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Pancreatic mixed acinar-neuroendocrine carcinomas are rare malignant tumors of the pancreas. They are composed histologically of both acinar and neuroendocrine cells. The pancreatic duct is known to be an important site of tumor growth for acinar cell carcinomas, neuroendocrine tumors, and intraductal tubulopapillary neoplasms. To the best of our knowledge, there has been only 1 report of a mixed acinar-neuroendocrine carcinoma growing into the pancreatic duct and no reports detailing imaging findings with this tumor. We here report a 69-year-old man who presented with worsening glycemic control. Multiphase contrast-enhanced computed tomography and magnetic resonance imaging revealed a well-circumscribed mass with poor contrast enhancement in the pancreatic tail region of the pancreatic duct. The intraductal mass showed diffusion restriction on magnetic resonance imaging. These imaging findings are consistent with the expansive, smooth-surfaced polypoid tumor of low vascularity and high cellularity that was diagnosed pathologically. Mixed acinar-neuroendocrine carcinomas should be included in the differential diagnosis of intraductal tumors of the pancreas with poor contrast enhancement and diffusion restriction.
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Cardiac hypertrophy is a crucial risk factor for hypertensive disorders during pregnancy, but its progression during pregnancy remains unclear. We previously showed cardiac hypertrophy in a pregnancy-associated hypertensive (PAH) mouse model, in which an increase in angiotensin II (Ang II) levels was induced by human renin and human angiotensinogen, depending on pregnancy conditions. Here, to elucidate the factors involved in the progression of cardiac hypertrophy, we performed a comprehensive analysis of changes in gene expression in the hearts of PAH mice and compared them with those in control mice. We found that alpha-1A adrenergic receptor (Adra1a) mRNA levels in the heart were significantly reduced under PAH conditions, whereas the renin-angiotensin system was upregulated. Furthermore, we found that Adra1a-deficient PAH mice exhibited more severe cardiac hypertrophy than PAH mice. Our study suggests that Adra1a levels are regulated by renin-angiotensin system and that changes in Adra1a expression are involved in progressive cardiac hypertrophy in PAH mice.
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Angiotensina II , Hipertensão Induzida pela Gravidez , Receptores Adrenérgicos alfa 1 , Animais , Feminino , Humanos , Camundongos , Gravidez , Angiotensina II/metabolismo , Cardiomegalia/metabolismo , Miocárdio/metabolismo , Receptores Adrenérgicos alfa 1/genética , Receptores Adrenérgicos alfa 1/metabolismo , Sistema Renina-Angiotensina , Hipertensão Induzida pela Gravidez/genética , Hipertensão Induzida pela Gravidez/metabolismoRESUMO
Fibroblast growth factor 21 (FGF21), which is mainly synthesized and secreted by the liver, plays a crucial role in systemic glucose and lipid metabolism, ameliorating metabolic diseases. In this study, we screened the WAKANYAKU library derived from medicinal herbs to identify compounds that can activate Fgf21 expression in mouse hepatocyte AML12 cells. We identified Scutellaria baicalensis root extract and one of its components, wogonin, as an activator of Fgf21 expression. Wogonin also enhanced the expression of activating transcription factor 4 (ATF4) by a mechanism other than ER stress. Knockdown of ATF4 by siRNA suppressed wogonin-induced Fgf21 expression, highlighting its essential role in wogonin's mode of action. Thus, our results indicate that wogonin would be a strong candidate for a therapeutic to improve metabolic diseases by enhancing hepatic FGF21 production.
