S. Carrara, F. Gavazzi, C. Ridolfi, P. Spaggiari, A. Malesci, A. Repici, A. Zerbi
Context An increased number of pancreatic cysts are being diagnosed due to the increased use of cross-sectional imaging and new technologies. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytology and molecular analysis of the cystic fluid have led to a better characterization the pancreatic cysts, but some diagnosis still remain an enigma until surgery. Case report We present the case of a 63-year-old female, with no history of pancreatitis, who came to our attention with a pancreatic cyst. An abdominal ultrasound was performed because of abdominal discomfort and a cyst of the pancreatic neck was detected. The patient underwent a CT that confirmed a 4 cm cyst, with thin wall. She underwent a first EUS that revealed a 4 cm cyst with thin septa and thin wall, not communicating with the pancreatic duct. The fluid aspirated under EUS guidance was clear, mildly viscous, and the CEA in the fluid was 1,200 ng/mL. Since the cyst had no clear signs of malignancy, the patient underwent a clinical and radiological follow up and the cyst was stable after one year. During the second year follow up the cyst was minimally increased. At EUS the wall and the septa were still thin, with no mural nodules. A small calcification was observed on the wall. The pancreatic duct run very close to the cyst, but a communication was not clearly visible and the duct was not dilated. An EUS-FNA was performed and the CEA level was 8,813 ng/mL. The viscosity of the fluid was low, but on the basis of the high level of the CEA a mucinous cystic neoplasm was suspected and the patient underwent a distal pancreatectomy. Surprisingly the final diagnosis was that of a pancreatic retention cyst (PRC). Conclusion PRCs typically present as a well-defined, round-shape cystic lesions. They can be associated to different pathologic conditions including pancreatic inflamemation and neoplasms. Smooth dilation of upstream pancreatic duct with uncommon communication to the cyst may be helpful for the differentiation. Combination of multiple imaging modalities should contribute to improve the diagnosis, but not always. To our knowledge, there are no cases in literature of PRC with such an high level of CEA.
{"title":"A Case of Pancreatic Retention Cyst Mimicking a Cystic Mucinous Neoplasm","authors":"S. Carrara, F. Gavazzi, C. Ridolfi, P. Spaggiari, A. Malesci, A. Repici, A. Zerbi","doi":"10.6092/1590-8577/1772","DOIUrl":"https://doi.org/10.6092/1590-8577/1772","url":null,"abstract":"Context An increased number of pancreatic cysts are being diagnosed due to the increased use of cross-sectional imaging and new technologies. Endoscopic ultrasound (EUS)-guided fine needle aspiration (FNA) cytology and molecular analysis of the cystic fluid have led to a better characterization the pancreatic cysts, but some diagnosis still remain an enigma until surgery. Case report We present the case of a 63-year-old female, with no history of pancreatitis, who came to our attention with a pancreatic cyst. An abdominal ultrasound was performed because of abdominal discomfort and a cyst of the pancreatic neck was detected. The patient underwent a CT that confirmed a 4 cm cyst, with thin wall. She underwent a first EUS that revealed a 4 cm cyst with thin septa and thin wall, not communicating with the pancreatic duct. The fluid aspirated under EUS guidance was clear, mildly viscous, and the CEA in the fluid was 1,200 ng/mL. Since the cyst had no clear signs of malignancy, the patient underwent a clinical and radiological follow up and the cyst was stable after one year. During the second year follow up the cyst was minimally increased. At EUS the wall and the septa were still thin, with no mural nodules. A small calcification was observed on the wall. The pancreatic duct run very close to the cyst, but a communication was not clearly visible and the duct was not dilated. An EUS-FNA was performed and the CEA level was 8,813 ng/mL. The viscosity of the fluid was low, but on the basis of the high level of the CEA a mucinous cystic neoplasm was suspected and the patient underwent a distal pancreatectomy. Surprisingly the final diagnosis was that of a pancreatic retention cyst (PRC). Conclusion PRCs typically present as a well-defined, round-shape cystic lesions. They can be associated to different pathologic conditions including pancreatic inflamemation and neoplasms. Smooth dilation of upstream pancreatic duct with uncommon communication to the cyst may be helpful for the differentiation. Combination of multiple imaging modalities should contribute to improve the diagnosis, but not always. To our knowledge, there are no cases in literature of PRC with such an high level of CEA.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"563-563"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233572","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. Maggino, L. Landoni, G. Malleo, T. Marchese, G. Mascetta, G. Butturini, R. Salvia, C. Bassi
