Detection Of Pancreatic Carcinoma Research Articles

Extracellular Vesicles as Potential Biomarkers for Early Detection and Diagnosis of Pancreatic Cancer.

Pancreatic carcinoma (PC) is highly metastatic, and it tends to be detected at advanced stages. Identifying and developing biomarkers for early detection of PC is crucial for a potentially curative treatment. Extracellular vesicles (EVs) are bilayer lipid membrane-structured nanovesicles found in various human bodily fluids, and they play important roles in tumor biogenesis and metastasis. Cancer-derived EVs are enriched with DNA, RNA, protein, and lipid, and they have emerged as attractive diagnostic biomarkers for early detection of PC. In this article, we provided an overview of the cell biology of EVs and their isolation and analysis, and their roles in cancer pathogenesis and progression. Multiplatform analyses of plasma-based exosomes for genomic DNA, micro RNA, mRNA, circular RNA, and protein for diagnosis of PC were critically reviewed. Numerous lines of evidence demonstrate that liquid biopsy with analysis of EV-based biomarkers has variable performance for diagnosis of PC. Future investigation is indicated to optimize the methodology for isolating and analyzing EVs and to identify the combination of EV-based biomarkers and other clinical datasets, with the goal of improving the predictive value, sensitivity, and specificity of screening tests for early detection and diagnosis of PC.

Diagnostic Significance of Serum IgG Galactosylation in CA19-9-Negative Pancreatic Carcinoma Patients.

Background: Although Carbohydrate antigen 19-9 (CA19-9) is considered clinically useful and informative for pancreatic carcinoma (PC), false positive results, and false negative results have restricted its clinical use. Especially missed or delayed diagnosis of PC patients with negative CA19-9 value limited the utility. To improve prognosis of PC patients, the discovery of reliable biomarkers to assist CA19-9 is desired. Serum IgG galactosylation based on our previous report was altered in PC patients comparing to healthy controls. The objective of this study was to explore the diagnostic significance of IgG galactosylation in assisting CA19-9 for PC in a comprehensive way.Methods: Serum IgG galactosylation profiles were analyzed by MALDI-MS in cohort 1 (n = 252) and cohort 2 in which all CA19-9 levels were negative (n = 133). In each cohort, not only healthy controls and PC patients but also benign pancreatic disease (BPD) patients were enrolled. Peaks were acquired by the software of MALDI-MS sample acquisition, followed by being processed and analyzed by the software of Progenesis MALDI. IgG Gal-ratio, which was calculated from the relative intensity of peaks G0, G1, and G2 according to the formula (G0/(G1+G2×2)), was employed as an index for indicating the distribution of IgG galactosylation.Results: The Gal-ratio was elevated in PC comparing with that in non-cancer group (healthy controls and BPD). The area under the receiver operating characteristic curve (AUC) of IgG Gal-ratio was higher than that of CA19-9 (0.912 vs. 0.814). The performance was further improved when Gal-ratio and CA19-9 were combined (AUC: 0.928). Meanwhile, Gal-ratio also had great diagnostic value with a sensitivity of 92.31% (AUC: 0.883) in detection of PC at early stage. Notably, IgG Gal-ratio has great sensitivity (90.63%) and specificity (76.81%) in CA19-9-negative PC patients.Conclusions: IgG Gal-ratio had a great performance in detection of PC and could be used to assist CA19-9 in improving diagnosis performance through early stage detection, differentiation from BPD, and PC diagnosis with CA19-9-negative level.

