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Pancreatic Adenocarcinoma (pancreatic + adenocarcinoma)
Kinds of Pancreatic Adenocarcinoma Selected AbstractsDiagnosis of pancreatic cancerHPB, Issue 5 2006Fumihiko Miura Abstract The ability to diagnose pancreatic carcinoma has been rapidly improving with the recent advances in diagnostic techniques such as contrast-enhanced Doppler ultrasound (US), helical computed tomography (CT), enhanced magnetic resonance imaging (MRI), and endoscopic US (EUS). Each technique has advantages and limitations, making the selection of the proper diagnostic technique, in terms of purpose and characteristics, especially important. Abdominal US is the modality often used first to identify a cause of abdominal pain or jaundice, while the accuracy of conventional US for diagnosing pancreatic tumors is only 50,70%. CT is the most widely used imaging examination for the detection and staging of pancreatic carcinoma. Pancreatic adenocarcinoma is generally depicted as a hypoattenuating area on contrast-enhanced CT. The reported sensitivity of helical CT in revealing pancreatic carcinoma is high, ranging between 89% and 97%. Multi-detector-row (MD) CT may offer an improvement in the early detection and accurate staging of pancreatic carcinoma. It should be taken into consideration that some pancreatic adenocarcinomas are depicted as isoattenuating and that pancreatitis accompanied by pancreatic adenocarcinoma might occasionally result in the overestimation of staging. T1-weighted spin-echo images with fat suppression and dynamic gradient-echo MR images enhanced with gadolinium have been reported to be superior to helical CT for detecting small lesions. However, chronic pancreatitis and pancreatic carcinoma are not distinguished on the basis of degree and time of enhancement on dynamic gadolinium-enhanced MRI. EUS is superior to spiral CT and MRI in the detection of small tumors, and can also localize lymph node metastases or vascular tumor infiltration with high sensitivity. EUS-guided fine-needle aspiration biopsy is a safe and highly accurate method for tissue diagnosis of patients with suspected pancreatic carcinoma. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been suggested as a promising modality for noninvasive differentiation between benign and malignant lesions. Previous studies reported the sensitivity and specificity of FDG-PET for detecting malignant pancreatic tumors as being 71,100% and 64,90%, respectively. FDG-PET does not replace, but is complementary to morphologic imaging, and therefore, in doubtful cases, the method must be combined with other imaging modalities. [source] Pancreatic adenocarcinoma in a young patient population,12-year experience at Memorial Sloan Kettering Cancer CenterJOURNAL OF SURGICAL ONCOLOGY, Issue 1 2009A. Duffy MD Abstract Background There is a dearth of data in a younger population of patients with pancreatic ductal adenocarcinoma (PAC) regarding epidemiology, genetics, prognosis, and outcome. This report examines a large cohort of patients with PAC ,45 years of age evaluated at MSKCC over a 12-year period. Methods A retrospective analysis of patients referred to MSKCC with PAC identified from the institutional tumor registry, who were ,45 years on the date of the diagnostic biopsy, between January 1995 and February 2008, was performed. Information reviewed included demographics, clinical and pathological staging, surgical management, therapy, date of relapse, death or last follow-up. Survival curves were estimated using the Kaplan,Meier method and compared using the log-rank test. Results One hundred thirty-six cases of PAC, age ,45 years at diagnosis, were identified. Seventy-four (54%) females, 62 (46%) males. Age range: 24,45; 4, 38, and 94 patients in age groups 20,29, 30,39, 40,45 years, respectively. Fifty (37%) had a smoking history. Fourteen (10.3%) had a positive family history of PAC. Thirty-five (25.7%) underwent a curative resection for localized disease. Twenty-eight (20.1%) presented with locally advanced, inoperable disease. Sixty-eight (50%) presented as AJCC Stage IV. Twenty-three (37%) of those resected underwent adjuvant chemoradiation. Thirteen received adjuvant gemcitabine. The median overall survival for the entire cohort was 12.3 months (95% CI 10.2,14.0 months). The median overall survival for the patients with locally resectable disease was 41.8 months (95% CI 20.3,47 months). The median overall survival for the patients who presented with locally advanced, unresectable disease was 15.3 months (95% CI 12,19.3 months). The median overall survival for those who presented with metastatic disease was 7.2 months (95% CI 5.2,9.5 months). Conclusions This is the largest reported cohort of young patients with PAC ,45 years of age. The data suggest that patients with stages I,II disease may have an improved prognosis, however the prognosis for stages III,IV patients appears to be similar to the typical (older) patient population with PAC. J. Surg. Oncol. 2009;100:8,12. © 2009 Wiley-Liss, Inc. [source] Magnetic resonance imaging in the detection of pancreatic neoplasmsJOURNAL OF DIGESTIVE DISEASES, Issue 3 2007Liang ZHONG Recently, with the rapid scanning time and improved image quality, outstanding advances in magnetic resonance (MR) methods have resulted in an increase in the use of MRI for patients with a variety of pancreatic neoplasms. MR multi-imaging protocol, which includes MR cross-sectional imaging, MR cholangiopancreatography and dynamic contrast-enhanced MR angiography, integrates the advantages of various special imaging techniques. The non-invasive all-in-one MR multi-imaging techniques may provide the comprehensive information needed for the preoperative diagnosis and evaluation of pancreatic neoplasms. Pancreatic neoplasms include primary tumors and pancreatic metastases. Primary tumors of the pancreas may be mainly classified as ductal adenocarcinomas, cystic tumors and islet cell tumors (ICT). Pancreatic adenocarcinomas can be diagnosed in a MRI study depending on direct evidence or both direct and indirect evidence. The combined MRI features of a focal pancreatic mass, pancreatic duct dilatation and parenchymal atrophy are highly suggestive of a ductal adenocarcinoma. Most cystic neoplasms of the pancreas are either microcystic adenomas or mucinous cystic neoplasms. Intraductal papillary mucinous tumors are the uncommon low-grade malignancy of the pancreatic duct. ICT are rare neoplasms arising from neuroendocrine cells in the pancreas or