid growth and did not show a tubular structure. She was diagnosed with triple-negative invasive ductal carcinoma. Post-operative positron emission tomography was performed as the serum calcitonin level increased after the operation. The accumulation of 18F-fluorodeoxyglucose in the bilateral breast tumors and lymph nodes in the neck was noted. The possibility of the breast tumors being metastasis of metastatic medullary thyroid carcinoma was considered. Needle aspiration was performed for three breast tumors. The calcitonin level of the washout fluid was measured and found to be ≥ 17,500 pg/mL. Immunohistochemistry showed that the tumor cells were calcitonin-positive and gross cystic disease fluid protein-15-negative. Vandetanib was started as recurrent metastatic medullary thyroid carcinoma with breast metastasis was finally diagnosed. The serum calcitonin level decreased after 1 month. CONCLUSION: Although breast metastasis of medullary thyroid carcinoma is rare, a correct diagnosis is indispensable for appropriate treatment. When a breast tumor shows atypical morphological features for breast cancer according to the histopathology in a patient with a history of cancer, metastasis to the breast should be considered. Calcitonin measurement of the needle washout fluid was useful for confirming metastatic medullary thyroid carcinoma.

6.
Gland Surg ; 9(5): 1698-1707, 2020 Oct.
Article in English | MEDLINE | ID: mdl-33224847

ABSTRACT

We have a unique history of using radioactive iodine (RAI) therapy and surgical treatment for thyroid cancer in Japan. Less than total thyroidectomy without RAI therapy was the most common management of papillary thyroid carcinoma (PTC) in the past. Limited availability of dedicated facilities for the RAI administration due to the strict regulations and insufficient coverage of the expenses were the major reasons that impacted on the management decisions. Following the publication of the Japanese clinical practice guidelines for thyroid tumors in 2010, the risk-adapted approach has become a standard where the high-risk and selected intermediate-risk PTC patients undergo total thyroidectomy followed by RAI therapy and thyrotropin suppression therapy. We are on the shoulders of pioneers who made every effort to bring the interventions closer to an ideal environment for patients. Armed with the revised clinical practice guidelines 2018 and devised inpatient/outpatient RAI therapy, Japanese physicians are ready to proceed to more rational management that would improve patients' outcomes. Directions for the future include further advancement of relevant clinical research to fill the gaps between current evidence and recommendations in the guidelines, and obtaining approval for high-dose RAI therapy on an outpatient basis to improve its effectiveness in both adjuvant and treatment settings.

7.
Surg Case Rep ; 6(1): 145, 2020 Jun 22.
Article in English | MEDLINE | ID: mdl-32572650

ABSTRACT

BACKGROUND: Parathyroid carcinoma as a cause of primary hyperparathyroidism in children is extremely rare. We report a case of parathyroid carcinoma which occurred in a 13-year-old girl who survived for more than 45 years after the first operation. CASE PRESENTATION: A woman was admitted to our hospital for the treatment of recurrent parathyroid carcinoma in the neck. She had been diagnosed with primary hyperparathyroidism from a fibula fracture and underwent parathyroidectomy at 13 years old. She had no family history of multiple endocrine neoplasia or jaw tumor syndrome. Genetic testing was not performed, and the histopathological diagnosis of the tumor had been parathyroid adenoma at the time. At 22 years old, she showed hypercalcemia after a femur fracture. Pulmonary metastases of parathyroid carcinoma in the bilateral lungs were found and surgically removed. Regarding the clinical course, her diagnosis was corrected from parathyroid adenoma to parathyroid carcinoma. At 33 years old, re-resection of the lung metastases was performed. For 10 years, her serum calcium level stayed within the normal range. However, her serum calcium level and intact parathyroid hormone eventually began to increase. Two masses suspected of being parathyroid carcinoma recurrence were found in the neck when she was 57 years old. En bloc resection was performed. Pathologically, the tumors were diagnosed as parathyroid adenoma. The serum calcium level and intact parathyroid hormone did not decrease after the operation. A 99mTc-methoxy-isobutyl-isonitrile- and 18F-fluorodeoxyglucose-negative, 11C-methionine-positive tumor was detected at the right side of the trachea in the neck. The tumor was removed, along with the thyroid, muscle, and trachea that were involved. The pathological diagnosis was parathyroid carcinoma recurrence. The serum calcium level and intact parathyroid hormone decreased temporarily but had increased again 8 months later. Methionine-positive tumors were found at the right side of the trachea and suspected of being a recurrence. Denosumab reduced her serum calcium level, and radiation successfully suppressed the growth of the recurrent tumors. CONCLUSION: We have reported a rare case of parathyroid carcinoma in a child who has survived for over 40 years. Positron emission tomography of 11C-methionine was useful for detecting local recurrence. This patient's long-term survival has been attributed to multimodality treatment including repeated surgery, medication, and radiation.

