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Cholangiocarcinoma (CC) is the second most common primary hepatic malignancy. Although the frequency of malignancy is generally increased in chronic liver disease, CC rarely presents in Wilson disease (WD). The incidence of hepatic malignancy in WD is only 1.2%, with CC accounting for 0.5%. A 66 year old male with history of hypertension, diabetes, and compensated cryptogenic cirrhosis presented with acute onset dyspnea and pleuritic chest pain. He was incidentally found to have a sizeable mass in the right hepatic lobe. Ultimately, a liver biopsy revealed dense demoplasia and increased mucin production, consistent with diagnosis of CC. Biopsy also demonstrated increased copper deposition consistent with WD, explaining the patient's underlying cirrhosis. Unlike other forms of chronic liver disease where incidence of liver cancer is increased, the lower rate of malignancy seen in WD may be explained by a protective effect of copper in WD. Copper acts to both directly stabilize DNA and inhibit angiogenesis. In this case, it is possible that the degree of copper deposition in his liver was mild, causing cirrhosis and the chronic liver inflammation that caused his CC. However, it may not have been sufficient to "protect" against development of CC.
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Neoplasias de los Conductos Biliares/diagnóstico , Neoplasias Óseas/diagnóstico por imagen , Colangiocarcinoma/diagnóstico , Degeneración Hepatolenticular/diagnóstico , Neoplasias Pulmonares/diagnóstico por imagen , Anciano , Neoplasias de los Conductos Biliares/complicaciones , Neoplasias de los Conductos Biliares/metabolismo , Neoplasias de los Conductos Biliares/patología , Neoplasias Óseas/secundario , Colangiocarcinoma/complicaciones , Colangiocarcinoma/metabolismo , Colangiocarcinoma/secundario , Cobre/metabolismo , Degeneración Hepatolenticular/complicaciones , Degeneración Hepatolenticular/patología , Humanos , Hallazgos Incidentales , Cirrosis Hepática/etiología , Cirrosis Hepática/patología , Neoplasias Pulmonares/secundario , MasculinoRESUMEN
BACKGROUND: Esophageal cancer is the 11th most common cause of cancer mortality in the United States. It is aggressive in nature and has an ability to spread rapidly through direct extension, lymphatic spread, or hematogenously. With an estimated incidence of 1%, cutaneous metastases from esophageal cancer are extremely rare. CASE PRESENTATION: In this case study and review, we describe a case of recurrent esophageal basaloid squamous cell carcinoma presenting as multiple, rapidly progressing and tender subcutaneous nodules. A 69-year-old male with history of basaloid squamous cell carcinoma of the esophagus treated with concurrent chemoradiation, presented to his oncologist with complaints of a large, painful nodule at the nape of his neck approximately two years after completing treatment. On further examination, he was noted to have multiple, well circumscribed, solid, tender nodules on his abdominal wall along with a painful nodule on the pulp of his index finger. Histopathology from all sites revealed skin infiltration by high-grade invasive basaloid subtype of squamous cell carcinoma, similar to patient's prior known and treated primary esophageal cancer. Further imaging work up showed extensive metastatic disease involving lung, liver, and brain. CONCLUSION: Esophageal squamous cell carcinoma rarely metastasize to the skin. Subcutaneous nodules can be the first presentation of recurrent disease. The lesions are commonly confused with skin infections and treated inappropriately with antibiotics, leading to delay in diagnosis of recurrent disease. Early biopsy of suspicious lesions should be performed, especially in patients with history of cancer, such that prompt diagnosis and treatment can occur to maximize patient outcomes.