the periampullary region. ICT are classified as functioning and non-functioning. The most frequent tumors to metastasize to the pancreas are cancers of the breast, lung, kidney and melanoma. The majority of metastases present as large solitary masses with well-defined margins. [source] Immunocytochemical study of the expression of mesothelin in fine-needle aspiration biopsy specimens of pancreatic adenocarcinomaDIAGNOSTIC CYTOPATHOLOGY, Issue 3 2007Amy C. Baruch M.D. Abstract Mesothelin is a potential marker of pancreatic adenocarcinoma that was recently identified by serial analysis of gene expression. We evaluated the sensitivity and specificity of mesothelin as a marker of pancreatic adenocarcinoma on destained Papanicolaou (Pap) smears and unstained cellblocks from 28 patients using a monoclonal antibody to mesothelin. Intensity and proportion of staining was semiquantitatively graded on a scale of 1,3, and as 0%, 1 to <10%, 10,50%, or >50%. Positive staining for mesothelin was seen in 64% of the direct smears and in 36% of cell block sections. Focal positivity for mesothelin was noted in benign pancreatic tissue in one of 10 cases. Staining was most often focal (<50% of cells) in both direct smears and cell block sections. The overall sensitivity and specificity of mesothelin as a marker for pancreatic adenocarcinoma were 68% and 90%, respectively. Sensitivity was higher in Pap smears than in cell block sections (64% versus 36%). The presence of occasional mesothelin expression in benign tissue, its very focal expression in malignant tissue may limit the utility of mesothelin as a marker of pancreatic adenocarcinomas in fine-needle aspiration (FNA) specimens. Diagn. Cytopathol. 2007;35:143,147. © 2007 Wiley-Liss, Inc. [source] Exfoliative sputum cytology of cancers metastatic to the lung,DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2005Tehmina Z. Ali M.D. Abstract Although largely replaced by fine-needle aspiration (FNA) and bronchoscopy, cytological examination of sputum for exfoliated malignant cells still is considered a valuable initial diagnostic test in patients presenting with a lung mass. Thirty-five cases of secondary/metastatic tumors involving the lung and diagnosed on sputum were retrospectively reviewed from our cytopathology files for a period of 22 yr (1980,2001). Clinical history and the relevant histopathological material were examined and correlated with the cytological findings. In all cases, a history of malignancy was known. Cytological diagnoses included colonic adenocarcinoma (7 cases); non-Hodgkin's lymphoma (NHL; 5 cases); malignant melanoma (MM; 5 cases); breast carcinoma (5 cases); Hodgkin's lymphoma (HL; 3 cases); pancreatic adenocarcinoma (2 cases); prostatic adenocarcinoma (2 cases); and 1 case each of urothelial carcinoma, endometrial carcinoma, renal cell carcinoma, hepatic small-cell carcinoma, squamous-cell carcinoma (cervix), and leiomyosarcoma (LMS). Cellular preservation was optimal in all cases. The smear background was relatively clean in 25 (71%) cases and predominantly inflamed and/or necrotic in 10 (29%) cases. In non-lymphoid tumors (27 cases), isolated single malignant cells were seen in 7 (26%) cases (all cases of MM and prostatic adenocarcinoma), whereas 20 (74%) cases displayed fragments with intact tumor architecture. Overall, only 10/35 (29%) cases showed noticeable tumor-cell necrosis. In one case (LMS), cell block sections were used for immunoperoxidase (IPOX) studies with positive staining for desmin and actin. Exfoliation of cancer cells in sputum from secondary tumors in the lung is a rare phenomenon in current-day practice, with metastatic colonic adenocarcinoma seen most commonly. Intact tumor architecture was observed in exfoliated cells in 75% of the cases. Diagn. Cytopathol. 2005;33:147,151. © 2005 Wiley-Liss, Inc. [source] Split sample comparison of ThinPrep and conventional smears in endoscopic retrograde cholangiopancreatography-guided pancreatic fine-needle aspirations,DIAGNOSTIC CYTOPATHOLOGY, Issue 2 2005Momin T. Siddiqui M.D. Abstract Fine-needle aspiration (FNA) of pancreatic lesions is a common procedure to establish a tissue diagnosis before chemotherapy or surgery. In this study, the authors attempt to compare the diagnostic value of the ThinPrep (TP) method with conventional smears (CSs) in samples obtained by endoscopic retrograde cholangiopancreatography (ERCP)-guided pancreatic FNAs. Material obtained, prospectively, from ERCP-guided pancreatic FNAs was split to prepare CSs (2,5 slides) first, the remainder being rinsed in PreservCyte, and in the laboratory, 1 TP slide was prepared. The diagnostic categories of unsatisfactory, benign, reactive, suspicious for malignancy, and malignant were compared. Fifty-one pancreatic FNAs prepared by split sample method yielded the following results: TP yielded unsatisfactory, 6 cases; benign, 3 cases; reactive, 5 cases; suspicious for malignancy, 11 cases; and malignant, 26 cases; in contrast, CS yielded unsatisfactory, 13 cases; benign, 4 cases; reactive, 3 cases; suspicious for malignancy, 13 cases; and malignant, 18 cases. Histological follow-up was available in 21 cases (reactive, 8 cases; suspicious for malignancy, 1 case, and malignant, 12 cases). The foregoing data indicate a higher sensitivity in detection of pancreatic adenocarcinoma by the TP method (TP, 91% vs. 58% CS) with equivalent specificity (100%). In addition, TP provides better preservation and cytological detail. Diagn. Cytopathol. 2005;32:70,75. © 2005 Wiley-Liss, Inc. [source] Validation of a prediction rule to maximize curative (R0) resection of early-stage pancreatic adenocarcinomaHPB, Issue 7 2009Philip Bao Abstract Background:, The surgeon's contribution to patients with localized pancreatic adenocarcinoma (PAC) is a margin negative (R0) resection. We hypothesized that a prediction rule based on pre-operative imaging would maximize the R0 resection rate while reducing non-therapeutic intervention. Methods:, The prediction rule was developed using computed tomography (CT) and endoscopic ultrasound (EUS) data from 65 patients with biopsy-proven PAC who underwent attempted resection. The rule classified patients as low or high risk for non-R0 outcome and was validated in 78 subsequent patients. Results:, Model variables were: any evidence of vascular involvement on CT; EUS stage and EUS size dichotomized at 2.6 cm. In the validation cohort, 77% underwent resection and 58% achieved R0 status. If only patients in the low-risk group underwent surgery, the prediction