The role of selected chemokines and their specific receptors in pancreatic cancer

Pancreatic carcinoma is a highly malignant disease associated with an extremely poor prognosis, which is caused by late presentation, aggressive invasion and metastases, as well as the detection of pancreatic carcinoma in its advanced stages. Thus, better understanding of the tumour biology of this malignancy is sorely needed to improve the clinical outcome. A great challenge for the medical practice is finding a new biomarker of pancreatic carcinoma that will be helpful in diagnosis, in prognosis and in making clinical decisions, including the assessment of patients' response to therapy. It is suggested that selected chemokines and their specific receptors play an important role in tumour progression, such as tumour growth, angiogenesis, proliferation and development of metastasis. In the present review, general characteristics of chemokines and their specific receptors as well as the significance of these molecules in tumour development are described. The crucial issue of this review is to summarise the importance of various chemokines and their specific receptors in pancreatic carcinoma. Understanding the role of chemokines in the pathogenesis of pancreatic carcinoma is extremely important since these proteins may be used as a potential tool in the diagnosis and prognosis of pancreatic carcinoma patients.

Detectiono of Pancreatic Carcinoma and Liver Metastases with Contrast-Enhanced Ultrasonography: Comparison with Contrast-Enhanced Multi-Detector Row CT

To compare Contrast-enhanced ultrasonography with contrast material-enhanced multi-detector row computed tomography (CT) in detection of pancreatic carcinoma and liver metastases. This study included 60 patients (48 men, 12 women; mean age, 63.2 years) consisting of 40 patients with pathologically confirmed pancreatic carcinoma (mean size, 3.6 cm) and 20 without a pancreatic lesion. seventy-six liver metastases (mean size, 1.5 cm) in 20 patients with pancreatic carcinoma were diagnosed at pathologic examination or multimodality assessment. Three readers blinded to the final diagnosis interpreted all contrast-enhanced ultrasonography and contrast-enhanced CT images and graded the presence (or absence) of pancreatic carcinoma and liver metastasis on patient-by-patient and lesion-by-lesion bases. Receiver operating characteristic analysis, to compare the diagnostic performance of contrast-enhanced ultrasonography and CT imaging. No significant differences were observed between CT and contrast-enhanced ultrasonography in depiction of pancreatic carcinoma. However, contrast-enhanced ultrasonography had greater sensitivity in depicting liver metastasis than did CT (P<0.05) and in the lesion-by-lesion analysis (P<0.05). Contrast-enhanced ultrasonography was equivalent to dynamic contrast-enhanced CT in depicting pancreatic carcinoma and had better sensitivity for depicting liver metastases, suggesting the usefulness of Contrast-enhanced ultrasonography for evaluation of patients with pancreatic carcinoma.

Diagnostic Accuracy of Computed Tomography Scan Keeping Endoscopic Ultrasound for Detection of Pancreatic Carcinoma

Diagnostic Accuracy of Computed Tomography Scan Keeping Endoscopic Ultrasound for Detection of Pancreatic Carcinoma

The Clinical Detection of Pancreatic Carcinoma: A Comparison of the Standard Biomarkers to that of a Newer Class of Biomarkers used for both Diagnosis and Therapy

One of the characteristics that defines many malignancies that metastasize via the circulatory system, is their ability to shed surface membrane proteins into the blood stream where they can be detected as tumor markers. The primary clinical application associated with defining these tumor markers, many representing carbohydrate antigens, has been in their use for specifically monitoring the status of the patient, in terms of their response to therapy. In the more than 40 years of the clinical measuring what we term tumor markers, none have been defined that are of value in their ability to help the clinician to diagnose the presence of an existing malignancy. Rather, their role has been assigned to that of a monitoring function. It appears essential that the ideal tumor marker, when defined, should be able detect the presence of an established tumor, as well as characterize the clinical state of such an existing neoplasm. This same marker should more importantly be expressed only in the malignant state and not be associated with inflammatory conditions developing in normal tissue adjacent to the tumor. In general, those markers presently available for clinical use are carbohydrate in origin, showing up in many conditions unrelated to the presence of cancer. Their use has been relegated to monitoring the clinical course of a known malignancy in terms of response or lack of to a therapeutic approach: that is radiation or chemotherapy. When the proper target proteins which are in the process of being defined and are detected by monoclonal antibodies directed against a specific epitope on the protein, the same monoclonal used for detection, when delivered intravenously can hunt, seek and destroy the existing neoplasm.

