NCI CANCERLIT^® Search: Diagnosis-Histopathology-Pathogenesis of Pancreatic Cancer - September 2001

Last Modified: November 1, 2001

[Contrast enhanced power Doppler sonography: comparison of various administration forms of the ultrasound contrast agent Levovist]
Histopathological study on mechanism and background of tumor-forming pancreatitis.
[Ultrafast magnetic resonance tomography changes the standard in pancreas diagnosis]
[Imaging of intraductal papillary mucinous tumor of the pancreas: literature review]
Irofulven (6-hydroxymethylacylfulvene, MGI 114) induces caspase 8 and 9-mediated apoptosis in human pancreatic adenocarcinoma cells.
Characterization of human mucin gene MUC4 promoter: importance of growth factors and proinflammatory cytokines for its regulation in pancreatic cancer cells.
Reversion of transcriptional repression of Sp1 by 5 aza-2' deoxycytidine restores TGF-beta type II receptor expression in the pancreatic cancer cell line MIA PaCa-2.
Physical activity, obesity, height, and the risk of pancreatic cancer.
Surveillance of pre-malignant disease of the pancreatico-biliary system.
Real-time quantitative PCR of telomerase mRNA is useful for the differentiation of benign and malignant pancreatic disorders.
Correlation between TGF-beta1 and p21 (WAF1/CIP1) expression and prognosis in resectable invasive ductal carcinoma of the pancreas.
CD95-related apoptotic machinery is functional in pancreatic cancer cells.
Growth rate of pancreatic adenocarcinoma: initial clinical experience.
Clinical management of intraductal papillary mucinous tumors of the pancreas based on imaging findings.
Pancreatic acinar cell carcinoma.
Expression of p73 and p63 proteins in pancreatic adenocarcinoma: p73 overexpression is inversely correlated with biological aggressiveness.
[Imaging of neuroendocrine tumors]
[Diagnosis and treatment of pancreatic carcinoma in the region of Amsterdam Comprehensive Cancer Care Center in 1997]
[Diagnostics and treatment of distal bile duct or pancreatic carcinoma; guidelines of the Amsterdam and Twente Comprehensive Cancer Centers]
Cell cycle effects of nonsteroidal anti-inflammatory drugs and enhanced growth inhibition in combination with gemcitabine in pancreatic carcinoma cells.
Incidence of cancer of the pancreas, extrahepatic bile duct and ampulla of Vater in the United States, before and after the introduction of laparoscopic cholecystectomy.
Molecular biology of pancreatic cancer: potential clinical implications.
Tumor cell lysate-pulsed human dendritic cells induce a T-cell response against pancreatic carcinoma cells: an in vitro model for the assessment of tumor vaccines.
Diagnosis of pancreatic cancer-EUS/FNA to the rescue?
Dose-response relation between acrylamide and pancreatic cancer.
The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines.
Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer.
Cysts and tumors of the pancreas.
State-of-the-art ultrasonography is as accurate as helical computed tomography and computed tomographic angiography for detecting unresectable periampullary cancer.
Alteration of the Langerhans islets in pancreatic cancer patients.
Cystic pancreatic neoplasms: computed tomography and magnetic resonance imaging findings.
Clinical significance of soluble form of HLA class I molecule in Japanese patients with pancreatic cancer.
Intraductal papillary components in invasive ductal carcinoma of the pancreas are associated with long-term survival of patients.
Deletion at 3p25.3-p23 is frequently encountered in endocrine pancreatic tumours and is associated with metastatic progression.
Intraoperative ultrasound and preoperative localization detects all occult insulinomas; discussion 1025-6.
Sister Mary Joseph's sign.

CancerMail from the National Cancer Institute

1
UI - 20333154
AU - Kratzer W; Kachele V; Merkle E; Mason RA; Buchner M; von Tirpitz C; Pfeiffer M
TI - [Contrast enhanced power Doppler sonography: comparison of various administration forms of the ultrasound contrast agent Levovist]
SO - Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 2000 May;172(5):443-8
AD - Abt. Innere Medizin I, Universitatsklinikum Ulm. wolfgang.kratzer@medizin.uni-ulm.de
PURPOSE: Objective of the present study was the comparison of various administration forms of the ultrasound contrast medium Levovist with regard to duration and intensity of contrast enhancement in patients with tumors of the liver or pancreas. PATIENTS AND METHODS: Seven patients with tumors of the liver or pancreas were examined prospectively using power Doppler sonography. Ultrasound contrast enhancement was achieved using Levovist (8 ml, 400 mg/ml) in three different administration forms: 1st as a bolus injection through the main channel, 2nd through the injection valve of an intravenous cannula, or 3rd as a continuous infusion. Semiquantitative evaluation of the degree of contrast enhancement over the course of the examination was conducted by three independent examiners. RESULTS: Levovist, administered by continuous infusion, resulted in a significantly longer average period of contrast enhancement (9:43 min (extratumoral), 7:34 min (intratumoral)) than did the same dosage administered as a bolus injection through the main channel (6:01 min (extratumoral), 4:54 min (intratumoral), p = 0.0156 (extratumoral); p = 0.0313 (intratumoral), but contrast intensity was decreased. Bolus injection through the injection valve of the i.v. cannula was associated with decreased duration and intensity of contrast enhancement compared with injection through the main channel. CONCLUSION: Compared with bolus injection, the continuous infusion of Levovist resulted in a significant prolongation of the duration but in a decreased intensity of contrast enhancement. Administration of Levovist through the injection valve does not result in optimal contrast enhancement and is therefore not recommended.

2
UI - 21317169
AU - Takase M; Suda K
TI - Histopathological study on mechanism and background of tumor-forming pancreatitis.
SO - Pathol Int 2001 May;51(5):349-54
AD - Department of Pathology, Juntendo University School of Medicine, Tokyo, Japan.
Fifteen cases of tumor-forming pancreatitis, detected as tumors by diagnostic imaging or by physical examination were histologically examined. Eleven of the 15 patients were heavy drinkers. Tumorous lesions were located in the head of the pancreas in 11 cases and in the body or tail of the pancreas in four cases. Macroscopic examination revealed tumorous swelling or sclerotic appearance in the pancreatic tissue. Histologically, these lesions showed tumorous swelling with (n = 12) or without (n = 3) a background of chronic pancreatitis. In the former, the tumorous lesions consisted of extensive fibrosis, including necrosis or abscesses, stones and reparative granulation tissue, and there was a successive transition to the surrounding chronic pancreatitis pattern. The latter three tumorous lesions presented with inter- and intralobular fibrosis with lymphoid hyperplasia or lymphoplasmacytic infiltration and were adjacent to normal pancreatic tissue. Therefore, tumor-forming pancreatitis shows at least two distinct types: a reparative tumorous swelling with a background of chronic pancreatitis, which is considered to have given rise to the tumor at some stage; and a lymphoid and fibrous proliferation in normal pancreatic tissue, which is considered to represent an autoimmune-related disease process.