rule would have increased the resection rate to 92% and the R0 rate to 73%. The R0 rate was 40% higher in low-risk compared with high-risk patients (P < 0.001). High risk was associated with a 67% rate of non-curative surgery (unresectable disease and metastases). Conclusion:, The prediction rule identified patients most likely to benefit from resection for PAC using pre-operative CT and EUS findings. Model predictions would have increased the R0 rate and reduced non-therapeutic interventions. [source] The anatomic location of pancreatic cancer is a prognostic factor for survivalHPB, Issue 5 2008Avo Artinyan Abstract Background. Pancreatic cancers of the body and tail (BT) appear to have poorer survival compared with head (HD) lesions. We hypothesized that potential disparities in outcome may be related to tumor location. Our objective was to examine the relationship between tumor location and survival. Methods. The Surveillance, Epidemiology, and End Results registry identified 33,752 patients with pancreatic adenocarcinoma and 6443 patients who underwent cancer-directed surgery between 1988 and 2004. Differences in survival and relationships between tumor location and clinical factors were assessed. Multivariate analysis was performed to determine the prognostic significance of tumor location. Results. Median survival for the entire cohort was five months and was significantly lower for BT compared to HD lesions (four vs. six months, p<0.001). Distant metastases (67% vs. 36%, p<0.001) were greater and cancer-directed surgery (16% vs. 30%, p<0.001) was lower for BT tumors. Of 6443 resected patients, HD patients (n=5118) were younger, had a greater number of harvested lymph nodes, were more likely to be lymph node-positive, and had a higher proportion of T3/T4 lesions. Significant univariate predictors of survival included age, T-stage, number of positive and harvested lymph nodes. On multivariate analysis, BT location was a significant prognostic factor for decreased survival (OR 1.11, 95% CI 1.00,1.23, p=0.05). Discussion. Pancreatic BT cancers have a lower rate of resectability and poorer overall survival compared to HD lesions. Prospective large-cohort studies may definitively prove that tumor location is a prognostic factor for survival in patients with pancreatic cancer. [source] An update on familial pancreatic cancer and the management of asymptomatic relativesHPB, Issue 1 2007John A. Windsor Families of patients with pancreatic adenocarcinoma (PC) often ask about their own risk of developing this disease. There is now a sufficient body of evidence to inform relatives of their relative risk of developing PC. The purpose of this review is to provide practical advice for the clinician when confronted with questions about the risk of PC in relatives, and the role of genetic testing and screening in high-risk individuals. [source] Diagnosis of pancreatic cancerHPB, Issue 5 2006Fumihiko Miura Abstract The ability to diagnose pancreatic carcinoma has been rapidly improving with the recent advances in diagnostic techniques such as contrast-enhanced Doppler ultrasound (US), helical computed tomography (CT), enhanced magnetic resonance imaging (MRI), and endoscopic US (EUS). Each technique has advantages and limitations, making the selection of the proper diagnostic technique, in terms of purpose and characteristics, especially important. Abdominal US is the modality often used first to identify a cause of abdominal pain or jaundice, while the accuracy of conventional US for diagnosing pancreatic tumors is only 50,70%. CT is the most widely used imaging examination for the detection and staging of pancreatic carcinoma. Pancreatic adenocarcinoma is generally depicted as a hypoattenuating area on contrast-enhanced CT. The reported sensitivity of helical CT in revealing pancreatic carcinoma is high, ranging between 89% and 97%. Multi-detector-row (MD) CT may offer an improvement in the early detection and accurate staging of pancreatic carcinoma. It should be taken into consideration that some pancreatic adenocarcinomas are depicted as isoattenuating and that pancreatitis accompanied by pancreatic adenocarcinoma might occasionally result in the overestimation of staging. T1-weighted spin-echo images with fat suppression and dynamic gradient-echo MR images enhanced with gadolinium have been reported to be superior to helical CT for detecting small lesions. However, chronic pancreatitis and pancreatic carcinoma are not distinguished on the basis of degree and time of enhancement on dynamic gadolinium-enhanced MRI. EUS is superior to spiral CT and MRI in the detection of small tumors, and can also localize lymph node metastases or vascular tumor infiltration with high sensitivity. EUS-guided fine-needle aspiration biopsy is a safe and highly accurate method for tissue diagnosis of patients with suspected pancreatic carcinoma. 18F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has been suggested as a promising modality for noninvasive differentiation between benign and malignant lesions. Previous studies reported the sensitivity and specificity of FDG-PET for detecting malignant pancreatic tumors as being 71,100% and 64,90%, respectively. FDG-PET does not replace, but is complementary to morphologic imaging, and therefore, in doubtful cases, the method must be combined with other imaging modalities. [source] Long-term survival with stage IV poorly differentiated pancreatic adenocarcinomaHPB, Issue 2 2004BF Levy Background Metastatic poorly differentiated adenocarcinoma of the pancreas has a poor outcome despite the use of various chemotherapy regimes. Case outline A 57-year-old woman presented with a 3-month history of generalised abdominal pain associated with weight loss. Computed tomography (CT) showed a large tumour in the head and body of pancreas, and needle biopsy confirmed a poorly differentiated adenocarcinoma. Laparoscopy revealed liver metastases in both lobes, again histologically shown to be poorly differentiated adenocarcinoma. Six cycles of cisplatin, epirubicin and infusional 5-fluorouracil were given. Five years later the patient remains completely well. Repeat CT scans show a complete radiological response. Discussion Previous studies using numerous chemotherapy regimes have not significantly altered the outcome of pancreatic cancer. To the best of our knowledge this is the longest surviving case of a patient with advanced metastatic adenocarcinoma (stage IV) of the pancreas treated with chemotherapy. [source] Resection of renal metastases