Metabolite detection of pancreatic carcinoma by in vivo proton MR spectroscopy at 3T: initial results

The authors sought to identify metabolic features of pancreatic carcinoma by in vivo proton magnetic resonance (MR) spectroscopy at 3 Tesla. Forty healthy volunteers and 40 patients with pancreatic carcinoma confirmed by histopathology underwent T2-weighted imaging for localisation of the single voxel. Respiration-triggered (1)H MR spectroscopy was used to detect metabolites in normal pancreas and cancerous tissue. All spectral data were processed with SAGE software. Unsuppressed water at 4.7 ppm was used as an internal reference to determine metabolite concentrations. Each ratio among the different peak areas was statistically evaluated between normal pancreas and pancreatic carcinoma. The following five groups of spectra were detected: unsaturated fatty acids (-CH = CH-) at 5.4 ppm; residual water at 4.7 ppm; choline metabolites at 3.2 ppm; unsaturated fatty acids (-CH2-CH = CH-) or a combination of N-acetylaspartate (NAA), N-acetylaspartylglutamate (NAAG), glutamine, glutamate, macromolecules and unsaturated fatty acids (-CH2-CH = CH-) at 2.0 ppm and lipids at 1.3 ppm. Ratio of lipids to unsuppressed water in normal pancreas was statistically greater than that in pancreatic cancer (p=0.004). Ratio of choline to unsuppressed water in normal pancreas was statistically greater than that in pancreatic cancer (p=0.0001). Ratio of fatty acids (-CH = CH-) to lipids in normal pancreas was statistically lower than that in pancreatic cancer (p=0.006). Compared with normal pancreas, pancreatic carcinoma has a higher ratio of fatty acids (-CH = CH-) to lipids and lower ratios of lipids to unsuppressed water and choline to unsuppressed water at 3T.

Detection of Pancreatic Carcinoma and Liver Metastases with Gadoxetic Acid–enhanced MR Imaging: Comparison with Contrast-enhanced Multi–Detector Row CT

To intraindividually compare gadoxetic acid-enhanced magnetic resonance (MR) imaging with contrast material-enhanced multi-detector row computed tomography (CT) in detection of pancreatic carcinoma and liver metastases. The ethics committee approved this retrospective study with waiver of informed consent. This study included 100 patients (53 men, 47 women; mean age, 67.8 years) consisting of 54 patients with pathologically confirmed pancreatic carcinoma (mean size, 33 mm) and 46 without a pancreatic lesion. Sixty-two liver metastases (mean size, 10 mm) in 15 patients with pancreatic carcinoma were diagnosed at pathologic examination or multimodality assessment. Three readers blinded to the final diagnosis interpreted all MR (precontrast T1- and T2-weighted and gadoxetic acid-enhanced dynamic and hepatocyte phase MR images) and tetraphasic dynamic contrast-enhanced CT images and graded the presence (or absence) of pancreatic carcinoma and liver metastasis on patient-by-patient and lesion-by-lesion bases. Receiver operating characteristic analysis, McNemar test, and Fisher test were performed to compare the diagnostic performance of CT and MR imaging. No significant differences were observed between CT and MR images in depiction of pancreatic carcinoma. However, MR imaging had greater sensitivity in depicting liver metastasis than did CT for two of the three readers in the MR imaging-versus-CT analysis (85% vs 69%, P = .046) and for all three readers in the lesion-by-lesion analysis (92%-94% vs 74%-76%, P = .030-.044). Gadoxetic acid-enhanced MR imaging was equivalent to dynamic contrast-enhanced CT in depicting pancreatic carcinoma and had better sensitivity for depicting liver metastases, suggesting the usefulness of gadoxetic acid-enhanced MR imaging for evaluation of patients with pancreatic carcinoma.