3
UI - 21362741
AU - Richter A; Gaa J; Niedergethmann M; Georgi M; Trede M; Post S
TI - [Ultrafast magnetic resonance tomography changes the standard in pancreas diagnosis]
SO - Chirurg 2001 Jun;72(6):697-703
AD - Chirurgische Klinik, Universitatsklinikum Mannheim, Klinische Fakultat der Universitat Heidelberg, Mannheim. a.richter@stk-hildesheim.de
BACKGROUND: Since the introduction of MRI, including imaging of the hepato-pancreatic duct system (MRCP) and 3D-MR angiography (3D-MRA), new pancreatic diagnostic procedures have been developed. METHODS AND PATIENTS: We report on 143 patients with benign and malignant diseases of the pancreas, who only received MRI preoperatively. All radiologic findings were confirmed intraoperatively. RESULTS: For resectability, MRI obtained sensitivity of 96.0% and specificity of 89.5% and for classification sensitivity of 99.1% and specificity of 95.2%. CONCLUSION: Based on our experience, the benign vs malignant nature of the disease, MRI is a safe and reliable method for pancreatic tumors being able to become the standard diagnostic procedure in the future.

4
UI - 21342215
AU - Valette O; Cuilleron M; Debelle L; Antunes L; Mosnier JF; Regent D; Veyret C
TI - [Imaging of intraductal papillary mucinous tumor of the pancreas: literature review]
SO - J Radiol 2001 Jun;82(6 Pt 1):633-45
AD - Service de Radiologie, Hopital Nord, 42055 Saint-Etienne, Cedex, France.
Intraductal papillary-mucinous tumor (IPMT) is defined as a syndrome consisting of dilatation of the main pancreatic duct and/or branch ducts associated with mucin overproduction. The purpose was to evaluate the usefulness of different imaging techniques (CT, EUS, ERCP) for determination of tumor invasion and pancreatic extension. Diagnosis often is delayed because it is confused with chronic pancreatitis or cystic neoplasms of the pancreas. It is difficult to rule out invasive malignancy. MRCP can be an essential imaging modality because it is a non-invasive technique. Intraductal ultrasound or pancreatoscopy could become in the future an additional useful preoperative procedure. A high frequency of invasive carcinoma in patients operated for pancreatic IPMT is observed. Surgical resection should be extended until a normal tissue margin is encountered.

5
UI - 21388220
AU - Wang W; Waters SJ; MacDonald JR; Von Hoff DD; Strodel WE; Miller AR
TI - Irofulven (6-hydroxymethylacylfulvene, MGI 114) induces caspase 8 and 9-mediated apoptosis in human pancreatic adenocarcinoma cells.
SO - Anticancer Res 2001 May-Jun;21(3B):1789-94
AD - Department of Surgery, University of Texas Health Science Center at San Antonio, 78229, USA.
BACKGROUND: Irofulven (MGI 114) is a novel, clinically active sesquiterpene whose mechanism of action is not fully understood. We sought to identify apoptotic effectors induced by this agent in human pancreatic cancer cells. MATERIALS AND METHODS: MTT assay was used to assess IC50-Apoptosis was quantitated by flow cytometry and DAPI staining. Caspase activation was identified by western blot analysis. RESULTS: Irofulven was cytotoxic against all pancreatic cancer cell lines tested (IC50 1-18 microM), and induced 10-fold (4%+/- 2, vs. 41% +/- 5) induction of apoptosis. Irofulven-treated cells also demonstrated PARP3 cleavage and DAPI staining. Apoptosis was reduced to baseline levels by Z-VAD-FMK, a broad-spectrum caspase inhibitor. Western blot analysis revealed that caspases-3, -7, -8, and -9 were activated by irofulven. Time course evaluation demonstrated that caspases-8 and -9 were the initial species activated. CONCLUSION: Our data demonstrate that the cytotoxicity of irofulven in human pancreatic carcinoma cell lines is mediated by caspase-induced apoptosis.

6
UI - 21391979
AU - Perrais M; Pigny P; Ducourouble MP; Petitprez D; Porchet N; Aubert JP; Van Seuningen I
TI - Characterization of human mucin gene MUC4 promoter: importance of growth factors and proinflammatory cytokines for its regulation in pancreatic cancer cells.
SO - J Biol Chem 2001 Aug 17;276(33):30923-33
AD - Unite INSERM 377, Place de Verdun, 59045 Lille Cedex, France.
The human mucin gene MUC4 encodes a large transmembrane mucin that is thought to play important roles in tumor cell biology and that is overexpressed in human pancreatic carcinomas. In this report, we describe the structure and functional activity of the 5'-flanking region, including 1.0 kilobase of the promoter. The long 5'-untranslated region (2.7 kilobases) is characterized by a high content of GC in its 3'-end. The first TATA box was located at -2672/-2668. Multiple transcription start sites and a high density of putative binding sites for Sp1 (GC and CACCC boxes), AP-1/-2/-4, cAMP-responsive element-binding protein, GATA, GR, and STAT transcription factors were found within the 5'-flanking region. Transcriptional activity of the promoter was assessed using pGL3-luciferase deletion mutants in two MUC4-expressing (CAPAN-1 and CAPAN-2) and one nonexpressing (PANC-1) pancreatic cancer cell line. Two highly active fragments (-219/-1 and -2781/-2572) that drive MUC4 transcription in CAPAN-1 and CAPAN-2 cells were identified. Gel retardation assays indicated that Sp1 and Sp3 bind to cognate cis-elements found in the 5'-flanking region and that Sp1 transactivates, whereas Sp3 inhibits the GC-rich region (-464/-1) in CAPAN-2 cells. Activation of protein kinase C with phorbol ester and treatment of cells with epidermal growth factor and transforming growth factor-alpha resulted in up-regulation of the promoter. Tumor necrosis factor-alpha and interferon (IFN)-gamma inflammatory cytokines had no or mild effect on MUC4 transcriptional activity when used alone. However, a very strong synergistic effect (10-12-fold activation) between IFN-gamma and tumor necrosis factor-alpha or IFN-gamma and transforming growth factor-alpha was obtained in CAPAN-2 cells. Altogether these results demonstrate that the 5'-flanking region of MUC4 contains epithelial cell-specific, positive, and negative regulatory cis-elements, that Sp1/Sp3 are important regulators of MUC4 basal expression, and that its regulation in pancreatic cancer cells involves complex interplay between several signaling pathways.