Context Liver cirrhosis is known to negatively affect the outcome of various types of surgery, but very poor data on the safety of pancreatic surgery in cirrhotic patients are available. As a consequence, a consensus on the operability of this subgroup of patients do not exist, and the fear of complications often results in the decision to avoid surgery. However, pancreatic surgery is presently the only curative option for malignant disease, and an aggressive tumor resection is therefore mandatory whenever possible. Only one published study has investigated the risk of pancreatic surgery in cirrhotic patients, concluding that whereas Child A patients display increased complications but a relatively low mortality, surgery in Child B patients should be avoided. Objective To investigate the outcome of cirrhotic patients who underwent surgery for a pancreatic disease at our institution. Methods Between 2003 and 2010, 53 patient with pancreatic pathology and concomitant liver cirrhosis came to our observation. Among these 17 were addressed to surgery. We retrospectively analyzed data about the clinical-pathological features of these patients, classified them on the basis of the Child score and evaluated the post-operative outcome. Fourteen patients were Child A, 3 Child B; 9 underwent a radical pancreatic resection, 6 a palliative procedure, 2 a laparoscopic abdominal exploration. The main indication for surgery was pancreatic adenocarcinoma (n=11). Results Among the 17 operated patients, 13 had a regular post-operative course (76%), 4 experienced a complication (24%). Only 1 patient (6%) died due to surgery-related complications. The mean post-operative hospital stay was 9.2 days. Significantly, all the Child B patients had a regular post-operative course. Conclusions In our experience, the presence of liver cirrhosis, even Child B cirrhosis, is not an absolute contraindication for pancreatic surgery. A careful preoperative selection and an adequate post-operative care can offer an acceptable clinical outcome even in those patients usually considered not eligible for surgery.
{"title":"Pancreatic Surgery in Patients with Concomitant Liver Cirrhosis: A Single Centre Experience","authors":"L. Maggino, L. Landoni, G. Malleo, T. Marchese, G. Mascetta, G. Butturini, R. Salvia, C. Bassi","doi":"10.6092/1590-8577/1861","DOIUrl":"https://doi.org/10.6092/1590-8577/1861","url":null,"abstract":"Context Liver cirrhosis is known to negatively affect the outcome of various types of surgery, but very poor data on the safety of pancreatic surgery in cirrhotic patients are available. As a consequence, a consensus on the operability of this subgroup of patients do not exist, and the fear of complications often results in the decision to avoid surgery. However, pancreatic surgery is presently the only curative option for malignant disease, and an aggressive tumor resection is therefore mandatory whenever possible. Only one published study has investigated the risk of pancreatic surgery in cirrhotic patients, concluding that whereas Child A patients display increased complications but a relatively low mortality, surgery in Child B patients should be avoided. Objective To investigate the outcome of cirrhotic patients who underwent surgery for a pancreatic disease at our institution. Methods Between 2003 and 2010, 53 patient with pancreatic pathology and concomitant liver cirrhosis came to our observation. Among these 17 were addressed to surgery. We retrospectively analyzed data about the clinical-pathological features of these patients, classified them on the basis of the Child score and evaluated the post-operative outcome. Fourteen patients were Child A, 3 Child B; 9 underwent a radical pancreatic resection, 6 a palliative procedure, 2 a laparoscopic abdominal exploration. The main indication for surgery was pancreatic adenocarcinoma (n=11). Results Among the 17 operated patients, 13 had a regular post-operative course (76%), 4 experienced a complication (24%). Only 1 patient (6%) died due to surgery-related complications. The mean post-operative hospital stay was 9.2 days. Significantly, all the Child B patients had a regular post-operative course. Conclusions In our experience, the presence of liver cirrhosis, even Child B cirrhosis, is not an absolute contraindication for pancreatic surgery. A careful preoperative selection and an adequate post-operative care can offer an acceptable clinical outcome even in those patients usually considered not eligible for surgery.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"577"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233580","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. Carbone, G. Piro, Anna Tamburrino, M. M. Mina, Silvia Zanini, G. Tortora, D. Melisi
Context The resistance of tumors to antiangiogenic therapies is becoming increasingly relevant. There are currently no validated predictive biomarkers for selecting which cancer patients will benefit from antiangiogenic therapy. Also lacking are resistance biomarkers that can identify which escape pathways should be targeted after tumors develop resistance to VEGF treatment. Recent studies showed that anti-VEGF treatment can make tumor cells more aggressive and metastatic. However, the mechanisms and mediators of this are unidentified. Objective We aimed this study at directly identifying the tumor cell-initiated mechanisms responsible for the resistance of pancreatic cancer to anti-VEGF treatment. Methods We established and validated two murine models of human pancreatic cancer resistant to the VEGF-specific antibody bevacizumab in vivo . We used a genome-wide analysis to directly identify which tumor-secreted factors were overexpressed by pancreatic cancer cells that were resistant to anti-VEGF treatment. Results Rather than direct proangiogenic factors, we identified several proinflammatory factors that were expressed at higher levels in cells resistant to anti-VEGF treatment than in treatment-sensitive control cells. These proinflammatory factors acted in a paracrine manner to stimulate the recruitment of CD11b + proangiogenic myeloid cells. Also, we found that secreted factors overexpressed by anti-VEGF treatment-resistant pancreatic cancer cells acted in an autocrine manner to induce epithelial-to-mesenchymal transition (EMT) and were thus responsible for increased aggressiveness of bevacizumab-resistant pancreatic tumors. Conclusions Our results identified proinflammatory factors and EMT markers as potential biomarkers for selecting patients with pancreatic cancer for antiangiogenic therapy.
