Type 2 diabetes (T2DM) is characterized hyperglycemia due to impaired insulin secretion and a deficit of pancreatic beta cells in the setting of insulin resistance. Most individuals are able to compensate for insulin resistance by increasing insulin secretion so the genetic basis of T2DM appears to be linked to the underlying mechanisms leading to this abnormal pancreatic islet response to insulin resistance. In support of this, pancreatic islets in T2DM have a specific pathology. The ~65% deficit in beta cells is presumably due to increased beta cell apoptosis, the underlying mechanisms of which include a misfolded protein induced endoplasmic reticulum stress, mitochondrial dysfunction and local release of inflammatory cytokines. It has long been recognized that there is an association between T2DM and pancreatic cancer. One explanation for this is the development of diabetes in relation to pancreatic cancer, when the diagnoses are temporarily related. However there is also an increased risk of pancreatic cancer with long standing T2DM. We propose that a plausible explanation for this association is the consequence of long term exposure of surrounding pancreas to cytokines release by inflamed islets. Further, we speculate that there is a common progenitor cell niche in the pancreas for exocrine and endocrine repair, comparable to that in other gastroenterological organs, repopulating the exocrine and endocrine pancreas. Chronic inflammatory mediated stimulus of such a progenitor would be expected with time, in those with underlying relevant mutations such as KRAS activating, to increase the risk of malignant transformation.
{"title":"Islet Inflammation: A Causal Link Between Diabetes and Pancreatic Cancer?","authors":"P. Butler","doi":"10.6092/1590-8577/2774","DOIUrl":"https://doi.org/10.6092/1590-8577/2774","url":null,"abstract":"Type 2 diabetes (T2DM) is characterized hyperglycemia due to impaired insulin secretion and a deficit of pancreatic beta cells in the setting of insulin resistance. Most individuals are able to compensate for insulin resistance by increasing insulin secretion so the genetic basis of T2DM appears to be linked to the underlying mechanisms leading to this abnormal pancreatic islet response to insulin resistance. In support of this, pancreatic islets in T2DM have a specific pathology. The ~65% deficit in beta cells is presumably due to increased beta cell apoptosis, the underlying mechanisms of which include a misfolded protein induced endoplasmic reticulum stress, mitochondrial dysfunction and local release of inflammatory cytokines. It has long been recognized that there is an association between T2DM and pancreatic cancer. One explanation for this is the development of diabetes in relation to pancreatic cancer, when the diagnoses are temporarily related. However there is also an increased risk of pancreatic cancer with long standing T2DM. We propose that a plausible explanation for this association is the consequence of long term exposure of surrounding pancreas to cytokines release by inflamed islets. Further, we speculate that there is a common progenitor cell niche in the pancreas for exocrine and endocrine repair, comparable to that in other gastroenterological organs, repopulating the exocrine and endocrine pancreas. Chronic inflammatory mediated stimulus of such a progenitor would be expected with time, in those with underlying relevant mutations such as KRAS activating, to increase the risk of malignant transformation.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"15 1","pages":"526-526"},"PeriodicalIF":0.2,"publicationDate":"2014-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234386","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
HepG2 cells, a human liver cancer cell line (hepatocellular carcinoma), are being considered as a future model for bioartificial liver studies. They have the ability to differentiate and demonstrate some features of normal liver cells. Our previous studies focused on examination of the morphological and functional properties of these cells under different extracellular environmental conditions. We have created a culture model that these cells demonstrate remarkable changes after 30days. These changes include an increase in the cytoplasmic organelles, formation of bile canaliculi, occurrence of junctional complexes between the adjacent cells, existence of microvilli on the apical surfaces, accumulation of glycogen particles in the cytoplasm, an increase at the density of albumin labeled areas and a rise at the Na-K ATPase level on cellular membranes. In addition to these changes, reproduction rate decreases which is another important difference between cancer cells and normal cells. All these changes demonstrate that these liver cancer cells have tendency to change their features and behave like “healthy-normal liver cells”. In other words, they become “specialized” or “mature”. These findings have made us think that if a cancer cell has ability to turn into a healthy cell again. The next step was to investigate the changes on the expression of 84 key genes involved in the progression of hepatocellular carcinoma. The genes in the array included those involved in DNA damage, cell growth, cell-cell adhesion, apoptosis, angiogenesis, epithelial to mesenchymal transition, proteolysis, and immune response. Specifically, EGFR, Flt-1, KDR, which are growth factor receptors, were highly expressed on 30 th days of the experiment, Similarly, growth factors HGF, IGF2 and VEGFA were markedly higher in these cells. Cell adhesion molecules; CDH1 and CDH13 were significantly upregulated. GADD45B, which is a p53 target gene and known to get induced during growth arrest, was more expressed. On the other hand, the genes that were downregulated included cell cycle regulators and apoptosis genes, such as BIRC5, CCND1, CDKN2A, E2F1, LEF1, MSH2, and TERT. Experiments related with the changes on the expression of some other genes, which are important for carcinogenesis, are also in progress. Behaviors of other cancer cell types under the same cultural conditions and importance of cancer stem cells in differentiation process are other questions to be answered. In future, differentiation of cancer cells in vivo and finally making them behave like “healthy cells” might be another therapeutic approach for cancer treatment.