Synthesis and Ex Vivo Autoradiographic Evaluation of Ethyl-β-d-galactopyranosyl-(1,4′)-2′-deoxy-2′-[18F]fluoro-β-d-glucopyranoside—A Novel Radioligand for Lactose-Binding Protein: Implications for Early Detection of Pancreatic Carcinomas with PET

Previous studies demonstrated that the lactose-binding protein (hepatocellular carcinoma-intestine-pancreas and pancreatitis-associated proteins (HIP/PAP)) is upregulated >130 times in peritumoral pancreatic tissue as compared to normal pancreatic tissue. Therefore, we developed a new radiolabeled ligand of HIP/PAP, the ethyl-β-D-galactopyranosyl-(1,4')-2'-deoxy-2'-[¹⁸F]fluoro-β-D-glucopyranoside (Et-[¹⁸F]FDL) for noninvasive imaging of pancreatic carcinoma using positron emission tomography and computerized tomography (PET/CT). The novel precursor and radiolabeling methods for synthesis of Et-[¹⁸F]FDL produced no isomers; the average decay-corrected radiochemical yield was 68%, radiochemical purity >99%, and specific activity >74 GBq/µmol. The radioligand properties of Et-[¹⁸F]FDL were evaluated using an ex vivo autoradiography and immunohistochemistry in pancreatic tissue sections obtained from mice-bearing orthotopic pancreatic tumor xenografts. Et-[¹⁸F]FDL binding to peritumoral pancreatic tissue sections strongly correlated with HIP/PAP expression (r = 0.81) and could be completely blocked by treatment with 1 mM lactose. These results suggest that Et-[¹⁸F]FDL is a promising agent which should be evaluated for detection of early pancreatic carcinomas by PET/CT imaging.

Abstract 4622: PAM4-antigen levels in the serum of patients with pancreatic carcinoma: Early detection of disease and correlation with responses to radioimmunotherapy

Abstract Background: A serum-based enzyme immunoassay (EIA) employing MAb-PAM4 demonstrates high specificity and sensitivity for detection of advanced pancreatic carcinoma (PC). We are currently exploring use of the immunoassay as a means to detect early-stage PC, as well as detection of nascent disease progression or relapse during routine post-treatment follow-up. We now also report initial results that provide correlation of serum PAM4-antigen levels with responses to radiolabeled PAM4 therapy. Methods: The PAM4-based EIA was employed for detection and quantitation of antigen in the serum of pancreatic carcinoma patients with known stage of disease (N=68). An additional 11 patients with stage-4 disease who participated in an ongoing phase-1b clinical trial to evaluate the combination of 90Y-hPAM4 IgG, (clivatuzumab tetrexate) radioimmunotherapy with low-dose, radiosensitizing, gemcitabine (Gem) were also examined. Serum specimens from this latter group were collected at baseline prior to treatment, at the end of the 4-week treatment cycle, and again at 4 weeks post-treatment (week 8 from baseline), when a CT scan was performed to determine tumor response. Results: Overall, the sensitivity of the immunoassay for detection of PC was 81%, with a 5% false-positive rate for the healthy volunteers (N=19). When examined by stage of disease, sensitivity rates were 91%, 86% and 62% for stages 3/4 advanced disease, stage-2, and stage-1 PC, respectively. For those patients who had treatment with 90Y-hPAM4 + Gem, a decrease in antigen levels greater than 40%, observed at the end of the treatment cycle (4 weeks), with sustained decline in the antigen levels at the 8-week post-treatment evaluation, provided presumptive evidence of tumor response, either stable disease (SD, N=2) or partial response (PR, N=5) by CT RECIST criteria. None of the patients with progressive disease (N=4) had a sustainable decrease in serum levels of PAM4-antigen, whereas all of the responders did. The median decrease in serum PAM4-mucin levels at the 8-week follow-up evaluation timepoint was 54% (range: 47% - 98% decrease), with a median tumor response (only SD and PR responders) being a decrease in tumor size of 37% (range: 46% decrease to 4% increase), from a baseline median primary tumor size of 10.0 cm (range 2.6 - 12.1 cm). Conclusions: These results suggest that the PAM4-based immunoassay should be further evaluated for use in the detection of early pancreatic carcinoma, as well as to evaluate tumor response to therapy. (Supported in part by grant CA096924 from the NIH.) Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4622.