to the pancreas: a surgical challengeHPB, Issue 3 2003D Zacharoulis Background Metastasis to the pancreas from renal cell carcinoma (RCC) is distinctly uncommon. Most cases are detected at an advanced stage of the disease and are thus unsuitable for resection. A solitary RCC metastasis to the head of pancreas is rarely encountered and, although it is potentially amenable to surgical resection, surgeons may be hesitant to perform pancreatoduodenectomy. Cases outlines Two patients with a solitary RCC metastasis to the head of pancreas were treated by pancreatoduodenectomy, while a third with multiple RCC metastases declined any treatment. Two of the patients were asymptomatic, and one presented with anaemia and mild abdominal pain. Computed tomography (CT) and angiography were used to exclude other metastases and to assess resectability of the pancreatic tumour. All three patients are still alive, those with resectable disease at 2 years and 9 years and the one with irresectable disease at 4 years. Discussion Isolated RCC metastasis to the pancreas is a rare event. Patients present either on follow-up imaging or with symptoms such as mild abdominal pain, weight loss, jaundice, anaemia or gastrointestinal bleeding (whether occult or overt). Dynamic spiral CT can visualise the tumour and exclude distant metastasis. Angiography often reveals a highly vascularised tumour and will help to assess resectability. In the absence of widespread disease, pancreatic resection can provide long-term survival in metastatic RCC, although few cases have been reported with lengthy follow-up. The prognosis is better than for pancreatic adenocarcinoma. [source] Effects of base excision repair gene polymorphisms on pancreatic cancer survivalINTERNATIONAL JOURNAL OF CANCER, Issue 8 2007Donghui Li Abstract To explore the association between single nucleotide polymorphisms of DNA repair genes and overall survival of patients with pancreatic cancer, we conducted a study in 378 cases of pancreatic adenocarcinoma who were treated at The University of Texas M. D. Anderson Cancer Center between February 1999 and October 2004 and were followed up to April 2006. Genotypes were determined using genomic DNA and the MassCode method. Overall survival was analyzed using the Kaplan,Meier plot, log-rank test and Cox regression. We observed a strong effect of the POLB A165G and T2133C genotypes on overall survival. The median survival time (MST) was 35.7 months for patients carrying at least 1 of the 2 homozygous variant POLB GG or CC genotypes, compared with 14.8 months for those carrying the AA/AG or TT/TC genotypes (p = 0.02, log rank test). The homozygous variants of hOGG1 G2657A, APEX1 D148E and XRCC1 R194W polymorphisms all showed a weak but significant effect on overall survival as demonstrated by either log rank test or multivariate COX regression after adjusting for other potential confounders. In combined genotype analysis, a predominant effect of the POLB homozygous variants on survival was observed. When POLB was not included in the model, a slightly better survival was observed among those carrying none of the adverse genotypes than those carrying at least one of the adverse genotypes. These observations suggest that polymorphisms of base excision repair genes significantly affect the clinical outcome of patients with pancreatic cancer. These observations need to be confirmed in a larger study of homogenous patient population. © 2007 Wiley-Liss, Inc. [source] Contrast-enhanced power Doppler sonography of ductal pancreatic adenocarcinomas: Correlation with digital subtraction angiography findingsJOURNAL OF CLINICAL ULTRASOUND, Issue 4 2004Chien-Hua Chen MD Abstract Purpose The purpose of this prospective study was to utilize contrast-enhanced power Doppler sonography to evaluate the enhancement characteristics of ductal pancreatic adenocarcinomas and correlate them with the tumor vascularity observed on digital subtraction angiography (DSA). Methods Twenty consecutive patients with ductal pancreatic adenocarcinoma underwent power Doppler sonography and DSA. Tumor vascularity was assessed using unenhanced and contrast-enhanced power Doppler sonography. The contrast agent Levovist was administered intravenously by bolus injection of a dose of 2.5 g at a concentration of 350 mg/mL; saline was administered immediately thereafter. The patients were asked to hold their breath for 30 seconds (for the period 15,45 seconds after saline injection) while the early phase of enhancement was studied; the delayed phase of enhancement was observed between 60 and 120 seconds after saline administration, while patients breathed gently. Results None of the 20 pancreatic carcinomas showed any color signals on power Doppler sonography before administration of the contrast medium. Seventeen (85%) of the 20 pancreatic carcinomas also showed no enhancement in the early and delayed phases of contrast-enhanced power Doppler sonography. However, in the early phase of contrast-enhanced power Doppler sonography; 1 lesion showed pronounced enhancement and 2 showed mild enhancement. On DSA, the 17 carcinomas showing no enhancement on power Doppler sonography were found to be hypovascular, whereas the remaining 3 carcinomas with contrast enhancement on power Doppler sonography were found to be hypervascular. Conclusions The enhancement characteristics of the ductal pancreatic adenocarcinomas correlated well with the tumor vascularity observed on DSA. However, further study is needed to determine the accuracy of contrast-enhanced sonography in the diagnosis of pancreatic masses. © 2004 Wiley Periodicals, Inc. J Clin Ultrasound 32:179,185, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jcu.20018 [source] Pathogenesis and outcome of extrahepatic biliary obstruction in catsJOURNAL OF SMALL ANIMAL PRACTICE, Issue 6 2002P. D. Mayhew Extrahepatic biliary obstruction (EHBO) was confirmed at surgery or necropsy in 22 cats. Biliary or pancreatic adenocarcinoma was diagnosed by histopathology in six cats and one cat had an undiagnosed mass in the common bile duct. The remaining 15 cats had at least one of a complex of inflammatory diseases including pancreatitis, cholangiohepatitis, cholelithiasis and cholecystitis. The most common clinical signs were jaundice, anorexia, lethargy, weight loss and vomiting. Hyperbilirubinaemia was present in all cases. Distension of the common bile duct and gall bladder was the most commonly observed finding on abdominal ultrasound. Nineteen cats underwent exploratory laparotomy for