{"title":"Anti-VEGF Treatment-Resistant Pancreatic Cancers Secrete Proinflammatory Factors That Contribute to Malignant Progression by Inducing an EMT Cell Phenotype","authors":"C. Carbone, G. Piro, Anna Tamburrino, M. M. Mina, Silvia Zanini, G. Tortora, D. Melisi","doi":"10.6092/1590-8577/1865","DOIUrl":"https://doi.org/10.6092/1590-8577/1865","url":null,"abstract":"Context The resistance of tumors to antiangiogenic therapies is becoming increasingly relevant. There are currently no validated predictive biomarkers for selecting which cancer patients will benefit from antiangiogenic therapy. Also lacking are resistance biomarkers that can identify which escape pathways should be targeted after tumors develop resistance to VEGF treatment. Recent studies showed that anti-VEGF treatment can make tumor cells more aggressive and metastatic. However, the mechanisms and mediators of this are unidentified. Objective We aimed this study at directly identifying the tumor cell-initiated mechanisms responsible for the resistance of pancreatic cancer to anti-VEGF treatment. Methods We established and validated two murine models of human pancreatic cancer resistant to the VEGF-specific antibody bevacizumab in vivo . We used a genome-wide analysis to directly identify which tumor-secreted factors were overexpressed by pancreatic cancer cells that were resistant to anti-VEGF treatment. Results Rather than direct proangiogenic factors, we identified several proinflammatory factors that were expressed at higher levels in cells resistant to anti-VEGF treatment than in treatment-sensitive control cells. These proinflammatory factors acted in a paracrine manner to stimulate the recruitment of CD11b + proangiogenic myeloid cells. Also, we found that secreted factors overexpressed by anti-VEGF treatment-resistant pancreatic cancer cells acted in an autocrine manner to induce epithelial-to-mesenchymal transition (EMT) and were thus responsible for increased aggressiveness of bevacizumab-resistant pancreatic tumors. Conclusions Our results identified proinflammatory factors and EMT markers as potential biomarkers for selecting patients with pancreatic cancer for antiangiogenic therapy.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"561-561"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233811","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. Granato, A. Amodio, N. D. Pretis, G. Marchi, T. Tumelero, E. Goni, A. Gabbrielli, I. Vantini, L. Benini, L. Frulloni
Context Chronic asymptomatic pancreatic hyperenzymemia (CAPH) has been described since 1996 as a benign disease. Pathological findings at magnetic resonance cholangiopancreatography (MRCP) with secretin stimulation (s-MRCP) have been found in 50% of CAPH subjects, but in 30% their clinical meaning remains undefined. Objective To investigate subjects with CAPH during the follow-up to assess the clinical and radiological outcome. Methods From January 2012 to March 2013, a cohort of 160 subjects previously studied for CAPH were re-evaluate with s-MRCP and biochemical tests. Results Clinical data relative to 108 subjects were collected, whereas 68 (47 males, 21 females; mean age: 49.8 ± 12.2 years) underwent s-MRCP. Clinically, acute pancreatitis was observed in one subject out of 108 (0.9%) after 5 years from the first detection of hyperenzymemia. Among the 68 subjects who underwent s-MRCP, 23 (33.8%) had previous s-RMCP normal and 45 (66.2%) pathological. No radiological alterations in 23 subjects with normal s-MRCP at first evaluation were observed at follow-up, whereas unchanged s-MRCP was documented in 41 out of 45 (91.1%) subjects with pathological s-MRCP at first evaluation after mean follow-up of 3±2 years. One out of 11 subject with IPMN had progression of the size of the cyst, 1 out of 11 with suspected sphincter of Oddi dysfunction showed an increase of Wirsung duct diameter, while a worsening of ductal morphology was observed in 2 out of 20 subjects with suspected chronic pancreatitis. Conclusion CAPH subjects remain asymptomatic during the follow-up. Subjects with previous normal MRCP-s did not show pathological findings at follow-up whereas only a small percentage of those with previous suspected sphincter of Oddi dysfunction or chronic pancreatitis, showed a progression at imaging in a short term follow-up.