{"title":"Can a Cancer Cell Turn into a Normal Cell","authors":"R. Aktas","doi":"10.6092/1590-8577/2789","DOIUrl":"https://doi.org/10.6092/1590-8577/2789","url":null,"abstract":"HepG2 cells, a human liver cancer cell line (hepatocellular carcinoma), are being considered as a future model for bioartificial liver studies. They have the ability to differentiate and demonstrate some features of normal liver cells. Our previous studies focused on examination of the morphological and functional properties of these cells under different extracellular environmental conditions. We have created a culture model that these cells demonstrate remarkable changes after 30days. These changes include an increase in the cytoplasmic organelles, formation of bile canaliculi, occurrence of junctional complexes between the adjacent cells, existence of microvilli on the apical surfaces, accumulation of glycogen particles in the cytoplasm, an increase at the density of albumin labeled areas and a rise at the Na-K ATPase level on cellular membranes. In addition to these changes, reproduction rate decreases which is another important difference between cancer cells and normal cells. All these changes demonstrate that these liver cancer cells have tendency to change their features and behave like “healthy-normal liver cells”. In other words, they become “specialized” or “mature”. These findings have made us think that if a cancer cell has ability to turn into a healthy cell again. The next step was to investigate the changes on the expression of 84 key genes involved in the progression of hepatocellular carcinoma. The genes in the array included those involved in DNA damage, cell growth, cell-cell adhesion, apoptosis, angiogenesis, epithelial to mesenchymal transition, proteolysis, and immune response. Specifically, EGFR, Flt-1, KDR, which are growth factor receptors, were highly expressed on 30 th days of the experiment, Similarly, growth factors HGF, IGF2 and VEGFA were markedly higher in these cells. Cell adhesion molecules; CDH1 and CDH13 were significantly upregulated. GADD45B, which is a p53 target gene and known to get induced during growth arrest, was more expressed. On the other hand, the genes that were downregulated included cell cycle regulators and apoptosis genes, such as BIRC5, CCND1, CDKN2A, E2F1, LEF1, MSH2, and TERT. Experiments related with the changes on the expression of some other genes, which are important for carcinogenesis, are also in progress. Behaviors of other cancer cell types under the same cultural conditions and importance of cancer stem cells in differentiation process are other questions to be answered. In future, differentiation of cancer cells in vivo and finally making them behave like “healthy cells” might be another therapeutic approach for cancer treatment.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"15 1","pages":"539-539"},"PeriodicalIF":0.2,"publicationDate":"2014-09-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234410","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Updates on Pancreatic Cancer - Highlights from the “48th Annual Pancreas Club Meeting”. Chicago, IL, USA. May 2-3, 2014","authors":"O. Vyas, M. Saif","doi":"10.6092/1590-8577/2509","DOIUrl":"https://doi.org/10.6092/1590-8577/2509","url":null,"abstract":"No abstract available. Image: Chicago view. (From the Program of the \"48th Annual Pancreas Club Meeting. Chicago, IL, USA. May 2-3, 2014).","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"15 1","pages":"225-227"},"PeriodicalIF":0.2,"publicationDate":"2014-05-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234232","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hot articles recently published in the field of pancreatology","authors":"A. Fioravanti","doi":"10.6092/1590-8577/1785","DOIUrl":"https://doi.org/10.6092/1590-8577/1785","url":null,"abstract":"","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"15 1","pages":"79-83"},"PeriodicalIF":0.2,"publicationDate":"2013-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Castino, Francesca Bergomas, G. Caro, F. Grizzi, C. Ridolfi, R. Gavazzi, L. Laghi, A. Mantovani, A. Zerbi, P. Allavena, F. Marchesi
