National Cancer Institute®
Last Modified: October 1, 2002
UI - 11926386
AU - Nitzsche EU; Hoegerle S; Mix M; Brink I; Otte A; Moser E; Imdahl A
TI - Non-invasive differentiation of pancreatic lesions: is analysis of FDG kinetics superior to semiquantitative uptake value analysis?
SO - Eur J Nucl Med Mol Imaging 2002 Feb;29(2):237-42
AD - Department of Radiology, Albert Ludwigs University, Medical Center, Freiburg, Germany. email@example.com
The diagnostic utility of fluorine-18 2-deoxy-D-glucose positron emission tomography (FDG PET) for the non-invasive differentiation of focal pancreatic lesions originating from cancer or chronic pancreatitis by combined visual image interpretation and semiquantitative uptake value analysis has been documented. However, in clinical routine some misdiagnosis is still observed. This is because there is potential overlap between the semiquantitative uptake values obtained for active inflammatory lesions and cancer. Therefore, this prospective study was undertaken to test the hypothesis that analysis of dynamic kinetics of focal pancreatic lesions based on FDG PET may more accurately determine the benign or malignant nature of such lesions. Thirty patients (56+/-17 years) were studied dynamically with FDG PET for a period of 60-90 min. Patients were assigned to one of four groups: control, acute pancreatitis, chronic pancreatitis or pancreatic cancer. Two observers, blinded to the clinical data, analysed the time-activity curves of FDG kinetics based on region of interest analysis. The diagnosis predicted by FDG PET was compared with the result of histological examination of the surgical specimen. Analysis of FDG kinetics revealed significant differences in the shape of the time-activity curve for controls, pancreatic cancer and inflammatory disease. Surprisingly, there was no significant difference in the time-activity curve shape for chronic pancreatitis and acute pancreatitis; this is, however, not a clinical issue. Furthermore, acquisition time (60 min vs 90 min) did not affect interpretation of the time-activity curve, so that scanning time may be regularly shortened to 60 min. Interobserver agreement was 1. Based on these findings, non-invasive differentiation between pancreatic cancer and chronic pancreatitis was correctly predicted in all cases, as confirmed by histology. In addition, the specificity was increased compared with that obtained from standardised uptake value analysis. Non-invasive differentiation between pancreatic cancer and chronic pancreatitis may best be achieved based on a dynamic FDG PET study including kinetic analysis. This approach yields results superior to those obtained from a semiquantitative analysis of pancreatic lesions.
UI - 11962246
AU - Barber MD; Fearon KC; Tisdale MJ; McMillan DC; Ross JA
TI - Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic cancer cachexia.
SO - Nutr Cancer 2001;40(2):118-24
AD - University Department of Surgery, Royal Infirmary of Edinburgh, Edinburgh EH3 9YW, UK.
Weight loss in advanced cancer patients is refractory to conventional nutritional support. This may be due to metabolic changes mediated by proinflammatory cytokines, hormones, and tumor-derived products. We previously showed that a nutritional supplement enriched with fish oil will reverse weight loss in patients with pancreatic cancer cachexia. The present study examines the effect of this supplement on a number of mediators thought to play a role in cancer cachexia. Twenty weight-losing patients with pancreatic cancer were asked to consume a nutritional supplement providing 600 kcal and 2 g of eicosapentaenoic acid per day. At baseline and after 3 wk, patients were weighed and samples were collected to measure serum concentrations of interleukin (IL)-6 and its soluble receptor tumor necrosis factor receptors I and II, cortisol, insulin, and leptin, peripheral blood mononuclear cell production of IL-1 beta, IL-6, and tumor necrosis factor, and urinary excretion of proteolysis inducing factor. After 3 wk of consumption of the fish oil-enriched nutritional supplement, there was a significant fall in production of IL-6 (from median 16.5 to 13.7 ng/ml, P = 0.015), a rise in serum insulin concentration (from 3.3 to 5.0 mU/l, P = 0.0064), a fall in the cortisol-to-insulin ratio (P = 0.0084), and a fall in the proportion of patients excreting proteolysis inducing factor (from 88% to 40%, P = 0.008). These changes occurred in association with weight gain (median 1 kg, P = 0.024). Various mediators of catabolism in cachexia are modulated by administration of a fish oil-enriched nutritional supplement in pancreatic cancer patients. This may account for the reversal of weight loss in patients consuming this supplement.
UI - 12136248
AU - Lage H; Dietel M
TI - Multiple mechanisms confer different drug-resistant phenotypes in pancreatic carcinoma cells.
SO - J Cancer Res Clin Oncol 2002 Jul;128(7):349-57
AD - Humboldt University Berlin, Charite Campus Mitte, Institute of Pathology, Schumannstr. 20/21, 10117 Berlin, Germany. firstname.lastname@example.org
PURPOSE: Drug-resistant phenotypes of cancer cells may be caused by complex multimodal mechanisms of resistance. In order to gain further insighte into these mechanisms, a P-glycoprotein-mediated multidrug-resistant phenotype induced by daunorubicin-selection and an alternative drug resistance due to treatment with mitoxantrone were investigated in pancreatic carcinoma-derived cells. METHODS: For assessing cross-resistance against various drugs, cell proliferation assays were performed. Drug accumulation was measured by flow cytometry. Messenger RNA expression was analyzed by Northern blot and RT-PCR, whereas protein expression was determined by Western blot. Catalytic activity of DNA-topoisomerases (Topo) II was determined by the decatenation assay. RESULTS: In mitoxantrone-selected EPP85-181RNOV cells a decreased accumulation of mitoxantrone and daunorubicin was observed in the absence of P-glycoprotein, multidrug resistance protein or breast cancer resistance protein over-expression. An approximately twofold decrease of DNA topoisomerase II catalytic activity could be observed in both drug-resistance-exhibiting cell lines. The reduction of Topo II catalytic activity was reflected by decreased expression of Topo IIalpha and IIbeta mRNAs and proteins. CONCLUSIONS: The decreased drug accumulation in EPP85-181RNOV cells indicates that alternative transport events are occurring. The decreased catalytic activity and expression of Topo II indicate that modulation of Topo II catalytic activity contributes to both drug-resistant phenotypes in pancreatic carcinoma cells.
