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MicroRNA expression profiles associated with pancreatic adenocarcinoma and ampullary adenocarcinoma.Modern Pathology : An Official Journal... Dec 2012MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue...
MicroRNAs have potential as diagnostic cancer biomarkers. The aim of this study was (1) to define microRNA expression patterns in formalin-fixed parafin-embedded tissue from pancreatic ductal adenocarcinoma, ampullary adenocarcinoma, normal pancreas and chronic pancreatitis without using micro-dissection and (2) to discover new diagnostic microRNAs and combinations of microRNAs in cancer tissue. The expression of 664 microRNAs in tissue from 170 pancreatic adenocarcinomas and 107 ampullary adenocarcinomas were analyzed using a commercial microRNA assay. Results were compared with chronic pancreatitis, normal pancreas and duodenal adenocarcinoma. In all, 43 microRNAs had higher and 41 microRNAs reduced expression in pancreatic cancer compared with normal pancreas. In all, 32 microRNAs were differently expressed in pancreatic adenocarcinoma compared with chronic pancreatitis (17 higher; 15 reduced). Several of these microRNAs have not before been related to diagnosis of pancreatic cancer (eg, miR-492, miR-614, miR-622). MiR-614, miR-492, miR-622, miR-135b and miR-196 were most differently expressed. MicroRNA profiles of pancreatic and ampullary adenocarcinomas were correlated (0.990). MicroRNA expression profiles for pancreatic cancer described in the literature were consistent with our findings, and the microRNA profile for pancreatic adenocarcinoma (miR-196b-miR-217) was validated. We identified a more significant expression profile, the difference between miR-411 and miR-198 (P=2.06 × 10(-54)) and a diagnostic LASSO classifier using 19 microRNAs (sensitivity 98.5%; positive predictive value 97.8%; accuracy 97.0%). We also identified microRNA profiles to subclassify ampullary adenocarcinomas into pancreatobiliary or intestinal type. In conclusion, we found that combinations of two microRNAs could roughly separate neoplastic from non-neoplastic samples. A diagnostic 19 microRNA classifier was constructed which without micro-dissection could discriminate pancreatic and ampullary adenocarcinomas from chronic pancreatitis and normal pancreas with high sensitivity and accuracy. Ongoing prospective studies will evaluate if these microRNA profiles are useful on fine-needle biopsies for early diagnosis of pancreatic cancer.
Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Ampulla of Vater; Biomarkers, Tumor; Carcinoma, Pancreatic Ductal; Chronic Disease; Common Bile Duct Neoplasms; Female; Formaldehyde; Gene Expression Profiling; Gene Expression Regulation, Neoplastic; Humans; Male; MicroRNAs; Middle Aged; Neoplasm Staging; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Pancreatitis; Paraffin Embedding; Reproducibility of Results
PubMed: 22878649
DOI: 10.1038/modpathol.2012.122 -
Gastroenterology Jun 2013Immune cells are important in the pathogenesis of acute pancreatitis and determine disease severity. Results from cytokine-based clinical trials for acute pancreatitis... (Review)
Review
Immune cells are important in the pathogenesis of acute pancreatitis and determine disease severity. Results from cytokine-based clinical trials for acute pancreatitis have been disappointing, so strategies that target and alter the behavior of infiltrating immune cells require consideration. Recurrent acute pancreatitis can progress to chronic pancreatitis, which is a well-described risk factor for pancreatic ductal adenocarcinoma (PDA). However, most patients with chronic pancreatitis do not develop PDA, and most patients with PDA do not have a history of pancreatitis. Interestingly, chronic pancreatitis and PDA tissues have similarities in their desmoplasia and inflammatory infiltrates, indicating overlapping inflammatory responses. Further studies are needed to determine the differences and similarities of these responses, improve our understanding of PDA pathogenesis, and develop specific immune-based therapies. Immune cells in PDA produce immunosuppressive signals that allow tumors to evade the immune response. Unlike single therapeutic agent studies that block immunosuppressive mechanisms, studies of combination therapies that include therapeutic vaccines have provided promising results.