biliary decompression and diversion. Mortality in cats with underlying neoplasia was 100 per cent and, in those with non-neoplastic lesions, was 40 per cent. Long-term complications, in those that survived, included recurrence of cholangiohepatitis, chronic weight loss and recurrence of obstruction. Based on these findings, the prognosis for EHBO in cats must be considered guarded. [source] Role of endoscopic ultrasound in pancreatic adenocarcinomaJOURNAL OF SURGICAL ONCOLOGY, Issue 4 2007Diego Kuperschmit MD No abstract is available for this article. [source] CD97, CD95 and Fas-L clearly discriminate between chronic pancreatitis and pancreatic ductal adenocarcinoma in perioperative evaluation of cryocut sectionsPATHOLOGY INTERNATIONAL, Issue 2 2002Carsten Boltze It is a major problem to distinguish between pancreatitis and pancreatic adenocarcinoma when it comes to the perioperative evaluation of pancreatic cryocut sections. In this respect, pathologists are showing a steadily growing interest in the potential application of apoptotic and dedifferentiation factors as diagnostic and prognostic markers. This study investigated the mRNA and protein expression of CD97, CD95 and Fas-L in snap-frozen material obtained from human pancreatic ductal adenocarcinomas (PDC; n = 50), tissues from pancreatitis (PT; n = 40) and normal pancreatic tissues (PN; n = 36). Reverse transcription,polymerase chain reaction (RT,PCR) analysis revealed that CD97, CD95 and Fas-L mRNA were expressed on a similarly high level in all tissues. In contrast, short time immunohistochemical evaluation showed that the CD95 protein was strongly expressed in PT and PN, but not in PDC. Fas-L protein was expressed strongly in PDC, whereas only weak or no expression was noted in PT or PN. CD97 protein expression was detected only in PT and in poorly differentiated PDC. Our data demonstrate that CD97, CD95 and Fas-L can be used as additional markers to distinguish between pancreatitis and pancreatic duct cell carcinoma in cryocut sections. [source] Pancreatitis-Associated Protein Is Related Closely to Neoplastic Proliferative Activity in Patients with Colorectal CarcinomaTHE ANATOMICAL RECORD : ADVANCES IN INTEGRATIVE ANATOMY AND EVOLUTIONARY BIOLOGY, Issue 2 2009Guang Cao Abstract Pancreatitis-associated protein (PAP) is a secretory protein that is not only expressed during acute pancreatitis but also in pancreatic adenocarcinoma, gastric carcinoma, hepatocellular carcinoma, and colorectal carcinoma. Expression in carcinoma might be another characteristic of PAP. The aim of our study was to assess, in 27 patients undergoing surgery for colorectal carcinoma, the expression of the PAP mRNA and to evaluate its association with DNA ploidy and proliferative activity (S-phase fraction, SPF) by reverse transcriptase-polymerase chain reaction (RT-PCR) and flow cytometric analysis (FCM). PAP mRNA was expressed in 29.6% (8 of 27) of the patients with colorectal carcinoma. DNA aneuploid and high SPF were found in 87.5% (7 of 8) of patients with PAP mRNA positive colorectal carcinoma. The serum PAP level was significantly elevated in patients with colorectal carcinoma when compared with the healthy subjects. Twelve of the 27 patients with colorectal carcinoma had high serum PAP concentrations (>25 ng/mL) and the mean SPF was 17.82% ± 8.02%, which was significantly higher compared with the normal colorectal tissue group (7.33% ± 3.18%, P < 0.05). The mean serum PAP concentration of DNA aneuploidy colorectal carcinomas was 46.67 ± 17.58 ng/mL, which was significantly different when compared with the DNA diploidy group (19.18 ± 8.89 ng/mL, P < 0.05). PAP mRNA expression and serum PAP levels are closely related to neoplastic proliferative activity in patients with colorectal carcinoma. No significant differences are observed between PAP mRNA expression and clinicopathologic parameters (P > 0.05). Anat Rec, 2009. © 2008 Wiley-Liss, Inc. [source] Cutaneous metastasis as the first clinical manifestation of pancreatic adenocarcinoma: A case treated with gemcitabineTHE JOURNAL OF DERMATOLOGY, Issue 9 2007Noriko TAKEMURA No abstract is available for this article. [source] Preclinical evaluation of carcinoembryonic cell adhesion molecule (CEACAM) 6 as potential therapy target for pancreatic adenocarcinoma,THE JOURNAL OF PATHOLOGY, Issue 3 2009Laura A Strickland Abstract Despite the availability of new targeted therapies, ductal pancreatic adenocarcinoma continues to carry a poor prognosis. Carcinoembryonic antigen-related cell adhesion molecule (CEACAM)6 has been reported as a potential biomarker and therapy target for this malignancy. We have evaluated CEACAM6 as a potential therapy target, using an antibody,drug conjugate (ADC). Expression of CEACAM6 in pancreatic adenocarcinomas was determined using immunohistochemistry on tissue microarrays. The expression pattern in granulocytes and granulocytic precursors was measured by flow cytometry. Murine xenograft and non-human primate models served to evaluate efficacy and safety, respectively. Robust expression of CEACAM6 was found in > 90% of invasive pancreatic adenocarcinomas as well as in intraepithelial neoplastic lesions. In the granulocytic lineage, CEACAM6 was expressed at all stages of granulocytic maturation except for the early lineage-committed precursor cell. The anti-CEACAM6 ADC showed efficacy against established CEACAM6-expressing tumours. In non-human primates, antigen-dependent toxicity of the ADC consisted of dose-dependent and reversible depletion of granulocytes and their precursors. This was associated with preferential and rapid localization of the antibody in bone marrow, as determined by sequential in vivo PET imaging of the radiolabelled anti-CEACAM6. Localization of the radiolabelled tracer could be attenuated by predosing with unlabelled antibody confirming specific accumulation in this compartment. Based on the expression pattern in normal and malignant pancreatic tissues, efficacy against established tumours and limited and reversible bone marrow toxicity, we propose that CEACAM6 should be considered for an ADC-based therapy approach against pancreatic adenocarcinomas and possibly other CEACAM6-positive neoplasms. Copyright © 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. [source] Curative resection is the single most important factor determining outcome in patients with pancreatic adenocarcinomaBRITISH JOURNAL OF SURGERY (NOW INCLUDES EUROPEAN JOURNAL OF SURGERY), Issue 5 2004M. Wagner Background: Mortality rates associated with