{"title":"Clinical and Radiological Follow-up of Subjects with Chronic Asymptomatic Pancreatic Hyperenzymemia","authors":"A. Granato, A. Amodio, N. D. Pretis, G. Marchi, T. Tumelero, E. Goni, A. Gabbrielli, I. Vantini, L. Benini, L. Frulloni","doi":"10.6092/1590-8577/1870","DOIUrl":"https://doi.org/10.6092/1590-8577/1870","url":null,"abstract":"Context Chronic asymptomatic pancreatic hyperenzymemia (CAPH) has been described since 1996 as a benign disease. Pathological findings at magnetic resonance cholangiopancreatography (MRCP) with secretin stimulation (s-MRCP) have been found in 50% of CAPH subjects, but in 30% their clinical meaning remains undefined. Objective To investigate subjects with CAPH during the follow-up to assess the clinical and radiological outcome. Methods From January 2012 to March 2013, a cohort of 160 subjects previously studied for CAPH were re-evaluate with s-MRCP and biochemical tests. Results Clinical data relative to 108 subjects were collected, whereas 68 (47 males, 21 females; mean age: 49.8 ± 12.2 years) underwent s-MRCP. Clinically, acute pancreatitis was observed in one subject out of 108 (0.9%) after 5 years from the first detection of hyperenzymemia. Among the 68 subjects who underwent s-MRCP, 23 (33.8%) had previous s-RMCP normal and 45 (66.2%) pathological. No radiological alterations in 23 subjects with normal s-MRCP at first evaluation were observed at follow-up, whereas unchanged s-MRCP was documented in 41 out of 45 (91.1%) subjects with pathological s-MRCP at first evaluation after mean follow-up of 3±2 years. One out of 11 subject with IPMN had progression of the size of the cyst, 1 out of 11 with suspected sphincter of Oddi dysfunction showed an increase of Wirsung duct diameter, while a worsening of ductal morphology was observed in 2 out of 20 subjects with suspected chronic pancreatitis. Conclusion CAPH subjects remain asymptomatic during the follow-up. Subjects with previous normal MRCP-s did not show pathological findings at follow-up whereas only a small percentage of those with previous suspected sphincter of Oddi dysfunction or chronic pancreatitis, showed a progression at imaging in a short term follow-up.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"73 1","pages":"545-545"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233993","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}
T. Tumelero, A. Amodio, L. Frulloni, L. Benini, A. Gabrielli, I. Vantini
Context Chronic pancreatitis (CP) is not common in elderly people. Idiopathic senile pancreatitis (SP) was described 30 years ago, occurring over 50s, but very little information was reported since that first reported so far. Painless course, steatorrhea or diabetes, and pancreatic calcification were the clinical features. Objective This study was aimed at identifying presence and characteristics of SP in patients with CP aged >65 years. Fifty patients out of a series of 620 CP (8.1%) were identified. In 28 the onset of CP occurred >65 years (Group A), in 22 it occurred before the age of 65 years, but they were referred to our unit after 65 years (Group B). Methods Demographic data, risk factors, clinical features, morphological changes, exocrine function, diabetes were collected. Parametric and non-parametric statistical analysis was carried-out. Results No difference in gender, alcohol consumption (30% of abstainers), smoking (36% of non-smokers), genetic factors was observed between the two groups, though heavy drinkers were 25% in Group A and 40.5% in Group B (P=0.360). Heavy drinkers were also smokers. 25.3% (7 cases) of Group A and 40.5% (9 cases) of Group B were classified as alcoholic CP. Obstructive CP was present in 28.6% of A (8 cases) and 18.8% (4 cases) of Group B (P=0.304). In 22 patients (44.0%) (13 A: 46.4%; 9 B: 40.1%) CP was idiopathic (P=0.46). Painful relapses were observed in 60.7% of Group A and 86.3% of B (P=0.04). No difference in jaundice, body weight loss, diabetes, age of onset and duration of diabetes, and exocrine insufficiency was found. Calcifications were found in 71.4% and 77.3% of A and B respectively. Wirsung duct dilation (>3 mm) was observed in 92.8% and 81.8% of the two groups, and the mean pancreatic duct size was 7.36±0.44 and 7.55±1.01 (P=0.856). Fourteen patients were painless pancreatitis, preceded by painful relapses in a single case. Out of the 13 primary painless CP, 10 (76.9%) belong to Group A, 3 (23.1%) to Group B, being painless CP represented in 35.7% of A and 13.6% of B patients (P=0.044). Alcohol intake was 52.7±16.1 and 24.0±8.2 g/day in non-painless and painless CP of Group A (P=0.01). Five of the 10 CP (A) and 2/3 cases (B) were idiopathic CP (idiopathic senile CP) (17.9% of group A). Conclusions CP with onset or diagnosis over 65 years is not clinically and morphologically different from CP in patient referred over 65 years, but with a preceding onset, except for a higher frequency of primary painless CP. Idiopathic senile CP represents a very small group (10% of patients with CP observed over 65 years), without clinical, morphological and functional distinction from the other CP patients. It does not seems to be a clinical-pathological entity.