Topics: Acute Disease; Adaptive Immunity; Animals; Carcinoma, Pancreatic Ductal; Disease Progression; Humans; Immunity, Innate; Immunotherapy; Pancreas; Pancreatic Neoplasms; Pancreatitis; Pancreatitis, Chronic; Risk Factors; Treatment Outcome
PubMed: 23622132
DOI: 10.1053/j.gastro.2012.12.042 -
Diagnostic and Interventional Imaging Dec 2016Pancreatic adenocarcinoma is one of the solid cancers associated with the poorest prognosis; the only curative treatment remains surgical resection but in most cases,... (Review)
Review
Pancreatic adenocarcinoma is one of the solid cancers associated with the poorest prognosis; the only curative treatment remains surgical resection but in most cases, this treatment is not possible because of distant metastasis or local extension. Irreversible electroporation is a new tumor ablation technique, which provides cellular apoptosis without any thermal coagulation effect. This technique helps preserve the ducts, vessels or nerves located in the treatment area. This article reviews the current knowledge regarding the use of electroporation for the treatment of pancreatic adenocarcinoma.
Topics: Adenocarcinoma; Electrochemotherapy; Humans; Neoplasm Staging; Pancreas; Pancreatic Neoplasms; Prognosis
PubMed: 27856215
DOI: 10.1016/j.diii.2016.10.001 -
Internal Medicine (Tokyo, Japan) Apr 2022Pancreatic colloid carcinoma, also known as mucinous non-cystic carcinoma, is a rare subtype of pancreatic cancer accounting for 1-3% of the pancreatic malignant...
Pancreatic colloid carcinoma, also known as mucinous non-cystic carcinoma, is a rare subtype of pancreatic cancer accounting for 1-3% of the pancreatic malignant neoplasms. We herein report a woman who initially presented for acute pancreatitis. Computed tomography showed pancreatic swelling due to acute pancreatitis and a 16-mm mass with an enhanced margin in the pancreatic tail. We performed endoscopic ultrasound fine-needle aspiration. The patient was diagnosed with pancreatic colloid carcinoma, and distal pancreatectomy was performed. This case indicates that pancreatic colloid carcinoma should be considered as a differential diagnosis of pancreatic tumor presenting with acute pancreatitis.
Topics: Acute Disease; Adenocarcinoma, Mucinous; Female; Humans; Pancreatic Neoplasms; Pancreatitis
PubMed: 34670880
DOI: 10.2169/internalmedicine.7345-21 -
PloS One 2017Genetic alterations in K-ras and p53 are thought to be critical in pancreatic cancer development and progression. However, K-ras and p53 expression in pancreatic...
Genetic alterations in K-ras and p53 are thought to be critical in pancreatic cancer development and progression. However, K-ras and p53 expression in pancreatic adenocarcinoma have not been systematically examined in The Cancer Genome Atlas (TCGA) Data Portal. Information regarding K-ras and p53 alterations, mRNA expression data, and protein/protein phosphorylation abundance was retrieved from The Cancer Genome Atlas (TCGA) databases, and analyses were performed by the cBioPortal for Cancer Genomics. The mutual exclusivity analysis showed that events in K-ras and p53 were likely to co-occur in pancreatic adenocarcinoma (Log odds ratio = 1.599, P = 0.006). The graphical summary of the mutations showed that there were hotspots for protein activation. In the network analysis, no solid association between K-ras and p53 was observed in pancreatic adenocarcinoma. In the survival analysis, neither K-ras nor p53 were associated with both survival events. As in the data mining study in the TCGA databases, our study provides a new perspective to understand the genetic features of K-ras and p53 in pancreatic adenocarcinoma.
Topics: Adenocarcinoma; Gene Expression Regulation, Neoplastic; Gene Regulatory Networks; Genes, p53; Genes, ras; Humans; Kaplan-Meier Estimate; Mutation; Pancreas; Pancreatic Neoplasms; Proto-Oncogene Proteins p21(ras); RNA, Messenger; Tumor Suppressor Protein p53
PubMed: 28742845
DOI: 10.1371/journal.pone.0181532 -
Scientific Reports Sep 2022Intraductal tubulopapillary neoplasms (ITPN) are rare pancreatic tumors (< 1% of exocrine neoplasms) and are considered to have better prognosis than classical...