pancreatic resection for cancer have steadily decreased with time, but improvements in long-term survival are less clear. This prospective study evaluated risk factors for survival after resection for pancreatic adenocarcinoma. Methods: Data from 366 consecutive patients recorded prospectively between November 1993 and September 2001 were analysed using univariate and multivariate models. Results: Fifty-eight patients (15·8 per cent) underwent surgical exploration only, 97 patients (26·5 per cent) underwent palliative bypass surgery and 211 patients (57·7 per cent) resection for pancreatic adenocarcinoma. Stage I disease was present in 9·0 per cent, stage II in 18·0 per cent, stage III in 68·7 per cent and stage IV in 4·3 per cent of patients who underwent resection. Resection was curative (R0) in 75·8 per cent of patients. Procedures included pylorus-preserving Whipple resection (41·2 per cent), classical Whipple resection (37·0 per cent), left pancreatic resection (13·7 per cent) and total pancreatectomy (8·1 per cent). The in-hospital mortality and cumulative morbidity rates were 2·8 and 44·1 per cent respectively. The overall actuarial 5-year survival rate was 19·8 per cent after resection. Survival was better after curative resection (R0) (24·2 per cent) and in lymph-node negative patients (31·6 per cent). A Cox proportional hazards survival analysis indicated that curative resection was the most powerful independent predictor of long-term survival. Conclusion: Resection for pancreatic adenocarcinoma can be performed safely. The overall survival rate is determined by the radicality of resection. Patients deemed fit for surgery who have no radiological signs of distant metastasis should undergo surgical exploration. Resection should follow if there is a reasonable likelihood that an R0 resection can be obtained. Copyright © 2004 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd. [source] Adjuvant therapy and survival after resection of pancreatic adenocarcinomaCANCER, Issue 12 2010A population-based analysis Abstract BACKGROUND: The use of adjuvant chemoradiation for pancreatic adenocarcinoma (PAC) is accepted in North America, but there is a paucity of data to support this practice. The relation between adjuvant therapy and survival was assessed in a population-based cohort of patients with PAC. METHODS: A review was conducted of all cases of resected PAC from 1996 to 2003 using data from the state cancer registry augmented with data from primary medical record review. Use of adjuvant therapy was ascertained from registry data. Survival was assessed using the Kaplan-Meier method, and a Cox proportional hazards model was developed for multivariate analysis. RESULTS: A total of 298 patients from 27 hospitals met criteria for inclusion. There were 228 patients (76.5%) who were resected with curative intent, with a median overall survival of 12 months. The 6-month, 1-year, and 5-year survival rates were 80.2%, 58.4%, and 6.7%, respectively. Of the 228 patients resected, 122 (53.5%) received adjuvant treatment and had a median survival of 13.0 months versus 11.0 months for those with no adjuvant treatment (P = .16). After adjustment for surrogates of performance status, significant predictors of overall survival included no weight loss, T1/T2 pathologic stage, a microscopically complete resection (R0), and receipt of adjuvant therapy. CONCLUSIONS: An R0 resection and adjuvant therapy were found to be independently associated with an increase in overall survival in patients with resected PAC. These data underscore the importance of adjuvant therapy in resected PAC and the need for ongoing clinical trials to refine the efficacy and timing of adjuvant therapy in this disease. Cancer 2010. © 2010 American Cancer Society. [source] Cystic fibrosis transmembrane conductance regulator (CFTR) gene mutations and risk for pancreatic adenocarcinomaCANCER, Issue 1 2010Robert R. McWilliams MD Abstract BACKGROUND: Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are common in white persons and are associated with pancreatic disease. The purpose of this case-control study was to determine whether CFTR mutations confer a higher risk of pancreatic cancer. METHODS: In a case-control study, the authors compared the rates of 39 common cystic fibrosis-associated CFTR mutations between 949 white patients with pancreatic adenocarcinoma and 13,340 white controls from a clinical laboratory database for prenatal testing for CFTR mutations. The main outcome measure was the CFTR mutation frequency in patients and controls. RESULTS: Overall, 50 (5.3%) of 949 patients with pancreatic cancer carried a common CFTR mutation versus 510 (3.8%) of 13,340 controls (odds ratio [OR], 1.40; 95% confidence interval [CI], 1.04-1.89; P = .027). Among patients who were younger when their disease was diagnosed (<60 years), the carrier frequency was higher than in controls (OR, 1.82; 95% CI, 1.14-2.94; P = .011). In patient-only analyses, the presence of a mutation was associated with younger age (median 62 vs 67 years; P = .034). In subgroups, the difference was seen only among ever-smokers (60 vs 65 years, P = .028). Subsequent sequencing analysis of the CFTR gene detected 8 (16%) compound heterozygotes among the 50 patients initially detected to have 1 mutation. CONCLUSIONS: Carrying a disease-associated mutation in CFTR is associated with a modest increase in risk for pancreatic cancer. Those affected appear to be diagnosed at a younger age, especially among smokers. Clinical evidence of antecedent pancreatitis was uncommon among both carriers and noncarriers of CFTR mutations. Cancer 2010. © 2010 American Cancer Society. [source] Carbohydrate antigen 19-9 change during chemotherapy for advanced pancreatic adenocarcinomaCANCER, Issue 12 2009Michele Reni MD Abstract BACKGROUND: Radiologic assessment of tumor response in pancreatic cancer is complicated by desmoplastic reactions within or around the tumor. The objective of this study was to evaluate the correlation between a decline in carbohydrate antigen 19-9 (CA 19-9) and survival in patients with advanced pancreatic cancer who received upfront chemotherapy. METHODS: CA 19-9 serum basal values were measured in 247 patients with advanced pancreatic cancer who were enrolled in 5 consecutive trials between 1997 and 2007. Survival curves were compared among patients who had a predefined CA 19-9 nadir variation (<50%. Group 1; 50% to 89%, Group 2; or >89%, Group 3). To eliminate guarantee-time bias, survival analysis was repeated using the