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1.
Acta Cytol ; 66(5): 379-388, 2022.
Article in English | MEDLINE | ID: mdl-35390805

ABSTRACT

INTRODUCTION: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is used to investigate pulmonary nodules, mediastinal lymphadenopathy, and mediastinal masses in both malignant and nonmalignant etiologies. EBUS-TBNA is most commonly used in the diagnosis and staging of patients with non-small-cell lung cancer in the middle-age and elderly populations. As lung cancer is uncommon in young adults, it is assumed that there are a distinct disease population and clinical background in young adults who undergo EBUS-TBNA. However, this population has not been well investigated. METHODS: We identified all EBUS-TBNA cases in young adults (aged 18-39 years) between January 1, 2008, and December 31, 2018, at our institution. Cytology diagnoses were correlated with the concurrent/subsequent histologic diagnosis and clinical decisions. A final patient classification was created based on the worst cytologic or histologic diagnosis (benign, low-grade, or malignant), with the exception of atypical cytology with subsequent long clinical follow-up with no evidence of malignancy, who were considered benign. All discordant cases and positive/suspicious cases with available slides were rereviewed together by the authors to confirm the diagnosis. RESULTS: In total, 257 EBUS-TBNA procedures were performed in 249 young adults (mean age of 31.2 years). The majority of indications were lymphadenopathy and lung nodule/mass. Final cytologic interpretations included 214 (83%) benign, 14 (5%) atypical, 5 (2%) low-grade neoplasm (carcinoid tumor), and 15 (6%) malignant cases. The final patient classification was 213 (86%) benign, 6 (2%) low-grade, and 30 (12%) malignant. Discordant results were found in 24 cases, most frequently due to sampling error (50%). Of 213 benign cases, 58% had granulomatous disease, with sarcoidosis being the most common, followed by histoplasmosis. Of 30 cases with a final malignant classification, metastatic tumor was the most common (n = 12, 4.8%), followed by primary lung tumor (n = 11, 4.4%) and lymphoma (n = 7, 2.8%). There was a variety of malignancies among primary lung cancer, including adenocarcinoma (n = 5), squamous-cell carcinoma (n = 3), inflammatory myofibroblastic tumor (n = 2), and epithelioid hemangioendothelioma (n = 1). CONCLUSION: In young adults, EBUS-TBNA was most frequently performed to evaluate lymphadenopathy and lung nodules, and granulomatous disease was the most common benign finding. Although rare, primary lung malignancies do occur in young adults along with metastasis from a variety of other sites, with sarcoma being the most common pathology.


Subject(s)
Carcinoma, Non-Small-Cell Lung , Lung Neoplasms , Lymphadenopathy , Adult , Aged , Bronchoscopy/methods , Carcinoma, Non-Small-Cell Lung/pathology , Child , Endoscopic Ultrasound-Guided Fine Needle Aspiration/methods , Humans , Lung/pathology , Lung Neoplasms/diagnosis , Lung Neoplasms/pathology , Lymph Nodes/pathology , Lymphadenopathy/diagnosis , Lymphadenopathy/pathology , Mediastinum/pathology , Middle Aged , Retrospective Studies , Young Adult
2.
ACR Open Rheumatol ; 1(1): 26-36, 2019 Mar.
Article in English | MEDLINE | ID: mdl-31777777

ABSTRACT

OBJECTIVE: We sought to determine if any histopathologic component of the pulmonary microcirculation can distinguish systemic sclerosis (SSc)-related pulmonary fibrosis (PF) with and without pulmonary hypertension (PH). METHODS: Two pulmonary pathologists blindly evaluated 360 histologic slides from lungs of 31 SSc-PF explants or autopsies with (n = 22) and without (n = 9) PH. The presence of abnormal small arteries, veins, and capillaries (pulmonary microcirculation) was semiquantitatively assessed in areas of preserved lung architecture. Capillary proliferation (CP) within the alveolar walls was measured by its distribution, extent (CP % involvement), and maximum number of layers (maximum CP). These measures were then evaluated to determine the strength of their association with right heart catheterization-proven PH. RESULTS: Using consensus measures, all measures of CP were significantly associated with PH. Maximum CP had the strongest association with PH (P = 0.013; C statistic 0.869). Maximum CP 2 or more layers and CP % involvement 10% or greater were the optimal thresholds that predicted PH, both with a sensitivity of 56% and specificity of 91%. The CP was typically multifocal rather than focal or diffuse and was associated with a background pattern of usual interstitial pneumonia. There was a significant but weaker relationship between the presence of abnormal small arteries and veins and PH. CONCLUSION: In the setting of advanced SSc-PF, the histopathologic feature of the pulmonary microcirculation best associated with PH was capillary proliferation in architecturally preserved lung areas.

