Clinical Features Of Pancreatic Cancer Research Articles

Value of serum miR-486-5p combined with carbohydrate antigen 19-9 in predicting resectable or borderline resectable pancreatic cancer

Objective To investigate the expression level of serum miR-486-5p in patients with pancreatic cancer and the value of serum miR-486-5p combined with carbohydrate antigen 19-9 (CA19-9) in predicting the resectability of pancreatic cancer. Methods A total of 60 patients who were diagnosed with pancreatic cancer in Qingdao Municipal Hospital from September 2018 to December 2020 were enrolled, among whom 32 patients had resectable or borderline resectable pancreatic cancer (operable group) and 28 had unresectable pancreatic cancer (non-operable group), and a benign pancreatic disease group with 30 patients and a healthy control group with 44 individuals were also established. Quantitative real-time PCR was used to measure the serum level of miR-486-5p in each group, and the relative expression level of miR-486-5p was calculated to analyze its association with the clinical features of pancreatic cancer, including age, sex, tumor location, tumor size, TNM stage, lymphatic metastasis, and distant metastasis. The Mann-Whitney U test was used for comparison of non-normally distributed continuous variables between two groups, and the chi-square test was used for comparison of categorical variables. The receiver operating characteristic (ROC) curve was plotted, and a binary logistic regression analysis was used to calculate the combined predictive value and then investigate the value of serum miR-486-5p combined with CA19-9 in predicting the resectability of pancreatic cancer. Results The relative expression level of serum miR-486-5p in the operable group [2.16 (1.38~3.30)] and the non-operable group [4.65 (2.80~9.90)] was significantly higher than that in the benign pancreatic disease group [1.01 (0.52~1.53)] and the healthy control group [0.99 (0.24~1.01)] (all P Conclusion MiR-486-5p can be used as a serum biomarker for the diagnosis of pancreatic cancer, and miR-486-5p combined with CA19-9 has a better clinical value than CA19-9 alone in predicting the resectability of pancreatic cancer in the patients with benign pancreatic diseases and the healthy population.

A Novel Four-Gene Score to Predict Pathologically Complete (R0) Resection and Survival in Pancreatic Cancer.

Simple SummaryA biomarker to predict survival is a critical need in pancreatic cancer treatment. We hypothesized that a four-gene score, which was previously reported to reflect cell proliferation, can be used as a predictive biomarker for pancreatic cancer. A total of 954 patients were analyzed for both discovery and validation of the four-gene score from publicly available datasets for pancreatic cancer, in order to investigate the relationship between the score and clinical features of pancreatic cancer, such as metastasis, cancer aggressiveness, immune cell infiltration, patient survival, and resectability. We found that the score correlated with clinical aggressiveness in pancreatic cancer, and did so to a higher degree compared to breast cancer cohorts. We found that the four-gene score identified poor survival in pancreatic cancer, and has potential as a predictive biomarker of treatment response in metastatic pancreatic cancer, as well completion of a pathologically complete (R0) resection. Appropriately utilized, the four-gene score could be a valuable prognostic and predictive tool for pancreatic cancer in the future.Pathologically complete (R0) resection is essential for prolonged survival in pancreatic cancer. Survival depends not only on surgical technique, but also on cancer biology. A biomarker to predict survival is a critical need in pancreatic treatment. We hypothesized that this 4-gene score, which was reported to reflect cell proliferation, is a translatable predictive biomarker for pancreatic cancer. A total of 954 pancreatic cancer patients from multiple cohorts were analyzed and validated. Pancreatic cancer had the 10th highest median score of 32 cancers in The Cancer Genome Atlas (TCGA) cohort. The four-gene score significantly correlated with pathological grade and MKI67 expression. The high four-gene score enriched cell proliferation-related and cancer aggressiveness-related gene sets. The high score was associated with activation of KRAS, p53, transforming growth factor (TGF)-β, and E2F pathways, and with high alteration rate of KRAS and CDKN2A genes. The high score was also significantly associated with reduced CD8+ T cell infiltration of tumors, but with high levels of interferon-γ and cytolytic activity in tumors. The four-gene score correlated with the area under the curve of irinotecan and sorafenib in primary pancreatic cancer, and with paclitaxel and doxorubicin in metastatic pancreatic cancer. The high four-gene score was associated with significantly fewer R0 resections and worse survival. The novelty of the study is in the application of the four-gene score to pancreatic cancer, rather than the bioinformatics technique itself. Future analyses of inoperable lesions are expected to clarify the utility of our score as a predictive biomarker of systemic treatments.