7
UI - 21397973
AU - Venkatasubbarao K; Ammanamanchi S; Brattain MG; Mimari D; Freeman JW
TI - Reversion of transcriptional repression of Sp1 by 5 aza-2' deoxycytidine restores TGF-beta type II receptor expression in the pancreatic cancer cell line MIA PaCa-2.
SO - Cancer Res 2001 Aug 15;61(16):6239-47
AD - Department of Surgery, University of Texas Health Science Center, San Antonio, Texas 78229-3900, USA.
The pancreatic cancer cell line, MIA PaCa-2 is not responsive to transforming growth factor beta (TGF-beta) because of a lack of expression of the TGF-beta type II receptor (RII). We show that the lack of RII expression is caused by a deficit of the transcription factor Sp1. Nuclear run-off assays and Western immunoblot showed low levels of transcription and protein levels of Sp1, respectively. Treatment of MIA PaCa-2 cells with the DNA methyl transferase inhibitor, 5-aza-2'-deoxycytidine, resulted in an increase in the rate of Sp1 transcription, in Sp1 protein expression, and in the binding of Sp1 to the RII promoter. Ectopic expression of Sp1 cDNA in MIA PaCa-2 cells led to an increase in RII promoter-chloramphenicol acetyltransferase activity and RII expression. Expression of Sp1 cDNA also caused a reduction in both growth and clonogenicity that was associated with restoration of responsiveness to TGF-beta. Conversely, cells that express RII (BxPC-3 and MIA PaCa-2 Sp1 transfectants) when treated with mithramycin, an inhibitor of Sp1 binding, showed a reduction in RII mRNA expression. The reduction of RII mRNA was attributed to a decrease in RII promoter-chloramphenicol acetyltransferase activity that was associated with a decrease in Sp1 binding to the RII promoter. These data indicate that transcriptional repression of the Sp1 gene in MIA PaCa-2 cells plays a role in the transcriptional inactivation of the RII gene and thus lack of responsiveness to TGF-beta.

8
UI - 21400907
AU - Michaud DS; Giovannucci E; Willett WC; Colditz GA; Stampfer MJ; Fuchs CS
TI - Physical activity, obesity, height, and the risk of pancreatic cancer.
SO - JAMA 2001 Aug 22-29;286(8):921-9
AD - National Cancer Institute, 6120 Executive Blvd, EPS Room 7026, Rockville, MD 20852, USA. michaudd@mail.nih.gov
CONTEXT: Diabetes mellitus and elevated postload plasma glucose levels have been associated with an increased risk of pancreatic cancer in previous studies. By virtue of their influence on insulin resistance, obesity and physical inactivity may increase risk of pancreatic cancer. OBJECTIVE: To examine obesity, height, and physical activity in relation to pancreatic cancer risk. DESIGN AND SETTING: Two US cohort studies conducted by mailed questionnaire, the Health Professionals Follow-up Study (initiated in 1986) and the Nurses' Health Study (initiated in 1976), with 10 to 20 years of follow-up. PARTICIPANTS: A total of 46 648 men aged 40 to 75 years and 117 041 women aged 30 to 55 years who were free of prior cancer at baseline and had complete data on height and weight. MAIN OUTCOME MEASURES: Relative risk of pancreatic cancer, analyzed by self-reported body mass index (BMI), height, and level of physical activity. RESULTS: During follow-up, we documented 350 incident pancreatic cancer cases. Individuals with a BMI of at least 30 kg/m(2) had an elevated risk of pancreatic cancer compared with those with a BMI of less than 23 kg/m(2) (multivariable relative risk [RR], 1.72; 95% confidence interval [CI], 1.19-2.48). Height was associated with an increased pancreatic cancer risk (multivariable RR, 1.81; 95% CI, 1.31-2.52 for the highest vs lowest categories). An inverse relation was observed for moderate activity (multivariable RR, 0.45; 95% CI, 0.29-0.70 for the highest vs lowest categories; P for trend <.001). Total physical activity was not associated with risk among individuals with a BMI of less than 25 kg/m(2) but was inversely associated with risk among individuals with a BMI of at least 25 kg/m(2) (pooled multivariable RR, 0.59; 95% CI, 0.37-0.94 for the top vs bottom tertiles of total physical activity; P for trend =.04). CONCLUSION: In 2 prospective cohort studies, obesity significantly increased the risk of pancreatic cancer. Physical activity appears to decrease the risk of pancreatic cancer, especially among those who are overweight.

9
UI - 21255260
AU - Friess H; Holzinger F; Liao Q; Buchler MW
TI - Surveillance of pre-malignant disease of the pancreatico-biliary system.
SO - Best Pract Res Clin Gastroenterol 2001 Apr;15(2):285-300
AD - Department of Visceral and Transplantation Surgery, University of Bern, Bern, Inselspital, Switzerland.
Technical advancements in ultrasonography, contrast-enhanced computed tomography and magnetic resonance imaging, as well as the wider availability of these ultramodern imaging techniques, have resulted in the early detection and a better classification of various asymptomatic and symptomatic pancreatico-biliary lesions. Pre-malignant biliary and pancreatic lesions are rare disorders, and no clear data are available to define their malignant potential. Because of the lack of controlled epidemiological data, the time span for malignant transformation and its frequency cannot be defined in the majority of these lesions. Adenomyomatosis of the gallbladder and gallbladder polyps larger than 10 mm should be treated by cholecystectomy even in asymptomatic patients because of an increased risk of malignant transformation. Chronic cholangitis, primary sclerosing cholangitis and choledochal cysts are also pre-malignant conditions. The timing of surgery, once it is advised for a pre-malignant condition that is still benign, should, however, be individualized to the particular patient situation. In patients with chronic pancreatitis, surgery may be indicated for disease-related complications. In as much as chronic pancreatitis predisposes to a higher risk of pancreatic cancer, any suspicion of malignancy should warrant a surgical exploration. Intraductal papillary tumours and mucin-producing pancreatic tumours are other pre-malignant pancreatic lesions whose malignant potential cannot be precisely determined pre-operatively. They should be resected in situations where there is a high degree of suspicion even without a clear objective diagnosis. In conclusion, pre-malignant hepato-biliary and pancreatic lesions of uncertain pathology should undergo early resection in view of treatment limitations and the dismal prognosis of established cancers. While hepato-biliary and pancreatic surgery is nowadays performed in specialized centres, with a low post-operative morbidity and mortality, it is equally important to understand that observation alone with regular computed tomography or magnetic resonance imaging control can no longer be recommended in the management of these lesions. Copyright 2001 Harcourt Publishers Ltd.