Intraductal tubulopapillary neoplasms (ITPN) are rare pancreatic tumors (< 1% of exocrine neoplasms) and are considered to have better prognosis than classical pancreatic ductal adenocarcinoma (PDAC). The present study aimed to evaluate imaging features of ITPN in computed tomography (CT) and magnetic resonance (MR) imaging. We performed monocentric retrospective analysis of 14 patients with histopathologically verified ITPN, operated in 2003-2018. Images were available for 12 patients and were analysed independently by two radiologists, blinded to reports. Imaging features were compared to a matched control group consisting of 43 patients with PDAC, matched for sex and age. Histopathologic analysis showed invasive carcinoma component in all ITPN patients. CT-attenuation values of ITPN were higher in arterial and venous phases (62.3 ± 14.6 HU and 68 ± 15.6 HU) than in unenhanced phase (39.2 ± 7.9 HU), compatible with solid lesion enhancement. Compared to PDAC, ITPN lesions had significantly higher HU-values in both arterial and venous phases (arterial and venous phases, p < 0.001). ITPN were significantly larger than PDAC (4.1 ± 2.0 cm versus 2.6 ± 0.84 cm, p = 0.021). ITPN lesions were more often well-circumscribed (p < 0.002). Employing a multiple logistic regression analysis with forward stepwise method, higher HU density in the arterial phase (p = 0.012) and well-circumscribed lesion margins (p = 0.047) were found to be significant predictors of ITPN versus PDAC. Our study identified key imaging features for differentiation of ITPN and PDAC. Isodensity or moderate hypodensity and well-circumscribed margins favor the diagnosis of ITPN over PDAC. Being familiar with CT-features of these rare pancreatic tumors is essential for radiologists to accelerate the diagnosis and narrow the differentials.
Topics: Carcinoma, Pancreatic Ductal; Humans; Pancreas; Pancreatic Neoplasms; Retrospective Studies
PubMed: 36114217
DOI: 10.1038/s41598-022-19517-6 -
World Journal of Gastroenterology Jun 2017Treatment of pancreatic cancer is multimodal and surgery is an essential part, mandatory for curative potential. Also chemotherapy is essential, and serious...
Treatment of pancreatic cancer is multimodal and surgery is an essential part, mandatory for curative potential. Also chemotherapy is essential, and serious postoperative complications or rapid disease progression may preclude completion of multimodal treatment. The sequence of treatment interventions has therefore become an important concern, and numerous ongoing randomized controlled trials compare clinical outcome after upfront surgery and neoadjuvant treatment with subsequent resection. In previous years, borderline resectable and locally advanced pancreatic cancer was most often considered unresectable. More effective chemotherapy together with the latest improvements in surgical expertise has resulted in extended operations, pushing the borders of resectability. Multivisceral resections with or without resection of major mesenteric vessels are now performed in numerous patients, resulting in better outcome, recorded as overall survival and/or patient reported outcome. But postoperative morbidity increases concurrently, and clinical benefit must be carefully evaluated against risk of potential harm, associated with new comprehensive multimodal treatment sequences. Even though cost/utility analyses are deficient, extended surgery has resulted in significantly longer and better life for many patients with no other treatment alternative. Improved selection of patients to surgery and/or chemotherapy will in the near future be possible, based on better tumor biology insight. Clinically available biomarkers enabling personalized treatment are forthcoming, but these options are still limited. The importance of surgical resection for each patient's prognosis is presently increasing, justifying sustained expansion of the surgical treatment modality.
Topics: Adenocarcinoma; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Combined Modality Therapy; Disease Progression; Humans; Neoplasm Staging; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Patient Reported Outcome Measures; Patient Selection; Postoperative Complications; Prognosis; Quality of Life; Risk Assessment; Treatment Outcome
PubMed: 28638216
DOI: 10.3748/wjg.v23.i21.3765 -
Diabetologia Oct 2020The islets of Langerhans are well embedded within the exocrine pancreas (the latter comprised of ducts and acini), but the nature of interactions between these... (Review)
Review
The islets of Langerhans are well embedded within the exocrine pancreas (the latter comprised of ducts and acini), but the nature of interactions between these pancreatic compartments and their role in determining normal islet function and survival are poorly understood. However, these interactions appear to be critical, as when pancreatic exocrine disease occurs, islet function and insulin secretion frequently decline to the point that diabetes ensues, termed pancreatogenic diabetes. The most common forms of pancreatogenic diabetes involve sustained exocrine disease leading to ductal obstruction, acinar inflammation, and fibro-fatty replacement of the exocrine pancreas that predates the development of dysfunction of the endocrine pancreas, as seen in chronic pancreatitis-associated diabetes and cystic fibrosis-related diabetes and, more rarely, MODY type 8. Intriguingly, a form of tumour-induced diabetes has been described that is associated with pancreatic ductal adenocarcinoma. Here, we review the similarities and differences among these forms of pancreatogenic diabetes, with the goal of highlighting the importance of exocrine/ductal homeostasis for the maintenance of pancreatic islet function and survival and to highlight the need for a better understanding of the mechanisms underlying these diverse conditions. Graphical abstract.