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Neoplasias Esofágicas/patología , Carcinoma de Células Escamosas de Esófago/secundario , Recurrencia Local de Neoplasia/patología , Neoplasias Cutáneas/secundario , Anciano , Humanos , MasculinoRESUMEN
PURPOSE: Based on suggestive findings from a recent study of high-risk Japanese patients, we sought to determine whether the risk of colorectal polyps associated with smoking may be modified by daily use of aspirin in an analysis of a large US screening population. METHODS: This is a cross-sectional study of 2,918 consecutive colonoscopy patients at a university hospital over a 30-month period. Data were abstracted from electronic medical records. Multivariate models of polyp counts were used to examine the competing risks of smoking and aspirin use. Models were further stratified by polyp location (proximal vs. distal) and pathologic subtype (dysplastic vs. serrated). RESULTS: Incidental rate of polyps was higher among active smokers [incidence rate ratio (IRR) 1.72; 95 % confidence interval (CI) 1.46-2.02] and lower among daily aspirin users (IRR 0.73; 95 % CI 0.61-0.86) compared to those who used neither. Smoking interacts significantly with aspirin use resulting in loss of aspirin protection (IRR 1.69; 95 % CI 1.28-2.24). Stratified analyses demonstrate that aspirin specifically reduces the risk of traditional dysplastic adenomas (IRR 0.72; 95 % CI 0.61-0.86) not serrated/hyperplastic polyps (IRR 0.92; 95 % CI 0.72-1.17) and that the modification of aspirin protection by smoking is primarily observed within the distal colorectum (p < 0.03). CONCLUSIONS: We report for the first time, in a typical risk US clinical population, a lack of protective association of aspirin for polyps among active smokers. Future prospective studies are recommended to confirm this mitigating effect in order to improve the precision of the growing evidence base about the chemopreventive benefit of aspirin in colorectal cancer.
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Antiinflamatorios no Esteroideos/uso terapéutico , Aspirina/uso terapéutico , Pólipos del Colon/prevención & control , Fumar , Anciano , Pólipos del Colon/epidemiología , Colonoscopía , Estudios Transversales , Femenino , Humanos , Incidencia , Masculino , Persona de Mediana Edad , Estudios Prospectivos , RiesgoRESUMEN
INTRODUCTION: Lipoid pneumonia is a rare, underdiagnosed disorder, and its combined presentation with sarcoidosis is even more unusual. METHODS: This paper presents a case in which both lipoid pneumonia and sarcoidosis were present, and includes the relevant literature review on lipoid pneumonia. RESULTS: Lipoid pneumonia may be acute or chronic in its presentation, resulting from exogenous or endogenous factors, or classified as idiopathic, with its precise incidence unknown. Radiographic changes maybe variable, but typically include lower lobe consolidation. Pathologic changes consist of an inflammatory giant cell reaction around lipid-related empty vacuoles and giant cell granulomas. Treatment in the case of exogenous lipoid pneumonia consists of removal of the offending oil ingestion. However, in endogenous lipoid pneumonia, treatment is aimed at the underlying cause, as there is no standard treatment. Repeated bronchoalveolar lavage, corticosteroids, and surgical resection have been used as therapies. The course of the disease is usually not progressive.
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Lavado Broncoalveolar , Glucocorticoides/uso terapéutico , Neumonectomía , Neumonía Lipoidea/complicaciones , Neumonía Lipoidea/terapia , Sarcoidosis/complicaciones , Adulto , Humanos , Masculino , Neumonectomía/métodos , Neumonía Lipoidea/diagnóstico por imagen , Radiografía , Resultado del TratamientoRESUMEN
BACKGROUND AND AIM: Second harmonic generation (SHG) is a novel imaging technology that could provide optical biopsy during endoscopy with advantages over current technology. SHG has the unique ability to evaluate the amount of extracellular matrix collagen protein and its alignment. METHODS: Hematoxylin- and eosin-stained slides from colon biopsies (normal, low-grade dysplasia (LGD), high-grade dysplasia (HGD), and cancer) were examined with SHG imaging. Both signal intensity and collagen fiber alignment were measured. Average intensity per pixel (AIPP) was obtained, and an analyzing polarizer was used to calculate ß, an alignment parameter. RESULTS: The mean AIPP for normal mucosa was 48, LGD was 38, HGD was 42, and malignancy was 123 (p < 0.01). The AIPP ROC curve between malignant versus non-malignant tissue was 0.96 (0.93-0.99). An AIPP value of 60 can differentiate malignancy with 87 % sensitivity and 90 % specificity. The mean ß for normal tissue was 0.490, LGD was 0.379, HGD was 0.345, and cancer was 0.453 (p = 0.013), with a normal tissue mean rank of 6.5 compared to 2.5 for HGD (p = 0.029). CONCLUSIONS: SHG signal intensity can differentiate malignant from non-malignant colonic polyp tissue with high sensitivity and specificity. Anisotropic polarization can discern HGD from normal colonic polyp tissue. SHG can thus distinguish both HGD and malignant lesions in an objective numeric fashion, without contrast agents or interpretation skills. SHG could be incorporated into endoscopy equipment to enhance white light endoscopy.