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Flavanonas , Scutellaria baicalensis , Fator 4 Ativador da Transcrição/genética , Fator 4 Ativador da Transcrição/metabolismo , Animais , Fatores de Crescimento de Fibroblastos , Flavanonas/farmacologia , Flavanonas/uso terapêutico , Glucose , Hepatócitos/metabolismo , Camundongos , Extratos Vegetais/farmacologia , RNA Interferente Pequeno , Scutellaria baicalensis/metabolismoRESUMO
Sterol regulatory element-binding proteins (SREBPs) are master transcription factors for lipid synthesis, and SREBP-1 is important for fatty acid and triglyceride synthesis. SREBP-1 has two isoforms, SREBP-1a and SREBP-1c, which are splicing variants transcribed from the Srebf1 gene. Although SREBP-1a exhibits stronger transcriptional activity than SREBP-1c, hepatic SREBP-1c is considered more physiologically important. We generated SREBP-1a flox mice using the CRISPR/Cas9 system and hepatocyte- and macrophage-specific SREBP-1a knockout (KO) mice (LKO, liver-knockout; and mΦKO, macrophage-knockout). There were no significant differences among all the mouse genotypes upon feeding with a normal diet. However, feeding with a methionine- and choline-deficient (MCD) diet resulted in exacerbated liver injury in both KO mice. In LKO mice, fatty liver was unexpectedly exacerbated, leading to macrophage infiltration and inflammation. In contrast, in mΦKO mice, the fatty liver state was similar to that in flox mice, but the polarity of the macrophages in the liver was transformed into a proinflammatory M1 subtype, resulting in the exacerbation of inflammation. Taken together, we found that SREBP-1a does not contribute to hepatic lipogenesis, but in either hepatocytes or macrophages distinctly controls the onset of pathological conditions in MCD diet-induced hepatitis.NEW & NOTEWORTHY Hepatocyte- and macrophage-specific SREBP-1a knockout mice were generated for the first time. This study reveals that SREBP-1a does not contribute to hepatic lipogenesis, but in either hepatocytes or macrophages distinctly controls the onset of pathological conditions in methionine- and choline-deficient diet-induced hepatitis.
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Hepatopatia Gordurosa não Alcoólica , Camundongos , Animais , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/metabolismo , Metionina , Colina/metabolismo , Camundongos Endogâmicos C57BL , Hepatócitos/metabolismo , Fígado/metabolismo , Camundongos Knockout , Dieta/efeitos adversos , Inflamação/metabolismo , Macrófagos/metabolismoRESUMO
Large-duct type pancreatic ductal adenocarcinoma (PDA) is a rare morphologic variant forming large duct elements. This case report, to our knowledge, is the first report of a large-duct type PDA with a "honeycomb" appearance resembling a serous cystic neoplasm (SCN) on CT and MRI. The patient is an 82-year-old woman who presented with upper abdominal pain. Dynamic contrast-enhanced CT revealed a multilocular cyst with honeycomb loculi, in which the cyst walls showed gradual enhancement. On T2-weighted MRI, the mass displayed inhomogeneous hyperintensity characterized by a honeycomb appearance with irregular and thick hypointense cyst walls. The patient underwent distal pancreatectomy; histopathological diagnosis was large-duct type PDA. Although the imaging features of large-duct type PDA may resemble those of SCN, this distinction between PDA and SCN is important because the treatment options are very different.
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OBJECTIVES: To clarify venous phase contrast-enhanced CT findings in early pancreatic adenocarcinomas by retrospectively evaluating CT images of pancreatic adenocarcinomas that developed during follow-up after treatment for non-pancreatic cancers. METHODS: The study cohort comprised six patients who developed pancreatic adenocarcinomas between April 2005 and April 2020 during follow-up after treatment for non-pancreatic primary cancers. Two radiologists retrospectively evaluated CT images and reached consensus on previously reported CT findings that were suggestive of small pancreatic adenocarcinomas; namely pancreatic duct interruption and dilatation, pancreatic parenchymal atrophy, focal hypoattenuated areas, and appearance of cystic lesions. Time intervals between the first CT with these suggestive findings and the latest pre-operative CT were recorded. Doubling times were calculated in patients with hypoattenuated areas on initial CT scans. RESULTS: Small (<10 mm) focal hypoattenuated areas with (n = 2) or without rim enhancement (n = 1) were identified on initial CT images of three patients. Pancreatic duct interruption and dilatation, pancreatic parenchymal atrophy, and cystic lesion were identified in two, one and one patient, respectively. Time intervals between initial and latest preoperative CT examination were 6-19 months (median, 14.5 months). Tumor doubling time according to CT findings was calculated as 46-407 days (median 106 days). CONCLUSION: Venous phase contrast-enhanced CT can provide findings that are suggestive of early pancreatic adenocarcinoma. Pancreatic phase contrast-enhanced CT should therefore be performed in patients with such findings with the aim of early detection of pancreatic adenocarcinoma. ADVANCES IN KNOWLEDGE: Pancreatic adenocarcinoma can develop subsequently in patients with non-pancreatic malignancies. Patients with non-pancreatic cancers are often followed up with monophasic contrast-enhanced CT in venous phase timing. Venous phase contrast-enhanced CT can provide some findings suggestive of early pancreatic adenocarcinoma. Knowledge of these findings is important for early detection of pancreatic adenocarcinoma.