Circ_0075829 facilitates the progression of pancreatic carcinoma by sponging miR-1287-5p and activating LAMTOR3 signalling.

Pancreatic cancer (PC) is a leading cause of cancer‐related mortality globally. Though increasing evidence has demonstrated that circular RNAs (circRNAs) are linked to the development and progression of cancers, the biological functions of circRNAs in PC remain largely unexplored so far. Based on previous studies, Hsc_circ_0075829 (circ_0075829) was screened out and then further identified in PC clinical specimens and cell lines by real‐time PCR. After the stability tests, a series of in vitro and in vivo functional experiments were performed to investigate the role of circ_0075829 in PC development. Furthermore, fluorescent in situ hybridization (FISH), bioinformatics tools, dual‐luciferase assays and rescue experiments were conducted to clarify the regulatory mechanisms of circ_0075829 in SW1990 and BxPC‐3 cells. Compared with paracancerous tissues, the expression of circ_0075829 was increased in PC tissues, which was positively correlated with the clinical features of PC. Knockdown of circ_0075829 significantly suppressed the proliferative, migratory and invasive rates of SW1990 and BxPC‐3 cells both in vitro and in vivo. Bioinformatics analysis and dual‐luciferase reporter gene assay indicated that circ_0075829 could bind to miR‐1287‐5p. Mechanism research and rescue experiments demonstrated that circ_0075829 could regulate the LAMTOR3/p‐ERK signalling pathway via sponging miR‐1287‐5p in PC cell lines. Our data reveal that the circ_0075829 could facilitate the proliferation and metastasis of PC through circ_0075829/miR‐1287‐5p/LAMTOR3 axis.

Subgroup analysis reveals molecular heterogeneity and provides potential precise treatment for pancreatic cancers.

BackgroundThe relationship between molecular heterogeneity and clinical features of pancreatic cancer remains unclear. In this study, pancreatic cancer was divided into different subgroups to explore its specific molecular characteristics and potential therapeutic targets.Patients and methodsExpression profiling data were downloaded from The Cancer Genome Atlas database and standardized. Bioinformatics techniques such as unsupervised hierarchical clustering was used to explore the optimal molecular subgroups in pancreatic cancer. Clinical pathological features and pathways in each subgroup were also analyzed to find out the potential clinical applications and initial promotive mechanisms of pancreatic cancer.ResultsPancreatic cancer was divided into three subgroups based on different gene expression features. Patients included in each subgroup had specific biological features and responded significantly different to chemotherapy.ConclusionThree distinct subgroups of pancreatic cancer were identified, which means that patients in each subgroup might benefit from targeted individual management.

Doublecortin-Like Kinase 1 (DCLK1) Regulates B Cell-Specific Moloney Murine Leukemia Virus Insertion Site 1 (Bmi-1) and is Associated with Metastasis and Prognosis in Pancreatic Cancer

Background/Aims: Cancer stem cells (CSCs) are largely responsible for tumor relapse and metastatic behavior. Doublecortin-like kinase 1 (DCLK1) was recently reported to be a biomarker for gastrointestinal CSCs and involved in the epithelial-mesenchymal transition (EMT) and tumor progression. B cell-specific Moloney murine leukemia virus insertion site 1 (Bmi-1) is a crucial regulator of CSC self-renewal, malignant transformation and EMT, and a previous study from our group showed that Bmi-1 is upregulated in pancreatic cancer progression and participates in EMT. However, it remains unclear whether DCLK1 is involved in pancreatic cancer or whether DCLK1 is associated with the altered level of Bmi-1 expression. Methods: The correlation of DCLK1 expression and clinical features of pancreatic cancer was analyzed in 210 paraffin-embedded archived pancreatic cancer specimens by immunohistochemical analysis. The biological effects of DCLK1 siRNA on cells were investigated by examining cell proliferation using a cell counting kit and cell colony assays, cell migration by wound healing assay and cell invasion by Transwell invasion assay. We further investigated the effect of therapeutic siRNA targeting DCLK1 on pancreatic cancer cell growth in vivo. Moreover, the molecular mechanism by which DCLK1 upregulates Bmi-1 expression was explored using real-time PCR, western blotting and Co-immunoprecipitation assay. Results: DCLK1 is overexpressed in pancreatic cancer and is related to metastasis and prognosis. Knockdown of DCLK1 markedly suppressed cell growth in vitro and in vivo and also inhibited the migration and invasion of pancreatic cancer cells. Furthermore, we found that DCLK1 silencing could inhibit EMT in cancer cells via downregulation of Bmi-1 and the mesenchymal markers Snail and Vimentin and upregulation of the epithelial marker E-cadherin. Moreover, high DCLK1 expression in human pancreatic cancer samples was associated with a mesenchymal phenotype and increased cell proliferation. Further co-immunoprecipitation indicated that DCLK1 did not interact with Bmi-1 directly. Conclusion: Our data suggest that upregulation of DCLK1 may contribute to pancreatic cancer metastasis and poor prognosis by increasing Bmi-1 expression indirectly. The findings indicate that inhibiting DCLK1 expression might be a novel strategy for pancreatic cancer therapy.