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Colon/patología , Neoplasias del Colon/patología , Colonoscopía/métodos , Mucosa Intestinal/patología , Imagen Óptica/métodos , Anisotropía , Pólipos del Colon/patología , Diagnóstico Diferencial , Estudios de Factibilidad , Humanos , Imagen Óptica/instrumentación , Curva ROC , Sensibilidad y EspecificidadRESUMEN
Introduction: While metastases of malignant thymomas have been shown, type A thymomas are often treated as benign. Type A thymomas often have excellent response to treatment, low recurrence rate, and a small malignant potential. To date, there have been no reports of type A thymomas with spinal metastases. Case Report: A 66-year-old female with a type A thymoma metastatic to the T7 and T8 vertebral bodies and brain, with associated pathologic burst fracture, collapse of T7, and significant focal kyphosis . The patient underwent successful T7-T8 posterior corpectomy and T4-T11 posterior spinal fusion. At 2 years of follow-up, she was ambulating without assistive devices and completed spinal radiation and initial chemotherapy. Conclusion: Metastatic type A thymoma is a rare phenomenon. While traditionally thought to have low recurrence rates and overall excellent survival rates, our case suggests that the biologic malignant potential of a type A thymoma may not be fully understood.
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Herpes simplex virus (HSV) can cause severe disseminated infections in immunocompromised patients. Gastrointestinal tract involvement seldom includes the colon. We present a rare case of disseminated cutaneous HSV infection with concomitant colonic involvement in an immunosuppressed patient. The patient's clinical presentation and computerized tomography (CT) findings were concerning for colitis. She failed to improve on antibiotic therapy and subsequently underwent flexible sigmoidoscopy. Gross findings and histopathology were consistent with herpes simplex virus colitis. It is essential to recognize this pathology in immunocompromised patients to evaluate the need to hold immunosuppressive therapy and ensure successful treatment to prevent fatal outcomes.
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Cbl-b is an E3 ubiquitin ligase that negatively regulates T cell activation. Cbl-b(-/-) mice develop spontaneous autoimmunity, and Cbl-b dysregulation has been described in both murine and human autoimmune diseases. Although the mechanisms underlying the development of autoimmunity in Cbl-b(-/-) mice are not yet clear, we have reported that Cbl-b(-/-) CD4(+)CD25(-) effector T cells (Teffs) are resistant to CD4(+)CD25(+) regulatory T cell (Treg)-mediated suppression in vitro and have suggested that this may be an important mechanism in the development of autoimmunity. To confirm the relevance of this resistance to autoimmune disease, we now show that Cbl-b(-/-) Teffs are resistant to suppression by Tregs in vivo and that this involves a resistance of truly naive Cbl-b(-/-) Teffs. Additionally, we show that Cbl-b(-/-) Tregs are fully functional in vivo, further suggesting that the regulatory abnormalities in Cbl-b(-/-) mice are related to defects in Teff, not Treg, function. To characterize the relevance of TGF-beta sensitivity in Treg resistance, we examined in vivo Th17 generation and report that Cbl-b(-/-) mice are able to mount a normal Th17 response in vivo. As Cbl-b(-/-) Teffs have been shown to be insensitive to the suppressive effects of TGF-beta in other in vivo models, the present results suggest that Cbl-b(-/-) Teffs demonstrate a context-dependent sensitivity to TGF-beta in vivo. Overall, our results suggest that resistance to Tregs may be a bona fide mechanism underlying autoimmunity and that Cbl-b(-/-) mice offer unique approaches for studying the interrelationships between Treg function, TGF-beta-mediated responses, and the development of autoimmunity.