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cAMP responsive element-binding protein H (CREBH) is a hepatic transcription factor to be activated during fasting. We generated CREBH knock-in flox mice, and then generated liver-specific CREBH transgenic (CREBH L-Tg) mice in an active form. CREBH L-Tg mice showed a delay in growth in the postnatal stage. Plasma growth hormone (GH) levels were significantly increased in CREBH L-Tg mice, but plasma insulin-like growth factor 1 (IGF1) levels were significantly decreased, indicating GH resistance. In addition, CREBH overexpression significantly increased hepatic mRNA and plasma levels of FGF21, which is thought to be as one of the causes of growth delay. However, the additional ablation of FGF21 in CREBH L-Tg mice could not correct GH resistance at all. CREBH L-Tg mice sustained GH receptor (GHR) reduction and the increase of IGF binding protein 1 (IGFBP1) in the liver regardless of FGF21. As GHR is a first step in GH signaling, the reduction of GHR leads to impairment of GH signaling. These data suggest that CREBH negatively regulates growth in the postnatal growth stage via various pathways as an abundant energy response by antagonizing GH signaling.
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Composição Corporal , Índice de Massa Corporal , Proteína de Ligação ao Elemento de Resposta ao AMP Cíclico/fisiologia , Fatores de Crescimento de Fibroblastos/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Hormônio do Crescimento/metabolismo , Fígado/metabolismo , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Transdução de SinaisRESUMO
OBJECTIVE: To determine the ability of multidetector computed tomography (MPR-MDCT) to identify and classify the juxtapapillary duodenal diverticulum (JPDD), with ERCP findings as the gold standard. METHODS: We retrospectively reviewed all ERCP examinations (n: 455) performed between January 2010 to December 2018 and selected 105 patients with JPDD as the inclusion criteria. Of those, 28 patients were excluded because of advanced pancreatic carcinoma, incomplete MDCT examinations and biliary catheter insertion. Finally, MDCT examinations of 77 patients with JPDD were assessed for the presence and type of JPDD. RESULTS: MPR-MDCT was able to identify 71 (92.2%) JPDD in 77 cases with 88.9% accuracy, 83.3% sensitivity, and 91.6% specificity in classifying the type of JPDD. MPR-MDCT performed best in determining type 1 JPDD, with accuracy of 95.4% compared with type 2 (83.3%) and type 3 (87.8%). There was no significant difference between age, gender, incidence of biliary stones and pancreatitis between each type of JPDD. No correlation of sizes with types of JPDD was found. CONCLUSIONS: MPR-MDCT can accurately identify and classify JPDD. This information will be useful in determining the difficulty of ERCP.