Detection of Pancreatic Carcinomas by Imaging Lactose-Binding Protein Expression in Peritumoral Pancreas Using [18F]Fluoroethyl-Deoxylactose PET/CT

BackgroundEarly diagnosis of pancreatic carcinoma with highly sensitive diagnostic imaging methods could save lives of many thousands of patients, because early detection increases resectability and survival rates. Current non-invasive diagnostic imaging techniques have inadequate resolution and sensitivity for detection of small size (∼2–3 mm) early pancreatic carcinoma lesions. Therefore, we have assessed the efficacy of positron emission tomography and computer tomography (PET/CT) imaging with β-O-D-galactopyranosyl-(1,4′)-2′-deoxy-2′-[18F]fluoroethyl-D-glucopyranose ([18F]FEDL) for detection of less than 3 mm orthotopic xenografts of L3.6pl pancreatic carcinomas in mice. [18F]FEDL is a novel radioligand of hepatocarcinoma-intestine-pancreas/pancreatitis-associated protein (HIP/PAP), which is overexpressed in peritumoral pancreatic acinar cells.Methodology/Principal FindingsDynamic PET/CT imaging demonstrated rapid accumulation of [18F]FEDL in peritumoral pancreatic tissue (4.04±2.06%ID/g), bi-exponential blood clearance with half-lives of 1.65±0.50 min and 14.14±3.60 min, and rapid elimination from other organs and tissues, predominantly by renal clearance. Using model-independent graphical analysis of dynamic PET data, the average distribution volume ratio (DVR) for [18F]FEDL in peritumoral pancreatic tissue was estimated as 3.57±0.60 and 0.94±0.72 in sham-operated control pancreas. Comparative analysis of quantitative autoradiographic images and densitometry of immunohistochemically stained and co-registered adjacent tissue sections demonstrated a strong linear correlation between the magnitude of [18F]FEDL binding and HIP/PAP expression in corresponding regions (r = 0.88). The in situ analysis demonstrated that at least a 2–4 fold apparent lesion size amplification was achieved for submillimeter tumors and to nearly half a murine pancreas for tumors larger than 3 mm.Conclusion/SignificanceWe have demonstrated the feasibility of detection of early pancreatic tumors by non-invasive imaging with [18F]FEDL PET/CT of tumor biomarker HIP/PAP over-expressed in peritumoral pancreatic tissue. Non-invasive non-invasive detection of early pancreatic carcinomas with [18F]FEDL PET/CT imaging should aid the guidance of biopsies and additional imaging procedures, facilitate the resectability and improve the overall prognosis.

Detection of early-stage pancreatic carcinoma

4613 Background: Invasive pancreatic carcinoma is a virtually lethal disease, mostly because of the failure to detect it at a sufficiently early timepoint for successful treatment. Our laboratory has identified a unique biomarker detected by MAb PAM4 that shows high specificity for a mucin glycoprotein expressed by pancreatic carcinoma (PC). While identified in almost 90% of PC and its precursor lesions, the antigen is not detectable in normal pancreas. We are investigating this biomarker for the early detection of PC. Methods: Both immunohistochemical (IHC) and enzyme immunoassay (EIA) were employed for detection and/or quantitation of PAM4-mucin in tissue and sera, respectively. Results: We have extended our prior IHC results with precursor lesions (Clin Cancer Res 2007;13:7380–7); PAM4 gave an intense, diffuse labeling pattern in 81% of mucinous cystic neoplasms (MCN), with an additional 11% showing a focal pattern (n=27). Thus, a total of 92% of MCN showed evidence of PAM4-antigen expression. Of interest, a difference in the labeling pattern was observed in association with the grade of dysplasia, providing easy identification of MCN with high- grade dysplasia. We previously reported use of an EIA for quantitation of PAM4-antigen in sera. The assay demonstrated a sensitivity and specificity of 77% and 95%, respectively, for identification of PC (J Clin Oncol, 2006;24:252–8). We have now confirmed these results in a set of serum specimens (n= 49 PC, 13 normal) for which staging information was available. Overall specificity and sensitivity were 82% and 85%, respectively, calculated by ROC curve analysis (AUC=0.878±0.045; 95% CI=0.769–0.947). Although only a small number of specimens were from patients with stage I disease (n=12), 92% of these were above the cutoff value for positive response. A correlation was observed for average concentration of antigen in the circulation with stage of disease (R2=0.988). Conclusions: IHC and EIA results indicate that PAM4 identifies a biomarker for PC that is present at the earliest stages of neoplastic transformation, thus warranting controlled analyses of larger specimen numbers. (Supported in part by USPHS grant CA096924 from the NIH.) [Table: see text]