UI - 12202711
AU - Prokesch RW; Chow LC; Beaulieu CF; Bammer R; Jeffrey RB Jr
TI - Isoattenuating pancreatic adenocarcinoma at multi-detector row CT: secondary signs.
SO - Radiology 2002 Sep;224(3):764-8
AD - Department of Radiology, Lucas MRS Center, Stanford University, Calif, USA. email@example.com
PURPOSE: To assess the frequency of isoattenuating pancreatic adenocarcinoma with multi-detector row computed tomography (CT) and determine whether there are specific secondary signs that aid in detection. MATERIALS AND METHODS: Fifty-three patients with pancreatic adenocarcinoma underwent contrast material-enhanced biphasic multi-detector row CT with curved planar reformation. Tumors were initially deemed isoattenuating or hypoattenuating to normal pancreatic parenchyma on the basis of visual inspection, and the degree of attenuation was confirmed by calculating the mean attenuation differences between normal pancreatic parenchyma and tumor (tumor-pancreas contrast) during the pancreatic phase. Indirect signs of pancreatic tumor were tabulated in patients with an isoattenuating tumor. RESULTS: Of the 53 patients, six (11%) had isoattenuating tumors with a mean tumor-pancreas contrast of 9.25 HU +/- 11.3 during the pancreatic phase and 4.15 HU +/- 8.5 during the portal venous phase. The secondary signs of pancreatic tumor in these six patients included an interrupted pancreatic duct (n = 5), dilated biliary and pancreatic ducts (n = 1), atrophic distal pancreatic parenchyma (n = 3), and mass effect and/or convex contour abnormality (n = 3). The mean tumor-pancreas contrast for the remaining 47 patients was 74.76 HU +/- 35.61 during the pancreatic phase. CONCLUSION: With no visible tumor-pancreas contrast for isoattenuating tumors, indirect signs such as mass effect, atrophic distal parenchyma, and an interrupted duct sign are important indicators for the presence of tumor. Copyright RSNA, 2002
UI - 1525759
AU - Kimura N; Yonekura H; Okamoto H; Nagura H
TI - Expression of human regenerating gene mRNA and its product in normal and neoplastic human pancreas.
SO - Cancer 1992 Oct 1;70(7):1857-63
AD - Department of Pathology, Tohoku University School of Medicine, Sendai, Japan.
BACKGROUND. Localization of human regenerating gene (reg) mRNA and its product was investigated in normal and neoplastic human pancreas with the in situ hybridization method and immunohistochemical studies. METHODS. Both reg mRNA and reg protein were observed in acinar cells of the pancreas, but neither was found in ductal or islet cells. Immunoreactive reg was observed in an acinar cell carcinoma, a pancreatoblastoma, a solid and cystic tumor, and 5 of 20 duct cell carcinomas, but it was not found in 15 endocrine tumors and 2 microcystic adenomas. RESULTS. For comparison with reg, alpha-1-antitrypsin (AAT), lysozyme, chromogranin A (CMG), CA 19-9, carcinoembryonic antigen (CEA), cytokeratin, vimentin, and alpha-fetoprotein (AFP) were assessed in those tumors. An acinar cell carcinoma and a pancreatoblastoma had positive results for AAT, lysozyme, cytokeratin, and AFP but negative results for vimentin. An acinar cell carcinoma showed cells focally immunoreactive for CMG and CEA. A solid and cystic tumor had strongly positive results for AAT and vimentin and focally positive results for CMG and pancreatic hormones. Microcystic adenomas had abundant glycogen and strong immunoreactivity for cytokeratin. Ductal cell carcinomas showed cells focally positive for AAT, lysozyme, CMG, CA 19-9, and CEA. CONCLUSIONS. The localization of reg protein was not consist with that of any other proteins examined in the current study. Thus, reg protein was considered a useful marker for acinar cell differentiation; however, ectopic expression of reg also was observed in ductal cell carcinomas. In ductal cell carcinomas, expression of reg immunoreactivity was considered as one of phenotypic heterogeneity, as seen in AAT, lysozyme, and CMG immunoreactivity.
UI - 11870779
AU - Takeuchi K; Nakamura K; Fujimoto M; Kaino S; Kondoh S; Okita K
TI - Heat stress-induced loss of eukaryotic initiation factor 5A (eIF-5A) in a human pancreatic cancer cell line, MIA PaCa-2, analyzed by two-dimensional gel electrophoresis.
SO - Electrophoresis 2002 Feb;23(4):662-9
AD - Department of Gastroenterology and Hepatology of Medicine, Yamaguchi University School of Medicine, Ube, Japan.
Alterations of intracellular proteins during the process of heat stress-induced cell death of a human pancreatic cancer cell line, MIA PaCa-2, were investigated using two-dimensional gel electrophoresis (2-DE), agarose gel electrophoresis, and cell biology techniques. Incubation of MIA PaCa-2 at 45 degrees C for 30 min decreased the cell growth rate and cell viability without causing chromosomal DNA fragmentation. Incubation at 51 degrees C for 30 min suppressed cell growth and again led to death without DNA fragmentation. The cell death was associated with the loss of an intracellular protein of M(r) 17,500 and pI 5.2 on 2-DE gel. This protein was determined to be eukaryotic initiation factor SA (eIF-5A) by microsequencing of the N-terminal region of peptide fragments obtained by cyanogen bromide treatment of the protein blotted onto a polyvinylidene difluoride (PVDF) membrane. The sequences detected were QXSALRKNGFVVLKGRP and STSKTGXHGHAKVHLVGID, which were homologous with the sequence of eIF-5A from Gln 20 to Pro 36 and from Ser 43 to Asp 61, respectively. Furthermore, the result of sequencing suggested that the protein was an active form of hypusinated eIF-5A, because Lys 46 could be detected but not Lys 49, which is the site for hypusination. These results suggest that loss of the active form of eIF-5A is an important factor in the irreversible process of heat stress-induced death of MIA PaCa-2 cells.