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Colangiopancreatografia Retrógrada Endoscópica , Divertículo/diagnóstico por imagem , Duodenopatias/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Sensibilidade e EspecificidadeRESUMO
PURPOSE: To elucidate the relationships between mural nodules (MNs) and invasive components in patients with invasive intraductal papillary mucinous neoplasm (IPMN) on the basis of thin-section contrast-enhanced multidetector CT (CE-MDCT) and pathologic findings. METHODS: This retrospective study included 28 patients with surgically confirmed invasive IPMN. Two radiologists independently evaluated the thin-section (1-mm section thickness, no overlap) triple-phase CE-MDCT images for MNs, invasive components, and the continuity between them using a five-point scale (confidence scores of 1-3 as negative, 4 and 5 as positive). Kappa statistic was used to evaluate interobserver agreement. The CE-MDCT findings were correlated with pathologic findings. RESULTS: Interobserver agreement was good or excellent. MNs consisting of tumor cells were recognized in 12 (42.9%) of 28 patients with no discrepancy between the two radiologists. Invasive components were detected in 85.7% and 82.1% in the pancreatic parenchymal phase for radiologist 1 and 2, respectively, and recognized as hypoattenuating areas. Pathologic continuities between MNs and invasive components were confirmed in five (41.7%) of 12 patients with MNs and these were detected on CE-MDCT. When combined seven patients without continuities between MNs and invasive components and 16 patients without MNs, the invasive components pathologically derived from non-nodular low-height papillary epithelium in 23 (82.1%) of 28 patients. CONCLUSIONS: The invasive components derived more often from low-height papillary epithelium without MN appearance on CE-MDCT than from MN. Careful attention should be paid to the existence of an invasive component even in the absence of an enhancing MN.
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Meios de Contraste , Aumento da Imagem/métodos , Tomografia Computadorizada Multidetectores/métodos , Neoplasias Intraductais Pancreáticas/diagnóstico por imagem , Neoplasias Intraductais Pancreáticas/patologia , Idoso , Idoso de 80 Anos ou mais , Diagnóstico Diferencial , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Estudos RetrospectivosRESUMO
PURPOSE: To reveal the prevalence of small (≤ 20 mm) pancreatic ductal carcinomas with enhanced rims on triple-phase contrast-enhanced CT and correlate the CT images with the pathologic findings. MATERIALS AND METHODS: Between April 2005 and April 2016, 45 patients underwent preoperative triple-phase contrast-enhanced CT and were pathologically diagnosed with small pancreatic ductal carcinoma. CT images were independently reviewed by two radiologists. The attenuation values of the enhanced rims, internal areas of the tumors, and surrounding pancreatic parenchyma were compared using Mann-Whitney U test. These areas were also correlated with the pathologic findings. Tumor invasiveness was compared between the tumors with and without enhanced rims using Fisher's exact test. RESULTS: Enhanced rims were identified in 18 tumors (40%) by consensus between the two reviewers. The enhanced rims showed significantly higher mean attenuation values compared with the internal areas of the tumors (p < 0.001) and surrounding pancreatic parenchyma (p < 0.0086), and were most clearly visualized on equilibrium phase. The enhanced rims pathologically reflected the abundant fibrotic stroma with cancer cells in all tumors. There was no statistically significant difference in tumor invasiveness between the tumors with and without enhanced rims (anterior peripancreatic invasion, p = 0.137; posterior peripancreatic invasion, p = 0.758; portal vein invasion, p = 0.639; and lymph node metastases, p = 0.359). CONCLUSIONS: Enhanced rims were detected at a rate of 40% in small pancreatic ductal carcinomas and could be an important finding for diagnosis on CT images, but did not suggest a less aggressive nature.
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Carcinoma Ductal Pancreático/diagnóstico por imagem , Carcinoma Ductal Pancreático/patologia , Meios de Contraste , Neoplasias Pancreáticas/diagnóstico por imagem , Neoplasias Pancreáticas/patologia , Intensificação de Imagem Radiográfica/métodos , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Estudos RetrospectivosRESUMO
BACKGROUND: Splenopancreatic fusion is a rare anomaly that is often associated with trisomy 13. Its diagnosis can be important in patients scheduled to undergo distal pancreatectomy or splenectomy, to avoid possible intraoperative or postoperative complications. CASE PRESENTATION: An 82-year-old Japanese man was referred to our hospital for further evaluation and treatment for a solitary hepatocellular carcinoma based on liver cirrhosis. Triple-phase contrast-enhanced multidetector-row computed tomography and magnetic resonance imaging showed a splenopancreatic fusion as well as a solitary hepatocellular carcinoma in segment VIII of his liver. CONCLUSIONS: Fusion of the pancreatic tail and spleen is a rare and asymptomatic anomaly. Its detection can be improved by the use of multidetector computed tomography or magnetic resonance imaging.