Context Stimulating the patient’s immune system to attack malignant tumor cells is considered a promising alternative therapeutic strategy to treat pancreatic adenocarcinoma (PDAC). Recent data point to the neogenesis of organized and vascularized ectopic (or tertiary) lymphoid tissue (TLT) at the tumor site, where B and T cell responses are efficiently initiated and sustained. Objective To investigate the occurrence of TLT in human PDAC and test whether a protocol of immunotherapy induces formation of TLT in a PDAC murine model. This might represent an alternative approach to target the tumor stroma, by creating a lymphoid like microenvironment, to increase the recruitment and activation of T cells. Methods Occurrence of TLT was evaluated by immunohistochemistry in PDAC tissue specimens from consecutive patients who underwent surgical resection at the Humanitas Clinical and Research Centre. A dendritic-cell (DC) based vaccine was used to immunize mice injected with Panc02 murine cells. Results In human PDAC tissue specimens, we identified organized lymphoid tissue, including compartmentalized T and B cell areas, DCs and high endothelial venules (HEV). In the heterogeneity of PDAC tissue, TLT occurred preferentially in the stromal compartment. The density of TLT correlated to the density of intra-tumor CD8 T cells, which displayed a phenotype indicating a defective activation status. In a murine model of PDAC, vaccination with DCs loaded with apoptotic PDAC cells occasionally induced formation of TLT. Conclusion Here we report the occurrence of lymphoid tissue in human PDAC, in the context of the desmoplastic stromal reaction and the correlation with CD8+ T cell infiltration. Immunotherapeutic approaches might induce formation of TLT and be exploited as alternative strategies to modify PDAC stroma and induce an anti-tumor immune response.
{"title":"Occurrence of Tertiary Lymphoid Tissue in Pancreatic Adenocarcinoma","authors":"G. Castino, Francesca Bergomas, G. Caro, F. Grizzi, C. Ridolfi, R. Gavazzi, L. Laghi, A. Mantovani, A. Zerbi, P. Allavena, F. Marchesi","doi":"10.6092/1590-8577/1708","DOIUrl":"https://doi.org/10.6092/1590-8577/1708","url":null,"abstract":"Context Stimulating the patient’s immune system to attack malignant tumor cells is considered a promising alternative therapeutic strategy to treat pancreatic adenocarcinoma (PDAC). Recent data point to the neogenesis of organized and vascularized ectopic (or tertiary) lymphoid tissue (TLT) at the tumor site, where B and T cell responses are efficiently initiated and sustained. Objective To investigate the occurrence of TLT in human PDAC and test whether a protocol of immunotherapy induces formation of TLT in a PDAC murine model. This might represent an alternative approach to target the tumor stroma, by creating a lymphoid like microenvironment, to increase the recruitment and activation of T cells. Methods Occurrence of TLT was evaluated by immunohistochemistry in PDAC tissue specimens from consecutive patients who underwent surgical resection at the Humanitas Clinical and Research Centre. A dendritic-cell (DC) based vaccine was used to immunize mice injected with Panc02 murine cells. Results In human PDAC tissue specimens, we identified organized lymphoid tissue, including compartmentalized T and B cell areas, DCs and high endothelial venules (HEV). In the heterogeneity of PDAC tissue, TLT occurred preferentially in the stromal compartment. The density of TLT correlated to the density of intra-tumor CD8 T cells, which displayed a phenotype indicating a defective activation status. In a murine model of PDAC, vaccination with DCs loaded with apoptotic PDAC cells occasionally induced formation of TLT. Conclusion Here we report the occurrence of lymphoid tissue in human PDAC, in the context of the desmoplastic stromal reaction and the correlation with CD8+ T cell infiltration. Immunotherapeutic approaches might induce formation of TLT and be exploited as alternative strategies to modify PDAC stroma and induce an anti-tumor immune response.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"535-535"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71231844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
L. Pugliese, M. Chiaro, J. D'haese, G. Marchegiani, P. Wenzel, G. Ceyhan, M. Keskin
Context The increasing detection of intraductal papillary mucinous neoplasm of the pancreas (IPMN) in general population over the last decade has led to observe a probable association with synchronous or metachronous extrapancreatic neoplasm (EPN) in these patients despite no unequivocal proof was found so far. Objectives A systematic review of the available literature has been performed to clarify the level of evidence and knowledge on this issue. Methods We performed a PubMed search with the following search terms: “extrapancreatic”, “non pancreatic”, “additional pancreatic”, “additional primary” and alternatively matched with “neoplasms/tumors/cancers/ malignancies/lesions”. Then we selected only those articles specific for IPMN among the obtained results and proceeded to the analyses of data. The review was conducted in a systematic manner according to the PRISMA statement rules. Results selection process led to identify and include a total of fifteen articles. An increased risk for extrapancreatic malignancies, mostly gastric and colon cancer, was described in the majority of the selected studies which were however all retrospective and only one of them multicentre. Unexpectedly, the association between IPMN and EPN was not reported by the largest and only prospective study available. Conclusion Current literature does not allow any definitive conclusion on this subject. The general opinion in favor of a higher prevalence of EPN in IPMN patients remains therefore controversial. No specific screening protocols in addition to standard surveillance and diagnostic examinations for common neoplasms should be recommended in these patients until further evidence will be provided.