UI - 11961486
AU - Yokoyama M; Ochi K; Ichimura M; Mizushima T; Shinji T; Koide N; Tsurumi
TI - T; Hasuoka H; Harada M Matrix metalloproteinase-2 in pancreatic juice for diagnosis of pancreatic cancer.
SO - Pancreas 2002 May;24(4):344-7
AD - Department of Laboratory Medicine, Okayama University Medical School, Okayama, Japan. firstname.lastname@example.org
INTRODUCTION: Matrix metalloproteinase-2 (MMP-2) has an activity to degrade type IV collagen and is associated with invasion angiogenesis of malignant tumor. AIM: A diagnostic value of MMP-2 in pancreatic juice was studied in the diagnosis of pancreatic cancer. METHODOLOGY: Using gelatin zymography, active MMP-2 and proMMP-2 were determined in pancreatic juice obtained endoscopically from 12 patients with pancreatic cancer, 11 with chronic pancreatitis, and 7 control subjects. RESULTS: ProMMP-2 was detected in 12 of 12 patients (100%) with pancreatic cancer, 6 of 11 (54.5%) with chronic pancreatitis, and 3 of 7 (42.9%) controls. Active MMP-2 was detected in 11 patients (91.6%) with pancreatic cancer, 2 (18.2%) with chronic pancreatitis, and none of the control subjects. An activation ratio of MMP-2 (active MMP-2/total MMP-2) in pancreatic juice is significantly higher in pancreatic cancer (23.4 +/- 4.4%, mean +/- SE) than in chronic pancreatitis (2.1 +/- 1.7%) and controls (0%) (p < 0.01). Active MMP-2 was also detected in pancreatic juice from three cases of small pancreatic cancer (tumor <2 cm in diameter). CONCLUSION: Our observation suggests that detection of active MMP-2 in pancreatic juice using gelatin zymography may be useful for the diagnosis of pancreatic cancer.
UI - 12167582
AU - Hiotis SP; Klimstra DS; Conlon KC; Brennan MF
TI - Results after pancreatic resection for metastatic lesions.
SO - Ann Surg Oncol 2002 Aug;9(7):675-9
AD - Department of Surgery, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. email@example.com
BACKGROUND: Unlike primary pancreatic carcinoma, isolated metastatic lesions to the pancreas are uncommon. Although the value of surgical resection is poorly documented, resection may be deemed appropriate in selected cases. The aim of this study was to review our experience with the operative management of pancreatic metastases. METHODS: Sixteen patients who underwent pancreatic resection for the treatment of metastatic disease were identified from a prospective pancreatic database. The clinical features of and results after resection were examined. RESULTS: Renal cell carcinoma was the most frequent primary histopathology (10 of 16; 62%). In the remaining patients, the primary histopathology was non-small-cell lung cancer (n = 3), sarcoma (n = 1), melanoma (n = 1), or transitional cell carcinoma of the bladder (n = 1). A prolonged disease-free interval (median, 7.5 years) was characteristic of most patients. Operative procedures performed included eight pancreaticoduodenectomies, seven distal pancreatectomies, and one total pancreatectomy. The operative mortality was 6%, and the morbidity was 25%. The overall 2- and 5-year actuarial survival rates were 62% and 25%, respectively. A trend toward improved survival was observed in the renal cell carcinoma patients, but this finding was not statistically significant. CONCLUSIONS: Long-term survival after pancreatic resection for metastatic disease is achievable, and patients with primary renal cell carcinoma seem to have a more favorable prognosis. Surgical resection should thus be offered to selected patients with isolated metastatic disease to the pancreas.
UI - 12233216
AU - Polus M; Bours V; Jerusalem G; Sautois B; Fillet G
TI - [How I treat...advanced cancer of the pancreas with a novel approach directed against new targets]
SO - Rev Med Liege 2002 Jul;57(7):428-32
AD - Service d'Oncologie medicale, CHU, Sart Tilman.
A better knowledge of fundamental mechanisms of carcinogenesis allows the development of novel therapeutic tools specifically targeting the cancer cell. Our understanding of cellular and molecular mechanisms controlling cellular cycle and cell survival is an important step for new anti-cancer treatments. This review will focus on new therapeutic's strategies in advanced pancreatic cancer.
UI - 12096319
AU - Saftoiu A; Ciurea T
TI - The role of imaging for the evaluation of pancreatic cancer resectability.
SO - Rom J Gastroenterol 2002 Mar;11(1):78-9; discussion 79-80
UI - 12216484
AU - Granov AM; Tiutin LA; Ryzhkova DV; Kostenikov NA; Fadeev NP; Savello VE;
TI - Pavlovskii AV; Tlostanova MS; Efimenko AV; Stanzhevskii AA [Assessment of 18FDG PET for diagnosis of pancreatic tumors]
SO - Vestn Rentgenol Radiol 2002 Mar-Apr;(2):18-22
AD - Central Research Institute of X-ray and Radiation Studies, Ministry of Health of the Russian Federation, Saint Petersburg.