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Pâncreas/anormalidades , Baço/anormalidades , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/complicações , Carcinoma Hepatocelular/diagnóstico por imagem , Humanos , Neoplasias Hepáticas/complicações , Neoplasias Hepáticas/diagnóstico por imagem , Imageamento por Ressonância Magnética , Masculino , Tomografia Computadorizada Multidetectores , Pâncreas/diagnóstico por imagem , Baço/diagnóstico por imagemRESUMO
PURPOSE: We sought to evaluate visualization of periportal lymphatics and lymph nodes (lymphatic system) on Gd-EOB-DTPA-enhanced magnetic resonance (MR) images using a fat-suppressed T2-weighted sequence with 3-dimensional (3D) volume isotropic turbo spin echo acquisition (VISTA) at 3.0 T in normal subjects and patients with chronic hepatitis C. METHODS: MR imaging was performed in 254 subjects between June 2013 and May 2016. After applying inclusion and exclusion criteria, the final population was 31 normal subjects and 34 patients with chronic hepatitis C. Images were acquired after the hepatobiliary phase following intravenous administration of Gd-EOB-DTPA, which causes signal loss in the bile ducts, to facilitate the visualization of the periportal lymphatic system. Two radiologists assessed the visualization of the periportal lymphatic system in 31 normal subjects. The axial dimensions of the main periportal lymphatic system in normal subjects were measured and compared with those of 34 patients with chronic hepatitis C using the Mann-Whitney U-test, and their correlation with a hepatic fibrosis marker, the Fibrosis-4 (FIB-4), was assessed using Spearman's rank correlation test. RESULTS: The periportal lymphatic system was detected as high signal intensity areas surrounding the portal vein up to the third branches by each reader in all normal subjects. The axial dimensions of the main periportal lymphatic system in patients with chronic hepatitis C were significantly larger than those in normal subjects (p < 0.0001), and showed a significantly positive correlation with the FIB-4 score (ρ = 0.73, p < 0.001). CONCLUSIONS: Fat-suppressed T2-weighted MR imaging with 3D-VISTA acquired after the hepatobiliary phase on Gd-EOB-DTPA-enhanced imaging may be a useful noninvasive method for evaluating the periportal lymphatic system and the degree of hepatic fibrosis.
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Gadolínio DTPA , Hepatite C Crônica/parasitologia , Sistema Linfático/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Artefatos , Meios de Contraste , Feminino , Humanos , Aumento da Imagem/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
PURPOSE: To analyze morphology/contour variations of the pancreatic body and tail in subjects free of pancreatic disease. METHODS: We retrospectively reviewed triple-phase, contrast-enhanced multi-detector row computed tomography (3P-CE-MDCT) examinations of 449 patients who had no clinical or CT evidence of pancreatic diseases. These patients were evaluated for morphologic/contour variations of the pancreatic body and tail, which were classified into two types. In Type I, a portion of normal pancreatic parenchyma protrudes >1 cm in maximum diameter from the body or tail (Ia-anteriorly; Ib-posteriorly). Type II was defined as a morphologic anomaly of the pancreatic tail (IIa-globular; IIb-lobulated; IIc-tapered; IId-bifid). RESULTS: Thirty-eight (8.5%) out of 449 patients had body or tail variations. Of those, 23 patients showed Type I variant: Ia in 21 and Ib in two. Type II variant was identified in 15 patients: IIa in eight, IIb in two, IIc in two and IId in three. Protrusion of the anterior surface of the normal pancreas, especially in the tail, was the most frequently occurring variant. CONCLUSIONS: Recognizing the types and subtypes of morphology/contour variations of the pancreatic body and tail could help prevent misinterpretation of normal variants as pancreatic tumors on unenhanced MDCT.