8.
Endocr J ; 65(2): 245-252, 2018 Feb 26.
Article in English | MEDLINE | ID: mdl-29225207

ABSTRACT

Primary hyperparathyroidism is the most common hormonal manifestation associated with multiple endocrine neoplasia 1 (MEN1). It is generally caused by parathyroid hyperplasia, and parathyroid carcinoma is rare. Here, we report a case of MEN1 with parathyroid carcinoma in two parathyroid glands causing primary hyperparathyroidism. A 40-year-old man with primary hyperparathyroidism due to MEN1 underwent a total parathyroidectomy. His corrected calcium and intact PTH (i-PTH) serum levels were 10.8 mg/dL and 203 pg/mL, respectively. Although three glands were successfully removed, the left upper parathyroid gland could not be detected. Since the right lower parathyroid lesion had invaded into the thyroid, right lobectomy was performed. A portion of the left lower parathyroid tissue was transplanted into his forearm. The histological findings of the left lower and the right upper parathyroid glands were consistent with hyperplasia while that of the right lower parathyroid gland was parathyroid carcinoma. Since the post-surgical i-PTH levels remained high, the intrathyroidal lesion of the left lobe, which was initally diagnosed as an adenomatous nodule, was suspected to contain parathyroid tumor. A fine needle aspiration of the tumor revealed a high concentration of i-PTH. One week after the first surgery, a left thyroid lobectomy was performed. The pathological diagnosis of the tumor was parathyroid carcinoma. After the surgery, calcium and i-PTH levels were normal. Although it is rare, parathyroid carcinoma should be considered as a cause of hyperparathyroidism in MEN1 patients. Since it is difficult to diagnose parathyroid carcinoma before surgery, intraoperative findings are important for the appropriate treatment.


Subject(s)
Choristoma/diagnosis , Hyperparathyroidism, Primary/diagnosis , Multiple Endocrine Neoplasia Type 1/diagnosis , Paraneoplastic Endocrine Syndromes/diagnosis , Parathyroid Glands , Parathyroid Neoplasms/diagnosis , Thyroid Neoplasms/diagnosis , Adult , Choristoma/complications , Choristoma/metabolism , Humans , Hyperparathyroidism, Primary/etiology , Male , Multiple Endocrine Neoplasia Type 1/complications , Multiple Endocrine Neoplasia Type 1/pathology , Neoplasms, Multiple Primary/diagnosis , Neoplasms, Multiple Primary/metabolism , Neoplasms, Multiple Primary/pathology , Pancreatic Neoplasms/complications , Pancreatic Neoplasms/diagnosis , Pancreatic Neoplasms/pathology , Paraneoplastic Endocrine Syndromes/complications , Paraneoplastic Endocrine Syndromes/metabolism , Parathyroid Hormone/metabolism , Parathyroid Neoplasms/pathology , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/secondary
9.
World J Surg ; 42(6): 1772-1778, 2018 06.
Article in English | MEDLINE | ID: mdl-29138914