4.
Cancer Res ; 79(19): 5022-5033, 2019 Oct 01.
Article in English | MEDLINE | ID: mdl-31142513

ABSTRACT

Epithelial cells in the field of lung injury can give rise to distinct premalignant lesions that may bear unique genetic aberrations. A subset of these lesions may escape immune surveillance and progress to invasive cancer; however, the mutational landscape that may predict progression has not been determined. Knowledge of premalignant lesion composition and the associated microenvironment is critical for understanding tumorigenesis and the development of effective preventive and interception strategies. To identify somatic mutations and the extent of immune cell infiltration in adenomatous premalignancy and associated lung adenocarcinomas, we sequenced exomes from 41 lung cancer resection specimens, including 89 premalignant atypical adenomatous hyperplasia lesions, 15 adenocarcinomas in situ, and 55 invasive adenocarcinomas and their adjacent normal lung tissues. We defined nonsynonymous somatic mutations occurring in both premalignancy and the associated tumor as progression-associated mutations whose predicted neoantigens were highly correlated with infiltration of CD8+ and CD4+ T cells as well as upregulation of PD-L1 in premalignant lesions, suggesting the presence of an adaptive immune response to these neoantigens. Each patient had a unique repertoire of somatic mutations and associated neoantigens. Collectively, these results provide evidence for mutational heterogeneity, pathway dysregulation, and immune recognition in pulmonary premalignancy.Significance: These findings identify progression-associated somatic mutations, oncogenic pathways, and association between the mutational landscape and adaptive immune responses in adenomatous premalignancy.See related commentary by Merrick, p. 4811.


Subject(s)
Adenocarcinoma , Adenoma , Lung Neoplasms , Precancerous Conditions , Genomics , Humans , Tumor Microenvironment
6.
Geriatr Gerontol Int ; 18(2): 211-215, 2018 Feb.
Article in English | MEDLINE | ID: mdl-28914998

ABSTRACT

AIM: We aimed to clarify the characteristics of malignancies in older adults focusing on distant metastasis in the whole body. METHODS: We retrospectively evaluated 7710 cases of autopsies (4011 men, 3699 women, median age of 80 years), and analyzed the characteristics of metastasis of adenocarcinoma, squamous cell carcinoma and urothelial carcinoma in each organ. RESULTS: The total number of cases with adenocarcinoma, squamous cell carcinoma or urothelial carcinoma was 2856, and most of them were adenocarcinomas. Among them, 1604 had metastatic lesions, and patients with metastasis were younger than those without metastasis. The major primary organs of adenocarcinoma were the stomach, colon, lung, prostate, gallbladder and pancreas, whereas those for squamous cell carcinoma were the lung, esophagus and uterus. Urothelial carcinoma cases were found in the urinary bladder, kidney and ureter. Metastatic adenocarcinomas mainly originated from the stomach, colon, lung, pancreas and gallbladder. Metastatic squamous cell carcinomas were from the lung, esophagus and uterus, whereas the kidney, bladder and ureter were the primary origins of metastatic urothelial carcinomas. Squamous cell carcinoma showed the highest incidence of metastasis, suggestive of it being of an aggressive phenotype. Furthermore, metastatic ability and the preferred metastatic sites varied among primary organs. CONCLUSIONS: We revealed an accurate incidence and the characteristics of metastatic cancer in a large-scale autopsy study of older Japanese patients from one institution. Identifying these features might prompt screening for malignancies, and consequently improve quality of life for older adults. Geriatr Gerontol Int 2018; 18: 211-215.