The paper examines the informational value of positron emission tomography (PET) using 18FDG in the diagnosis of malignant of neoplasms of the pancreas and in the estimation of the extent of a metastatic involvement. Forty-four patients (26 males and 18 females whose age ranged from 28 to 60 years) with histologically verified cancer of the pancreas were examined. The study was conducted in the whole body mode on an Ecat Exact 47 positron emission tomograph following 70-90 minutes of administration of 18FDG, 370-420 MBk. To assess the findings, the differential accumulation ratio (DAR) of formation/liver was calculated. The mean DAR in patients with benign and malignant pancreatic tumors was 1.17 +/- 0.064 and 4.90 +/- 0.3 (p < 0.05). There was a false positive case in a patient with an exacerbation of chronic pancreatitis in the study. A relationship was observed between the level of tumor tissue 18FDG capture and the degree of malignancy. PET scanning in the whole body mode estimates the extent of a tumorous process. The authors' data show that the liver was most commonly involved in a metastatic process (96.6%). Hence, 18FDG PET is a highly informative technique in the diagnosis of malignant pancreatic tumors and in the estimation of the extent of a metastatic process and permits a differential diagnosis between benign and malignant tumors.
UI - 12354980
AU - Pinol V; Castells A; Bordas JM; Real MI; Llach J; Montana X; Feu F;
TI - Navarro S Percutaneous self-expanding metal stents versus endoscopic polyethylene endoprostheses for treating malignant biliary obstruction: randomized clinical trial.
SO - Radiology 2002 Oct;225(1):27-34
AD - Department of Gastroenterology, Institut de Malalties Digestives, Hospital Clinic, Villarroel 170, 08036 Barcelona, Spain.
PURPOSE: To compare percutaneous self-expanding metal stents with conventional endoscopic polyethylene endoprostheses for treatment of malignant biliary obstruction by means of a prospective randomized clinical trial. MATERIALS AND METHODS: Patients with biliary obstruction due to inoperable primary carcinoma of the pancreas, gallbladder, or bile ducts or regional lymph node metastases were included. Evaluated outcomes included technical and therapeutic success rates, morbidity and 30-day mortality rates, hospital stay length and readmission, biliary reobstruction, and overall survival rates. Data were analyzed according to both the intention-to-treat principle and the treatment actually administered. Univariate (Kaplan-Meier method) and multivariate (Cox model) analyses were performed. RESULTS: After randomization, 28 patients were assigned to receive a percutaneous self-expanding metal stent and 26 patients to receive a 12-F endoscopic polyethylene prosthesis. The technical success rates of both implantation procedures were similar (percutaneous, 75% [21 of 28 patients]; endoscopic, 58% [15 of 26 patients]; P =.29), whereas therapeutic success was higher in the percutaneous group (71% [20 of 28 patients] vs 42% [11 of 26 patients]; P =.03). However, major complications were more common in the percutaneous group (61% [17 of 28 patients] vs 35% [nine of 26 patients]; P =.09) but did not account for differences in 30-day mortality rates (percutaneous, 36% [10 of 28 patients]; endoscopic, 42% [11 of 26 patients]; P =.83). Overall median survival was significantly higher in the percutaneous group than in the endoscopic group (3.7 vs 2.0 months; P =.02). Cox regression analysis enabled identification of placement of the percutaneous self-expanding metal stent as the only independent predictor of survival (relative risk, 2.19; 95% CI: 1.11, 4.31; P =.02). CONCLUSION: Placement of a percutaneous self-expanding metal stent is an alternative to placement of an endoscopic polyethylene endoprosthesis in patients with malignant biliary obstruction.
UI - 12324754
AU - Mossner J; Teich N
TI - Genetic disorders in pancreatitis: Implications in the pathogenesis of acute and chronic pancreatitis.
SO - Surgery 2002 Sep;132(3):421-3
AD - University of Leipzig, Medizinische Klinik und Poliklinik II, Germany.
UI - 12358243
AU - Tada M; Komatsu Y; Kawabe T; Sasahira N; Isayama H; Toda N; Shiratori Y;
TI - Omata M Quantitative analysis of K-ras gene mutation in pancreatic tissue obtained by endoscopic ultrasonography-guided fine needle aspiration: clinical utility for diagnosis of pancreatic tumor.
SO - Am J Gastroenterol 2002 Sep;97(9):2263-70
AD - Department of Gastroenterology, Faculty of Medicine, University of Tokyo, Japan.
OBJECTIVES: Endoscopic ultrasonography-guided fine needle aspiration (EUS-FNA) has become established in the diagnosis of pancreatic cancer. The combination of pathological diagnosis and analysis for mutant K-ras gene was investigated to improve the accuracy of diagnosis. METHODS: EUS-FNA was performed in 34 patients with pancreatic masses (26 adenocarcinomas and eight chronic pancreatitis). Mutant ras gene was analyzed semiquantitatively in the specimens obtained by EUS-FNA as well as in pancreatic juice obtained by ERCP. RESULTS: Mutant gene was detected at high amounts (more than 2% of total ras genes) in 20 of 26 (77%) specimens of EUS-FNA and in 12 of 19 (63%) of pancreatic juice in cases with pancreatic carcinoma. Cytological diagnosis of malignancy by EUS-FNA was found in 16 of 26 (62%) patients with pancreatic cancer. Accurate diagnosis of the carcinoma was 21 of 26 (81%) by combined cytology and molecular method of EUS-FNA, and increased to 23 of 26 (88%) by adding molecular analysis of pancreatic juice. In contrast, mutant gene was absent or low level despite suspicious cytology in patients with benign pancreatic lesion. CONCLUSION: Quantitative analysis of mutant ras gene supplemented conventional cytology of EUS-FNA and ERCP. Detection of mutation at high amounts may represent pancreatic cancer, whereas its absence increased the possibility of benign lesion.
UI - 11115825
AU - Malats N; Casals T; Porta M; Guarner L; Estivill X; Real FX
TI - Cystic fibrosis transmembrane regulator (CFTR) DeltaF508 mutation and 5T allele in patients with chronic pancreatitis and exocrine pancreatic cancer. PANKRAS II Study Group.