ABSTRACT

BACKGROUND: Whether total parathyroidectomy (TPTX) or subtotal parathyroidectomy (SPTX) should be performed for primary hyperparathyroidism (PHPT) in patients with multiple endocrine neoplasia type 1 (MEN1) is controversial. At our institution, the parathyroidectomy strategy is based on the number of enlarged intraoperative parathyroid glands. We retrospectively analyzed our parathyroidectomy procedures. METHODS: Data of PHPT treatment in patients with MEN1 who underwent parathyroidectomy from 1982 to 2012 at our department were retrospectively collected. The data were grouped according to the surgical procedure: TPTX, SPTX, and less than SPTX (LPTX). TPTX or SPTX was selected based on the preoperative examination findings and number of enlarged intraoperative parathyroid glands. The outcomes were the disease-free survival (DFS) rate and postoperative calcium replacement rate based on Kaplan-Meier analysis for each type of surgical procedure. RESULTS: Forty-five patients were analyzed. The overall 5- and 10-year DFS was 91.7 and 55.8%, respectively. The 5- and 10-year DFS in each subgroup was 100.0 and 85.7% in the TPTX group, 89.4 and 57.3% in the SPTX group, and 91.6 and 57.3% in the LPTX group, respectively. The postoperative calcium replacement rate at 1 and 12 months was 91.7 and 58.3% in the TPTX group, 21.1 and 7.0% in the SPTX group, and 30.0 and 0.0% in the LPTX group, respectively. CONCLUSIONS: Although LPTX was not satisfactory as a standard procedure, both SPTX and TPTX are effective treatment methods for PHPT in patients with MEN1. The parathyroidectomy strategy should be based on intraoperative evaluation of the parathyroid glands.


Subject(s)
Hyperparathyroidism, Primary/surgery , Multiple Endocrine Neoplasia Type 1/surgery , Parathyroidectomy/methods , Adult , Female , Humans , Hyperparathyroidism, Primary/mortality , Male , Middle Aged , Retrospective Studies
10.
Thyroid ; 22(4): 383-94, 2012 Apr.
Article in English | MEDLINE | ID: mdl-22280229

ABSTRACT

BACKGROUND: In patients without metastases, capsular and vascular invasion must be noted to make the diagnosis of follicular thyroid carcinoma (FTC). Some patients are initially diagnosed as follicular adenoma (FA) but develop metastases, indicating the original lesion was FTC. A diagnostic marker for FTCs that appear to be FAs by conventional histopathology is urgently needed. CD147 is a transmembrane glycoprotein that induces matrix metalloproteinases (MMPs) and participates in carcinoma invasion. The objective of this study was to determine whether CD147 is upregulated in FTC and if measures directed against it could reduce the invasive activity of FTC cells. METHODS: The expression levels of CD147, MMP-1, MMP-2, MMP-3, MMP-7, and MMP-9 in surgical specimens of normal thyroid (n=8), FA (n=20), and FTC (n=9) was determined using immunoblot and immunohistochemical techniques. CD147 protein expression levels of epithelial growth factor stimulated FTC-133 cell lines was measured by immunoblotting with and without cell signaling inhibitors such as wortmannin, PD98059, SP600125, and SB203580. This was also done after exposure to short-hairpin interference RNA directed against CD147. RESULTS: Immunoblot analysis of thyroid tissues revealed significant increases in signals for CD147, MMP-3, MMP-7, and MMP-9 in FTC compared with FA or normal tissue, or both. Immunohistochemical analysis revealed colocalization of determinants of CD147 with those of all of MMPs studied, mainly in follicular cells in normal and neoplastic cells in FA and FTC; their immunoreactivities were to some extent more intense in the FTC than FA or normals. In FTC-133 cells, immunoreactive signals for CD147 were upregulated by epidermal growth factor (EGF), and the EGF-driven increases in CD147 were prevented by inhibitors against phosphoinositol-3 kinase (PI3K), extracellular signal-regulated protein kinase (ERK), or c-Jun N-terminal kinase (JNK) but not p38. RNA interference targeted against CD147 reduced the invasive activity of FTC-133 cells and was associated with downregulation of MMP-2, MMP-3, MMP-7, and MMP-9. CONCLUSIONS: These results provide in vivo evidence for CD147 upregulation in FTC and in vitro evidence for EGF-stimulated CD147 induction via the PI3K, ERK, and JNK pathways. They suggest the involvement of CD147 in the invasiveness of FTC cells via regulation of MMPs.