Hochauflösende Bildgebung beim Pankreaskarzinom: Prospektiver Vergleich von MRT und 4-Zeilen-Spiral-CT

To evaluate multislice-CT versus MRI in the diagnosis and staging of pancreatic carcinoma in a prospective multi-reader analysis. Fifty patients with suspected pancreatic carcinoma underwent both multislice-CT (4-Row, "hydro-technique") and state-of-the-art MRI (two 1.5 T units). In correlation with histopathologic findings or in case of a non-lesion diagnosis by follow-up (6-month interval), we evaluated MRI versus CT in a multi-reader analysis (2 reader pairs) for: 1. diagnostic quality; 2. examination time; 3. accuracy of potential resectability; 4. kappa analysis of observer variations; and 5. overall diagnostic reliability. A total of 28 lesions (n = 22 malignant, n = 6 benign) were present in the cohort group versus 22 patients without a focal lesion (n = 10 pancreatitis, n = 12 no tumor). For lesion detection, CT had a sensitivity of 100/89 % (reader pair 1/2) and specificity of 77 %, and MRI had a sensitivity of 75/89 % and specificity of 77/73 %. For the subgroup of adenocarcinomas of the pancreas (n = 17), we found a sensitivity of 100 % and a specificity of 61 % for CT versus a sensitivity of 82/94 % and a specificity of 67/61 % for MRI. The accuracy for determining the resectability was 91/82 % for CT and 90/82 % for MRI. The kappa analysis showed a good correlation for CT (0.71) and a moderate correlation of both groups for MRI (0.49). CT and MRI showed comparable results in the detection of pancreatic carcinomas as well as in the determination of resectability. Chronic pancreatitis as a "tumor-like-lesion" was the major factor of a missed diagnosis. The results of multi-reader analysis for both reading groups were almost identical with a moderate to good kappa correlation. There is no reason to prefer MRI (more expensive) over CT for patients with the presumptive diagnosis of pancreatic cancer.

Pancreatic ductal carcinoma-specific genes identified by DNA microarray analysis with ductal cells

Pancreatic ductal carcinoma (PDC) remains the most intractable disorder amonggastroenterological malignancies, with a 5-year survival rate of <5%. Given the low 5-year survival rate even of individuals with small, resectable tumors, the sensitivity of current technologies is not sufficient to allow detection of pancreatic carcinoma at curable early stages. A cure for this disorder will thus depend on development of an approach that is able to detect tumors at an early stage of carcinogenesis. DNA microarray analysis allows the simultaneous monitor[ng of the expression of thousands of genes and is therefore a potentially suitable approach to identify PDC-specific genes. The high throughput of this methodology also may be disadvantageous, however. Without careful selection of samples for analysis or data normalization procedures, DNA microarray experiments yield a large number of pseudopositive and pseudonegative results We therefore adopted the strategy of background-matched population (BAMP) screening, in which the sample characteristics are matched as closely as possible, with the exception of the feature of interest (in this case, transformation), before microarray analysis. To achieve this goal, we purified pancreatic carcinoma cells and normal ducta[ cells from pancreatic juice with the use of affinity chromatography based on the shared surface marker MUC1. Analysis of these background-matched samples with DNA microarrays representing 33000 human genes resulted in the identification of several carcinoma-specific genes, including those for AC133 and carcinoembryonic antigen-related cell adhesion molecule 7 (CEACAM7) Cancer-specific expression of these genes was confirmed by quantitative real-time polymerase chain reaction analysis. Microarray analysis with purified pancreatic ducta[ cells has thus provided a basis for the development of a sensitive method for the detection of PDC that relies on pancreatic juice, which is routinely obtained in the clinical setting

Detection of pancreatic carcinoma: diagnostic value of K-ras mutations in circulating DNA from serum.