SO - Gut 2001 Jan;48(1):70-4
AD - Grup de Recerca d'Epidemiologia Clinica i Molecular del Cancer, Institut Municipal d'Investigacio Medica, Universitat Pompeu Fabra, Barcelona, Universitat Autonoma de Barcelona, Spain. firstname.lastname@example.org
BACKGROUND: An increased risk of chronic pancreatitis has been described among carriers of the cystic fibrosis transmembrane regulator (CFTR) mutation. In addition, patients with cystic fibrosis may have a higher risk of exocrine pancreatic cancer. AIMS: To determine the prevalence of the DeltaF508 mutation and 5T allele, the most common CFTR disease related variants, and to assess their association with lifestyle factors in an unselected series of patients with chronic pancreatitis or pancreatic cancer. SUBJECTS: Patients recruited to the multicentre PANKRAS II study with a diagnosis of chronic pancreatitis and pancreatic cancer from whom normal DNA was available. METHODS: The DeltaF508 mutation and 5T allele were analysed using polymerase chain reaction amplified normal DNA. Information on clinical and lifestyle factors was obtained through personal interviews. RESULTS: Among patients with pancreatitis, no DeltaF508 alleles were found and the prevalence of the 5T allele was 10.5%, similar to that described in the general population. Among patients with pancreatic cancer, the prevalence of the DeltaF508 mutation and the 5T allele was 2.4% and 5.5%, respectively. 5T allele carriers with cancer consumed significantly less alcohol than non-carriers (p=0.038). CONCLUSIONS: Our findings do not support the view that the DeltaF508 mutation and 5T allele confer a higher risk of chronic pancreatitis or pancreatic cancer. Nevertheless, our data suggest that interactions between CFTR polymorphism and environmental factors may play a role in the pathogenesis of these diseases. Our study emphasises the need for a multinational study to conclusively establish the role of CFTR variants as genetic susceptibility factors for chronic pancreatitis and pancreatic cancer.
UI - 11677475
AU - Pugliese V; Pujic N; Saccomanno S; Gatteschi B; Pera C; Aste H; Ferrara
TI - GB; Nicolo G Pancreatic intraductal sampling during ERCP in patients with chronic pancreatitis and pancreatic cancer: cytologic studies and k-ras-2 codon 12 molecular analysis in 47 cases.
SO - Gastrointest Endosc 2001 Nov;54(5):595-9
AD - Center for Gastrointestinal Endoscopy, the Department of Oncology, University of Genoa, Italy.
BACKGROUND: A preoperative tissue diagnosis of pancreatic cancer is desirable but difficult to obtain. METHODS: Pancreatic brush cytology, salvage cytology, and collection of pancreatic juice were attempted prospectively during ERCP in 34 patients with pancreatic cancer and 11 with chronic pancreatitis. K-ras-2 codon 12 was analyzed for presence and type of point mutations. RESULTS: Brush cytology coupled with salvage cytology had a sensitivity of 74%. The addition of cytologic analysis of pancreatic juice did not substantially improve sensitivity (76%). K-ras-2 was mutated in both cancer (87%) and pancreatitis (40%). The specificity for cytology was 100% and for K-ras-2 mutations 60%. Combining cytology with mutation analysis increased sensitivity to 93% but reduced the positive predictive value. The negative predictive value never exceeded 75%. None of the patients with chronic pancreatitis had cancer develop (median follow-up 60 months). CONCLUSIONS: Pancreatic ductal brushing with salvage cytology is useful in the diagnosis of cancer, whereas cytologic analysis of pancreatic juice can be abandoned. At present, K-ras-2 mutation is not useful for differentiating pancreatic cancer from chronic pancreatitis or the identification of patients with chronic pancreatitis at risk for malignant transformation.
UI - 11921523
AU - Mery CM; Duarte-Rojo A; Paz-Pineda F; Gomez E; Robles-Diaz G
TI - [Does cholestasis change the clinical usefulness of CA 19-9 in pacreatobiliary cancer?]
SO - Rev Invest Clin 2001 Nov-Dec;53(6):511-7
AD - Departamento de Gastroenterologia, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran.
BACKGROUND: CA 19-9 is used for diagnosis of gastrointestinal neoplasia, mainly pancreatic and biliary cancer. False positive results have been described in cholestasis. OBJECTIVE: To establish the clinical value of CA 19-9 in the diagnosis of pancreatic and biliary cancer in patients with and without cholestasis. METHODS: Five hundred forty-eight medical records of patients with serum CA 19-9 determination performed from May-1996 to June-1998 were reviewed. Cases were grouped by final diagnosis; malignancy was established by histology or clinical and radiological characteristics. ROC curves were used to calculate ideal cut-off values (ICV) for the test. Cholestasis was defined as bilirrubinemia above 3 mg/dL. RESULTS: Thirty percent of serum determinations were done in patients with non-pancreatic and non-hepatobiliary benign diseases (only 1.3% with values > or = 100 U/mL). CA 19-9 levels were higher in pancreatic and hepatobiliary malignancy compared to benign diseases of the same origin, as well as in pancreatic cancer when compared with hepatobiliary cancer. ICV for differentiation of malignant hepatobiliary diseases was set around 100 U/mL, with increased specificity when compared with the usual cut-off value (37 U/mL). Cholestasis increased the values of the antigen in malignant and benign diseases and modified the efficacy of the test by increasing sensitivity while decreasing specificity. The ICV for determining resectability in pancreatic tumors was 224 U/mL. CONCLUSIONS: CA 19-9 is a valuable test for diagnosis of malignant pancreato-hepatobiliary disease. Given that cholestasis modifies the operational characteristics of the test, a cut-off value has to be tailored for each patient depending on the clinical setting, so to maintain the usefulness of the marker.