Subject(s)
Basigin/physiology , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Adenocarcinoma, Follicular , Adenoma/genetics , Adenoma/pathology , Adolescent , Adult , Aged , Basigin/genetics , Blotting, Western , Cell Line, Tumor , Cell Movement/genetics , Cell Movement/physiology , Epidermal Growth Factor/pharmacology , Female , Gene Silencing , Humans , Immunohistochemistry , Male , Matrix Metalloproteinases/metabolism , Middle Aged , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , Neoplasm Invasiveness/genetics , Neoplasm Invasiveness/pathology , Phosphatidylinositol 3-Kinases/metabolism , Phosphoinositide-3 Kinase Inhibitors , Signal Transduction/drug effects , Young Adult
11.
Histol Histopathol ; 26(1): 79-86, 2011 01.
Article in English | MEDLINE | ID: mdl-21117029

ABSTRACT

An examination was performed on 16 intraductal proliferative breast lesions diagnosed as intraductal papillomas (IP) or usual ductal hyperplasia (UDH), which were followed up for more than 3 years. An immunohistochemical marker panel combining myoepithelial markers, high-molecular-weight keratin (HMWK) and neuroendocrine markers was used. Two of 11 IP cases were re-evaluated as atypical ductal hyperplasia (ADH) and ductal carcinoma in situ (DCIS). These cases developed breast cancer after the first operation. One IP case showed repeated recurrences. None of the other IP and UDH cases had breast cancer or recurrence. The ADH, DCIS and the recurrent IP showing a solid growth lacked myoepithelia, but the recurrent IP expressed HMWK, immunohistochemically. Interestingly, these three lesions were weakly positive for neuroendocrine markers. All other IPs and UDHs, including lesions having solid components, were negative for neuroendocrine markers, and most of them were positive for myoepithelial markers and/or HMWK. A combination of the above immunohistochemical markers seems useful to evaluate intraductal proliferative lesions and to predict their prognosis. In particular, intraductal proliferative lesions with solid components exhibiting positivity for neuroendocrine markers should be followed up carefully to monitor breast cancer risk or recurrence.


Subject(s)
Breast Neoplasms/diagnosis , Breast Neoplasms/metabolism , Carcinoma, Intraductal, Noninfiltrating/diagnosis , Carcinoma, Intraductal, Noninfiltrating/metabolism , Immunohistochemistry/methods , Papilloma, Intraductal/diagnosis , Papilloma, Intraductal/metabolism , Adult , Aged , Biomarkers, Tumor/metabolism , Breast Neoplasms/pathology , Breast Neoplasms, Male/diagnosis , Breast Neoplasms, Male/metabolism , Breast Neoplasms, Male/pathology , Carcinoma, Intraductal, Noninfiltrating/pathology , Chromogranin A/metabolism , Diagnosis, Differential , Female , Humans , Hyperplasia , Keratins/metabolism , Male , Membrane Proteins/metabolism , Microfilament Proteins/metabolism , Middle Aged , Neoplasm Recurrence, Local/metabolism , Neoplasm Recurrence, Local/pathology , Papilloma, Intraductal/pathology , Prognosis , Smooth Muscle Myosins/metabolism
12.
Neuropathology ; 30(4): 353-60, 2010 Aug.
Article in English | MEDLINE | ID: mdl-19925559

ABSTRACT

Signal transducer and activator of transcription-3 (STAT3) is a member of the proinflammatory transcription factor STAT family. Several studies have documented implications for neuroinflammation in amyotrophic lateral sclerosis (ALS). We recently demonstrated activation of STAT3 in spinal cords obtained at autopsy from sporadic ALS patients. To determine the involvement of STAT3 and effects of pioglitazone on STAT3 activity in familial ALS with superoxide dismutase-1 (SOD1) mutation, we performed immunoblot and immunohistochemical analyses of the active form of STAT3 (p-STAT3) in spinal cords from mice overexpressing mutant SOD1 (ALS mice) and nontransgenic littermates (control mice). Immunoblot analysis delineated significant increases in nuclear p-STAT3 levels in non-treated ALS mice as compared with pioglitazone-treated ALS mice and non-treated and pioglitazone-treated control mice. Immunohistochemical analysis revealed prominent p-STAT3 accumulations in the nucleus of motor neurons, reactive astrocytes and activated microglia in non-treated ALS mice but not pioglitazone-treated ALS mice and non-treated and pioglitazone-treated control mice. The present results provide in vivo evidence for increased phosphorylative activation and nuclear translocation of STAT3 in motor neurons and glia in mouse motor neuron disease, suggesting a common pathological process between sporadic and SOD1-mutated familial forms of ALS. Moreover, it is likely that pioglitazone may exert inhibitory effects on STAT3-mediated proinflammtory mechanisms in this disease.