Somatic activating mutations at codon 12 of the K-ras gene are present in the majority of exocrine pancreatic cancers and occur early in tumorgenesis. The aim of this study was to test the feasibility of using a mutated K-ras gene from the serum as a potential tumor marker for detection of exocrine pancreatic carcinoma. Codon 12 K-ras mutations were examined in DNA extracted from the sera of 20 patients with pancreatic carcinomas, six patients with chronic pancreatitis, and five healthy individuals. K-ras gene mutations at codon 12 were detected in the sera of 14 of 20 patients with pancreatic carcinoma and in none of the six patients with chronic pancreatitis, or in the five healthy controls. Elevation of either CA19-9 or K-ras mutation was detected in 19/20 patients. These results suggest that K-ras abnormalities in serum could be used as a potential tumor marker in patients with a pancreatic lesion. The absence of K-ras mutations in serum and presence of CA19-9 in the normal range make the diagnosis of pancreatic cancer unlikely.

P53 autoantibodies in patients with pancreatitis and pancreatic carcinoma.

In human pancreatic carcinoma (PCa) mutations in the p53 tumor suppressor gene are present in up to 50% of cases. Conformational change and cellular accumulation, together with subsequent release of mutant and normal p53 protein from transformed cells, may initiate a B-cell response with generation of circulating autoantibodies to p53 protein (anti-p53). In the present study we analyzed the sera of 85 consecutive patients with acute pancreatitis (N = 19), chronic pancreatitis (N = 33), and PCa (N = 33) to evaluate the specificity of autoantibodies to p53 protein as a serological marker for PCa. Detection of anti-p53 was performed using an enzyme-linked immunosorbent assay system with immobilized recombinant wild-type p53 protein. Autoantibodies to p53 were detectable in 1 of 19 patients with acute (5.3%) and in 4 of 33 patients with chronic pancreatitis (12.1%). All anti-p53-positive patients with acute or chronic pancreatitis were carefully examined and no underlying malignant disease was found. During follow-up (range, 281-647 days; mean, 472 days) none of these patients showed any evidence for subsequent development of PCa or any other malignant disease. In patients with PCa, anti-p53 was detected in 6 of 33 cases, resulting in a sensitivity of 18.2% with a specificity of 90.4%. In contrast to anti-p53, detection of serum carbohydrate antigen (CA 19-9) resulted in a sensitivity and specificity of 69.7 and 71.2% (CA 19-9, > 37 U/ml) and 51.5 and 96.2% (CA 19.9, > 100 U/ml) for the detection of PCa, respectively. Taken together, the sensitivity of anti-p53 formation was low in patients with PCa (18.2%). Furthermore, the detection of anti-p53 was not specific for malignancy, indicating that severe inflammatory processes may also induce anti-p53 formation.

Endoscopic Ultrasound-Guided Fine Needle Aspiration in the Diagnosis and Staging of Pancreatic Tumors

Endoscopic ultrasound (EUS) is useful in the detection of pancreatic carcinoma. One of its major limitations is the lack of specificity for malignancy, both for the primary tumor and for associated lymph nodes due to its inability to distinguish malignant infiltration from benign inflammation. EUS-guided fine needle aspiration (FNA) has now been developed, which allows for a tissue diagnosis of the primary tumor as well as lymph nodes, liver metastasis, and peritoneal/pleural fluid. The addition of EUS-guided FNA, with the specificity of a tissue diagnosis, to the high sensitivity and vascular assessment of EUS alone makes this the modality of choice for the diagnosis and staging of pancreatic carcinoma. The results of preliminary studies along with discussion regarding the technique, safety, cytologic adequacy, diagnostic accuracy, clinical utility, and future trends of EUS-guided FNA in pancreatic tumors are presented.