{"title":"Extrapancreatic Neoplasms in Patients with IPMN: Is There an Increased Risk?","authors":"L. Pugliese, M. Chiaro, J. D'haese, G. Marchegiani, P. Wenzel, G. Ceyhan, M. Keskin","doi":"10.6092/1590-8577/1706","DOIUrl":"https://doi.org/10.6092/1590-8577/1706","url":null,"abstract":"Context The increasing detection of intraductal papillary mucinous neoplasm of the pancreas (IPMN) in general population over the last decade has led to observe a probable association with synchronous or metachronous extrapancreatic neoplasm (EPN) in these patients despite no unequivocal proof was found so far. Objectives A systematic review of the available literature has been performed to clarify the level of evidence and knowledge on this issue. Methods We performed a PubMed search with the following search terms: “extrapancreatic”, “non pancreatic”, “additional pancreatic”, “additional primary” and alternatively matched with “neoplasms/tumors/cancers/ malignancies/lesions”. Then we selected only those articles specific for IPMN among the obtained results and proceeded to the analyses of data. The review was conducted in a systematic manner according to the PRISMA statement rules. Results selection process led to identify and include a total of fifteen articles. An increased risk for extrapancreatic malignancies, mostly gastric and colon cancer, was described in the majority of the selected studies which were however all retrospective and only one of them multicentre. Unexpectedly, the association between IPMN and EPN was not reported by the largest and only prospective study available. Conclusion Current literature does not allow any definitive conclusion on this subject. The general opinion in favor of a higher prevalence of EPN in IPMN patients remains therefore controversial. No specific screening protocols in addition to standard surveillance and diagnostic examinations for common neoplasms should be recommended in these patients until further evidence will be provided.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"590-590"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71232182","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
C. Zingaretti, C. Ricci, G. Taffurelli, M. D'ambra, S. Buscemi, R. Casadei, F. Minni
Context The natural history of intraductal papillary mucinous neoplasms (IPMNs) is unknown even if we well-know that a pancreatic IPMN has malignant potential as the disease process follows the adenoma-carcinoma sequence. The vast majority of our resections were done to prevent the development of invasive cancer. Herein, we report the 14-year natural history of a IPMN. Case report In 1999, a 60-year-old man was observed for the incidental US finding of a cystic lesion (diameter 30 mm) in the head of the pancreas. MRI and cholangiopancreatography confirmed the finding. The past medical history reported a diagnosis of diabetes mellitus in 1998. FNA-US aspiration was performed and high levels of CEA (104 ng/mL) and amylase (1,230 U/L) were detected. The patient underwent surgery but an explorative laparotomy was performed because cystic lesion disappeared. The patient undergone to a surveillance program with yearly US scans. After five years (2004), an US showed a cystic lesion (diameter: 17 mm) of the pancreatic head without Wirsung dilatation. Re-evaluations by US scan showed stable disease until April 2013, when an increased size of the cystic lesion (diameter 29x32 mm) was revealed. A cholangio-Wirsung magnetic resonance (CWMR) showed a further cystic enlargement (60x26 mm) and showed a diffuse Wirsung duct dilatation (8 mm). Finally, an endosonography revealed the presence of “fish-eye” sign, confirmed the diffuse dilatation of the Wirsung duct (maximum diameter 15 mm), a 3 cm cyst communicating with the main duct and revealed several contrast-enhancing mural nodules. A FNA did not show malignant cells. Considering the presence of these “high-risk-stigmata” the diagnosis of main duct IPMN with high risk of progression to invasive carcinoma was made and the patient underwent a total pancreatectomy. Pathological diagnosis confirmed an IPMN diffuse to the whole pancreas with an invasive carcinoma of the pancreatic head. Conclusions Our case showed that in fourteen years an IPMN may become malignant. Thus, a surveillance program has to be performed for a long time, especially in young patients with a long expectancy of life. Surgery has to be strongly considered in young fit patients with cystic lesion greater than 2 cm in diameter.