{"title":"Chronic Pancreatitis in Elderly: Does Idiopathic Senile Pancreatitis Exist as an Entity?","authors":"T. Tumelero, A. Amodio, L. Frulloni, L. Benini, A. Gabrielli, I. Vantini","doi":"10.6092/1590-8577/1872","DOIUrl":"https://doi.org/10.6092/1590-8577/1872","url":null,"abstract":"Context Chronic pancreatitis (CP) is not common in elderly people. Idiopathic senile pancreatitis (SP) was described 30 years ago, occurring over 50s, but very little information was reported since that first reported so far. Painless course, steatorrhea or diabetes, and pancreatic calcification were the clinical features. Objective This study was aimed at identifying presence and characteristics of SP in patients with CP aged >65 years. Fifty patients out of a series of 620 CP (8.1%) were identified. In 28 the onset of CP occurred >65 years (Group A), in 22 it occurred before the age of 65 years, but they were referred to our unit after 65 years (Group B). Methods Demographic data, risk factors, clinical features, morphological changes, exocrine function, diabetes were collected. Parametric and non-parametric statistical analysis was carried-out. Results No difference in gender, alcohol consumption (30% of abstainers), smoking (36% of non-smokers), genetic factors was observed between the two groups, though heavy drinkers were 25% in Group A and 40.5% in Group B (P=0.360). Heavy drinkers were also smokers. 25.3% (7 cases) of Group A and 40.5% (9 cases) of Group B were classified as alcoholic CP. Obstructive CP was present in 28.6% of A (8 cases) and 18.8% (4 cases) of Group B (P=0.304). In 22 patients (44.0%) (13 A: 46.4%; 9 B: 40.1%) CP was idiopathic (P=0.46). Painful relapses were observed in 60.7% of Group A and 86.3% of B (P=0.04). No difference in jaundice, body weight loss, diabetes, age of onset and duration of diabetes, and exocrine insufficiency was found. Calcifications were found in 71.4% and 77.3% of A and B respectively. Wirsung duct dilation (>3 mm) was observed in 92.8% and 81.8% of the two groups, and the mean pancreatic duct size was 7.36±0.44 and 7.55±1.01 (P=0.856). Fourteen patients were painless pancreatitis, preceded by painful relapses in a single case. Out of the 13 primary painless CP, 10 (76.9%) belong to Group A, 3 (23.1%) to Group B, being painless CP represented in 35.7% of A and 13.6% of B patients (P=0.044). Alcohol intake was 52.7±16.1 and 24.0±8.2 g/day in non-painless and painless CP of Group A (P=0.01). Five of the 10 CP (A) and 2/3 cases (B) were idiopathic CP (idiopathic senile CP) (17.9% of group A). Conclusions CP with onset or diagnosis over 65 years is not clinically and morphologically different from CP in patient referred over 65 years, but with a preceding onset, except for a higher frequency of primary painless CP. Idiopathic senile CP represents a very small group (10% of patients with CP observed over 65 years), without clinical, morphological and functional distinction from the other CP patients. It does not seems to be a clinical-pathological entity.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"599-599"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234117","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. Leo, R. Zuppardo, A. Mariani, M. Petrone, G. Cavestro, P. Arcidiacono, P. Testoni
Context A long-standing increase of serum pancreatic enzymes in asymptomatic subjects is considered a benign idiopathic condition called “non-pathological chronic pancreatic hyperenzymemia” (CPH). However, recent studies showed secretin-MRCP (s-MRCP) has brought to light abnormal pancreatic findings in a significant proportion of these subjects. Objective To evaluate pancreatic morphological abnormalities using s-MRCP and EUS in CPH patients. Methods Consecutive patients affected by CPH were investigated with s-MRCP and EUS. EUS findings were compared with consecutive age- and sex-matched controls who underwent EUS investigation for unrelated to pancreaticobiliary disease (CTR). Results Fifty-five CPH subjects and 55 CTR patients were enrolled. Abnormal s-MRCP pancreatic findings were present in 23 CPH cases (41.8%): 10 chronic pancreatitis, according to Cambridge classification; 5 pancreas divisum; 3 pancreatic cyst; 5 Vater’s papilla dysfunction. Pathological EUS pancreatic findings were present in 28 CPH cases (50.9%): 7 pancreatic cystic lesion, 5 pancreas divisum, 1 papillitis, 1 NET, 14 chronic pancreatitis (CP) defined by presence of “consistent with CP” or “suggestive of CP” findings using Rosemont criteria. All cases of CP who undergone s-MRCP had pathological EUS findings suggestive for CP too. Normal EUS findings were more significantly frequent in control patients (n=45) than CPH patient (n=27) (P<0.05). The two groups have same frequencies in detection of cystic lesions, pancreas divisum, papillitis, NET, but chronic pancreatitis was more common in CPH (25.5% vs . 7.3%; P<0.05). Conclusions About half of the patients with asymptomatic chronic pancreatic hyperenzymemia had some pancreatic abnormalities using s-MRCP and EUS. Both these procedures should characterize the diagnostic work-up of these subjects before the hyperenzymemia can be defined with certainly as non-pathological or benign.