UI - 12045867
AU - Nakagohri T; Asano T; Kenmochi T; Urashima T; Ochiai T
TI - Long-term surgical outcome of noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma of the pancreas.
SO - World J Surg 2002 Sep;26(9):1166-9
AD - Second Department of Surgery, Chiba University School of Medicine, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan. email@example.com
The objective of this study was to clarify the long-term outcome after surgical resection in patients with noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma. We performed a retrospective review of the clinicopathological features and outcome in patients who underwent pancreatic resection for noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma between invasive structures were pathologically observed in five cases. The mean age of patients with either noninvasive (n = 16) or minimally invasive n = 5) adenocarcinoma was 61 years. Of the patients with minimally invasive adenocarcinoma, 4 had abdominal pain. Conversely, 7 patients with noninvasive adenocarcinoma had no complaint. The mean size of noninvasive and minimally invasive tumors was 2.5 cm (range 0.8 to 4.0) and 3.3 cm (range 2.5 to 4.5), respectively. The overall 5-year and 10-year survival rates for all 21 patients were 89% and 47%, respectively. Disease recurred in 3 patients; 2 patients with minimally invasive adenocarcinoma and 1 with noninvasive adenocarcinoma. Recurrence sites were peritoneum = 2) and main pancreatic duct of the remnant pancreas (n = 1); 5 disease-free patients died of unrelated causes. The remaining 13 patients are alive and disease free 3 to 12 years after surgery. Noninvasive and minimally invasive intraductal papillary mucinous adenocarcinoma had a favorable prognosis after surgical treatment.
UI - 10817437
AU - Yamaguchi K; Noshiro H; Shimizu S; Morisaki T; Chijiiwa K; Tanaka M
TI - Long-term and short-term survivors after pancreatectomy for pancreatic cancer.
SO - Int Surg 2000 Jan-Mar;85(1):71-6
AD - Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan. firstname.lastname@example.org
Out of 63 Japanese patients with pancreatic carcinoma who underwent surgical resection, 8 short-term survivors who died within 3 months after resection and 6 long-term survivors who were alive for more than 3 years after resection were compared regarding 26 clinicopathological parameters. The 8 short-term survivors were significantly older than the 6 long-term survivors (63.7 versus 47.8 years, P = 0.0099). The mean peripheral lymphocyte count was significantly smaller in the short-term survivors than in the long-term survivors (1,212 versus 2,115 /microl, P = 0.0459). Operative blood loss was significantly larger in the short-term survivors than in the long-term survivors (2,393 versus 1,043 g, P = 0.0157). The surgical margin was affected by malignant cells in 7 of the 8 short-term survivors, but in only 2 of the 6 long-term survivors (P = 0.0362). Of the 8 short-term survivors, 5 were in comprehensive stage IV and 3 in stage III, while 3 of the 6 long-term survivors were in stage III, two in stage II, and one in stage I (P = 0.0487). All the 8 short-term survivors were of the comprehensive curability C, while 3 of the 6 long-term survivors were of A, one B and the other two C (P = 0.0239). Multiple regression analysis of these 6 profound factors showed that the peripheral lymphocyte count was an independent significant parameter to differentiate the short-term and long-term survivors. These findings suggest that, although the aggressive nature of pancreatic cancer has been accepted, the clinical course after pancreatectomy would also depend upon the immunological state of the patient.
UI - 12377966
AU - Brett BT; Smith SC; Bouvier CV; Michaeli D; Hochhauser D; Davidson BR;
TI - Kurzawinski TR; Watkinson AF; Van Someren N; Pounder RE; Caplin ME Phase II study of anti-gastrin-17 antibodies, raised to G17DT, in advanced pancreatic cancer.
SO - J Clin Oncol 2002 Oct 15;20(20):4225-31
AD - Department of Medicine, Royal Free Hospital National Health Service Trust, London, United Kingdom.
PURPOSE: The prognosis for advanced pancreatic cancer remains poor. Gastrin acts as a growth factor for pancreatic cancer. We describe the first study of the antigastrin immunogen G17DT in pancreatic cancer. Our aims were to determine the antibody response, safety, tolerability, and preliminary evidence of efficacy of G17DT in advanced pancreatic cancer. PATIENTS AND METHODS: Thirty patients with advanced pancreatic cancer were immunized with three doses of either 100 micro g or 250 micro g of G17DT. RESULTS: In the whole group, 20 (67%) of 30 patients produced an antibody response. The 250- micro g dose resulted in a significantly greater response rate of 82% compared with 46% for the 100- micro g group (P =.018). The most significant side effects, seen in three patients, were local abscess and/or fever. The median survival for the whole group from the date of the first immunization was 187 days; median survival was 217 days for the antibody responders and 121 days for the antibody nonresponders. The difference in survival between the antibody responders and nonresponders was significant (P =.0023). CONCLUSION: Patients with advanced pancreatic cancer are able to mount an adequate antibody response to G17DT. The 250- micro g dose is superior to the 100- micro g dose, and it appears to be generally well tolerated. Antibody responders demonstrate significantly greater survival than antibody nonresponders. Phase III studies are currently underway in order to determine efficacy.
UI - 2154467
AU - Smeekens SP; Steiner DF
TI - Identification of a human insulinoma cDNA encoding a novel mammalian protein structurally related to the yeast dibasic processing protease Kex2.
SO - J Biol Chem 1990 Feb 25;265(6):2997-3000
AD - Howard Hughes Medical Institute, Chicago, Illinois.