10
UI - 21241385
AU - Buchler P; Conejo-Garcia JR; Lehmann G; Muller M; Emrich T; Reber HA; Buchler MW; Friess H
TI - Real-time quantitative PCR of telomerase mRNA is useful for the differentiation of benign and malignant pancreatic disorders.
SO - Pancreas 2001 May;22(4):331-40
AD - Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
The presence of telomerase activity has been proposed as a specific and sensitive marker for malignant tissue, and positivity rates of up to 95% have been reported in pancreatic cancer. In the present study telomerase activity analysis was reevaluated in 29 pancreatic cancer tissues compared with 36 chronic pancreatitis tissues and 21 normal controls, and a study was made of whether malignant and benign pancreatic disorders can be better differentiated using a novel technique real-time quantitative PCR analysis-analyzing telomerase mRNA expression. Telomerase activity was present in 35% (10 of 29) of pancreatic cancer samples, 3% (one of 36) of chronic pancreatitis samples, and none of the normal pancreatic tissue samples in the TRAP assay. Real-time quantitative PCR analysis revealed the presence of telomerase mRNA expression in 50% (10 of 20) of normal, 86% (31 of 36) of chronic pancreatitis, and 90% (26 of 29) of pancreatic cancer samples. However, quantification of the expression data revealed that the relative increase above normal was 5.5 (range, 3.5-8.6) for chronic pancreatitis and 23.9 (range, 18.6-30.7) for pancreatic cancer samples (p < 0.01). No relationship was found between telomerase activity and the fold increase of telomerase mRNA above normal and gender, patient age, tumor stage, or tumor grade. These data indicate that detection of telomerase activity using the TRAP assay has limitations in differentiating benign and malignant pancreatic disorders. However, telomerase mRNA analysis by real-time quantitative PCR analysis allows a highly sensitive detection and differentiation of pancreatic cancer from normal pancreas and chronic pancreatitis and thereby may serve as a new reliable, easy, and effective diagnostic tool for cancer diagnosis.

11
UI - 21241386
AU - Hashimoto K; Nio Y; Sumi S; Toga T; Omori H; Itakura M; Yano S
TI - Correlation between TGF-beta1 and p21 (WAF1/CIP1) expression and prognosis in resectable invasive ductal carcinoma of the pancreas.
SO - Pancreas 2001 May;22(4):341-7
AD - First Department of Surgery, Shimane Medical University, Izumo, Japan.
Transforming growth factor-beta1 (TGF-beta1) inhibits the growth of a variety of epithelial cells; however, in many types of tumors it loses its inhibitory effect. p21(WAF1/CIP1), one of the cyclin-dependent kinase (Cdk) inhibitors induced by TGF-beta1, is considered a downstream effector of the growth-inhibitory function of TGF-beta1. We assessed the clinicopathologic significance of TGF-beta1 and p21 expression in resectable invasive ductal carcinoma (IDC) of the pancreas. Immunohistochemical examination of the expression of TGF-beta1 and p21 in 62 patients revealed positive expression of TGF-beta1 in 28 (45%) and of p21 in 25 (40%) of the 62 patients, and a significant correlation between the two expressions. The survival curve of patients with TGF-beta1(+) tumors was significantly higher than that of patients with TGF-beta1(-) tumors; p21(+) patients showed a higher survival curve than did p21(-) patients, but the difference was not statistically significant. Simultaneous analysis of TGF-beta1 and p21 expression showed that the patients with TGF-beta1(+)/p21(+) tumors had a significantly better prognosis than the others. Multivariate analysis showed that TGF-beta1 was a significantly low risk factor for death due to IDC. The concurrent evaluation of TGF-beta1 and p21 expression would be an effective tool in the prediction of the prognosis of patients with pancreatic cancer.

12
UI - 21241388
AU - Glazyrin AL; Adsay VN; Vaitkevicius VK; Sarkar FH
TI - CD95-related apoptotic machinery is functional in pancreatic cancer cells.
SO - Pancreas 2001 May;22(4):357-65
AD - Department of Pathology, Karmanos Cancer Institute, Wayne State University School of Medicine, Detroit, MI 48201, USA.
The CD95 (FAS, Apo-1) system is a major death pathway in normal and tumor cells. Recent evidence indicates that pancreatic cancer cells express CD95R and CD95L but are insensitive to CD95-mediated apoptosis. Here we show that treatment of human pancreatic cancer cells with RNA synthesis inhibitor actinomycin D (ActD) converted the phenotype of cancer cells from CD95 resistant to CD95 sensitive. Flow cytometric analysis demonstrated that all pancreatic cancer cell lines studied responded with cell surface CD95R and CD95L upregulation to bleomycin treatment, and PANC1 (mt p53) cells demonstrated a dose-dependent response to interferon gamma and bleomycin treatment with CD95R and CD95L up-regulation. However, only bleomycin sensitized PANC1 cells to CD95-mediated apoptosis. Taxol sensitized PANC1 and HPAC cells to CD95-mediated apoptosis without surface up-regulation of CD95R. These data suggest that pancreatic cancer cells possess a p53-independent mechanism of CD95R and CD95L surface upregulation and that surface expression of CD95R is not predictive of apoptotic function. Protein extracts of HPAC and PANC1 cells treated for 24 hours with a combination of ActD/agonist anti-CD95 antibodies demonstrated significantly higher Acetyl-Asp-Glu-Val-Asp-ase (DEVDase) cleavage activity (caspase 3-like activity) than extracts from cells treated with ActD only. In the present study, we also investigated the time kinetics of DEVDase (caspase 3-like) activation in PANC1 (mt p53) and HPAC (wt p53) pancreatic cancer cell lines. We found that DEVDase activity in PANC1 cells responds to ActD and ActD/anti-CD95 antibodies earlier than in HPAC cells; however, at 24 hours HPAC cells demonstrated much stronger activation. Cytosolic protein extracts from untreated cells did not influence caspase 3-like activity when added to extracts from the ActD/anti-CD95 antibody-treated cells. Collectively, these data suggest that pancreatic cancer cells have functional CD95-related apoptotic machinery with preserved apoptotic signal transduction, CD95R upregulation. and caspase activation. However, this system is blocked by some unknown protein(s) that is either located in the organelle fraction of the cell and/or requires an intact cell for manifestation of its activity.