landmark method. RESULTS: In both univariate and multivariate analysis, the basal CA 19-9 value significantly predicted survival. The median survival was 15.5 months for 34 patients who had normal basal CA 19-9 values, 11.9 months for 108 patients who had basal values between 38 U/mL and 1167 U/mL, and 8 months for 105 patients who had basal values >1167 U/mL. At least 1 CA 19-9 follow-up value was available for 204 patients who had baseline values greater than normal. A significant difference in overall survival was observed in univariate and multivariate analyses between Groups 1 and 2, between Groups 1 and 3, and between Groups 2 and 3. The results were confirmed using the landmark method. CONCLUSIONS: In this study, baseline CA 19-9 was confirmed as an independent prognostic factor for survival, and it may be considered as a stratification factor in trials in patients with advanced pancreatic cancer. Biochemical response may be used as a complementary measure to radiologic response to provide a better assessment of chemotherapy activity and to drive treatment decisions in clinical practice. Cancer 2009. © 2009 American Cancer Society. [source] Myeloperoxidase and superoxide dismutase polymorphisms are associated with an increased risk of developing pancreatic adenocarcinomaCANCER, Issue 5 2008Paul Wheatley-Price MB Abstract BACKGROUND. Pancreatic cancer risk has been linked to chronic pancreatitis and periodontitis, suggesting a role for inflammation in disease etiology. Myeloperoxidase (MPO) and superoxide dismutase (SOD2) are enzymes that regulate reactive oxygen species and contain recognized single nucleotide polymorphisms (SNPs) that confer altered enzyme activity. METHODS. One hundred twenty-two patients with pancreatic cancer and 331 age- and sex-matched controls were analyzed for polymorphisms of the MPO , guanine 463 adenine (,G463A) and the SOD2 alanine (Ala)-to-valine (Val) polymorphism at codon 16 (Ala16Val) genes. Cases and controls were analyzed for associations between these polymorphisms, adjusting for sex, age, history of alcohol use and smoking history. RESULTS. The variant A allele of MPO ,G463A was associated with a lower risk of pancreatic cancer (adjusted odds ratio [OR] for pancreatic cancer, 0.57; 95% confidence interval [95% CI], 0.4,0.9; P = .02). The SOD2 homozygous variant genotype (Val/Val) was associated with a greater risk of pancreatic cancer (adjusted OR, 1.96; 95% CI, 1.0,3.8; P = .04). Compared with individuals who carried both low-risk alleles (A/, and Ala/,), significantly more cases than controls carried both high-risk genotypes (G/G and Val/Val; adjusted OR, 4.31; 95% CI, 1.8,10; P = .001), or 1 high-risk genotype (adjusted OR, 1.96; 95% CI, 1.1,3.4; P = .01). CONCLUSIONS. Polymorphisms of the inflammatory pathway genes MPO ,G463A and SOD2Ala16Val are associated with elevated pancreatic cancer risk. Oxidative stress may play an important role in pancreatic cancer carcinogenesis. Cancer 2008. © 2008 American Cancer Society. [source] Vascular endothelial growth factor, FLT-1, and FLK-1 analysis in a pancreatic cancer tissue microarray,CANCER, Issue 8 2006Gina G. Chung M.D. Abstract BACKGROUND Measures of vascular endothelial growth factor (VEGF) expression in pancreatic cancer typically have been qualitative or semiquantitative. The objective of this study was to use a series of algorithms called AQUA that quantitatively assesses protein expression on tissue microarrays (TMAs) to compare in situ expression of VEGF and its primary receptors, VEGF receptor 1 (FLT-1) and VEGF receptor 1 (FLK-1), on a pancreatic cancer TMA. METHODS TMAs were constructed by arraying 1.5-mm cores from 76 samples of pancreatic adenocarcinoma (1996-2002) that were obtained from the archives of the Yale Department of Pathology. The staining for AQUA was similar to standard immunohistochemistry and involved antigen retrieval and the application of primary antibodies, but with epifluorescence detection. Slides were counterstained with 4,,6-diamidino-2-phenylindole for nuclear visualization and cytokeratin for membrane visualization. The primary antibodies used were VEGF, FLT-1, FLK-1, and cytokeratin. RESULTS Disease stage was highly prognostic for outcome, as expected. Total amounts of VEGF and its receptors were assessed within the tumor mask and were divided into quartiles. Kaplan,Meier survival curves showed that VEGF and FLK-1 were not associated clearly with outcome. However, the expression of FLT-1 was correlated significantly, and the patients who had tumors with the lowest expression FLT-1 levels had the worst survival (P = .0038). In multivariate analysis, FLT-1 expression was an independent prognostic factor for overall survival (P = .0044). CONCLUSIONS VEGF and its 2 principal receptors were expressed to varying degrees in tumors of the pancreas. A significant association was found between low expression of FLT-1 and both poor prognosis and advanced stage, suggesting that tumor expression of this VEGF receptor is a marker of less aggressive disease. Cancer 2006. © 2006 American Cancer Society. [source] Cytokeratin 20 expression identifies a subtype of pancreatic adenocarcinoma with decreased overall survivalCANCER, Issue 3 2006Evan Matros M.D. Abstract BACKGROUND Cytokeratins are markers of epithelial cell differentiation useful in determining histogenesis for malignancies with an unknown primary. Application of this principle to a single malignancy may identify cancer subtypes with altered developmental programs. Herein, we investigate the relevance of two widely used cytokeratins (CKs), 7 and 20, to subtype pancreas cancer and identify associations with clinical features. METHODS A tissue microarray was constructed using tumor specimens from 103 patients who underwent resection for pancreatic adenocarcinoma with curative intent. A subset of resection specimens was evaluated for pancreatic intraepithelial neoplasia (PanIN) lesions. Tissues were immunostained by using specific anticytokeratin 7 and 20 monoclonal antibodies. RESULTS CK 7 and 20 expression was present in 96% and 63% cases of pancreatic adenocarcinoma, respectively. Ubiquitous CK 7 expression precluded further analysis. Tumoral CK 20 expression was not associated with any histopathologic parameter but correlated with worse prognosis when considered as either a dichotomous (P = 0.0098) or continuous (P = 0.007) variable. In a multivariate model, tumoral CK 20 expression remained a significant independent prognosticator. CK 20 expression was absent in all PanIN lesions from