{"title":"EUS And s-MRCP Findings In Asymptomatic Subjects with Chronic Pancreatic Hyperenzymemia","authors":"M. Leo, R. Zuppardo, A. Mariani, M. Petrone, G. Cavestro, P. Arcidiacono, P. Testoni","doi":"10.6092/1590-8577/1710","DOIUrl":"https://doi.org/10.6092/1590-8577/1710","url":null,"abstract":"Context A long-standing increase of serum pancreatic enzymes in asymptomatic subjects is considered a benign idiopathic condition called “non-pathological chronic pancreatic hyperenzymemia” (CPH). However, recent studies showed secretin-MRCP (s-MRCP) has brought to light abnormal pancreatic findings in a significant proportion of these subjects. Objective To evaluate pancreatic morphological abnormalities using s-MRCP and EUS in CPH patients. Methods Consecutive patients affected by CPH were investigated with s-MRCP and EUS. EUS findings were compared with consecutive age- and sex-matched controls who underwent EUS investigation for unrelated to pancreaticobiliary disease (CTR). Results Fifty-five CPH subjects and 55 CTR patients were enrolled. Abnormal s-MRCP pancreatic findings were present in 23 CPH cases (41.8%): 10 chronic pancreatitis, according to Cambridge classification; 5 pancreas divisum; 3 pancreatic cyst; 5 Vater’s papilla dysfunction. Pathological EUS pancreatic findings were present in 28 CPH cases (50.9%): 7 pancreatic cystic lesion, 5 pancreas divisum, 1 papillitis, 1 NET, 14 chronic pancreatitis (CP) defined by presence of “consistent with CP” or “suggestive of CP” findings using Rosemont criteria. All cases of CP who undergone s-MRCP had pathological EUS findings suggestive for CP too. Normal EUS findings were more significantly frequent in control patients (n=45) than CPH patient (n=27) (P<0.05). The two groups have same frequencies in detection of cystic lesions, pancreas divisum, papillitis, NET, but chronic pancreatitis was more common in CPH (25.5% vs . 7.3%; P<0.05). Conclusions About half of the patients with asymptomatic chronic pancreatic hyperenzymemia had some pancreatic abnormalities using s-MRCP and EUS. Both these procedures should characterize the diagnostic work-up of these subjects before the hyperenzymemia can be defined with certainly as non-pathological or benign.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"571-571"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71231919","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}
F. Iannone, A. Porzia, P. Birarelli, B. Milana, M. Santilli, L. Sacco, A. Ripanti, G. Dinatale, G. Prezioso, R. Caronna, S. Morrone, F. Mainiero, P. Chirletti
Context The study of the immune responses to pancreatic cancer is an emerging field of clinical and laboratory research since accumulating evidence indicate that the lymphocyte count, the Th2 polarization, the profile of cytokines and chemokines produced by cancer and immune cells and the presence of CD8+ tumor-infiltrating lymphocytes (TILs) correlate with the tumor prognosis. Objective The purpose of our study is to analyze the lymphocyte population distribution and natural killer (NK) cell cytotoxic activity before and after curative pancreatic resection (radical exeresis of mesopancreas and extended lymphadenectomy). Methods We collected blood samples from 17 pancreatic cancer patients at three different time points, before surgery and 7 and 30 days after surgery, and we evaluated the peripheral blood lymphocyte profile by cytofluorimetric analysis and the NK cytotoxic activity by a 51 chromium release assay. Seventeen blood samples from healthy subjects were used as control. Results The analysis of five lymphocyte subpopulations (T CD3+, T CD4+, T CD8+, NK CD56+, and B CD19+ cells) reveals a statistically significant increase (P=0.04) of NK CD56+ cells between the blood samples of patients, but not of controls, collected before and 30 days after surgery. Moreover, we observed a correlated modulation of NK cytotoxic activity. A more detailed classification of cancer pancreatic patients based on TNM and histological type revealed a further statistically significant modulation of T CD3+, T CD4+ and B CD19+ lymphocyte subpopulations and of NK cytotoxic activity. Conclusions Data show the importance of a radical pancreatic resection with complete mesopancreas removal and extended lymphadenectomy in the resumption of the NK cells and in the modulation of other lymphocyte subpopulations which may affect pancreatic cancer prognosis.