Subject(s)
Adenocarcinoma/pathology , Carcinoma, Squamous Cell/pathology , Carcinoma, Transitional Cell/pathology , Neoplasm Metastasis/pathology , Ureteral Neoplasms/pathology , Aged , Aged, 80 and over , Autopsy , Female , Humans , Japan , Male , Retrospective Studies
7.
Case Rep Gastroenterol ; 11(3): 545-553, 2017.
Article in English | MEDLINE | ID: mdl-29033776

ABSTRACT

Carbohydrate antigen 19-9 (CA19-9) is a well-known tumor marker for pancreatobiliary cancer, and several studies have shown that an elevated serum CA19-9 level is associated with more aggressive biological behavior in gastric cancer (GC). However, the clinicopathological characteristics of CA19-9-positive GC remain unclear. We herein report an autopsy case of CA19-9-positive GC in an 84-year-old man who was admitted to our hospital because of paralysis and anemia. Autopsy revealed an ulcerative-invasive tumor measuring 72 × 60 mm in the anterior wall of the gastric body. The tumor had invaded beyond the muscularis propria, and metastasized to the lung, liver, and regional lymph nodes. Histologically, the tumor cell had oval nuclei with abundant clear cytoplasm, and tubular and/or papillary features with prominent lymphovascular permeation and perineural invasion, mimicking pancreatobiliary carcinoma. Immunohistochemically, the tumor cells showed diffuse immunopositivity for CA19-9 and carcinoembryonic antigen. According to a review of cases reported in the literature, CA19-9-positive GCs show clinicopathological characteristics such as antral location, ulcerative-infiltrating gross feature, differentiated histology, prominent lymphatic and venous invasion, higher proportion of metastasis, and higher clinical stage. These results suggest that CA19-9-positive GC is pathologically a distinctive type of tumor with aggressive biological behavior.

8.
Cancer Prev Res (Phila) ; 10(9): 514-524, 2017 Sep.
Article in English | MEDLINE | ID: mdl-28754664

ABSTRACT

Lung cancers are documented to have remarkable intratumoral genetic heterogeneity. However, little is known about the heterogeneity of biophysical properties, such as cell motility, and its relationship to early disease pathogenesis and micrometastatic dissemination. In this study, we identified and selected a subpopulation of highly migratory premalignant airway epithelial cells that were observed to migrate through microscale constrictions at up to 100-fold the rate of the unselected immortalized epithelial cell lines. This enhanced migratory capacity was found to be Rac1-dependent and heritable, as evidenced by maintenance of the phenotype through multiple cell divisions continuing more than 8 weeks after selection. The morphology of this lung epithelial subpopulation was characterized by increased cell protrusion intensity. In a murine model of micrometastatic seeding and pulmonary colonization, the motility-selected premalignant cells exhibit both enhanced survival in short-term assays and enhanced outgrowth of premalignant lesions in longer-term assays, thus overcoming important aspects of "metastatic inefficiency." Overall, our findings indicate that among immortalized premalignant airway epithelial cell lines, subpopulations with heritable motility-related biophysical properties exist, and these may explain micrometastatic seeding occurring early in the pathogenesis of lung cancer. Understanding, targeting, and preventing these critical biophysical traits and their underlying molecular mechanisms may provide a new approach to prevent metastatic behavior. Cancer Prev Res; 10(9); 514-24. ©2017 AACRSee related editorial by Hynds and Janes, p. 491.


Subject(s)
Bronchi/cytology , Cell Movement/genetics , Cell Proliferation/genetics , Epithelial Cells/pathology , Lung Neoplasms/genetics , Animals , Bronchi/pathology , Cell Line, Tumor , Cell Survival/genetics , Epithelial Cells/cytology , Epithelial Cells/metabolism , Gene Expression Profiling , Humans , Lung Neoplasms/pathology , Mice , Mice, Inbred NOD , Specific Pathogen-Free Organisms , Xenograft Model Antitumor Assays , rac1 GTP-Binding Protein/metabolism
10.
Pancreas ; 46(5): 658-664, 2017.
Article in English | MEDLINE | ID: mdl-28196020

ABSTRACT

OBJECTIVE: We sought to identify clinicopathological characteristics of high-grade pancreatic intraepithelial neoplasia (PanIN)/carcinoma in situ to facilitate screening for pancreatic ductal adenocarcinoma. METHODS: We evaluated PanIN lesions in 173 consecutive autopsy cases with no evidence of pancreatic ductal adenocarcinoma and/or intraductal papillary mucinous neoplasm (mean age, 80.5 years) by submitting the entire pancreas for microscopic examination. RESULTS: PanIN-3 was found in 4% of examined cases, whereas PanIN-1 and PanIN-2 were present in 77% and 28%, respectively. PanIN-3 was more frequently identified in patients with diabetes mellitus and/or older age. PanIN-3 lesions were always multifocal, and the number of PanIN-3 foci was positively associated with those of PanIN-1 or PanIN-2. PanIN-3 was located more frequently in the pancreatic body and tail than in the head and predominantly involved small interlobular/intralobular ducts rather than the main duct. Notably, 71% of pancreata with PanIN-3 showed cystic changes in PanIN-3 and lower grade PanIN lesions. PanIN-3 was also accompanied by higher grade extralobular fibrosis. CONCLUSIONS: We found that 4% of the examined pancreata harbored PanIN-3 lesions that were associated with several unique clinicopathological features. The cystic change along with fibrotic pancreatic parenchyma may be detected by imaging studies such as endoscopic ultrasound.