Retraction note to: the hypoxia-inducible factor-1 regulates the microRNA185 expression through binding to hypoxia response elements sequence 2.

This study aimed to investigate the interaction and regulatory mechanism of microRNA185 (miR185) and hypoxia-inducible factor-1 (HIF-1) in pancreatic cancer. The significance of miR185 on the clinicopathologic characteristics and prognosis was further explored. qRT-PCR and immunohistochemistry examined miR185 and HIF-1 expression of tumor tissues. Western blot analyzed HIF-1 protein expression. We regulated HIF-1 via transfection to observe the impact of HIF-1 on miR185 expression. ChIP sequencing and dual luciferase identified binding sites of HIF-1 and miR185. MiR185 expression was significantly higher in pancreatic tumors. MiR185 closely associated with tumor size, pTNM stage, lymph node, and perneural invasion. After hypoxic culture, both HIF-1 and miR185 expression of MiaPaCa2 and AsPc1 cells increased significantly. Up- or down-regulating HIF-1 expression via transfection leads to synchronous alteration of miR185. In ChIP sequencing, only the HRE2 (−938 bp) was significantly brighter under hypoxia among four hypoxia response elements’ (HREs) sequence of miR185 promoter. After pGL3-miR185 and HIF-1 over-expressing plasmids co-transfect the MiaPaCa2 cells, its relative expression of bioluminescence increased. MiR185 expression was significantly higher in tumor tissues and closely associated with the clinical features of pancreatic cancer. Expression of HIF-1 in pancreatic cancer cells increased in hypoxia. HIF-1 may bind to HRE2 of miR185 and initiate its transcription.

RETRACTED ARTICLE: The hypoxia-inducible factor-1 regulates the microRNA185 expression through binding to hypoxia response elements sequence 2

This study aimed to investigate the interaction and regulatory mechanism of microRNA185 (miR185) and hypoxia-inducible factor-1 (HIF-1) in pancreatic cancer. The significance of miR185 on the clinicopathologic characteristics and prognosis was further explored. qRT-PCR and immunohistochemistry examined miR185 and HIF-1 expression of tumor tissues. Western blot analyzed HIF-1 protein expression. We regulated HIF-1 via transfection to observe the impact of HIF-1 on miR185 expression. ChIP sequencing and dual luciferase identified binding sites of HIF-1 and miR185. MiR185 expression was significantly higher in pancreatic tumors. MiR185 closely associated with tumor size, pTNM stage, lymph node, and perneural invasion. After hypoxic culture, both HIF-1 and miR185 expression of MiaPaCa2 and AsPc1 cells increased significantly. Up- or down-regulating HIF-1 expression via transfection leads to synchronous alteration of miR185. In ChIP sequencing, only the HRE2 (-938 bp) was significantly brighter under hypoxia among four hypoxia response elements' (HREs) sequence of miR185 promoter. After pGL3-miR185 and HIF-1 over-expressing plasmids co-transfect the MiaPaCa2 cells, its relative expression of bioluminescence increased. MiR185 expression was significantly higher in tumor tissues and closely associated with the clinical features of pancreatic cancer. Expression of HIF-1 in pancreatic cancer cells increased in hypoxia. HIF-1 may bind to HRE2 of miR185 and initiate its transcription.