{"title":"Study of Lymphocyte Subpopulations and Cytotoxic Activity in the Blood of Patients Undergoing Surgery for Pancreatic Cancer","authors":"F. Iannone, A. Porzia, P. Birarelli, B. Milana, M. Santilli, L. Sacco, A. Ripanti, G. Dinatale, G. Prezioso, R. Caronna, S. Morrone, F. Mainiero, P. Chirletti","doi":"10.6092/1590-8577/1750","DOIUrl":"https://doi.org/10.6092/1590-8577/1750","url":null,"abstract":"Context The study of the immune responses to pancreatic cancer is an emerging field of clinical and laboratory research since accumulating evidence indicate that the lymphocyte count, the Th2 polarization, the profile of cytokines and chemokines produced by cancer and immune cells and the presence of CD8+ tumor-infiltrating lymphocytes (TILs) correlate with the tumor prognosis. Objective The purpose of our study is to analyze the lymphocyte population distribution and natural killer (NK) cell cytotoxic activity before and after curative pancreatic resection (radical exeresis of mesopancreas and extended lymphadenectomy). Methods We collected blood samples from 17 pancreatic cancer patients at three different time points, before surgery and 7 and 30 days after surgery, and we evaluated the peripheral blood lymphocyte profile by cytofluorimetric analysis and the NK cytotoxic activity by a 51 chromium release assay. Seventeen blood samples from healthy subjects were used as control. Results The analysis of five lymphocyte subpopulations (T CD3+, T CD4+, T CD8+, NK CD56+, and B CD19+ cells) reveals a statistically significant increase (P=0.04) of NK CD56+ cells between the blood samples of patients, but not of controls, collected before and 30 days after surgery. Moreover, we observed a correlated modulation of NK cytotoxic activity. A more detailed classification of cancer pancreatic patients based on TNM and histological type revealed a further statistically significant modulation of T CD3+, T CD4+ and B CD19+ lymphocyte subpopulations and of NK cytotoxic activity. Conclusions Data show the importance of a radical pancreatic resection with complete mesopancreas removal and extended lymphadenectomy in the resumption of the NK cells and in the modulation of other lymphocyte subpopulations which may affect pancreatic cancer prognosis.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"576-576"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71232955","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}
J. Nifosi, F. Aleotti, G. Capretti, N. Pecorelli, S. Chiappetta, R. Castoldi, M. Braga, C. Staudacher, G. Balzano
Context The laparoscopic approach for benign and malignant lesions of the left pancreas is increasingly applied. Methods Retrospective study on prospectively collected data. Perioperative data and operative outcome of consecutive laparoscopic distal pancreatectomies performed between March 2006 and March 2013 were analyzed (intent-to-treat analysis). Operative outcome of the subgroup of patients with conversion to open surgery was compared to patients with successful laparoscopy to assess the consequences of conversion. Results Among 341 distal pancreatectomies, 100 patients (29%) had a laparoscopic approach (with a progressively increasing rate from 6% in 2006 to 62% in 2012). Malignancy was not a contraindication. Mean age was 57.4 years (range: 24-83 years; 42 males and 58 females). Mean BMI was 25.3 kg/m 2 (range: 17-39 kg/m 2 ). Conversion rate was 19% (11 cases because of the difficulty to isolate the pancreas or lesion from the peripancreatic vessels, 6 cases due to intraoperative bleeding, 2 cases due to the site and/or dimension of the lesion). Mean operative time was 244 min (range: 110-490 min). Median blood loss was 250 mL (range: 30-1,800 mL), with 20 patients receiving blood transfusion. Mortality was nihil, morbidity was 68%, with 5% grade ≥3 according to Clavien-Dindo classification (2 cases percutaneous drainage, 3 cases relaparotomy). Pancreatic fistula occurred in 55 cases (of which 8 grade B, 1 grade C). Mean postoperative stay was 8.2 days (range: 4-23 days). Readmission occurred in 7 cases. Spleen preservation (performed with preservation of splenic vessels) was planned in 64% of cases and was successful in 48%; in 12 cases splenectomy was intraoperatively decided due to adhesions with splenic vessels, in 4 cases due to bleeding. The 19 patients with conversion to open surgery, when compared to patients without conversion, had a longer operative time (P=0.01), higher blood loss (P<0.001), higher transfusion amount (P<0.001), and longer postoperative stay (P=0.001); no difference was observed in morbidity rate (P=0.42). At final histology 25 cases were adenocarcinoma, 33 NET (9 insulinoma), 23 cystoadenoma (17 mucinous, 6 serous), 8 IPMN, 5 solid pseudopapillary tumors, 4 chronic pancreatitis and pseudocysts, 2 metastases from RCC. R0 resection was obtained in 97% of cases. Mean number of retrieved lymph nodes was 14.4. Conclusions Laparoscopic distal pancreatectomy can be performed in more than 60% of overall distal pancreatectomy, with a successful spleen preservation rate of 75% of cases. A worse operative outcome is to be expected in patients requiring conversion to open surgery.