Subject(s)
Carcinoma in Situ/pathology , Pancreas/pathology , Pancreatic Neoplasms/pathology , Precancerous Conditions/pathology , Adult , Aged , Aged, 80 and over , Autopsy , Carcinoma in Situ/epidemiology , Carcinoma, Pancreatic Ductal/diagnosis , Female , Humans , Incidence , Male , Middle Aged , Neoplasm Grading , Pancreatic Neoplasms/epidemiology , Precancerous Conditions/epidemiology , Prevalence
11.
Thorac Cancer ; 8(3): 271-274, 2017 05.
Article in English | MEDLINE | ID: mdl-28239985

ABSTRACT

An 81-year-old female patient was admitted to our institute because of abnormal X-ray results. Chest computed tomography showed a 7.7 × 5.3 cm mass located in the left lower lobe and multiple swollen lymph nodes. 18F-fluorodeoxyglucose-positron emission tomography indicated high standard uptake values in the mass and swollen lymph nodes. The patient was diagnosed with stage cT3N2M0-IIIA squamous cell carcinoma. Although the patient had multiple lymph node metastases and severe obstructive pulmonary function, four cycles of platinum doublet chemotherapy were initially performed and no side effect greater than grade 3 was experienced. As the lung cancer was downstaged to ycT2aN0M0-IB and pulmonary function had improved, a bronchodilating preparation, an uneventful left lower lobectomy, and a lymphadenectomy were performed. The patient was discharged 39 days after surgery and exhibited good health for a year at pathological stage ypT1aN0M0-IA (Ef2).


Subject(s)
Carcinoma, Squamous Cell/surgery , Lung Neoplasms/surgery , Lymph Node Excision , Lymphatic Metastasis/diagnostic imaging , Aged, 80 and over , Carcinoma, Squamous Cell/diagnostic imaging , Carcinoma, Squamous Cell/pathology , Female , Humans , Lung Neoplasms/diagnostic imaging , Lung Neoplasms/pathology , Lymph Nodes/diagnostic imaging , Lymph Nodes/pathology , Lymphatic Metastasis/pathology , Positron-Emission Tomography , Salvage Therapy
12.
Asian Cardiovasc Thorac Ann ; 24(8): 818-821, 2016 Oct.
Article in English | MEDLINE | ID: mdl-27510987

ABSTRACT

A 77-year-old woman with a 3-month history of muscle weakness was diagnosed with elderly-onset generalized myasthenia gravis (Myasthenia Gravis Foundation of America classification IIa) based on a high serum acetylcholine receptor antibody level (25.4 nmol·L-1) and neurological findings. Computed tomography detected a small nodule (diameter 15 mm) in the anterior mediastinum, which was suspected to be a thymoma. An extended thymectomy was performed. The pathological examination revealed a 6-mm-diameter thymoma, termed a microthymoma, accompanied with a unilocular thymic cyst without capsule formation (type B2 according to the World Health Organization classification). Some fat tissue was also found within the tumor.


Subject(s)
Myasthenia Gravis/complications , Thymoma/complications , Thyroid Neoplasms/complications , Thyroid Nodule/complications , Aged , Biomarkers, Tumor/analysis , Biopsy , Female , Humans , Immunohistochemistry , Myasthenia Gravis/diagnosis , Myasthenia Gravis/surgery , Thymectomy , Thymoma/chemistry , Thymoma/diagnostic imaging , Thymoma/surgery , Thyroid Neoplasms/chemistry , Thyroid Neoplasms/diagnostic imaging , Thyroid Neoplasms/surgery , Thyroid Nodule/chemistry , Thyroid Nodule/diagnostic imaging , Thyroid Nodule/surgery , Tomography, X-Ray Computed , Treatment Outcome , Tumor Burden
13.
Pathol Int ; 66(8): 466-71, 2016 Aug.
Article in English | MEDLINE | ID: mdl-27427341