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Proteínas Proto-Oncogénicas c-cbl/inmunología , Linfocitos T Reguladores/inmunología , Linfocitos T/inmunología , Factor de Crecimiento Transformador beta/inmunología , Animales , Anticuerpos/inmunología , Anticuerpos/farmacología , Enfermedades Autoinmunes/inmunología , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/inmunología , Células Cultivadas , Citotoxicidad Inmunológica/efectos de los fármacos , Citotoxicidad Inmunológica/inmunología , Femenino , Citometría de Flujo , Enfermedad Injerto contra Huésped/inmunología , Interferón gamma/inmunología , Interferón gamma/metabolismo , Interleucina-12/inmunología , Interleucina-12/metabolismo , Interleucina-17/inmunología , Interleucina-17/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas Proto-Oncogénicas c-cbl/genética , Linfocitos T/citología , Linfocitos T/metabolismo , Linfocitos T Colaboradores-Inductores/citología , Linfocitos T Colaboradores-Inductores/inmunología , Linfocitos T Colaboradores-Inductores/metabolismo , Linfocitos T Reguladores/citología , Linfocitos T Reguladores/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Factor de Crecimiento Transformador beta/farmacologíaRESUMEN
Granulomas that consist of focal accumulations of macrophages are commonly found in the liver due to stimulation of the immune system by a number of agents. Manifestations are variable depending on whether the underlying cause is a systemic disease or a primary hepatic granulomatous reaction. This article describes the common causes, presentation, histopathology, and manifestations of granulomatous diseases as well as various diagnostic and management strategies.
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Granuloma/etiología , Hepatopatías/etiología , Enfermedades Transmisibles/complicaciones , Granuloma/diagnóstico , Humanos , Cirrosis Hepática Biliar/complicaciones , Hepatopatías/diagnóstico , Macrófagos/patología , Sarcoidosis/complicaciones , Tuberculosis/complicacionesRESUMEN
Stromal cells play a central role in promoting the progression of colorectal cancer. Here, we analyze molecular changes within the epithelial and stromal compartments of dysplastic aberrant crypt foci (ACF) formed in the ascending colon, where rapidly developing interval cancers occur. We found strong activation of numerous neutrophil/monocyte chemokines, consistent with localized inflammation. The data also indicated a decrease in interferon signaling and cell-based immunity. The immune checkpoint and T-cell exhaustion gene PDCD1 was one of the most significantly upregulated genes, which was accompanied by a decrease in cytotoxic T-cell effector gene expression. In addition, CDKN2A expression was strongly upregulated in the stroma and downregulated in the epithelium, consistent with diverse changes in senescence-associated signaling on the two tissue compartments. IMPLICATIONS: Decreased CD8 T-cell infiltration within proximal colon ACF occurs within the context of a robust inflammatory response and potential stromal cell senescence, thus providing new insight into potential promotional drivers for tumors in the proximal colon.
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Neoplasias del Colon/genética , Células Epiteliales/metabolismo , Células del Estroma/metabolismo , Neoplasias del Colon/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Microambiente TumoralRESUMEN
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL), previously known as Type-II enteropathy-associated T-cell lymphoma (EATL), is a rare subset of relatively aggressive lymphoma with a poor prognosis. We present a case of a previously healthy 59-year-old male with a 2-week history of abdominal distention who was found to have a non-bleeding ulcerated segment in the proximal jejunum secondary to MEITL. This exceedingly rare type of lymphoma usually presents with non-specific symptoms and can be challenging to diagnose. Our case demonstrates the importance of understanding the endoscopic and histological findings to allow the prompt diagnosis and treatment of this aggressive disease.
