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![Diagram of vascular anatomy of pituitary gland. SHA, Superior hypophyseal artery; IHA, inferior hypophyseal artery. [Reproduced with permission from R. M. Bergland and R. B. Page: Science 204:18-24, 1979 (238). © American Association for the Advancement of Science.]](profile/Jean-Chayvialle/publication/13223683/figure/fig2/AS:601656756547593@1520457557300/Diagram-of-vascular-anatomy-of-pituitary-gland-SHA-Superior-hypophyseal-artery-IHA.png)
Diagram of vascular anatomy of pituitary gland. SHA, Superior hypophyseal artery; IHA, inferior hypophyseal artery. [Reproduced with permission from R. M. Bergland and R. B. Page: Science 204:18-24, 1979 (238). © American Association for the Advancement of Science.]
Source publication
Endocrine tumors are characteristically hypervascularized. This property recalls that of normal endocrine tissues, which possess a dense and specialized capillary network. The cellular and molecular mechanisms of the angiogenesis process associated with endocrine tumorigenesis are poorly known. Most normal endocrine cells constituvely express high...
Context in source publication
Context 1
... unusual in receiving a dual blood supply, unlike the majority of other tissues in which angiogenesis has been studied. The main vascular source is the hypothalamo-hypophyseal portal system carrying blood with releasing and inhibitory factors from the hypothalamus. There is also a direct arterial blood supply derived from the systemic vasculature (Fig. 4). The source of the blood supply to tumors is currently unknown, raising further questions regarding the source of new tumor vessel formation and potential for alteration in hormonal regulatory feedback ...
Citations
... In CT and MRI with multiphase acquisition, these tumors are typically more conspicuous during the early arterial phase of the scan. [9] However, it is important to note that this is not universally applicable to all cases of biliary NETs. Due to the non-specific nature of radiologic findings, the definitive diagnosis is usually made post-operatively through histological and immunohistochemical examination of the surgical specimen. ...
... In CT and MRI with multiphase acquisition, these tumors are typically more conspicuous during the early arterial phase of the scan. [9] However, it is important to note that this is not universally applicable to all cases of biliary NETs. Due to the non-specific nature of radiologic findings, the definitive diagnosis is usually made post-operatively through histological and immunohistochemical examination of the surgical specimen. ...
... Indeed, understanding the malignant risk in incidental NETs is essential to select an appropriate management strategy. In previous articles on this topic, authors have preferentially focused on the imaging appearance of various NETs including the benign and malignant types in symptomatic subjects [11,15,33,36,37]. However, whether those observations can be applied to NETs that are incidentally detected in asymptomatic patients is unclear. ...
The objective of our study was to evaluate the MDCT features of incidentally detected neuroendocrine tumors (NETs) of the pancreas, identify features that can predict tumor biology or aggressiveness and long-term outcome, and determine the incidence of "nonbenign" behavior.
In this retrospective study, 60 histologically verified pancreatic NETs incidentally detected with contrast-enhanced MDCT were included. Various MDCT features such as size, morphology, enhancement, and presence of calcifications were evaluated and were correlated with tumor biology on histopathology. The sensitivity, specificity, predictive values, and accuracy were calculated for MDCT features in predicting nonbenign biology and risk of recurrence.
A total of 32 of 60 (53%) NETs were nonbenign: most were large (mean, 29.1 mm) with a solid or complex pattern. NET size of 3 cm or larger yielded a positive predictive value of 61% for nonbenign tumors and 100% when calcification was present. In 12 patients with recurrence, 92% of NETs were nonbenign. The presence of calcification, local invasion, main pancreatic duct dilatation, vascular invasion, and lymph node enlargement along with angioinvasion and a Ki-67 index greater than 2% on histology were associated with a nonbenign diagnosis and a higher risk of recurrence.
Approximately 50% of incidental NETs show uncertain or malignant behavior. Solid tumors 3 cm or larger are commonly nonbenign; however, about 30% of tumors smaller than that size cutoff can be malignant. Nonbenign tumors and those with invasive features on MDCT have a higher incidence of recurrence.
... Indeed, understanding the malignant risk in incidental NETs is essential to select an appropriate management strategy. In previous articles on this topic, authors have preferentially focused on the imaging appearance of various NETs including the benign and malignant types in symptomatic subjects [11,15,33,36,37]. However, whether those observations can be applied to NETs that are incidentally detected in asymptomatic patients is unclear. ...
Objective:
The purpose of this study is to describe the MDCT findings of anomalous pulmonary venous drainage (APVD) in a pediatric population using a 256-MDCT dual-source scanner with a high-pitch protocol.
Conclusion:
MDCT is a fast and noninvasive technique that allows detailed and comprehensive visualization of APVD characteristics in a pediatric population. High-pitch acquisitions with scanners using a high volume of coverage permit low radiation doses and are an accurate modality for assessing these patients.