ABSTRACT

A 76-year-old man was admitted with general fatigue, weight loss, fever, headache, renal failure, and a high serum level of myeloperoxidase-antineutrophil cytoplasmic antibody. Biopsy revealed citrullinated histone H3 (citH3)-positive neutrophils adherent to the temporal artery endothelium. Three days after completing pulse steroid therapy, he suffered from a sudden disturbance of consciousness and died. On autopsy, the kidneys showed the most severe vasculitis with dense infiltration of citH3-positive neutrophils. The lungs showed intra-alveolar hemorrhage due to capillaritis. Severe brain hemorrhage was found in the left frontal lobe and putamen with uncal herniation. No vasculitis or thrombi was observed in the brain. The right dura mater was thickened due to fibrosis and inflammation. In conclusion, autopsy revealed systemic vasculitis with infiltration of abundant citH3-positive neutrophils, suggesting that the neutrophil extracellular trap formation and citH3 might play important roles in the early phases and development of microscopic polyangiitis.


Subject(s)
Extracellular Traps , Histones/metabolism , Microscopic Polyangiitis/pathology , Neutrophils/pathology , Aged , Autopsy , Citrulline , Humans , Male
14.
J Thorac Dis ; 8(5): E330-3, 2016 May.
Article in English | MEDLINE | ID: mdl-27162693

ABSTRACT

We experienced an uncommon presentation of Kikuchi-Fujimoto disease (KFD) with sole mediastinal lymphadenopathy in senior age, which was histologically diagnosed by thoracoscopic biopsy leading to appropriate therapy. A 69-year-old man was admitted due to intermittent high fever, general malaise, and appetite loss lasting over 3 months along with 10-kg weight loss in 6 months. Chest computed tomography (CT) showed isolated mediastinal lymphadenopathy, and malignant diseases including malignant lymphoma or metastatic carcinoma, tuberculous lymphadenitis, and sarcoidosis were considered. Therefore thoracoscopic biopsy should be performed for the correct diagnosis, even in uncommon portion of lymph node swelling and age for KFD.

16.
J Exp Med ; 212(12): 2147-63, 2015 Nov 16.
Article in English | MEDLINE | ID: mdl-26552708

ABSTRACT

Although much progress has been made in identifying the mechanisms that trigger endothelial activation and inflammatory cell recruitment during atherosclerosis, less is known about the intrinsic pathways that counteract these events. Here we identified NOTCH1 as an antagonist of endothelial cell (EC) activation. NOTCH1 was constitutively expressed by adult arterial endothelium, but levels were significantly reduced by high-fat diet. Furthermore, treatment of human aortic ECs (HAECs) with inflammatory lipids (oxidized 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine [Ox-PAPC]) and proinflammatory cytokines (TNF and IL1ß) decreased Notch1 expression and signaling in vitro through a mechanism that requires STAT3 activation. Reduction of NOTCH1 in HAECs by siRNA, in the absence of inflammatory lipids or cytokines, increased inflammatory molecules and binding of monocytes. Conversely, some of the effects mediated by Ox-PAPC were reversed by increased NOTCH1 signaling, suggesting a link between lipid-mediated inflammation and Notch1. Interestingly, reduction of NOTCH1 by Ox-PAPC in HAECs was associated with a genetic variant previously correlated to high-density lipoprotein in a human genome-wide association study. Finally, endothelial Notch1 heterozygous mice showed higher diet-induced atherosclerosis. Based on these findings, we propose that reduction of endothelial NOTCH1 is a predisposing factor in the onset of vascular inflammation and initiation of atherosclerosis.


Subject(s)
Atherosclerosis/metabolism , Endothelial Cells/metabolism , Inflammation/metabolism , Lipids/blood , Receptor, Notch1/metabolism , Adult , Animals , Atherosclerosis/etiology , Atherosclerosis/genetics , Cell Line, Tumor , Cells, Cultured , Diet, High-Fat/adverse effects , Endothelial Cells/drug effects , Female , Humans , Inflammation/genetics , Interleukin-1beta/pharmacology , Male , Mice, Inbred C57BL , Mice, Knockout , Mice, Transgenic , Microscopy, Confocal , Oligonucleotide Array Sequence Analysis , Phosphatidylcholines/pharmacology , RNA Interference , Receptor, Notch1/genetics , Reverse Transcriptase Polymerase Chain Reaction , Transcriptome/drug effects , Transcriptome/genetics , Tumor Necrosis Factor-alpha/pharmacology
17.
Cancer Res ; 75(22): 4910-22, 2015 Nov 15.
Article in English | MEDLINE | ID: mdl-26574479