13
UI - 21241389
AU - Furukawa H; Iwata R; Moriyama N
TI - Growth rate of pancreatic adenocarcinoma: initial clinical experience.
SO - Pancreas 2001 May;22(4):366-9
AD - Department of Diagnostic Radiology, National Cancer Center Hospital, Tokyo, Japan. hsfuruka@gan2.ncc.go.jp
A better understanding of the growth rate of pancreatic carcinoma is important in determining its natural course and in evaluating the effects of treatment or prognosis. The authors studied the growth rate of pancreatic carcinoma and the relation between its tumor volume doubling time (TVDT) and host survival. Nine patients with pancreatic carcinoma who underwent serial examinations by helical computed tomography but no anticancer treatment during the observation period were included. The TVDTs were calculated by measuring the tumor size on the helical computed tomograms. The mean TVDT of the nine primary lesions of pancreatic carcinoma was 159 +/- 67 days (median, 144 days), and the range was 64 to 255 days. The correlation between TVDT and survival time was positive and significant (r = 0.793, p = 0.011). This preliminary study suggests that examination of TVDT may be useful in the clinical evaluation of prognosis for patients with pancreatic carcinoma in certain situations.

14
UI - 21241390
AU - Wakabayashi T; Kawaura Y; Morimoto H; Watanabe K; Toya D; Asada Y; Satomura Y; Watanabe H; Okai T; Sawabu N
TI - Clinical management of intraductal papillary mucinous tumors of the pancreas based on imaging findings.
SO - Pancreas 2001 May;22(4):370-7
AD - Department of Gastroenterology, Saiseikai Kanazawa Hospital, Japan.
The aim of this study was to assess the imaging findings of pathologically proven intraductal papillary-mucinous tumors of the pancreas and the natural history of follow-up cases, and to optimize the therapeutic management of patients with these tumors according to their imaging findings. All nine patients with main duct type tumors were histologically diagnosed as having adenocarcinoma or adenoma, with no hyperplastic lesion. The images failed to discriminate between the two histologic types. In 26 patients with branch duct type tumors, all but one with intraductal mural nodules or tumors of > or = 30 mm had adenocarcinoma or adenoma, regardless of the caliber of the main duct. Of the nine patients with tumors < 30 mm and no mural nodules. three had adenoma, and six had hyperplasia. All of four patients had hyperplasia, with the additional caliber of the main duct being < 6 mm. In a series of 23 cases in which the patient was followed-up, no apparent progression was found in 17 patients who had no mural nodules and tumors of < 30 mm. Given these results, patients with main duct type tumors, and those with branch duct type tumors showing mural nodules or a tumor diameter of > or = 30 mm, are at high risk of developing neoplasms, including adenocarcinoma, for which surgical resection should be considered, whereas those patients with tumors < 30 mm and no mural nodules can be followed.

15
UI - 21241492
AU - Ordonez NG
TI - Pancreatic acinar cell carcinoma.
SO - Adv Anat Pathol 2001 May;8(3):144-59
AD - The University of Texas M.D. Anderson Cancer Center, Houston 77030, USA.
Acinar cell carcinomas (ACCs) are rare neoplasms that represent less than 2% of all exocrine tumors of the pancreas. Although they occur more often in adults between the 5th and 7th decades of life, a few cases have been reported in children. Histologically, ACCs can resemble islet cell tumors, but they differ in their ultrastructural and immunohistochemical features. Although ACCs present a bland histology, they are highly malignant and the survival of patients with these tumors, even though better than that of those with ductal cell carcinomas, is generally poor.

16
UI - 21301537
AU - Ito Y; Takeda T; Wakasa K; Tsujimoto M; Sakon M; Matsuura N
TI - Expression of p73 and p63 proteins in pancreatic adenocarcinoma: p73 overexpression is inversely correlated with biological aggressiveness.
SO - Int J Mol Med 2001 Jul;8(1):67-71
AD - Department of Surgery, Osaka Seamen's Insurance Hospital, Minato-ku, Osaka 552-0021, Japan.
The significance of p53, a prominent tumor suppressor gene, and its product in various neoplasms including pancreatic adenocarcinoma has been established. We investigated the expression of two types of homologue of p53, p73 and p63, in pancreatic adenocarcinoma by means of immunohistochemistry. Overexpression of p73 was observed in 45.6% of the cases and this phenomenon was more frequently seen in cystic adenocarcinomas than in ductal carcinomas. Furthermore, p73 overexpression was inversely linked to lymph node metastasis, tumor size, and Ki-67 labeling index. On the other hand, p63 overexpression was observed in 68.2% of the cases, but was not related to any clinicopathological features. No correlation was established between the expression of these proteins and aberrant p53 expression. These results suggest that decreased expression of p73 protein and over-expression of p63 protein may play a role in the development of pancreatic adenocarcinoma.

17
UI - 21335446
AU - Gualdi GF; Casciani E; Polettini E
TI - [Imaging of neuroendocrine tumors]
SO - Clin Ter 2001 Mar-Apr;152(2):107-21
AD - Servizio TC-RM, I Clinica Medica, Universita degli Studi di Roma La Sapienza, Policlinico Umberto I, Roma, Italia.
Neuroendocrine tumors (NET) of the pancreas are distinguished in functional (85%) and non functional (15%) in relation to the production and release of the hormone produced. Functional tumors show early, because the neoplasm release the hormone produced when they are still small. Non functional tumors show late when the tumor grows. The localization and the evaluation of the extensive of these tumors has come fundamentally important both in correct presurgical detection and also in the diagnosis of metastases which excluded surgery. Also, as the survival of 20% of the patients with metastases is only five years, the use of non-invasive imaging techniques is very important for the evaluation of results of the various therapies (chemotherapy, interferon, somatostatin). Recent studies have shown that in patients with Zollinger-Ellison syndrome, SRS is the most sensitive non invasive method in localizing primitive tumors and metastases. The accuracy of this technique has not yet been provided in the study of tumors like insulinomas which do not have a high percentage of somatostatine receptors on their cell membranes. The sensitivity obtained in recent studies on a large number of patient and the low cost, lower than all the other imaging technique in use today, surely make SRS the first choice in the study of NET. Where SRS is negative and surgery is possible, Spiral CT or better still MRI is the best tool to check the results of chemotherapy in patients with hepatic metastases (already detected by SRS), because it is easier to compare the changes in size and morphology of metastases.