Clinical Features of Pancreatic Cancer Associated with Chronic Pancreatitis

Pancreatic cancer remains one of the most deadly diseases, despite significant advances in medicine over the past decade. Patients with chronic pancreatitis are known to have an increased risk of pancreatic cancer compared with the general population. There are few studies about the clinical features of pancreatic cancer associated with chronic pancreatitis. A recent retrospective study by Choi et al. showed that pancreatic cancer with chronic pancreatitis patients were younger at the time of the diagnosis and computed tomography findings showed only pancreatic duct dilatation without a mass in some cases. However, there were no differences between the two groups regarding resectability and the preoperative stage. Recent data indicate that imaging tests can detect asymptomatic precursor benign lesions in individuals with an inherited predisposition or strong family history. However, there are no consensus data about screening program in patient with chronic pancreatitis. (Korean J Med 2013;85:38-40)

Clinical Features of Pancreatic Cancer Associated with Chronic Pancreatitis in Korean Patients

ëª©ì : 췌장암은 예후가 매우 불량한 암으로 만성 췌장염은 췌장암의 위험인자로 ì•Œë ¤ì ¸ 있는데, 본 연구에서는 이런 환자에서 발생한 췌장암의 특징을 분석하여 조기진단 가능성을 ì•Œì•„ë³´ê³ ìž 하였다. 방법: 1989ë „ 1월 1일부터 2009ë „ 4월 30일까지 서울아산병원에 췌장암으로 ìž ì›í•œ 환자 중 만성 췌장염의 ê³¼ê±°ë ¥ì´ 있는 38ëª ê³¼ 대조군으로 만성 췌장염 없이 췌장암으로 진단된 환자 중 무작위 추출을 통해 ì„ íƒëœ 50ëª ì„ 대상으로 í›„í–¥ì ìœ¼ë¡œ 두 êµ° 간의 특징을 비교하였다. ê²°ê³¼: 췌장염이 있는 êµ°ê³¼ 없는 군에서 모두 남성이 많았으며 췌장암 진단 당시 나이는 췌장염 군에서 57.42 ± 11.55세, 췌장염 없는 êµ° 63.94 ± 11.42세 (p= 0.01)로 췌장염군이 더 ì–´ë ¸ìœ¼ë©° 흡연은 췌장염군(71.1% vs. 50.0%, p= 0.047)이 더 높았다. 췌장암 진단 당시의 임상 증상은 두 êµ° 간 차이가 없었다. 두 êµ° 모두에서 췌장 두부에서 암이 가장 호발했으며(57.9% vs. 64.0%), CA 19-9 값은 대부분 상승되어 ìžˆì—ˆê³ , í‰ê· ê°’ë„ ìœ ì˜í•œ 차이가 없었다. 진단 당시 ì „ì‚°í™” 단층촬영 이미지는 췌장염군에서 ì¢ ê´´ 없이 췌관확장만 존재하는 경우(15.8% vs. 2.0%, p= 0.018)가 ìœ ì˜í•˜ê²Œ 많았으며 진단 및 치료법에 있어 췌장염군에서 ìˆ˜ìˆ ì„ ì„ íƒí•˜ëŠ” 빈도가 높았다. ê²°ë¡ : 췌장염군은 영상 검사에서 ë¹„ì „í˜•ì ìœ¼ë¡œ ëšœë ·í•œ ì¢ ê´´ 없이 췌관확장만 있는 경우가 있으므로 ìž„ìƒì ìœ¼ë¡œ 췌장암이 의심된다면 ìˆ˜ìˆ ì´ë‚˜ 내시경 초음파 ìœ ë„í•˜ 조직 검사 등을 통하여 ì ê·¹ì ì¸ 진단을 하여야 한다. 췌장염군의 췌장암 진단 당시 ì—°ë ¹ì´ 더 ì–´ë ¤ 좀 더 ì ê·¹ì ìœ¼ë¡œ ìˆ˜ìˆ ì„ 하는 경우가 많았으므로 만성 췌장염 환자에서 ì¶”ì ê´€ì°°ì„ ì ê·¹ì ìœ¼ë¡œ 한다면 좀 더 조기에 발견하여 치료율을 높일 수 있을 것이다. 중심 단어: 만성 췌장염; 췌장암; 조기진단

Potential plasticity of T regulatory cells in pancreatic carcinoma in relation to disease progression and outcome

