Dynamic contrast-enhanced (DCE) MRI assessment of microvascular characteristics in the murine orthotopic pancreatic cancer model.

OBJECT: The aim of this study was to assess the dynamic contrast enhanced magnetic resonance imaging (DCE-MRI)-derived pharmacokinetic parameters between two contrast agents in a murine orthotopic pancreatic cancer model and to evaluate the tumor heterogeneity and the potential association between kinetic parameters and angiogenic markers such as the microvessel density (MVD) and vascular endothelial growth factor (VEGF) expression by immunohistochemistry. MATERIALS AND METHODS: Human pancreatic adenocarcinoma cell line MIAPaCa-2 was injected into the pancreas of BALB/C nu/nu mice. DCE-MRI was performed using Gd-DTPA and Gd-EOB-DTPA. Quantitative and semi-quantitative vascular parameters (K(trans), Kep, Ve and AUC) were calculated by using a dedicated postprocessing software program. Values were compared with tumor rim, tumor core and the entire tumor. The MVD and VEGF expressions between tumor rim and tumor core were also compared. RESULTS: There were no significant differences in K(trans), Kep, Ve, and AUC values of the three groups when using Gd-DTPA. However there were significant differences in K(trans), Kep, and AUC values of the three groups when using Gd-EOB-DTPA (P=0.014, 0.022, 0.007, respectively), in addition, the K(trans) and Kep values of tumor core were significantly lower than those of the entire tumor (adjusted P=0.014 and 0.027, respectively), the AUC values of core were significantly lower than those of the entire tumor and rim (adjusted P=0.039 and 0.009, respectively). Immunohistology results revealed that MVD and VEGF expression in the tumor rim was significantly higher than that in the core. There was positive correlation between AUC and MVD, VEGF. CONCLUSION: The murine orthotopic pancreatic cancer model provides an ideal animal model to study human pancreatic cancer. It can more sensitively semi-quantitatively and quantitatively analyze tumor angiogenesis through selecting the albumin-binding contrast agent.

Ultrastructural alterations in field carcinogenesis measured by enhanced backscattering spectroscopy.

Optical characterization of biological tissue in field carcinogenesis offers a method with which to study the mechanisms behind early cancer development and the potential to perform clinical diagnosis. Previously, low-coherence enhanced backscattering spectroscopy (LEBS) has demonstrated the ability to discriminate between normal and diseased organs based on measurements of histologically normal-appearing tissue in the field of colorectal (CRC) and pancreatic (PC) cancers. Here, we implement the more comprehensive enhanced backscattering (EBS) spectroscopy to better understand the structural and optical changes which lead to the previous findings. EBS provides high-resolution measurement of the spatial reflectance profile P(rs) between 30 microns and 2.7 mm, where information about nanoscale mass density fluctuations in the mucosa can be quantified. A demonstration of the length-scales at which P(rs) is optimally altered in CRC and PC field carcinogenesis is given and subsequently these changes are related to the tissue's structural composition. Three main conclusions are made. First, the most significant changes in P(rs) occur at short length-scales corresponding to the superficial mucosal layer. Second, these changes are predominantly attributable to a reduction in the presence of subdiffractional structures. Third, similar trends are seen for both cancer types, suggesting a common progression of structural alterations in each.

DNA ploidy and markovian analysis of neoplastic progression in experimental pancreatic cancer.

Computer-assisted analysis of DNA ploidy and nuclear morphology were used to elucidate changes in the cell nucleus that occur during the development of experimental pancreatic cancer. Ductal pancreatic adenocarcinoma was induced in 49 Syrian hamsters by SC injection of N-nitrosobis (2-oxopropyl) amine; twenty hamsters served as controls. Groups of animals were sacrificed every 4 weeks for 20 weeks and adjacent sections of pancreatic tissue were H&E and Feulgen-stained for light microscopy and computer assisted cytometry. Pancreatic ductal cells were classified as normal, atypical, or malignant; tissue inflammation (pancreatitis) was also noted when present. DNA ploidy and nuclear morphology evaluation (Markovian analysis) identified an atypical cell stage clearly distinguishable from either normal or malignant cells; pancreatitis preceded this atypia. The DNA ploidy histogram of these atypical cells revealed a major diploid peak and a minor aneuploid peak. The receiver operator characteristic curve areas for a logistic regression model of normal vs atypical cells was 0.94 and for atypical vs malignant was 0.98, numbers indicative of near-perfect discrimination among these three cell types. The ability to identify an atypical cell population should be useful in establishing the role of these cells in the progression of human pancreatic adenocarcinoma.

[Quantitative assessment of beta-cell ultrastructure from mono- and polyhormonal insulinomas]. / Kolichestvennaia otsenka ul'trastruktury beta-kletok mono- i poligormonal'nykh insulinom.

Surgical biopsies from 21 patients with syndrome of organic hyperinsulinism were studied. Precise quantitative characteristics of "typical" and "atypical" beta-granules in tumor cells were obtained by means of quantitative and qualitative analysis. The criteria for establishing the tumor type (mono- or polyhormonal) and the degree of hormonal activity are established. The validity of these criteria is confirmed by positive correlation between the secretory activity of the tumor and insulin level in the patient's blood.

Rapid assessment of Diff-Quik-stained pancreatic aspirates. A retrospective study of 40 intraoperative fine needle aspiration consultations, with measurement of nuclear size of look-alike small tissue fragments by image analysis.

Pancreatic cytomorphology based on Papanicolaou-stained smears has been studied extensively; however, studies on Diff-Quik-stained pancreatic smears are rather limited. Air-dried, Diff-Quik-stained smears lack crisp nuclear details, the cells are flattened on the slides, and the nuclei appear large and hyperchromatic. Between January 1988 and June 1992, 40 cases of intraoperative pancreatic fine needle aspirates were assessed by Diff-Quik stain. The objective of this study was to find practical clues applicable to the rapid and accurate assessment of Diff-Quik-stained pancreatic aspirates for intraoperative consultations. All cases were reviewed and correlated with histopathology. In particular, three cases that proved to be adenocarcinoma on subsequent frozen section but were not so diagnosed during intraoperative fine needle aspiration evaluation were analyzed. The nuclear sizes of small tissue fragments with overlapping nuclei, including three cases of normal pancreatic acini (mean diameter, 0.98, 1.17 and 1.04 x RBCs; coefficient of variation, 0.53, 0.83 and 0.62 x RBCs), 2 cases of islet cell tumor (mean diameter, 1.19 and 1.32 x RBCs; coefficient of variation, 1.88 and 1.4 x RBCs) and 3 cases of adenocarcinoma (mean diameter, 1.55, 1.86 and 1.72 x RBCs; coefficient of variation, 1.5, 1.7 and 1.9 x RBCs) were obtained with an image analyzer. The adjacent RBCs served as internal size controls. In Diff-Quik-stained, air-dried smears we relied on the accurate identification of pancreatic acini, which had the same size as the adjacent RBCs. Islet cell tumors had slightly larger nuclei, which were much more variable in size. The nuclei of adenocarcinoma were much larger than the surrounding RBCs and also showed marked variation in size. The composition of the pancreatic aspirate is important: ductal epithelium predominates in ductal carcinoma, and acini predominate in pancreatitis.