eight resection specimens in which the tumor component was negative for CK 20. In contrast, presence of tumoral CK 20 was highly concordant with its expression in corresponding PanINs. CONCLUSIONS CK 20 expression defines a subtype of pancreas cancer with important biologic properties. When present, CK 20 expression is an early event in pancreatic carcinogenesis identifiable in precursor lesions. Further studies to identify the underlying genetic changes associated with this altered developmental pathway are warranted. Cancer 2006. © 2005 American Cancer Society. [source] Risk of pancreatic adenocarcinomaCANCER, Issue 2 2005Disparity between African Americans, other race/ethnic groups Abstract BACKGROUND African Americans have a higher incidence of pancreatic adenocarcinoma compared with non-Hispanic whites. Whether other clinical differences exist between these two groups is not well known. METHODS The authors conducted a population-based retrospective analysis of all patients with pancreatic adenocarcinoma in both a regional and a statewide database between 1988 and 1998. Their goal was to evaluate differences in incidence rates, clinical presentation, including age at diagnosis, gender, and tumor characteristics, and treatment among race/ethnic groups. RESULTS African Americans had a higher age-adjusted incidence rate of pancreatic adenocarcinoma (8.78) compared with non-Hispanic whites (5.89), Hispanics (5.09), Asians (4.75), and all race/ethnicities combined (5.82). African Americans also presented at a later stage of disease and received less surgery than all other race/ethnicities, despite equal availability of medical insurance. The analyses also revealed gender differences. In general, males maintained a higher incidence rate of pancreatic adenocarcinoma than females across all race/ethnicities. In all race/ethnic groups, females were diagnosed at an older age and an earlier stage of disease than males. The proportional hazard mortality ratio for females age < 60 was significantly less than that for males in the same age group (P < 0.02), even after accounting for stage and treatment. CONCLUSIONS African Americans in California had a higher incidence rate of pancreatic adenocarcinoma, had a slightly higher risk of presenting with advanced-stage diseas and with nonresectable tumors (i.e., tumors located in the body or tail of the pancreas), and underwent less surgical treatment than all other race/ethnicities. Younger females in all race/ethnic groups had a survival advantage over males of the same age. Cancer 2005. © 2004 American Cancer Society. [source] Overexpression of synuclein-, in pancreatic adenocarcinomaCANCER, Issue 1 2004Zhongkui Li Ph.D. Abstract BACKGROUND Currently, pancreatic adenocarcinoma is the fourth leading cause of cancer-related death in the United States. Despite the advances in pancreatic carcinoma research, patients with this devastating disease have a very poor prognosis. To identify the gene expression profile of pancreatic carcinoma, an important step in the process of developing new diagnostic and therapeutic strategies, the authors investigated the alteration of gene expression in this disease. METHODS The authors analyzed a public serial analysis of gene expression (SAGE) database and examined in greater detail the expression of synuclein-, mRNA in several pancreatic carcinoma cell lines and tumor tissue samples by reverse transcriptase,polymerase chain reaction (RT-PCR) analysis and Northern blot analysis. The expression of synuclein-, protein was investigated further by immunohistochemical and Western blot analyses using tumor cell lines, tumor tissue, and serum samples. RESULTS Synuclein-, mRNA was overexpressed in 11 of 12 pancreatic carcinoma cell lines, including AsPc-1, MDAPanc28, Capan-1, Capan-2, PANC-1, HS766T, MDAPanc3, MDAPanc48, Colo357FG, MiaPaCa2, CFPac1, and BxPc3. The expression of synuclein-, protein was detectable in 8 of 12 pancreatic carcinoma cell lines (67%) and in 22 of 32 pancreatic tumor tissue samples (69%) by Western blot analysis. On immunohistochemical staining, synuclein-, protein was present in 61% of the tumor tissue samples examined from patients with Stage I and II pancreatic carcinoma. The overexpression of synuclein-, is correlated with perineural and lymph node invasion. Synuclein-, protein also was detectable by Western blot in serum samples from 21 of 56 patients (38%) with pancreatic carcinoma. CONCLUSIONS Synuclein-,, which initially was described as a breast carcinoma,specific gene involved in invasion, metastasis, and chemotherapy resistance, was frequently overexpressed in pancreatic carcinoma. Overexpression of synuclein-, may play a role in pancreatic carcinoma invasion. Further studies will be necessary to determine the role of synuclein-, in pancreatic carcinoma. Cancer 2004. © 2004 American Cancer Society. [source] Genome-wide array-based comparative genomic hybridization analysis of pancreatic adenocarcinoma: Identification of genetic indicators that predict patient outcomeCANCER SCIENCE, Issue 3 2007Panayiotis Loukopoulos We analyzed the subchromosomal numerical aberrations of 44 surgically resected pancreatic adenocarcinomas by array-based comparative genomic hybridization. The aberration profile ranged widely between cases, suggesting the presence of multiple or complementary mechanisms of evolution in pancreatic cancer, and was associated with lymph node metastasis and venous or serosal invasion. A large number of small loci, previously uncharacterized in pancreatic cancer, showed non-random loss or gain. Frequent losses at 1p36, 4p16, 7q36, 9q34, 11p15, 11q13, 14q32-33, 16p13, 17p11-13, 17q11-25, 18q21-tel, 19p13, 21q22 and 22q11-12, and gains at 1q25, 2p16, 2q21-37, 3q25, 5p14, 5q11-13, 7q21, 7p22, 8p22, 8q21-23, 10q21, 12p13, 13q22, 15q13-22 and 18q11 were identified. Sixteen loci were amplified recurrently. We identified novel chromosomal alterations that were significantly associated with a range of malignant phenotypes. Gain of LUNX, HCK, E2F1 and DNMT3b at 20q11, loss of p73 at 1p36 and gain of PPM1D at 17q23 independently predicted patient outcome. Expression profiling of amplified genes identified Smurf1 and TRRAP at 7q22.1, BCAS1 at 20q13.2-3, and VCL at 10q22.1 as potential novel oncogenes. Our results contribute to a complete description of genomic structural aberrations and the identification of potential therapeutic targets and genetic indicators that predict patient outcome in pancreatic adenocarcinoma. (Cancer Sci 2007; 98: 392,400) [source] |