{"title":"Natural History of Intraductal Papillary Mucinous Neoplasms: A Case Report","authors":"C. Zingaretti, C. Ricci, G. Taffurelli, M. D'ambra, S. Buscemi, R. Casadei, F. Minni","doi":"10.6092/1590-8577/1751","DOIUrl":"https://doi.org/10.6092/1590-8577/1751","url":null,"abstract":"Context The natural history of intraductal papillary mucinous neoplasms (IPMNs) is unknown even if we well-know that a pancreatic IPMN has malignant potential as the disease process follows the adenoma-carcinoma sequence. The vast majority of our resections were done to prevent the development of invasive cancer. Herein, we report the 14-year natural history of a IPMN. Case report In 1999, a 60-year-old man was observed for the incidental US finding of a cystic lesion (diameter 30 mm) in the head of the pancreas. MRI and cholangiopancreatography confirmed the finding. The past medical history reported a diagnosis of diabetes mellitus in 1998. FNA-US aspiration was performed and high levels of CEA (104 ng/mL) and amylase (1,230 U/L) were detected. The patient underwent surgery but an explorative laparotomy was performed because cystic lesion disappeared. The patient undergone to a surveillance program with yearly US scans. After five years (2004), an US showed a cystic lesion (diameter: 17 mm) of the pancreatic head without Wirsung dilatation. Re-evaluations by US scan showed stable disease until April 2013, when an increased size of the cystic lesion (diameter 29x32 mm) was revealed. A cholangio-Wirsung magnetic resonance (CWMR) showed a further cystic enlargement (60x26 mm) and showed a diffuse Wirsung duct dilatation (8 mm). Finally, an endosonography revealed the presence of “fish-eye” sign, confirmed the diffuse dilatation of the Wirsung duct (maximum diameter 15 mm), a 3 cm cyst communicating with the main duct and revealed several contrast-enhancing mural nodules. A FNA did not show malignant cells. Considering the presence of these “high-risk-stigmata” the diagnosis of main duct IPMN with high risk of progression to invasive carcinoma was made and the patient underwent a total pancreatectomy. Pathological diagnosis confirmed an IPMN diffuse to the whole pancreas with an invasive carcinoma of the pancreatic head. Conclusions Our case showed that in fourteen years an IPMN may become malignant. Thus, a surveillance program has to be performed for a long time, especially in young patients with a long expectancy of life. Surgery has to be strongly considered in young fit patients with cystic lesion greater than 2 cm in diameter.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"602-602"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233068","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Partelli, Sébastien Gaujouox, F. Maire, P. Coletta, B. Larroque, S. Crippa, A. Sauvanet, M. Falconi, P. Ruszniewski
Context Asymptomatic sporadic non-functioning well-differentiated pancreatic neuroendocrine tumors (AS-NF-PNET) are increasingly diagnosed, and their management is controversial because of their overall good but heterogeneous prognosis. Objective The aim of the present study was to assess the natural history of AS-NF-PNET below 2 cm in size, and the benefit-risk balance of a non-operative management. Methods From January 2000 to June 2012, 46 patients with proven AS-NF-PNET below 2 cm in size were followed-up for at least 18 months with serial imaging. Results Patients were mainly female (65%), with a median age of 60 years. Tumors were mainly located in the pancreatic head (52%), with a median lesion size of 13 mm (range: 9-15 mm). Distant or nodal metastases appeared on imaging in none of the patients after a median follow-up of 34 months (range: 24-52 mm) and an average of 4 (range: 3-6) serial imaging. A ≥20% increase in size was observed in 6 (13%) patients. Overall median tumor growth was 0.12 mm per years and nor patients neither tumor characteristics were found to be significant predictors of tumor growth. Overall, 8 patients (17%) underwent surgery after a median time from initial evaluation of 41 months (range: 27-58 months); all resected lesions were ENETS T stage 1 (n=7) or 2 (n=1), grade 1, node negative, with neither vascular nor peripancreatic fat invasion. Conclusion In selected patients non-operative management of AS-NF-PNET below 2 cm in size is safe. Larger and prospective multicentre studies with long-term follow-up are now needed to validate this “wait and see” policy.