We have identified a human insulinoma cDNA (PC2) that encodes a protein homologous to the precursor processing Kex2 endoprotease of yeast by using a polymerase chain reaction to detect and amplify conserved sequences within the catalytic site. The 638-residue amino acid sequence of PC2 begins with a cleavable signal peptide, indicating that it enters the secretory pathway, and contains a 282-residue domain that is homologous to the catalytic modules of both Kex2 and the related bacterial subtilisins. Within this region 49 and 27% of the amino acids are identical to those in the aligned Kex2 and subtilisin BPN' sequences, respectively, and the catalytically essential Asp, His, and Ser residues are all conserved. Northern blot analysis revealed the presence of 2.8- and 5.0-kilobase hybridizing bands in mRNA from the insulinoma. The PC2 protein also shows great similarity to the incomplete NH2-terminal sequence of the human furin gene product, a putative membrane-inserted receptor-like molecule. We propose that PC2 is a member of a family of mammalian Kex2/subtilisin-like proteases that includes members involved in a number of specific proteolytic events within cells, including the processing of prohormones.
UI - 11953884
AU - Rohloff J; Zinke J; Schoppmeyer K; Tannapfel A; Witzigmann H; Mossner J;
TI - Wittekind C; Caca K Heparanase expression is a prognostic indicator for postoperative survival in pancreatic adenocarcinoma.
SO - Br J Cancer 2002 Apr 22;86(8):1270-5
AD - Department of Medicine II, Leipzig University, Philipp-Rosenthal-Str. 27, 04103 Leipzig, Germany.
Pancreatic ductal adenocarcinoma has a median survival of less than 6 months from diagnosis. This is due to the difficulty in early diagnosis, the aggressive biological behaviour of the tumour and a lack of effective therapies for advanced disease. Mammalian heparanase is a heparan-sulphate proteoglycan cleaving enzyme. It helps to degrade the extracellular matrix and basement membranes and is involved in angiogenesis. Degradation of extracellular matrix and basement membranes as well as angiogenesis are key conditions for tumour cell spreading. Therefore, we have analysed the expression of heparanase in human pancreatic cancer tissue and cell lines. Heparanase is expressed in cell lines derived from primary tumours as well as from metastatic sites. By immunohistochemical analysis, it is preferentially expressed at the invading edge of a tumour at both metastatic and primary tumour sites. There is a trend towards heparanase expression in metastasising tumours as compared to locally growing tumours. Postoperative survival correlates inversely with heparanase expression of the tumour reflected by a median survival of 34 and 17 month for heparanase negative and positive tumours, respectively. Our results suggest, that heparanase promotes cancer cell invasion in pancreatic carcinoma and could be used as a prognostic indicator for postoperative survival of patients. Copyright 2002 Cancer Research UK
UI - 10937052
AU - Geradts J; Hruban RH; Schutte M; Kern SE; Maynard R
TI - Immunohistochemical p16INK4a analysis of archival tumors with deletion, hypermethylation, or mutation of the CDKN2/MTS1 gene. A comparison of four commercial antibodies.
SO - Appl Immunohistochem Mol Morphol 2000 Mar;8(1):71-9
AD - Nuffield Department of Pathology & Bacteriology, University of Oxford, John Radcliffe Hospital, United Kingdom. email@example.com
The MTS1/CDKN2/p16 gene encoding the p16INK4a tumor-suppressor protein is commonly inactivated by homozygous deletion or hypermethylation of the promoter in a wide range of human malignancies. In select tumor types, including pancreatic adenocarcinomas, intragenic mutations are found in a significant percentage of cases. The immunoreactivity of mutant p16 proteins has not been comprehensively studied. Moreover, the immunohistochemical properties of commercially available antibodies have not been described in detail. We studied 35 pancreatic adenocarcinomas with a molecularly defined p16 status (16 homozygous deletions, 3 hypermethylated cases, and 16 tumors with an intragenic mutation in one allele associated with loss of the second allele). In addition, we studied nine cell lines (three homozygous deletions, three hypermethylated lines, and three intragenic mutations). Paraffin sections of the tumors and cell blocks were reacted with four different anti-p16 antibodies: polyclonal and monoclonal (clone G175-405) antibodies from PharMingen, monoclonal antibody DCS-50 from Oncogene Science, and monoclonal antibody ZJ11 from Neo-Markers. Optimal staining conditions were established for each antibody. The pancreatic carcinomas with homozygous p16 deletions were largely devoid of nuclear staining (admixed nonneoplastic cells served as internal positive controls); only one adenocarcinoma each reacted with DCS-50 and the polyclonal antibody, and five were positive with ZJ11, suggesting that nonspecific nuclear staining can occur under certain conditions. Antibody DCS-50 produced nuclear staining in all three hypermethylated carcinomas, whereas G175-405 stained none of them. Three of the four antibodies produced nuclear immunoreactivity in 7 to 14 of the 16 carcinomas carrying p16 mutations; G175-405 showed only weak reactivity in one case. Cytoplasmic staining was present in all carcinomas and cell lines and with all antibodies and therefore cannot be considered specific; it was strongest with G175-405. Thus, we found antibody G175-405 to be the most specific, and monoclonals DCS-50 and ZJ11 the least specific for wild-type p16. However, the former tends to give stronger cytoplasmic background staining. For tumor types in which p16 mutations are uncommon, the PharMingen polyclonal antibody may be a suitable alternative.
UI - 10981872
AU - Skacel M; Ormsby AH; Petras RE; McMahon JT; Henricks WH
TI - Immunohistochemistry in the differential diagnosis of acinar and endocrine pancreatic neoplasms.