18
UI - 21377739
AU - Tilleman EH; Benraadt J; Bossuyt PM; Obertop H; Gouma DJ
TI - [Diagnosis and treatment of pancreatic carcinoma in the region of Amsterdam Comprehensive Cancer Care Center in 1997]
SO - Ned Tijdschr Geneeskd 2001 Jul 14;145(28):1358-62
AD - Afd. Chirurgie, Academisch Medisch Centrum, Postbus 22660, 1100 DD Amsterdam.
OBJECTIVE: To describe the diagnostic work-up and treatment of patients with a pancreatic carcinoma in the Amsterdam area, the Netherlands, particularly in general hospitals. DESIGN: Retrospective, descriptive. METHOD: During 1997, 286 patients with a pancreatic carcinoma were diagnosed in 20 hospitals in the Amsterdam area. Diagnostic work-up and treatment data were collected from the medical records and analysed. RESULTS: Ninety percent of the patients presented in one of the 17 general hospitals (n = 252; 132 men and 154 women; mean age: 70 years). Thirty-five percent of them underwent diagnostic investigations which did not focus directly on pancreatic pathology. Ultrasound was performed in 97% of patients (4% in combination with Doppler) and CT in 60% (4% spiral CT). Endoscopic retrograde cholangiopancreatography (ERCP) was performed in 39% of these patients and endoprostheses were only inserted in half the cases. Thirty-five percent of the patients who underwent both CT and ERCP underwent ERCP first. Ninety-nine patients (39%) were referred to a reference hospital for further investigation or treatment. The period between the first investigation and the histological diagnosis was 4 weeks. CONCLUSION: In the diagnostic work-up of patients with a pancreatic carcinoma, invasive diagnostic procedures were often performed before the non-invasive tests. Spiral CT was used minimally and ERCP was frequently performed without subsequent biliary drainage. The mean duration of diagnostic work-up was relatively long.

19
UI - 21377740
AU - Gouma DJ; Tilleman EH; Benraadt J; Bossuyt PM
TI - [Diagnostics and treatment of distal bile duct or pancreatic carcinoma; guidelines of the Amsterdam and Twente Comprehensive Cancer Centers]
SO - Ned Tijdschr Geneeskd 2001 Jul 14;145(28):1362-4
AD - Afd. Chirurgie, Academisch Medisch Centrum, Postbus 22.660, 1100 DD Amsterdam. d.j.gouma@amc.uva.nl
A project on the diagnostic work-up and treatment of distal bile duct and pancreatic carcinoma was carried out in the region covered by the Comprehensive Cancer Centre in Amsterdam, the Netherlands. It consisted of (a) describing the diagnostic work-up in the area, (b) developing the guidelines, (c) spreading the recommendations. The implementation and application of the guidelines are currently being evaluated.

20
UI - 21396314
AU - Yip-Schneider MT; Sweeney CJ; Jung SH; Crowell PL; Marshall MS
TI - Cell cycle effects of nonsteroidal anti-inflammatory drugs and enhanced growth inhibition in combination with gemcitabine in pancreatic carcinoma cells.
SO - J Pharmacol Exp Ther 2001 Sep;298(3):976-85
AD - Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. mtipschn@iupui.edu
Increased cyclooxygenase-2 (COX-2) expression in human pancreatic adenocarcinomas, as well as the growth-inhibitory effect of nonsteroidal anti-inflammatory drugs (NSAIDs) in vitro, suggests that NSAIDs may be an effective treatment for pancreatic cancer. Gemcitabine is currently the most effective chemotherapeutic drug available for patients with pancreatic cancer, but is only minimally effective against this aggressive disease. Clearly, other treatment options must be identified. To design successful therapeutic strategies involving compounds either alone or in combination with others, it is necessary to understand their mechanism of action. In the present study, we evaluated the effects of three NSAIDs (sulindac, indomethacin, and NS-398) or gemcitabine in two human pancreatic carcinoma cell lines, BxPC-3 (COX-2-positive) and PaCa-2 (COX-2-negative), previously shown to be growth-inhibited by these NSAIDs. Effects on cell cycle and apoptosis were investigated by flow cytometry or Western blotting. Treatment with NSAIDs or gemcitabine altered the cell cycle phase distribution as well as the expression of multiple cell cycle regulatory proteins in both cell lines, but did not induce substantial levels of apoptosis. Furthermore, we demonstrated that the combination of the NSAID sulindac or NS-398 with gemcitabine inhibited cell growth to a greater degree than either compound alone. These results indicate that the antiproliferative effects of NSAIDs and gemcitabine in pancreatic tumor cells are primarily due to inhibition of cell cycle progression rather than direct induction of apoptotic cell death, regardless of COX-2 expression. In addition, NSAIDs in combination with gemcitabine may hold promise in the clinic for the treatment of pancreatic cancer.

21
UI - 21404880
AU - Urbach DR; Swanstrom LL; Khajanchee YS; Hansen PD
TI - Incidence of cancer of the pancreas, extrahepatic bile duct and ampulla of Vater in the United States, before and after the introduction of laparoscopic cholecystectomy.
SO - Am J Surg 2001 Jun;181(6):526-8
AD - Department of Minimally Invasive Surgery and Surgical Research, Legacy Health System, Portland, Oregon, USA. david.urbach@uhn.on.ca
BACKGROUND: Some epidemiologic studies have identified cholecystectomy as a risk factor for pancreatic and biliary cancer. METHODS: We compared the incidence of cancers of the pancreas, extrahepatic bile duct and ampulla of Vater before and after the widespread adoption of laparoscopic cholecystectomy in the United States in 1991, when the use of cholecystectomy increased dramatically. RESULTS: Compared with 1980 to 1991, there was no increase in the incidence of cancer of the pancreas (adjusted incidence rate ratio [IRR] 0.97, 95% confidence interval [CI] 0.94 to 0.99) or extrahepatic bile duct (IRR 0.80, 95% CI 0.74 to 0.87) during 1992 to 1996. There was a small increase in the incidence of ampullary cancer (IRR 1.14, 95% CI 1.03 to 1.26). CONCLUSIONS: We did not find clear evidence of a short-term increase in the incidence of cancers of the pancreas, bile duct, and ampulla of Vater, that was attributable to the increased use of cholecystectomy.