Subject(s)
Amyotrophic Lateral Sclerosis/metabolism , Mutation , Neuroprotective Agents/pharmacology , STAT3 Transcription Factor/metabolism , Superoxide Dismutase/genetics , Thiazolidinediones/pharmacology , Amyotrophic Lateral Sclerosis/genetics , Animals , Disease Models, Animal , Enzyme Activation/drug effects , Humans , Immunoblotting , Immunohistochemistry , Mice , Mice, Inbred C57BL , Mice, Transgenic , Motor Neurons/metabolism , Neuroglia/metabolism , Phosphorylation , Pioglitazone , Protein Transport/drug effects , Spinal Cord/metabolism , Superoxide Dismutase-1
13.
Acta Histochem Cytochem ; 42(4): 105-9, 2009 Aug 29.
Article in English | MEDLINE | ID: mdl-19759871

ABSTRACT

Microsomal prostaglandin E(2) synthase-1 (mPGES-1) is an inducible enzyme that catalyzes the conversion of prostaglandin (PG) H(2) to PGE(2) in downstream of cyclooxygenase-2 (COX-2). Recent studies have obtained in vitro evidence that PGE(2) participates in carcinogenesis, angiogenesis, and induction of matrix metalloproteinase-9 (MMP-9), which plays a crucial role in cancer invasion. However, implications for mPGES-1 in thyroid carcinomas remain to be determined. To address this issue, we performed an immunohistochemical analysis for mPGES-1, COX-2 and MMP-9 in 20 papillary thyroid carcinoma (PTC) patients. mPGES-1 immunoreactivity was localized in the cytoplasm of carcinoma cells in 19 cases, with an intensity that tended to be distinct at the interface between the tumor and the surrounding non-neoplastic tissue. Staining was more intense in regions with papillary arrangement, while it was less intense in regions with trabecular or solid arrangement. In many cases, immunohistochemical localization of COX-2 and MMP-9 resemble that of mPGES-1. Taken together, our results suggest the involvement of mPGES-1 in proliferation and differentiation of PTC as well as local invasion of PTC.

14.
Intern Med ; 47(8): 757-62, 2008.
Article in English | MEDLINE | ID: mdl-18421194

ABSTRACT

We report the treatment of four thyrotoxic patients. Two were cases of type I amiodarone-induced thyrotoxicosis (AIT) treated with methimazole. The third Graves' disease patient, who became hypothyroid 25 years after subtotal thyroidectomy, developed type II AIT. Furthermore, one case with heart failure and ventricular tachycardia, who developed an adverse reaction to antithyroid agents and was prescribed amiodarone, underwent total thyroidectomy. The clinical course was uneventful, and the patient is doing well. Since amiodarone contains a large amount of iodine, it is frequently difficult to make a differential diagnosis. Surgical treatment of Graves' disease patients is recommended when immediate control of hyperthyroidism and heart failure is required.


Subject(s)
Amiodarone/therapeutic use , Arrhythmias, Cardiac/drug therapy , Graves Disease/complications , Methimazole/therapeutic use , Thyroidectomy , Thyrotoxicosis/diagnosis , Thyrotoxicosis/therapy , Adult , Anti-Arrhythmia Agents/therapeutic use , Antithyroid Agents/adverse effects , Antithyroid Agents/therapeutic use , Diagnosis, Differential , Humans , Male , Methimazole/adverse effects , Middle Aged , Thyrotoxicosis/etiology
15.
Breast Cancer ; 12(3): 203-10, 2005.
Article in English | MEDLINE | ID: mdl-16110290