CD4(+)CD25(+)FoxP3(+) regulatory T cells (Tregs) are understood to maintain peripheral tolerance to self-antigens and inhibit antitumor immune responses. However, compelling evidence suggests that, Tregs provide no anti-inflammatory protection in the tumor microenvironment, but rather contribute to a T helper 17 (Th17)-driven pro-carcinogenic process. Using three-color flow cytometry, we evaluated the percentage of circulating CD4(+)CD25(+)FoxP3(+) Tregs in the peripheral blood of pancreatic carcinoma patients prior to and after chemotherapy [gemcitabine (GEM) alone, or GEM+oxaliplatin (GEMOX) or bevacizumab+capecitabine+radiotherapy (BEV+CAPE+RT)]. Correlations were sought between Treg counts and plasma levels of cytokines relevant to controlling the Treg/Th17 balance, i.e., interleukin (IL)-23, IL-17A, IL-6 and transforming growth factor β 1 (TGF-β1), as measured by ELISA and the clinical features of pancreatic cancer. Treg, IL-6 and TGF-β1 levels were higher in locally advanced and metastatic pancreatic carcinoma patients compared to controls. No parameter was correlated with disease stage except IL-6. IL-17A and TGF-β1 were significantly associated with increased risk of poor prognosis. IL-17A was positively correlated with IL-23. Treg and IL-6 levels decreased following GEM monochemotherapy, IL-17A levels decreased after GEMOX, and IL-6 levels were reduced subsequent to BEV+CAPE+RT treatment. IL-23, IL-17A and TGF-β1 levels were significantly lower in patients responding to chemotherapy (partial remission/stable disease) than in nonresponders to chemotherapy (progressive disease). These results suggest an impact of the Treg/Th17-balance in pancreatic carcinoma, highlighting the significance of TGF-β1 and IL-17A as potential prognostic and predictive indicators. Immunological changes induced by mono and/or combined chemotherapy indicate specific windows of opportunity for introducing integrative interventions on a new target in pancreatic cancer, i.e. IL-17A, possibly improving survival in this highly lethal disease.

2型糖尿病に発症する膵癌の臨床的特徴

2型糖尿病に発症する膵癌の臨床的特徴

Pilot study to relate clinical outcome in pancreatic carcinoma and angiogenic plasma factors/circulating mature/progenitor endothelial cells: Preliminary results

Circulating endothelial cells (CEC) and bone marrow-derived endothelial progenitors (ECP) play important roles in tumor growth and have been proposed as non-invasive markers of angiogenesis. However, CEC and ECP levels have not been investigated in pancreatic carcinoma patients. Using four-color flow cytometry procedures, we evaluated the count of resting (rCEC) and activated (aCEC) endothelial cells and ECP in the peripheral blood of pancreatic carcinoma patients before and after chemotherapy, consisting of gemcitabine (GEM) alone or in combination with oxaliplatin (OX), or with 5-fluorouracil (5-FU). We also correlated CEC and ECP levels with plasma levels of relevant angiogenic factors, such as vascular endothelial growth factor (VEGF)-A, VEGF-D, angiopoietin (Angio)-1, and chemokine C-X-C motif ligand (CXCL)12, measured by ELISA, and with clinical features of pancreatic cancer. The aCEC, rCEC, ECP, and VEGF-A plasma levels were significantly higher in locally-advanced and metastatic patients than controls. Both ECP and VEGF-A levels correlated positively with disease stage and inversely with patient's overall survival. Measurements after the treatment course showed that VEGF-A plasma concentrations and ECP counts had decreased significantly. In particular, VEGF-A and rCEC were significantly down after treatment with GEM alone or in combination with OX. No significant differences in terms of circulating angiogenic factor or endothelial cell subtype levels were found between responders (patients entering partial remission or with stable disease) and non-responders (patients with progressive disease). The study provides insights into angiogenesis mechanisms in pancreatic carcinoma, for which anti-angiogenic targeting of VEGF-A and ECP could be of interest.

High Risk Group Developing Pancreatic Cancer in Patients with Chronic Pancreatitis

Background/Aims: Pancreatic cancer sometimes occurs during the course of chronic pancreatitis. However, as most pancreatic cancers associated with chronic pancreatitis are diagnosed in an advanced stage, it is necessary to recognize high risk group developing pancreatic cancer in patient with chronic pancreatitis. To make a strategy detecting pancreatic cancer associated with chronic pancreatitis in an early stage, we analyzed the clinical features of pancreatic cancer associated with chronic pancreatitis.