22
UI - 21411407
AU - Sakorafas GH; Tsiotos GG
TI - Molecular biology of pancreatic cancer: potential clinical implications.
SO - BioDrugs 2001;15(7):439-52
AD - Department of Surgery, Hellenic Air Force Hospital, Athens, Greece. georgesakorafas@yahoo.com
The development of cancer involves the accumulation of genetic changes. Over the past decade there has a been spectacular advance in the knowledge of the genetic basis of cancer, mainly as a result of the rapid progression of molecular technology. Pancreatic cancer is one of the most lethal cancers. Conventional therapeutic approaches have not had much impact on the course of this aggressive neoplasm. Knowledge of the molecular biology of pancreatic cancer has grown rapidly. Genetic alterations in pancreatic cancer include oncogene mutations (most commonly K-ras mutations), and tumour suppressor gene alterations (mainly p53, p16, DCC, etc.). These advances have potential implications for the management of this deadly disease. Identification of a hereditary genetic predisposition to pancreatic cancer has led to the formation of pancreatic cancer registries around the world, with voluntary screening of patients and siblings for the hereditary genetic defect. Asymptomatic population screening remains unrealistic, but the recognition of subpopulations at increased risk from pancreatic cancer, along with novel and sensitive detection techniques, means that targeted population screening is a step closer. Intensive research is performed in specialist laboratories to improve the diagnostic approach in patients with pancreatic cancer. The use of such molecular diagnostic methods is likely to expand. Molecular biology may also have a great impact on the treatment of pancreatic cancer, and many therapeutic approaches are being evaluated in clinical trials, including gene replacement therapy, genetic prodrug activation therapy, antisense immunology and peptide technology. The 'molecular age' has the promise of delivering still better results. This review summarises recent data relating to the molecular biology of pancreatic cancer, with emphasis on features that may be of clinical significance for diagnosis and/or therapy.

23
UI - 21413550
AU - Schnurr M; Galambos P; Scholz C; Then F; Dauer M; Endres S; Eigler A
TI - Tumor cell lysate-pulsed human dendritic cells induce a T-cell response against pancreatic carcinoma cells: an in vitro model for the assessment of tumor vaccines.
SO - Cancer Res 2001 Sep 1;61(17):6445-50
AD - Division of Clinical Pharmacology, Department of Medicine, Ludwig-Maximilians-University of Munich, 80336 Munich, Germany.
Dendritic cells (DCs) are potent antigen-presenting cells and play a pivotal role in T cell-mediated immunity. DCs have been shown to induce strong antitumor immune responses in vitro and in vivo, and their efficacy is being investigated in clinical trials. Compared with vaccination strategies directed against a single tumor antigen, tumor-cell lysate as the source of antigen offers the potential advantage of inducing a broad T-cell response against multiple known, as well as unknown, tumor-associated antigens expressed by the individual tumor. We used pancreatic carcinoma cell lines to develop an in vitro model for monitoring T-cell responses induced by lysate-pulsed DCs. Monocyte-derived DCs of HLA-A2(+) donors were pulsed with lysate generated from the HLA-A2(+) pancreatic carcinoma cell line Panc-1. In some experiments, the immunogenic protein keyhole limpet hemocyanin (KLH) was added to the lysate. Subsequently, the antigen-loaded DCs were activated with tumor necrosis factor-alpha and prostaglandin E(2). Autologous mononuclear cells were cocultured with DCs in the presence of low-dose interleukin (IL)-2 and IL-7 and were restimulated weekly with new DCs. High levels of IL-12 and IFN-gamma could be detected in the supernatants, indicating a T-helper type 1-type immune response. This cytokine profile was associated with the expression of the activation marker CD69 on both T helper and CTLs and with an antigen-induced proliferative T-cell response. After 4 weeks, CTL-mediated cytotoxicity was assessed. Tumor cell lysis was specific for Panc-1 tumor cells and was MHC class I-restricted. Cytokine secretion, CD69 expression of T cells, and antigen-induced T-cell proliferation correlated with the cytotoxic activity and were more pronounced when KLH was added to the lysate. This is the first study to show that T cells specific for pancreatic carcinoma cells can be generated in vitro by lysate-pulsed DCs and that the T-cell response can be enhanced by KLH. This in vitro model can be applied to compare different strategies in the development of DC-based tumor vaccines.

24
UI - 21404107
AU - Harewood GC; Wiersema MJ
TI - Diagnosis of pancreatic cancer-EUS/FNA to the rescue?
SO - Am J Gastroenterol 2001 Aug;96(8):2501-2
AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota, USA.

25
UI - 21418685
AU - Schulz MR; Hertz-Picciotto I; van Wijngaarden E; Hernandez JC; Ball LM
TI - Dose-response relation between acrylamide and pancreatic cancer.
SO - Occup Environ Med 2001 Sep;58(9):609

26
UI - 21405500
AU - Liao Q; Ozawa F; Friess H; Zimmermann A; Takayama S; Reed JC; Kleeff J; Buchler MW
TI - The anti-apoptotic protein BAG-3 is overexpressed in pancreatic cancer and induced by heat stress in pancreatic cancer cell lines.
SO - FEBS Lett 2001 Aug 17;503(2-3):151-7
AD - Department of Visceral and Transplantation Surgery, University of Bern, Inselspital, Switzerland.
Pancreatic cancer cells are usually resistant to apoptosis mediated by intrinsic or extrinsic factors. BAG-3 (Bis, CAIR), which was identified as a BAG-1-related protein, is a novel modulator of cellular anti-apoptotic activity that functions through its interaction with Bcl-2. In this study we analyzed BAG-3 expression in human pancreatic cancer tissues and cell lines. BAG-3 mRNA was expressed at moderate to high levels in all pancreatic cancer samples, but at low levels in normal pancreas tissues. In situ hybridization and immunohistochemistry analysis revealed that BAG-3 was present in the cancer cells within the pancreatic tumor mass. When BAG-3 mRNA was analyzed in other gastrointestinal cancers (hepatocellular carcinoma; esophageal, stomach and colon cancer), no difference was found from their corresponding normal controls. In pancreatic cancer cells, BAG-3 mRNA expression levels were strongly induced after heat stress, but not in response to members of the tumor necrosis factor (TNF)-alpha family (TNF-alpha, TRAIL, FasL). These findings indicate that in pancreatic cancer, in contrast to other gastrointestinal malignancies, increased levels of BAG-3 might function to block apoptosis. This characteristic of pancreatic cancer might contribute to its more aggressive growth behavior and poor responsiveness to treatment in vivo.