ABSTRACT

BACKGROUND: Although sentinel lymph node biopsy(SLNB)is highly accurate in predicting axillary nodal status in patients with breast cancer, it has been shown that the procedure is associated with a few false negative results. The risk of leaving metastatic nodes behind in the axillary basin when SLNB is negative should be estimated for an individual patient if SLNB is performed to avoid conventional axillary lymph node dissection(ALND). METHODS: A retrospective analysis of 512 women with T1-3N0M0 breast cancer was conducted to derive a prevalence of nodal metastasis by T category as a pre-test(i.e., before SLNB)probability and to examine potential confounders on the relationship between T category and axillary nodal involvement. Probability of nodal metastasis when SLNB was negative was estimated by means of Bayes' theorem which incorporated the pre-test probability and sensitivity and specificity of SLNB. RESULTS: Axillary nodal metastasis was observed in 6.1% of T1a-b, 25.1% of T1c, 28.7% of T2, 35.0% of T3 tumors. Point estimates for the probability of nodal involvement when SLNB was negative ranged from 0.3-1.3% for T1a-b, 1.6-6.3% for T1c, 2.0-7.5% for T2, and 2.6-9.7% for T3 tumors with representative sensitivities of 80%, 85%, 90% and 95%, respectively. The risk may be higher when the tumor involves the upper outer quadrant of the breast, while it may be lower for an underweight woman. CONCLUSIONS: The probability of axillary lymph node metastasis when SLNB is negative can be estimated using a Bayesian approach. Presenting the probability to the patient may guide the decision of surgery without conventional ALND.


Subject(s)
Breast Neoplasms/pathology , Carcinoma, Ductal, Breast/pathology , Lymph Nodes/pathology , Sentinel Lymph Node Biopsy , Adult , Aged , Aged, 80 and over , Axilla , Bayes Theorem , Breast Neoplasms/surgery , Carcinoma, Ductal, Breast/surgery , False Negative Reactions , Female , Humans , Lymphatic Metastasis , Mastectomy , Middle Aged , Neoplasm Staging , Predictive Value of Tests , Probability , Retrospective Studies
16.
Surgery ; 134(6): 1066-72; discussion 1072-3, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14668742

ABSTRACT

BACKGROUND: There have been few reports of laparoscopic adrenal-sparing surgery for bilateral adrenal tumors. We review our experience with this type of surgery with the aim of evaluating its feasibility and safety. METHODS: Over a 4-year period, we treated 9 patients with bilateral benign adrenal tumors. Seven patients had bilateral pheochromocytomas (MEN 2: 5, VHL: 1, sporadic: 1), and 2 patients had Cushing's syndrome caused by bilateral adrenocortical adenomas. Laparoscopic procedures were performed by a flank approach. The mean diameter of the tumors was 3.7 cm (range, 2.0-8.5 cm). RESULTS: All the tumors were removed laparoscopically. Four patients with hereditary pheochromocytomas underwent bilateral total adrenalectomy because of the large tumor size and multiplicity. The other 5 patients were treated successfully with preservation of adrenocortical function. In 4 of these 5 patients, the adrenal tumors were 3 cm or less in diameter. None of the patients experienced surgical complications. At a mean follow-up of 16 months (range, 4-40 months), none of the 5 patients who were treated by adrenal-sparing surgery required corticosteroid replacement. CONCLUSION: Laparoscopic surgery is feasible for the treatment of bilateral adrenal tumors. Adrenal-preserving laparoscopic surgery may be practicable for the removal of these tumors, if the tumor on either side is 3 cm or less in diameter; however, our follow up is short (mean, 16 months).


Subject(s)
Adrenal Gland Neoplasms/surgery , Adrenalectomy/methods , Adrenocortical Adenoma/surgery , Laparoscopy/methods , Pheochromocytoma/surgery , Adult , Feasibility Studies , Female , Humans , Male , Middle Aged , Retrospective Studies , Treatment Outcome
17.
Surg Today ; 33(10): 785-90, 2003.
Article in English | MEDLINE | ID: mdl-14513331

ABSTRACT

A case of ganglioneuroblastoma in the adrenal gland of a 50-year-old man is reported. The patient was incidentally found to have a nonfunctioning tumor in the right adrenal gland. The tumor, measuring 4.5 cm, was successfully removed using laparoscopy. Histologically, the tumor was diagnosed to be a ganglioneuroblastoma. Immunohistochemically, a few MIB-1-positive cells and no S-100 protein-positive cells were observed. There has been no evidence of recurrence for 2.5 years to date after the operation. Adrenal ganglioneuroblastoma is extremely rare in adults, and only seven such cases have been previously reported in the literature.


Subject(s)
Adrenal Gland Neoplasms/surgery , Ganglioneuroblastoma/surgery , Laparoscopy , Adrenal Gland Neoplasms/diagnostic imaging , Adrenal Gland Neoplasms/pathology , Ganglioneuroblastoma/diagnostic imaging , Ganglioneuroblastoma/pathology , Humans , Male , Middle Aged , Tomography, X-Ray Computed
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