The Notch Signaling Pathway Is Related to Neurovascular Progression of Pancreatic Cancer

To analyze the potential role of the Notch signaling pathway in pancreatic cancer angiogenesis and invasion. Angiogenesis, pain, and early neuroinvasion are clinical features of pancreatic cancer. Blood vessels and nerves develop together and use common routes through the organism. The Notch pathway (Notch-1/4, Jagged-1/2, Delta-1) appears crucial in this process. The current study analyzed the Notch pathway in pancreatic cancer and characterized its angiogenic and invasive effects. Five PaCa cell lines were cultured for the in vitro experiments. Real-time quantitative RT-PCR was done to quantify mRNA expression in 31 human PaCa specimens, and immunohistochemistry was used to localize protein expression within tumor specimens. Activation of the Notch signaling was done by transfection of PaCa cells with a constitutive active Notch-1 mutant (Notch-IC). Overexpression of Jagged and Delta was achieved by transfection of full-length cDNA. Spheroid assays were used to study angiogenesis and ELISAs to measure VEGF, bFGF, and angiogenin expression. Matrigel invasion assays were used to analyze tumor cell invasion. Notch-3 and Notch-4 mRNA were significantly (P < 0.001) overexpressed in PaCa. Immunohistochemistry revealed protein accumulation of Notch-1 as well. All ligands were significantly up-regulated. A positive immunosignal of ligands was seen in nerves, blood vessels, and ductal tumor cells. Transfection of PaCa cells with the constitutive active Notch-IC mutant and with Jagged-1 revealed increased levels for VEGF. Concomitantly, recombinant Jagged-1 increased sprouting of endothelial cells in the spheroid assay. The Notch pathway most likely regulates neurovascular development in pancreatic cancer. Activation of this signaling pathway by constitutive Notch-1 mutants and by Jagged-1 causes an angiogenic and invasive tumor phenotype. Specific blockade of Notch signaling may therefore be beneficial for patients with pancreatic cancer.

Molecular Diagnosis of Early Pancreatic Ductal Adenocarcinoma in High-Risk Patients

The prevalence of pancreatic cancer in the general population is too low – even in high-prevalence areas such as Northern Europe and North America (8–12 per 10⁵ population) – relative to the diagnostic accuracy of present detection methods to permit primary screening in the asymptomatic adult population. The recognition that the lifetime risk of developing pancreatic cancer for patients with hereditary pancreatitis (HP) is extremely high (20% by the age of 60 years and 40% by the age of 70 years) poses considerable challenges and opportunities for secondary screening in those patients without any clinical features of pancreatic cancer. Even for secondary screening, the detection of cancer at a biological stage that would be amenable to cure by surgery (total pancreatectomy) still requires diagnostic modalities with a very high sensitivity and specificity. Conventional radiological imaging methods such as endoluminal ultrasound and endoscopic retrograde pancreatography, which have proved to be valuable in the early detection of early neoplastic lesions in patients with familial pancreatic cancer, may well be applicable to patients with HP but only in those without gross morphological features of chronic pancreatitis (other than parenchymal atrophy). Unfortunately, most cases of HP also have associated gross features of chronic pancreatitis that are likely to seriously undermine the diagnostic value of these conventional imaging modalities. Pre-malignant molecular changes can be detected in the pancreatic juice of patients. Thus, the application of molecular screening in patients with HP is potentially the most powerful method of detection of early pancreatic cancer. Although mutant (mt) K-ras can be detected in the pancreatic juice of most patients with pancreatic cancer, it is also present in patients with non-inherited chronic pancreatitis who do not progress to pancreatic cancer (at least in the short to medium term), as well as increasingly in the older population without pancreatic disease. Nevertheless, the presence of mt-K-ras may identify a genuinely higher-risk group, enabling additional diagnostic imaging and molecular resources to be focussed on such a group. What is clear is that prospective multi-centre studies, such as that being pursued by the European Registry of Hereditary Pancreatitis and Familial Pancreatic Cancer (EUROPAC), are essential for the development of an effective secondary screening programme for these patients.

DIAGNOSTIC APPROACH TO PANCREATIC CANCER

Adenocarcinoma of the pancreas ranks fourth as a cause of cancer death in adults in the United States and is the second most common cause of cancer deaths of all gastrointestinal-related carcinomas. It usually presents late in its course. In this article, the authors discuss the clinical features of pancreatic cancer, with emphasis on those that allow early detection of the disease. They also review diagnostic methods and preoperative and perioperative staging that allows the appropriate application of surgical and palliative therapeutic modalities. Despite the significant progress that has been made, further research studies are needed to advance the therapeutic approach to this aggressive cancer.