{"title":"Natural History of Small Sporadic Non-Functioning Pancreatic Neuroendocrine Tumors: An Observational Bi-Centric Study","authors":"S. Partelli, Sébastien Gaujouox, F. Maire, P. Coletta, B. Larroque, S. Crippa, A. Sauvanet, M. Falconi, P. Ruszniewski","doi":"10.6092/1590-8577/1760","DOIUrl":"https://doi.org/10.6092/1590-8577/1760","url":null,"abstract":"Context Asymptomatic sporadic non-functioning well-differentiated pancreatic neuroendocrine tumors (AS-NF-PNET) are increasingly diagnosed, and their management is controversial because of their overall good but heterogeneous prognosis. Objective The aim of the present study was to assess the natural history of AS-NF-PNET below 2 cm in size, and the benefit-risk balance of a non-operative management. Methods From January 2000 to June 2012, 46 patients with proven AS-NF-PNET below 2 cm in size were followed-up for at least 18 months with serial imaging. Results Patients were mainly female (65%), with a median age of 60 years. Tumors were mainly located in the pancreatic head (52%), with a median lesion size of 13 mm (range: 9-15 mm). Distant or nodal metastases appeared on imaging in none of the patients after a median follow-up of 34 months (range: 24-52 mm) and an average of 4 (range: 3-6) serial imaging. A ≥20% increase in size was observed in 6 (13%) patients. Overall median tumor growth was 0.12 mm per years and nor patients neither tumor characteristics were found to be significant predictors of tumor growth. Overall, 8 patients (17%) underwent surgery after a median time from initial evaluation of 41 months (range: 27-58 months); all resected lesions were ENETS T stage 1 (n=7) or 2 (n=1), grade 1, node negative, with neither vascular nor peripancreatic fat invasion. Conclusion In selected patients non-operative management of AS-NF-PNET below 2 cm in size is safe. Larger and prospective multicentre studies with long-term follow-up are now needed to validate this “wait and see” policy.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"553-553"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233103","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
M. Marco, C. Zingaretti, C. Ricci, S. Vecchiarelli, G. Taffurelli, M. Macchini, M. D'ambra, S. Buscemi, F. Monari, R. Casadei, G. Biasco, F. Minni
Context Patients with locally advanced pancreatic cancer are usually treated with chemoradiotherapy and rarely they became resectable. Herein, we present the case of a patient with locally advanced pancreatic cancer. Case report A 56-year-old man was observed in October 2011 because of high blood levels of CA 19.9 (>230 U/mL) and the presence of a pancreatic mass of the uncinate process (diameter 3.8x3.5 cm) revealed by US and CT scan. An US-guided biopsy allowed the diagnosis of well differentiated pancreatic adenocarcinoma, biliopancreatic type. CT scan showed a vascular involvement of both superior mesenteric vein and artery. The disease was defined as locally advanced unresectable pancreatic cancer. The patient started chemotherapy with gemcitabine and oxaliplatin. Five months later, CT scan re-evaluation of the disease showed a stable disease. Thus, a protocol of radio-chemotherapy was suggested. Eight months later from diagnosis, the mass was still unresectable. Other eight cycles of gemcitabine and oxaliplatin were performed. In February 2013 a further CT scan evaluation demonstrated a smaller lesion (3.5x2.2 cm) and also the vascular involvement was decreased, still without a normal fat plane between the tumor and the vessels. Another cycle of gemcitabine and oxaliplatin was completed. At the end of May 2013, the 18 FDG-PET was negative; CT scan demonstrated a further decreased of the mass (maximum diameter: 2.5 cm) while the mesenteric vessels involvement still remained. Moreover, the genomic characteristics of the patient DNA were different from other the pancreatic cancer. Because of the long-term survival of the young patient, the partial regression of the disease and the genomic characteristics of the tumor, a surgical approach was indicated. The patient underwent to a total pancreatectomy with splenectomy plus segmental resection of portal mesenteric trunk. Pathological diagnosis confirmed a well-differentiated ductal pancreatic carcinoma, biliopancreatic type (T4), with R0 resection. Conclusion Our case suggests that there are locally advanced pancreatic cancers in which chemoradiotherapy can allow surgical pancreatic resection probably because they have particular genomic characteristics.