SO - Appl Immunohistochem Mol Morphol 2000 Sep;8(3):203-9
AD - Department of Anatomic Pathology, Cleveland Clinic Foundation, Ohio 44195, USA. firstname.lastname@example.org
Histologic differential diagnosis of acinar cell carcinoma (ACC), mixed acinar-endocrine cell carcinoma (MAEC), and pancreatic endocrine tumors (PET) can be difficult but is important because of differences in their clinical behavior. This study investigates the utility of immunohistochemistry (IHC) in this differential diagnosis using immunohistochemical stains that are available in most laboratories. IHC was performed on paraffin-embedded tissue in ACC (n = 6), MAEC (n = 2), and PET (n = 13), using synaptophysin (SYN), chromogranin (CHR), chymotrypsin (CHY), and alpha-1-antitrypsin (AAT). Electron microscopy (EM) was performed in all cases to confirm the diagnosis. Long-term follow-up and death of disease (DOD) was known in all patients. The ACCs stained as follows: CHY (4/6), AAT (3/6), SYN (4/6); CHR was negative in all cases. Both cases of MAEC stained with CHY, AAT, and SYN (2/2); CHR was negative. PET stained as follows: SYN (13/13), CHR (8/13), CHY (4/13), AAT (5/13). In the ACC/ MAEC group, six of eight patients were DOD at mean follow-up of 11 months. Among the PET, two of 16 patients were DOD at mean follow-up of 37 months. Considerable immunophenotypic overlap exists between ACC, MAEC, and PET. Consequently, one can neither confirm nor rule out a diagnosis of ACC or MAEC using generally available immunohistochemical stains alone. These findings support a role for EM in the evaluation of exocrine and endocrine pancreatic neoplasms.
UI - 11360677
AU - Zhang SN; Yuan SZ; Zhu ZH; Wen ZF; Huang ZQ; Zeng ZY
TI - Apoptosis induced by 5-flucytosine in human pancreatic cancer cells genetically modified to express cytosine deaminase.
SO - Acta Pharmacol Sin 2000 Jul;21(7):655-9
AD - Department of Gastroenterology, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University of Medical Sciences, Guangzhou 510120, China.
AIM: To elucidate the pattern of 5-flucytosine (5-FC)-induced apoptosis and its role in gene therapy of human pancreatic cancer. METHODS: The human pancreatic cancer SW1990 cells (CEA-producing) were infected with recombinant adenoviruses (Adex1CEA-prCD or Adex1CEA-prZ). Expression of CD gene protein was examined by western blot. Apoptosis induced by 5-FC in human pancreatic cancer SW1990 cells genetically modified to express cytosine deaminase was observed by means of electron microscopy, DNA electrophoresis, and flow cytometry analysis techniques. RESULTS: The SW1990 cells infected with Adex1CEA-prCD were treated with 5-FC at 100 mumol.L-1 for 48 h, and cell apoptosis was observed. Typical apoptosis morphological feature appeared and DNA ladder could be demonstrated on DNA electrophoresis. Apoptosis peak was also showed by flow cytometry. Apoptotic cells accounted for 34.6% of the cell population. Cells in G1, S, and G2/M phase of cell cycle were 64%, 11%, and 7%, respectively. CONCLUSION: The apoptosis induced by 5-FC may be a primary mechanism in CD gene therapy of pancreatic cancer.
UI - 11893038
AU - Oh YL; Song SY; Ahn G
TI - Expression of maspin in pancreatic neoplasms: application of maspin immunohistochemistry to the differential diagnosis.
SO - Appl Immunohistochem Mol Morphol 2002 Mar;10(1):62-6
AD - Department of Diagnostic Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Maspin is a unique member of the serpin family, which inhibits tumor invasion and metastasis of the human breast and prostate cancers. Immunohistochemical evaluation of the maspin expression in pancreatic neoplasms has never been performed. The authors examined the expression of maspin in various pancreatic neoplasms to investigate its usefulness as an adjunct diagnostic marker. Formalin-fixed, paraffin-embedded tissue sections from 107 pancreatic neoplasms were immunostained with anti-maspin antibody using an EnVision+ System. Maspin was expressed in all ductal adenocarcinomas, of which 78.9% (30/38) were high expressors and 21.1% (8/38) were low expressors. All 13 intraductal papillary mucinous tumors and 11 of the 13 mucinous cystic tumors reacted to maspin with stronger expressions in carcinomatous lesions. In contrast, acinar cell carcinoma, pancreatic endocrine tumors, solid-pseudopapillary tumors, and serous cystadenomas demonstrated no maspin expression. In addition, nonneoplastic pancreatic parenchyma and chronic pancreatitis lacked expression. The current study suggests that maspin may be of importance in the pathobiology of pancreatic neoplasms with epithelial origin, especially pancreatic tumors that are composed of mucin-producing cells. It may be useful in separating ductal adenocarcinoma from acinar cell carcinoma, pancreatic endocrine tumor, solid-pseudopapillary tumor, and chronic pancreatitis, especially in needle biopsy specimens.
UI - 3022894
AU - Thivolet C; Chatelain P; Haftek M; Durand A; Pugeat M
TI - [Morphologic and functional study of a human insulin-secreting cell line]
SO - C R Acad Sci III 1986;303(10):381-6
Monolayer cell cultures were obtained from a human insulinoma (HIN) after collagenase digestion. HIN cells were initially plated on extracellular matrix (ECM) secreted by bovine corneal endothelial cells. Capsular integrity from cell clusters quickly interrupted and cell began to migrate as adhesive sheets onto ECM. After 2 months on ECM cell attachment and proliferation occurred on plastic allowing cloning of cells by limiting dilution. 9 clones were successfully cultured for 7 months with 20 subsequent passages. Immunoreactivity for insulin by indirect immunofluorescence typical secretory granules by electron microscopy and stable amounts of immunoreactive insulin in culture media suggest that HIN cells are beta cell related. One clone HIN D8 when challenged for half an hour with either 30 mM glucose, 1 mM isobutyl Methylxanthine 4 mM Tolbutamide, 10(-6) M glucagon responded respectively with a 1.5, 2, 3 and 1.5 fold increase in insulin output. Population doubling time of HIN D8 was 42 hrs. Establishment of such insulin secreting cell lines provides a valuable tool for d