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Linfoma de Células T Asociado a Enteropatía , Linfoma de Células T , Linfoma de Células T Asociado a Enteropatía/diagnóstico , Humanos , Intestino Delgado/diagnóstico por imagen , Linfoma de Células T/diagnóstico , Masculino , Persona de Mediana Edad , Linfocitos TRESUMEN
Sarcoidosis is an inflammatory disease characterized by non-caseating granulomas in the absence of other autoimmune processes, infectious diseases, or foreign agents. The etiology of sarcoidosis is not completely understood. Several organ systems can be affected, of which the most frequently involved include the lungs and lymph nodes. Intra-abdominal sarcoidosis is less common, but can be found in the absence of pulmonary or lymphatic disease. Intra-abdominal sarcoidosis is most often asymptomatic. However, long-standing unrecognized disease can result in life-threatening complications. The identification, monitoring and prevention of these complications will be discussed, with emphasis on both clinical and histological presentations of intra-abdominal sarcoidosis.
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Enfermedades del Sistema Digestivo/etiología , Sarcoidosis/complicaciones , Abdomen/patología , Biopsia , Diagnóstico Diferencial , Enfermedades del Sistema Digestivo/patología , Enfermedades del Sistema Digestivo/fisiopatología , Humanos , Sarcoidosis/patología , Sarcoidosis/fisiopatologíaRESUMEN
Eosinophilic digestive diseases (EDD) are relatively rare disorders associated with increased gastrointestinal eosinophilic infiltrates without any underlying primary etiology. The pathophysiology of EDD is unclear, but is suspected to be related to a hypersensitivity reaction given its correlation with other atopic disorders and clinical response to corticosteroid therapy. Given the overall relative increase of various atopic conditions, it is important for clinicians to understand the presentation and diagnosis and treatment options available. We present here a review of EDD, including the proposed pathophysiology, diagnosis and current treatment options for these disorders.
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Colitis/terapia , Eosinofilia/terapia , Esofagitis/terapia , Gastroenteritis/terapia , Colitis/diagnóstico , Colitis/patología , Diagnóstico Diferencial , Eosinofilia/diagnóstico , Eosinofilia/patología , Esofagitis/diagnóstico , Esofagitis/patología , Gastroenteritis/diagnóstico , Gastroenteritis/patología , HumanosRESUMEN
Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesions in the colon that can be detected by high-definition chromoendoscopy with contrast dye spray. Although frequently associated with synchronous adenomas, their role in colorectal tumor development, particularly in the proximal colon, is still not clear. The goal of this study was to evaluate the profile of colon-adherent bacteria associated with proximal ACF and to investigate their relationship to the presence and subtype of synchronous polyps present throughout the colon. Forty-five subjects undergoing a screening or surveillance colonoscopy were included in this retrospective study. Bacterial cells adherent to the epithelia of ACF and normal mucosal biopsies were visualized by in situ hybridization within confocal tissue sections. ACF showed significantly greater heterogeneity in their bacterial microbiome profiles compared with normal mucosa. One of the bacterial community structures we characterized was strongly correlated with the presence of synchronous polyps. Finally, using DNA mass spectrometry to evaluate a panel of colorectal cancer hotspot mutations present in the ACF, we found that three APC gene mutations were positively associated with the presence of Instestinibacter sp., whereas KRAS mutations were positively correlated with Ruminococcus gnavus. This result indicates a potential relationship between specific colon-associated bacterial species and somatically acquired CRC-related mutations. Overall, our findings suggest that perturbations to the normal adherent mucosal flora may constitute a risk factor for early neoplasia, demonstrating the potential impact of mucosal dysbiosis on the tissue microenvironment and behavior of ACF that may facilitate their progression towards more advanced forms of neoplasia.
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A 72-year-old man receiving etanercept for the treatment of psoriatic arthritis had an exudative pleural effusion with nonspecific fluid analysis and pleural biopsy findings. He was ultimately found to have drug-induced lupus erythematosus due to the etanercept. The spectrum of autoimmune disease due to the use of tumor necrosis factor inhibitors is reviewed.