Small pancreatic adenocarcinomas: efficacy of MR imaging with fat suppression and gadolinium enhancement.

To compare the efficacy of fat-suppressed T1-weighted magnetic resonance (MR) imaging and dynamic MR imaging in the diagnosis of small pancreatic adenocarcinomas. Pancreatic adenocarcinomas in 15 patients were evaluated with dynamic computed tomography (CT) and five MR imaging sequences that included fat-suppressed T1-weighted technique and dynamic multiplanar gradient-recalled acquisition in the steady state technique. The difference in contrast-to-noise ratios between tumor and normal pancreas was significantly different (P < .05) between the five MR imaging sequences used. In six patients, the combination of dynamic MR imaging and fat-suppressed imaging was superior to dynamic CT in the detection of tumors. Tumors accompanied by chronic pancreatitis were less distinct on fat-suppressed images but were clearly visible on dynamic MR images. Peripancreatic extension of tumors was better recognized on T1-weighted images and CT scans than on fat-suppressed images. Fat-suppressed T1-weighted images and dynamic MR images were useful in the detection of pancreatic carcinomas. T1-weighted images and CT scans were superior in the evaluation of tumor extension.

Angiographic Evaluation of Pancreatic Carcinoma

There is considerable divergence of opinion regarding the reliability of angiography in the evaluation of adenocarcinoma of the pancreas. The incidence of angiographic abnormalities in proved cases ranges from 90 per cent in a retrospective analysis by Lunderquist (1) to 29 per cent in a prospective analysis by Nebesar and Pollard (3). Ranniger and Saldino (4) reported positive findings in 58 per cent of cases. Moskowitz et al. (2) emphasized the difficulty in distinguishing the angiographic features of chronic pancreatitis from those of carcinoma. In view of these conflicting reports, we recently reviewed our own angiographic experience in pancreatic carcinoma. The results indicate that pancreatic angiography is reliable in the detection of pancreatic carcinoma, usually reliable in differentiating carcinoma from pancreatitis, and helpful in evaluating inoperability. Material and Methods Since 1964, 300 patients with suspected pancreatic carcinoma have had angiographic evaluation at The University of Michigan Medical Center or Wayne County General Hospital. Forty-one of these patients had a final diagnosis of carcinoma of the pancreas, with histologic confirmation in 36. In 5 patients, clinical and angiographic features were sufficiently characteristic to justify the diagnosis of pancreatic carcinoma, although for a variety of reasons histologic confirmation was not obtained. The clinical records and angiograms of these 41 patients were reviewed. In addition, records and arteriograms were reviewed in 9 patients in whom a false positive angiographic diagnosis of carcinoma was made. Cases of ampullary carcinoma and cholangiocarcinoma, although angiographically similar to pancreatic carcinoma, are not included in this study. Data for this report are also derived from an angiographic study of 51 cases of pancreatitis by Reuter et al. (5), and from review of angiograms in 28 cases of pancreatitis studied at The University of Michigan Medical Center. Angiographic features which were specifically studied included: 1. Encasement: Abnormal arterial narrowing, suggestive of compression or invasion by an adjacent neoplasm. Although more frequently smooth (Fig. 2), encasement may appear serpiginous or serrated (Figs. 1 and 4). Serrated irregularity is usually recognized in large vessels, while serpiginous encasement is seen in small vessels. 2. Pathologic Vessels: Very small vessels of abnormal course and irregular caliber. Some of these vessels probably represent neovascularity (Figs. 2 and 6). Other represent deformed or invaded pre-existing vessels and the appearance merges with that of small vessel encasement. 3. Arterial Obstructions: May be seen in large arteries (celiac, superior mesenteric, hepatic, splenic, gastroduodenal) (Fig. 3) or small arteries of less then 2 mm diameter (pancreaticoduodenal arcades, dorsal pancreatic, pancreatico magna and their branches) (Fig. 5).