ABSTRACT

Inactivation of the LKB1 tumor suppressor is a frequent event in non-small cell lung carcinoma (NSCLC) leading to the activation of mTOR complex 1 (mTORC1) and sensitivity to the metabolic stress inducer phenformin. In this study, we explored the combinatorial use of phenformin with the mTOR catalytic kinase inhibitor MLN0128 as a treatment strategy for NSCLC bearing comutations in the LKB1 and KRAS genes. NSCLC is a genetically and pathologically heterogeneous disease, giving rise to lung tumors of varying histologies that include adenocarcinomas and squamous cell carcinomas (SCC). We demonstrate that phenformin in combination with MLN0128 induced a significant therapeutic response in KRAS/LKB1-mutant human cell lines and genetically engineered mouse models of NSCLC that develop both adenocarcinomas and SCCs. Specifically, we found that KRAS/LKB1-mutant lung adenocarcinomas responded strongly to phenformin + MLN0128 treatment, but the response of SCCs to single or combined treatment with MLN0128 was more attenuated due to acquired resistance to mTOR inhibition through modulation of the AKT-GSK signaling axis. Combinatorial use of the mTOR inhibitor and AKT inhibitor MK2206 robustly inhibited the growth and viability of squamous lung tumors, thus providing an effective strategy to overcome resistance. Taken together, our findings define new personalized therapeutic strategies that may be rapidly translated into clinical use for the treatment of KRAS/LKB1-mutant adenocarcinomas and squamous cell tumors.


Subject(s)
Antineoplastic Combined Chemotherapy Protocols/pharmacology , Apoptosis/drug effects , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/genetics , Stress, Physiological/drug effects , AMP-Activated Protein Kinase Kinases , AMP-Activated Protein Kinases , Animals , Benzoxazoles/pharmacology , Cell Line, Tumor , Disease Models, Animal , Humans , Immunohistochemistry , Mice , Phenformin/pharmacology , Protein Serine-Threonine Kinases/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Pyrimidines/pharmacology
18.
Cardiovasc Pathol ; 23(6): 381-2, 2014.
Article in English | MEDLINE | ID: mdl-25108499

ABSTRACT

Posterolateral hypertrophic cardiomyopathy (HCM) is a rare variant of HCM. Segmental HCM is seen in 12% of cases of HCM. Among the patterns of segmental HCM, posterolateral HCM is the least common type. Our case of an 18-year old male documents this unusual type of cardiomyopathy. In this form of HCM, left ventricular thickness and the extent of hypertrophy might be underestimated by 2-dimensional echocardiography. This case illustrates the echocardiographic and pathologic features of posterolateral HCM.


Subject(s)
Cardiomyopathy, Hypertrophic/pathology , Adolescent , Cardiomyopathy, Hypertrophic/diagnostic imaging , Cardiomyopathy, Hypertrophic/surgery , Echocardiography , Heart Transplantation , Heart Ventricles/diagnostic imaging , Heart Ventricles/pathology , Humans , Male , Myocytes, Cardiac/pathology
20.
Cardiovasc Pathol ; 23(5): 253-60, 2014.
Article in English | MEDLINE | ID: mdl-24972526

ABSTRACT

Cardiac transplantation is a lifesaving therapy for patients with end-stage cardiovascular disease. There has been remarkable progress in controlling acute rejection, and the early survival rate after the heart transplantation has significantly improved. Cardiac allograft vasculopathy (CAV) is one of the common causes of death and a major limiting factor for long-term graft survival years after heart transplantation. CAV is a progressive occlusion of arteries and veins of the transplanted heart. CAV is often clinically silent because of the denervation of the transplanted heart. CAV tends to be found at an advanced stage of disease, including myocardial infarction (MI), congestive heart failure, arrhythmia, and/or sudden cardiac death. Because of the serious sequelae of CAV, risk factors, prevention, and prediction of CAV have been investigated. Despite the effort by many researchers, the pathogenesis is not yet completely understood. There are a number of both immune and nonimmune factors in the donor and recipient that are related to the development of CAV. In addition, several biomarkers in blood and tissue are found to correlate with the presence of CAV, and that may be able to predict CAV. Here, we review the pathology, pathogenesis, risk factors, diagnosis, and the potential for prediction of CAV.


Subject(s)
Graft Rejection/immunology , Graft Survival/immunology , Heart Diseases/etiology , Heart Transplantation/adverse effects , Allografts , Humans , Risk Factors
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