Topics: Animals; Carcinoma, Pancreatic Ductal; Cystic Fibrosis; Diabetes Mellitus; Humans; Islets of Langerhans; Pancreas, Exocrine; Pancreatic Diseases; Pancreatic Neoplasms; Pancreatitis, Chronic
PubMed: 32894313
DOI: 10.1007/s00125-020-05210-8 -
Pancreas Jul 2018Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. To improve outcomes, there is a critical need for improved tools for detection, accurate staging, and... (Review)
Review
Pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. To improve outcomes, there is a critical need for improved tools for detection, accurate staging, and resectability assessment. This could improve patient stratification for the most optimal primary treatment modality. Molecular imaging, used in combination with tumor-specific imaging agents, can improve established imaging methods for PDAC. These novel, tumor-specific imaging agents developed to target specific biomarkers have the potential to specifically differentiate between malignant and benign diseases, such as pancreatitis. When these agents are coupled to various types of labels, this type of molecular imaging can provide integrated diagnostic, noninvasive imaging of PDAC as well as image-guided pancreatic surgery. This review provides a detailed overview of the current clinical imaging applications, upcoming molecular imaging strategies for PDAC, and potential targets for imaging, with an emphasis on intraoperative imaging applications.
Topics: Carcinoma, Pancreatic Ductal; Diagnosis, Differential; Humans; Molecular Imaging; Monitoring, Intraoperative; Pancreas; Pancreatic Neoplasms; Prognosis; Reproducibility of Results; Sensitivity and Specificity
PubMed: 29894417
DOI: 10.1097/MPA.0000000000001075 -
Archives of Pathology & Laboratory... Jan 2022Pancreatic adenocarcinoma is the third leading cause of cancer death in the United States. Surgery remains the mainstay of treatment, and frozen section analysis is used...
CONTEXT.—
Pancreatic adenocarcinoma is the third leading cause of cancer death in the United States. Surgery remains the mainstay of treatment, and frozen section analysis is used to confirm diagnosis and determine resectability and margin status.
OBJECTIVE.—
To evaluate use and accuracy of frozen section and how diagnosis impacts surgical procedure.
DESIGN.—
We reviewed patients with planned pancreatic resections between January 2014 and March 2019 with at least 1 frozen section. Pathology reports including frozen sections, preoperative cytology, and operative notes were reviewed. Frozen sections were categorized by margin, primary pancreatic diagnosis, metastasis, or vascular resectability. The deferral and error rates and surgeons' response were noted.
RESULTS.—
We identified 898 planned pancreatic resections and 221 frozen sections that were performed on 152 cases for 102 margins, 94 metastatic lesions, 20 primary diagnoses, and 5 to confirm vascular resectability. The diagnosis was deferred to permanent sections in 13 of 152 cases (8.6%) on 16 of 221 frozen sections (7.2%): 6 for metastasis, 8 for margins, and 2 for primary diagnosis. Discrepancies/errors were identified in 4 of 152 cases (2.6%) and 4 of 221 frozen sections (1.8%). Surgeons' responses were different than expected in 8 of 221 frozen sections (3.6%), but their actions were explained by other intraoperative findings in 6 of 8.
CONCLUSIONS.—
Frozen section remains an important diagnostic tool used primarily for evaluation of margins and metastasis during pancreatectomy. In most cases, a definitive diagnosis is rendered, with occasional deferrals and few errors. Intraoperative findings explain most cases where surgeons act differently than expected based on frozen section diagnosis.
Topics: Adenocarcinoma; Diagnostic Errors; Frozen Sections; Humans; Pancreas; Pancreatectomy; Pancreatic Neoplasms; Retrospective Studies
PubMed: 33769446
DOI: 10.5858/arpa.2020-0483-OA