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Antiinflamatorios no Esteroideos/efectos adversos , Inmunoglobulina G/efectos adversos , Lupus Eritematoso Sistémico/inducido químicamente , Lupus Eritematoso Sistémico/diagnóstico , Derrame Pleural/etiología , Anciano , Etanercept , Humanos , Lupus Eritematoso Sistémico/terapia , Masculino , Derrame Pleural/patología , Derrame Pleural/terapia , Receptores del Factor de Necrosis TumoralRESUMEN
Herpes virus hepatitis varies in presentation, ranging from asymptomatic to acute liver failure, in both immunocompetent and immunocompromised individuals. Hepatitis caused by the Herpesviridae family is uncommon and usually results in mild disease. It is also often self-limiting, although in certain populations especially immunosuppressed patients, it can cause severe infections, leading to acute to fulminant hepatic failure. In addition, some isolated cases of fulminant disease in immunocompetent individuals have been reported. As the presentation is frequently non-specific, it is important to maintain a high level of suspicion for these viral etiologies and start empiric therapy with antiviral agents as soon as possible. Liver transplantation is the last resort. Mortality remains high in fulminant hepatic failure caused by Herpesviridae without liver transplantation. Here we review the literatures on hepatitis caused by three members of the Herpesviridae family, cytomegalovirus, Epstein-Barr virus and herpes simplex virus to discuss the epidemiology, diagnostic methods, clinical features and current management, and also to determine which aspects need to be investigated in further detail. Herpesviridae-mediated acute liver failure is rare but is associated with a poor prognosis, even after early treatment.
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Infecciones por Citomegalovirus/complicaciones , Infecciones por Virus de Epstein-Barr/complicaciones , Hepatitis/virología , Herpes Simple/complicaciones , Antivirales/uso terapéutico , Infecciones por Citomegalovirus/diagnóstico , Infecciones por Citomegalovirus/tratamiento farmacológico , Infecciones por Virus de Epstein-Barr/diagnóstico , Infecciones por Virus de Epstein-Barr/tratamiento farmacológico , Hepatitis/diagnóstico , Herpes Simple/diagnóstico , Herpes Simple/tratamiento farmacológico , HumanosRESUMEN
BACKGROUND/AIMS: The aims of the study were to identify whether a mucous-cap predicts the presence of serrated polyps, and to determine whether additional endoscopic findings predict the presence of a sessile serrated adenomas/polyp (SSA/P). METHODS: We analyzed 147 mucous-capped polyps with corresponding histology, during 2011-2014. Eight endoscopic features (presence of borders, elevation, rim of debris, location in the colon, size ≥10 mm, varicose vessels, nodularity, and alteration in mucosal folds) of mucous-capped polyps were examined to see if they can predict SSA/Ps. RESULTS: A total of 86% (n=126) of mucous-capped polyps were from the right sided serrated pathway (right-sided hyperplastic [n=83], SSA/Ps [n=43], traditional serrated adenoma [n=1]), 10% (n=15) were left-sided hyperplastic polyps, and 3% (n=5) were from the adenoma-carcinoma sequence. The presence of a mucous cap combined with varicose vessels was the only significant predictor for SSA/Ps. The other seven characteristics were not found to be statistically significant for SSA/Ps, although location in the colon and the presence of nodularity trended towards significance. CONCLUSIONS: Our study suggests that mucous-capped polyps have high predictability for being a part of the serrated pathway. Gastroenterologists should be alert for a mucous-capped polyp with varicose veins, as these lesions have a higher risk of SSA/P.
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Pigmented villonodular synovitis (PVNS) is a benign proliferative joint disease, which is a rare finding after total knee arthroplasty (TKA). There is currently no link between PVNS and TKA, and it has been described infrequently in the literature. Its presentation has varied along with the time that it presents postoperatively. We describe a case of a patient who presents with recurrent hemarthrosis 4 years after TKA. The patient had no previous history of PVNS and had an arthroscopy 1 year after the index operation with no evidence of synovitis. We present details of the first case with a review of imaging and pathology and a brief review of the literature on PVNS occurring after TKA.