... Unenhanced scans are generally performed to evaluate for the presence of calcification or hemorrhage within the lesions and to plan the cranial-to-caudal extent for the subsequent dynamic phase acquisitions following contrast agent injection. As GEP-NETs and their metastases are often hypervascular, they are usually more conspicuous in the early arterial phase of the acquisition (40,41). A multiphase acquisition is, therefore, more appropriate to evaluate these tumors (42,43). ...
Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are a heterogeneous group of neoplasms that arise from cells of the diffuse neuroendocrine system and are characterized by a wide spectrum of clinical manifestations. All NETs are potentially malignant but differ in their biologic characteristics and the probability of metastatic disease. The pathologic classification of these tumors relies on their proliferation and differentiation. In the past decades, several nomenclatures have been proposed to stratify neuroendocrine tumors, but the World Health Organization classification is the one that is most widely accepted and used. The diagnosis of neuroendocrine tumor relies on clinical manifestation, laboratory parameters, imaging features, and tissue biomarkers in a biopsy specimen. With improved understanding of the natural history and lesion biology, management of GEP-NETs has also evolved. Although surgery remains the only potentially curative therapy for patients with primary GEP-NETs, other available treatments include chemotherapy, interferon, somatostatin analogs, and targeted therapies. Recent improvements in both morphologic and functional imaging methods have contributed immensely to patient care. Morphologic imaging with contrast agent-enhanced multidetector computed tomography and magnetic resonance imaging is most widely used for initial evaluation and staging of disease in these patients, whereas functional imaging techniques are useful both for detection and prognostic evaluation and can change treatment planning. ©RSNA, 2013.
... Tumor growth is highly dependent on the development of a vascular supply, and blood vessel growth regulators have been shown to play a key role in the progression of many tumors (7). Like normal endocrine tissue, endocrine tumors often have a dense capillary network (8). This high vascular density results in the characteristic enhancement feature, which has been described at contrast material-enhanced computerized tomography (CT) (9)(10)(11). ...
To prospectively correlate multidetector computed tomographic (CT) perfusion measurement of pancreatic endocrine tumors with tumor microvascular density (MVD) assessed by using histologic techniques and to determine whether perfusion CT parameters differ between tumor grades.
Institutional review board approval and informed consent were obtained. Thirty-six patients (15 men, 21 women; mean age, 53 years; range, 18-78 years) with resectable pancreatic endocrine tumors underwent presurgical dynamic perfusion CT. Twenty-eight (78%) of 36 patients were included in the study group; eight were excluded because of artifacts that were not compatible with perfusion postprocessing. Multidetector CT perfusion data were analyzed to calculate tumor and normal pancreatic blood flow, blood volume, mean transit time, and permeability-surface area product. Multidetector CT perfusion parameters were compared with intratumoral MVD by using the Spearman correlation coefficient and with World Health Organization (WHO) classification, tumor size, tumor proliferation index, hormonal profile, and presence of metastases by using Mann-Whitney tests.
High correlation (r = 0.620, P < .001) was observed between tumor blood flow and intratumoral MVD. Blood flow was significantly higher (P = .02) in the group of benign tumors (WHO 1) than in the groups of tumors of indeterminate prognosis (WHO 2) or well-differentiated carcinomas (WHO 3). Blood flow was significantly higher in tumors with a proliferation index of 2% or less (P = .005) and in those without histologic signs of microscopic vascular involvement (P = .008). Mean transit time was longer in tumors with lymph node (P = .02) or liver (P = .05) metastasis.
Perfusion CT is feasible in patients with pancreatic endocrine tumors and reflects MVD. Perfusion CT measurements are correlated with histoprognostic factors, such as proliferation index and WHO classification.
... This association can be due to the dependence of early angiogenesis on VEGF (the angiogenic switch) that may be lost as carcinogenesis progresses, reflecting the less critical role of VEGF on an already initiated process, 31 the need for other angiogenic factors (ie, matrix metalloproteinases), or the loss of antiangiogenic regulators. 12,33 Finally, we found no ER immunostaining in any EPT, excluding its utility as a marker of benign behavior, as suggested in breast, ovarian, and colon cancer, 16,17,34 or its possible role as a regulator of apoptosis and angiogenesis, according to some proapoptotic and antiangiogenic properties previously attributed to this receptor. 35,36 In conclusion, topo II␣ is a potentially useful marker of malignancy that can help the clinician to formulate a more specific approach for the search for metastasis and that can facilitate the early administration of adjuvant chemotherapy and/or somatostatin analogs. ...
Context.—Endocrine pancreatic tumors (EPTs) are rare lesions with varying biological behavior. Establishing malignancy is a challenge for clinicians and pathologists.
Objective.—To establish the role of proliferative, apoptotic, angiogenic, and hormonal markers as predictors of malignancy in EPTs.