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Tomografia Computadorizada Multidetectores/métodos , Pâncreas/anatomia & histologia , Pâncreas/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Meios de Contraste , Feminino , Humanos , Iopamidol , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
OBJECTIVES: Periportal low attenuation (PPLA) associated with metastatic liver cancer is occasionally seen on multi-detector-row CT (MDCT). The purpose of this study was to investigate the MDCT patterns of the PPLA and to correlate it with pathological findings. METHODS: We retrospectively reviewed the MDCT images of 63 patients with metastatic liver cancers from colorectal adenocarcinoma. On MDCT scans, PPLA associated with liver metastasis was visualized in six patients with colorectal cancer. In these six patients who had undergone surgical resection, the radiologic-pathologic correlation was analyzed. All patients underwent a single contrast-enhanced MDCT within 1 month before surgical resection. The six liver cancers were pathologically proven to be moderately differentiated adenocarcinoma. We assessed the PPLA on MDCT concerning the distribution patterns and contrast enhancement with pathological correlation. RESULTS: In five of the patients, the PPLA extended to the hilar side from metastatic liver cancer. Pathologically, there was no cancer invasion into the intra-hepatic periportal area; however, massive lymphedema and fibrosis occurred in all six cases. CONCLUSIONS: PPLA on the hilar and peripheral sides of hepatic metastasis from colorectal cancer may be present suggesting lymphedema and fibrosis of portal tracts not always indicating cancer infiltration.
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Neoplasias Colorretais/patologia , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/secundário , Fígado/diagnóstico por imagem , Fígado/patologia , Tomografia Computadorizada Multidetectores/métodos , Idoso , Meios de Contraste , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Intensificação de Imagem Radiográfica , Estudos RetrospectivosAssuntos
Anticorpos Monoclonais/efeitos adversos , Antineoplásicos/efeitos adversos , Antígeno CTLA-4/genética , Diabetes Mellitus Tipo 1/induzido quimicamente , Antígenos HLA/genética , Pâncreas/patologia , Diabetes Mellitus Tipo 1/genética , Feminino , Humanos , Melanoma/tratamento farmacológico , Melanoma/secundário , Pessoa de Meia-Idade , Nivolumabe , Tamanho do Órgão/genética , Polimorfismo Genético , Neoplasias Cutâneas/tratamento farmacológico , Neoplasias Cutâneas/patologiaRESUMO
OBJECTIVE: We aimed to evaluate the pancreatic uncinate process with a beak-like extension (BLE) beyond the left border of the superior mesenteric artery, to define the cause of BLE, and to differentiate BLE from hyperplasia. METHODS: We retrospectively reviewed 1042 triple-phase contrast-enhanced multidetector-row computed tomography (3P-CE-MDCT) examinations of 500 patients. Finally, 38 patients (28 men, 10 women; mean age, 66 years) with 140 3P-CE-MDCT images showing BLE were studied regarding BLE size, contour, and cause. The superior mesenteric artery position was also evaluated. RESULTS: Beak-like extensions were found in 7.6% of patients. Most were caused by movement of the small bowel mesentery (n = 21, 55%), with deviation of mesenteric vessels or mass effect from expanded adjacent organs (n = 3, 8%). Seven patients (18.5%) had true hyperplasia. CONCLUSIONS: Beak-like extension is caused by movement of the small bowel mesentery with deviation of mesenteric vessels or by adjacent organ expansion. Beak-like extension closely mimics other pathology on nonenhanced MDCT.