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Aberrant crypt foci (ACF) are the earliest morphologically identifiable lesion found within the human colon. Despite their relatively high frequency in the distal colon, few studies have examined the molecular characteristics of ACF within the proximal colon. In the following study, clinical participants (n = 184) were screened for ACF using high-definition chromoendoscopy with contrast dye-spray. Following pathologic confirmation, ACF biopsies were subjected to laser capture microdissection (LCM), and epithelial cells were evaluated for somatic mutations with a customized colorectal cancer mutation panel using DNA-mass spectrometry. Samples were further characterized for microsatellite instability (MSI). Logistic models were used to associate proximal ACF with synchronous (detected during the same procedure) neoplasia. Thirty-nine percent of participants had at least one histologically confirmed proximal ACF. Individuals with a proximal ACF were significantly more likely to present with a synchronous neoplasm (P = 0.001), and specifically, a proximal, tubular, or tubulovillous adenoma (multivariable OR = 2.69; 95% confidence interval, 1.12-6.47; P = 0.027). Proximal ACF were more likely to be dysplastic (52%) compared with distal ACF (13%; P < 0.0001). Somatic mutations to APC, BRAF, KRAS, NRAS, and ERBB2 were detected in 37% of proximal ACF. Hyperplastic ACF were more often MSI-high, but there were no differences in MSI status observed by colonic location. In summary, ACF are identified in the proximal colons of approximately 40% of individuals undergoing chromoendoscopy and more often in patients with synchronous proximal adenomas.Implications: This study provides the most complete set of data, to date, that ACF represent the earliest step in the adenoma-carcinoma sequence but remain below the detection limit of conventional endoscopy.Visual Overview: http//mcr.accrjournals.org/content/molcanres/16/3/486/F1.large.jpg Mol Cancer Res; 16(3); 486-95. ©2017 AACR.
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Focos de Criptas Aberrantes/patología , Neoplasias del Colon/patología , Neoplasias Primarias Múltiples/patología , Progresión de la Enfermedad , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
Colon cancers often display perturbations in arachidonic acid metabolism, with elevated levels of cyclooxygenase (COX)-2 expression and prostaglandin E(2) (PGE(2)) production frequently observed. Whereas COX-2 and PGE(2) are associated with cancer cell survival and tumor angiogenesis, arachidonic acid itself is a strong apoptotic signal that may facilitate cancer cell death. To further explore how cancer cells exploit the progrowth actions of prostaglandins while suppressing the proapoptotic actions of intracellular arachidonic acid, we determined the cytoplasmic phospholipase A(2) (cPLA(2)) and COX-2 expression levels in a panel of human colon tumors by immunohistochemistry. Although high levels of cPLA(2) and COX-2 expression are predicted to facilitate maximal prostaglandin production, tumors frequently displayed a high-COX-2/low-cPLA(2) phenotype. The least represented phenotype was the high expression of cPLA(2), a characteristic predicted to generate the highest levels of intracellular arachidonic acid. The potential proapoptotic role of cPLA(2) was supported by a higher frequency of terminal deoxynucleotidyl transferase-mediated nick end labeling staining in cPLA(2)-positive tumors. Moreover, analysis of preneoplastic aberrant crypt foci from high-risk patients suggests that acquisition of the high-COX-2/low-cPLA(2) phenotype may arise at an early stage of colon carcinogenesis. We additionally inhibited cPLA(2) in HT-29 cells using antisense oligonucleotides. Our results indicate that cPLA(2) plays an important role in tumor necrosis factor alpha-induced apoptosis in human colon cancer cells. Our data further support the model in which colon cancer growth is favored when intracellular arachidonic acid levels are suppressed by inhibition of cPLA(2) or by a high-COX-2/low-cPLA(2) phenotype.