{"title":"Locally Advanced Pancreatic Cancer: Is It Possible Pancreatic Resection? A Case Report","authors":"M. Marco, C. Zingaretti, C. Ricci, S. Vecchiarelli, G. Taffurelli, M. Macchini, M. D'ambra, S. Buscemi, F. Monari, R. Casadei, G. Biasco, F. Minni","doi":"10.6092/1590-8577/1752","DOIUrl":"https://doi.org/10.6092/1590-8577/1752","url":null,"abstract":"Context Patients with locally advanced pancreatic cancer are usually treated with chemoradiotherapy and rarely they became resectable. Herein, we present the case of a patient with locally advanced pancreatic cancer. Case report A 56-year-old man was observed in October 2011 because of high blood levels of CA 19.9 (>230 U/mL) and the presence of a pancreatic mass of the uncinate process (diameter 3.8x3.5 cm) revealed by US and CT scan. An US-guided biopsy allowed the diagnosis of well differentiated pancreatic adenocarcinoma, biliopancreatic type. CT scan showed a vascular involvement of both superior mesenteric vein and artery. The disease was defined as locally advanced unresectable pancreatic cancer. The patient started chemotherapy with gemcitabine and oxaliplatin. Five months later, CT scan re-evaluation of the disease showed a stable disease. Thus, a protocol of radio-chemotherapy was suggested. Eight months later from diagnosis, the mass was still unresectable. Other eight cycles of gemcitabine and oxaliplatin were performed. In February 2013 a further CT scan evaluation demonstrated a smaller lesion (3.5x2.2 cm) and also the vascular involvement was decreased, still without a normal fat plane between the tumor and the vessels. Another cycle of gemcitabine and oxaliplatin was completed. At the end of May 2013, the 18 FDG-PET was negative; CT scan demonstrated a further decreased of the mass (maximum diameter: 2.5 cm) while the mesenteric vessels involvement still remained. Moreover, the genomic characteristics of the patient DNA were different from other the pancreatic cancer. Because of the long-term survival of the young patient, the partial regression of the disease and the genomic characteristics of the tumor, a surgical approach was indicated. The patient underwent to a total pancreatectomy with splenectomy plus segmental resection of portal mesenteric trunk. Pathological diagnosis confirmed a well-differentiated ductal pancreatic carcinoma, biliopancreatic type (T4), with R0 resection. Conclusion Our case suggests that there are locally advanced pancreatic cancers in which chemoradiotherapy can allow surgical pancreatic resection probably because they have particular genomic characteristics.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"572-572"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233125","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A. Casarotto, Claudio Bosio, G. Bosco, Luca Guizzon, Zhongjin Yang, A. Megighian, Marta Cannato, L. Toniolo, E. Nasole, E. Camporesi, C. Reggiani, G. Garetto, C. Bassi
Context Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies with dismal prognosis. Gemcitabine is one of first-line therapies for locally advanced PDAC; however, severe resistance is responsible for poor survival and response rate. There is evidence that administration of HBOT can enhance the delivery of oxygen to hypoxic tumor cells and increase their susceptibility to the cytotoxic effects of chemotherapy. We hypothesized that the anticancer activity of gemcitabine may be enhanced if tumor cells were placed in oxygen rich environment. Objective This study was designed to evaluate the effects of gemcitabine, hyperbaric oxygen treatment (HBOT) and their combination on apoptosis of tumor cells. Materials and methods PANC-1 and AsPc-1 tumor cell lines were used because they are sensitive to gemcitabine. Cultured tumor cells were treated with gemcitabine at its growth-inhibitory concentration (IC 50 )value for the cell line PANC-1: 3.25x10 -8 M and AsPc-1: 1.27x10 -7 M, and HBOT at 2.5 ATAfor 90 minutes or combination of both. Twenty-four hours after treatment, the apoptotic cells in each group were analyzed and apoptotic index (AI) was calculated. Results PANC-1 cell line: HBOT alone had no effect on AI: 6.5±0.03 vs . 