Design.—Paraffin-embedded EPT samples were studied for prognostic markers.
Patients.—Twenty-one consecutive patients with a diagnosis of EPT.
Main Outcome Measures.—The proliferative fraction (topoisomerase IIα), microvascular density (CD34), vascular endothelial growth factor expression, and estrogen receptor-beta (ERβ) expression were studied by immunohistochemistry on all EPTs. Apoptosis was also assessed with terminal deoxynucleotidyl transferase nick-end labeling.
Results.—We identified 13 benign and 8 malignant tumors. Topoisomerase IIα was significantly increased in malignant tumors (P = .001), while there were no differences in apoptosis, microvascular density, or vascular endothelial growth factor expression in association with malignancy. No correlation could be identified between microvascular density and vascular endothelial growth factor expression, and ERβ was not detected. A receiver operating characteristic curve for topoisomerase IIα disclosed that above a labeling index of 13, the test had 88% sensitivity and 100% specificity for predicting malignancy.
Conclusion.—Cellular proliferation measured with topoisomerase IIα is a simple prognostic marker for malignancy in EPTs, unlike apoptosis, angiogenesis, or the presence of ERβ, which were not associated with malignant behavior. These findings designate a defined field for future research on endocrine pancreatic carcinogenesis and a possible target for chemotherapeutic agents.
The purpose of this study was to assess the value of intravoxel incoherent motion and diffusion-weighted imaging for predicting the histologic grade of pancreatic neuroendocrine tumors (PNETs).
Forty patients with surgically diagnosed PNETs who underwent preoperative magnetic resonance imaging, including diffusion-weighted imaging with a series of 10 b values (0-1000 s/mm), were included in this institutional review board-approved retrospective study. The apparent diffusion coefficient (ADCtotal), the intravoxel incoherent motion parameters (pure diffusion coefficient [D], pseudodiffusion coefficient [D*], and perfusion fraction [f]) were measured on the tumors. Histologic grading was performed on the basis of the World Health Organization 2010 classification system. Logistic regression analysis and receiver operating curve analysis were performed to identify the significant factors predicting the histologic grades.
Grades 2 and 3 tumors were significantly larger than grade 1 tumors (average 3.62 cm vs 2.17 cm in diameter; P = 0.001). Grades 2 and 3 tumors showed significantly lower D values than did grade 1 tumors (0.95 vs 1.21 × 10 mm/s; P = 0.009), although the ADCtotal showed no significant difference. When any of the following 2 criteria was used, (a) tumor size smaller than 2.0 cm in diameter and (b) D value greater than 1.2 × 10 mm/s, the sensitivity, specificity, and positive predictive value for diagnosing grade 1 PNETs were 76.92%, 100%, and 100%, respectively.
Pure diffusion coefficient (D) is possibly a better marker than ADCtotal is for differentiating grade 1 from grade 2 or 3 PNET and, combined with tumor size, can predict grade 1 PNET with a high specificity.
Introduction:
Therapeutic angiogenesis is a strategy of inducing new collateral vessels and stimulating new capillaries that enhance tissue oxygen exchange in ischemic cardiovascular disorders, including acute myocardial infarction, chronic cardiac ischemia, peripheral artery disease and stroke.
Areas covered:
Over the last 10 years, promising results of early clinical trials have generated great expectation on the potential of therapeutic angiogenesis. However, even if large randomized placebo-controlled and double-blinded Phase II clinical trials have confirmed the feasibility, safety and potential effectiveness of therapeutic angiogenesis, they provided very limited evidence of its efficacy in terms of clinical benefit.
Expert opinion:
Results of the latest trials on therapeutic angiogenesis have not provided satisfactory results. Much is still unknown about the optimal delivery of angiogenic factors. Trials using alternative growth factors, dose regimens and methods of delivery are needed to enhance the treatment benefit of therapeutic angiogenesis.
To investigate the effects of melatonin on cellular proliferation and endogenous vascular endothelial growth factor (VEGF) expression in pancreatic carcinoma cells (PANC-1).
PANC-1 cells were cultured for this study. The secreted VEGF concentration in the culture medium was determined using ELISA method, VEGF production in the tumor cells was detected by immunocytochemistry, and VEGF mRNA expression was determined by RT-PCR.
Higher melatonin concentrations significantly inhibited cellular proliferation, with 1 mmol/L concentration exhibiting the highest inhibitory effect (P<0.01). VEGF concentrations in the cell culture supernatants and intra-cellules were all significantly reduced after melatonin (1 mmol/L) incubation (P<0.05). VEGF mRNA expression decreased markedly in a time-dependent manner during the observation period (P<0.05).
High melatonin concentrations markedly inhibited the proliferation of pancreatic carcinoma cells. The endogenous VEGF expression was also suppressed by melatonin incubation.