27
UI - 21413772
AU - Chari ST; Klee GG; Miller LJ; Raimondo M; DiMagno EP
TI - Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer.
SO - Gastroenterology 2001 Sep;121(3):640-5
AD - Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA. chari.suresh@mayo.edu
BACKGROUND & AIMS: Islet amyloid polypeptide (IAPP) levels are elevated in pancreatic cancer and may be a useful marker of pancreatic cancer-associated diabetes. The aim of this study was to compare the sensitivity and specificity for pancreatic cancer of IAPP with that of CA19-9, examine clinical characteristics of diabetes in pancreatic cancer, and define the relationship of IAPP to diabetes of pancreatic cancer. METHODS: Fasting serum glucose, IAPP, and CA 19-9 were measured in 130 subjects with pancreatic cancer, 250 subjects with other pancreatic and peripancreatic diseases, and 116 controls. In pancreatic cancer patients, we noted tumor stage and the presence and duration of diabetes. RESULTS: IAPP was markedly elevated in pancreatic cancer, especially in patients with diabetes. However, the sensitivity of IAPP for pancreatic cancer was less than that of CA 19-9 (40% vs. 75%; P < 0.001). Diabetes was present in 46% of pancreatic cancers and 55% of resectable tumors. In pancreatic cancer with diabetes, the sensitivity of IAPP was only 50%. In resectable cancer it was 27%. CONCLUSIONS: IAPP is elevated in pancreatic cancer but is not sensitive enough to replace or complement existing tests. Diabetes occurs early and frequently in pancreatic cancer. Development of a sensitive and specific marker for pancreatic-associated diabetes might lead to diagnosis of resectable pancreatic cancer.

28
UI - 20564939
AU - Johnson PR; Spitz L
TI - Cysts and tumors of the pancreas.
SO - Semin Pediatr Surg 2000 Nov;9(4):209-15
AD - Institute of Child Health and Great Ormond Street Hospital for Children, NHS Trust, London, UK.
Both pancreatic cysts and pancreatic tumors rarely occur in childhood. However, when encountered they can present a diagnostic and therapeutic challenge to the pediatric surgeon. The aim of this review is to discuss the different types of pancreatic cysts and tumours that may be encountered in the pediatric population, to note the modes available for their diagnosis, and to outline treatment options. Copyright 2000 by W.B. Saunders Company

29
UI - 21241358
AU - Morrin MM; Kruskal JB; Raptopoulos V; Weisinger K; Farrell RJ; Steer ML; Kane RA
TI - State-of-the-art ultrasonography is as accurate as helical computed tomography and computed tomographic angiography for detecting unresectable periampullary cancer.
SO - J Ultrasound Med 2001 May;20(5):481-90
AD - Department of Radiology, Beth Israel Deacones Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA.
OBJECTIVE: To compare the ability of state-of-the-art ultrasonography with that of helical computed tomography and computed tomographic angiography in detecting unresectable periampullary cancer. In most patients periampullary cancer is unresectable because of either distant metastasis or local vascular involvement. The advent of gray scale and color Doppler ultrasonography has improved the ability of ultrasonography to detect vascular involvement. METHODS: Twenty-three consecutive patients with periampullary cancer were enrolled for prospective staging of their disease by comparing helical computed tomography and computed tomographic angiography with gray scale and color Doppler ultrasonography of the abdomen. Portal vein, superior mesenteric vein, splenic vein, and superior mesenteric artery involvement was graded 0 to 4, grade 0 being no vascular involvement and grade 4 being total occlusion of the vessel. Agreement between ultrasonography and computed tomographic angiography for determining vascular involvement was measured by chi2 analysis. RESULTS: Two patients (9%) were excluded because excessive overlying bowel gas hampered the ability of ultrasonography to visualize the pancreas. For the remaining 21 patients, there was significant agreement between ultrasonography and computed tomographic angiography for detecting vascular involvement in all vessels (P < .001; portal vein, kappa = 0.67; superior mesenteric vein, kappa = 0.67; splenic vein, kappa = 0.85; and superior mesenteric artery, kappa = 0.59). Ultrasonography was in agreement with computed tomographic angiography in all cases of unresectability. Both modalities were equally poor in preoperatively showing lymphadenopathy and metastases. CONCLUSIONS: Provided that there is adequate visualization on ultrasonography of the head of the pancreas in the periampullary region, then state-of-the-art gray scale and color Doppler ultrasonography are as accurate as helical computed tomography and computed tomographic angiography for detecting the unresectability of periampullary cancer. If performed as the initial investigation and the region of the pancreatic head is clearly shown, and if vascular encasement or occlusion or distant metastasis is identified, further investigations are unnecessary.

30
UI - 21265970
AU - Schmied BM; Ulrich AB; Matsuzaki H; Li C; Friess H; Bochler MW; Andron-Sandberg A; Adrian TE; Pour PM
TI - Alteration of the Langerhans islets in pancreatic cancer patients.
SO - Int J Pancreatol 2000 Dec;28(3):187-97
AD - UNMC Eppley Cancer Center, University of Nebraska Medical Center, Omaha 68198-6805, USA.
An abnormal glucose metabolism occurs in up to 80% of pancreatic cancer patients shortly or a few months before the first clinical admission. Reasons for this abnormality are obscure. We investigated immunohistochemically the pattern of islets in 14 pancreatic cancer specimens and used 14 chronic pancreatitis samples and 10 normal pancreata as controls. To study the topographical relationship of these islets to the cancer, islets in four different arbitrary zones within and around the cancer were evaluated. Ten out of 14 cancer specimens showed a significant loss of beta cells (p < 0.005) and eight of them also showed a significant increase of alpha cells (p < 0.005), all of them from hyperglycemic patients. Most affected islets were found within zone 1 (intratumoral) and zone 2 (peritumoral), to a lesser extent in zone 3 (acini close to tumor) and none in zone 4 (acini remote from tumor). No comparable changes were found in chronic pancreatitis patients. The incidence of 72% with alteration of islets in our material correlates with the frequency of abnormal glucose levels in human pancreatic cancer patients. Our findings support the notion that islet cell abn