5.9±0.01. HBOT before and after gemcitabine did not increase AI in comparison to gemcitabine alone: AI: 8.2±0.02, 8.5±0.02 vs . 8.1±0.02. Combination of HBOT and gemcitabine significantly increased AI 10.7±0.02 (P<0.001 vs . all groups). AsPc-1 cell line: HBOT alone had no effect on AI: 5.9±0.03 vs . 5.9±0.01. HBOT before and after gemcitabine did not increase AI in comparison to gemcitabine alone: 8.2±0.02, 8.4±0.02 vs . 8.0±0.01. Combination of HBOT and gemcitabine significantly increased AI 9.7±0.02 (P<0.001 vs . all groups). Conclusion Our data show that HBOT alone, or administered before and after gemcitabine has no effect on apoptosis in PDAC cells in vitro . HBOT significantly increased apoptosis when administered with gemcitabine.
{"title":"Effect of Hyperbaric Oxygen Treatment and Gemcitabine on Apoptosis in Pancreatic Ductal Adenocarcinoma Cells","authors":"A. Casarotto, Claudio Bosio, G. Bosco, Luca Guizzon, Zhongjin Yang, A. Megighian, Marta Cannato, L. Toniolo, E. Nasole, E. Camporesi, C. Reggiani, G. Garetto, C. Bassi","doi":"10.6092/1590-8577/1823","DOIUrl":"https://doi.org/10.6092/1590-8577/1823","url":null,"abstract":"Context Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive human malignancies with dismal prognosis. Gemcitabine is one of first-line therapies for locally advanced PDAC; however, severe resistance is responsible for poor survival and response rate. There is evidence that administration of HBOT can enhance the delivery of oxygen to hypoxic tumor cells and increase their susceptibility to the cytotoxic effects of chemotherapy. We hypothesized that the anticancer activity of gemcitabine may be enhanced if tumor cells were placed in oxygen rich environment. Objective This study was designed to evaluate the effects of gemcitabine, hyperbaric oxygen treatment (HBOT) and their combination on apoptosis of tumor cells. Materials and methods PANC-1 and AsPc-1 tumor cell lines were used because they are sensitive to gemcitabine. Cultured tumor cells were treated with gemcitabine at its growth-inhibitory concentration (IC 50 )value for the cell line PANC-1: 3.25x10 -8 M and AsPc-1: 1.27x10 -7 M, and HBOT at 2.5 ATAfor 90 minutes or combination of both. Twenty-four hours after treatment, the apoptotic cells in each group were analyzed and apoptotic index (AI) was calculated. Results PANC-1 cell line: HBOT alone had no effect on AI: 6.5±0.03 vs . 5.9±0.01. HBOT before and after gemcitabine did not increase AI in comparison to gemcitabine alone: AI: 8.2±0.02, 8.5±0.02 vs . 8.1±0.02. Combination of HBOT and gemcitabine significantly increased AI 10.7±0.02 (P<0.001 vs . all groups). AsPc-1 cell line: HBOT alone had no effect on AI: 5.9±0.03 vs . 5.9±0.01. HBOT before and after gemcitabine did not increase AI in comparison to gemcitabine alone: 8.2±0.02, 8.4±0.02 vs . 8.0±0.01. Combination of HBOT and gemcitabine significantly increased AI 9.7±0.02 (P<0.001 vs . all groups). Conclusion Our data show that HBOT alone, or administered before and after gemcitabine has no effect on apoptosis in PDAC cells in vitro . HBOT significantly increased apoptosis when administered with gemcitabine.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"533-533"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233541","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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