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Artefatos , Mesentério/diagnóstico por imagem , Mesentério/patologia , Tomografia Computadorizada Multidetectores/métodos , Pâncreas/diagnóstico por imagem , Pâncreas/patologia , Diagnóstico Diferencial , Feminino , Humanos , Hiperplasia/diagnóstico por imagem , Hiperplasia/patologia , Masculino , Pessoa de Meia-Idade , Movimento (Física) , Movimento , Variações Dependentes do Observador , Reprodutibilidade dos Testes , Sensibilidade e EspecificidadeRESUMO
The progression from precursor lesions of pancreatic cancer, including pancreatic intraepithelial neoplasia and intraductal papillary mucinous neoplasm (IPMN), to invasive disease is characterized by stepwise accumulation of genetic alterations. However, it remains unclear whether additional alterations are required for the progression of high-grade neoplasms to invasive pancreatic carcinoma. We compared the genomic profiles of paired noninvasive and invasive carcinoma tissues collected from patients with IPMN. We demonstrate that the frequency of genomic copy-number aberrations significantly increased during the course of invasion, and the loss of 8p11.22-ter was more often associated with invasive tissues. Expression profiling in pancreatic cancer cell lines with and without 8p11.22-ter revealed that DUSP4, an MAPK phosphatase, was significantly downregulated in cells lacking 8p11.22-ter as well as in invasive carcinomas due to genomic loss. Restoration of DUSP4 expression in pancreatic cancer cells significantly suppressed invasiveness and anoikis resistance via ERK inactivation. Accordingly, we found that blockade of ERK signaling by MEK inhibition was effective in an orthotopic xenograft model and significantly extended survival. Collectively, our findings demonstrate a genetic mechanism by which pancreatic precursor lesions progress to invasive carcinomas and highlight DUSP4 as a novel invasion suppressor that can be therapeutically exploited through manipulation of ERK signaling. Cancer Res; 76(9); 2612-25. ©2016 AACR.
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Adenocarcinoma in Situ/patologia , Carcinoma Ductal Pancreático/patologia , Fosfatases de Especificidade Dupla/metabolismo , Fosfatases da Proteína Quinase Ativada por Mitógeno/metabolismo , Neoplasias Pancreáticas/patologia , Adenocarcinoma in Situ/genética , Adenocarcinoma Mucinoso/genética , Adenocarcinoma Mucinoso/mortalidade , Adenocarcinoma Mucinoso/patologia , Adenocarcinoma Papilar/genética , Adenocarcinoma Papilar/mortalidade , Adenocarcinoma Papilar/patologia , Animais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/mortalidade , Hibridização Genômica Comparativa , Progressão da Doença , Fosfatases de Especificidade Dupla/genética , Xenoenxertos , Humanos , Estimativa de Kaplan-Meier , Camundongos , Microscopia Confocal , Fosfatases da Proteína Quinase Ativada por Mitógeno/genética , Invasividade Neoplásica , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/mortalidade , TranscriptomaRESUMO
PURPOSE: To evaluate the normal anatomy of the perirenal lymphatics using spectral presaturation with inversion recovery (SPIR) T2 -weighted magnetic resonance imaging (MRI) with 3D volume isotropic turbo spin-echo acquisition (VISTA) at 3.0T. MATERIALS AND METHODS: This retrospective study was approved by the two Institutional Review Boards and informed consent was waived. Thin-collimated axial images obtained using SPIR T2 -weighted MR imaging sequences with 3D VISTA at 3.0T from 50 patients (100 kidneys) with normal renal function were retrospectively reviewed. The perirenal lymphatic vessels were defined as fluid signal intensity structures on this MRI sequence. Two readers independently assessed the degree of visualization of the perirenal lymphatics using a 4-point scale in four anatomical regions, including the renal hilar, capsular, communicating pericapsular, and subfascial lymphatics, and interobserver agreement was evaluated with weighted kappa statics. The detectability of each lymphatic system was calculated for each reader using confidence level ratings of grades 1 and 2 as positive and grades 3 and 4 as negative. RESULTS: Interobserver agreement for the visualization grades was almost perfect (kappa value = 0.9). The renal hilar lymphatics along the renal vein were clearly identified in all patients. The detectability of other perirenal lymphatics was 44% for the capsular lymphatics, 39% for communicating pericapsular lymphatics, and 22% for the subfascial lymphatics. There was no laterality regarding the detectability of the perirenal lymphatics. CONCLUSION: The findings of this study support the feasibility of SPIR T2 -weighted MR images with 3D-VISTA at 3.0T for evaluating the perirenal lymphatic systems. J. MAGN. RESON. IMAGING 2016;44:897-905.
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Imagem de Difusão por Ressonância Magnética/métodos , Interpretação de Imagem Assistida por Computador/métodos , Imageamento Tridimensional/métodos , Rim/diagnóstico por imagem , Sistema Linfático/diagnóstico por imagem , Processamento de Sinais Assistido por Computador , Adulto , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Viabilidade , Feminino , Humanos , Aumento da Imagem/métodos , Rim/anatomia & histologia , Sistema Linfático/anatomia & histologia , Masculino , Pessoa de Meia-Idade , Valores de Referência , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Marcadores de SpinRESUMO
OBJECTIVE: To investigate the medial pathways of the right retromesenteric plane by reviewing multidetector CT (MDCT) findings in patients with acute pancreatitis and pyelonephritis. METHODS: 112 patients with acute pancreatitis and 114 patients with pyelonephritis underwent MDCT scans. 64 of the 112 patients with acute pancreatitis and 34 of the 114 patients with pyelonephritis had right retromesenteric plane thickening because of inflammatory extensions. The medial pathways of the right retromesenteric plane were evaluated by two radiologists in consensus. RESULTS: In 18 (28%) of the 64 patients with acute pancreatitis and 10 (29%) of the 34 patients with pyelonephritis, the right retromesenteric plane continued to the central retroperitoneum behind the descending duodenum and pancreatic head (Type 1 pathway). The right retromesenteric plane extended to the right wall of the descending duodenum (Type 2 pathway) in 46 patients (72%) with acute pancreatitis and 24 patients (71%) with pyelonephritis. There was no significant difference in the pathway patterns of the right retromesenteric plane between the acute pancreatitis group and the pyelonephritis group (Type 1 pathway, p = 0.89; Type 2 pathway, p = 0.76). CONCLUSION: Two patterns were confirmed regarding the medial pathways of the right retromesenteric plane; this anatomical knowledge is important for evaluating the extension of retroperitoneal diseases. ADVANCES IN KNOWLEDGE: Medial aspect of the right retromesenteric plane is thought to have two pathways. The right retromesenteric plane continuing to the right duodenal wall is a common type. Knowledge of these variations is important when evaluating the retroperitoneal diseases.
Assuntos
Mesentério/diagnóstico por imagem , Tomografia Computadorizada Multidetectores , Pancreatite/diagnóstico por imagem , Pielonefrite/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pâncreas/diagnóstico por imagem , Pancreatite/complicações , Pielonefrite/complicações , Espaço Retroperitoneal/diagnóstico por imagem , Estudos Retrospectivos , Adulto JovemRESUMO
PURPOSE: To evaluate the utility of spectral presaturation with inversion recovery (SPIR) T2-weighted images with 3-dimensional (3D) volume isotropic turbo spin echo acquisition (VISTA) at 3.0-T for the detection of the normal lymphatic systems located around the pancreatic head and extrahepatic bile duct. MATERIALS AND METHODS: Fifty-six patients with suspected hepatic or pancreaticobiliary diseases and diagnosed as normal or benign pathologies were evaluated as having normal lymphatic systems. The protocol consisted of SPIR T2-weighted sequences with 3D-VISTA. The lymphatic systems were defined as fluid signal intensity structures and divided into eight portions and interobserver agreement was evaluated using weighted kappa statistics. Three readers graded the visualization of each portion using a five-point scale. The detectability of each portion was calculated by defining grades 1-2 as detectable and grades 3-5 as undetectable. RESULTS: Interobserver agreement regarding the visualization grades was moderate to almost perfect. All readers rated the detectability of the lymphatic systems of the superior and posterior portions of the pancreatic head, pericholedochal, right abdominoaortic, and interaorticovenous portions as 100%, and that of the anterior portion of the pancreatic head as 98.2%. For the inferior portion of the pancreatic head, the detectability was 100% for reader 2 and 96.4% for readers 1 and 3. CONCLUSION: The lymphatic systems located around the pancreatic head and extrahepatic bile duct could be sufficiently visualized on SPIR T2-weighted images with 3D-VISTA at 3.0-T.