{"title":"One-Hundred Laparoscopic Distal Pancreatectomies in a Single Institution","authors":"J. Nifosi, F. Aleotti, G. Capretti, N. Pecorelli, S. Chiappetta, R. Castoldi, M. Braga, C. Staudacher, G. Balzano","doi":"10.6092/1590-8577/1774","DOIUrl":"https://doi.org/10.6092/1590-8577/1774","url":null,"abstract":"Context The laparoscopic approach for benign and malignant lesions of the left pancreas is increasingly applied. Methods Retrospective study on prospectively collected data. Perioperative data and operative outcome of consecutive laparoscopic distal pancreatectomies performed between March 2006 and March 2013 were analyzed (intent-to-treat analysis). Operative outcome of the subgroup of patients with conversion to open surgery was compared to patients with successful laparoscopy to assess the consequences of conversion. Results Among 341 distal pancreatectomies, 100 patients (29%) had a laparoscopic approach (with a progressively increasing rate from 6% in 2006 to 62% in 2012). Malignancy was not a contraindication. Mean age was 57.4 years (range: 24-83 years; 42 males and 58 females). Mean BMI was 25.3 kg/m 2 (range: 17-39 kg/m 2 ). Conversion rate was 19% (11 cases because of the difficulty to isolate the pancreas or lesion from the peripancreatic vessels, 6 cases due to intraoperative bleeding, 2 cases due to the site and/or dimension of the lesion). Mean operative time was 244 min (range: 110-490 min). Median blood loss was 250 mL (range: 30-1,800 mL), with 20 patients receiving blood transfusion. Mortality was nihil, morbidity was 68%, with 5% grade ≥3 according to Clavien-Dindo classification (2 cases percutaneous drainage, 3 cases relaparotomy). Pancreatic fistula occurred in 55 cases (of which 8 grade B, 1 grade C). Mean postoperative stay was 8.2 days (range: 4-23 days). Readmission occurred in 7 cases. Spleen preservation (performed with preservation of splenic vessels) was planned in 64% of cases and was successful in 48%; in 12 cases splenectomy was intraoperatively decided due to adhesions with splenic vessels, in 4 cases due to bleeding. The 19 patients with conversion to open surgery, when compared to patients without conversion, had a longer operative time (P=0.01), higher blood loss (P<0.001), higher transfusion amount (P<0.001), and longer postoperative stay (P=0.001); no difference was observed in morbidity rate (P=0.42). At final histology 25 cases were adenocarcinoma, 33 NET (9 insulinoma), 23 cystoadenoma (17 mucinous, 6 serous), 8 IPMN, 5 solid pseudopapillary tumors, 4 chronic pancreatitis and pseudocysts, 2 metastases from RCC. R0 resection was obtained in 97% of cases. Mean number of retrieved lymph nodes was 14.4. Conclusions Laparoscopic distal pancreatectomy can be performed in more than 60% of overall distal pancreatectomy, with a successful spleen preservation rate of 75% of cases. A worse operative outcome is to be expected in patients requiring conversion to open surgery.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"586-586"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71233614","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. Nappo, D. Borzomati, S. Valeri, G. Mascianá, R. Coppola
Context Pancreaticoduodenectomy (PD) is the treatment of choice for patients affected by peri-ampullary cancer. Para-aortic nodes dissection during PD for cancer is not routinely performed, even in high volume pancreatic hospitals. However, according to the American Joint Committee on Cancer (AJCC), the neoplastic involvement of para-aortic lymph-nodes is considered expression of metastatic disease (M1). Objective The aims of this prospective analysis were to evaluate the incidence of para-aortic lymph-nodes involvement in patients undergoing PD for periampullary cancer and its prognostic value. Materials and methods We evaluated 127 consecutive patients undergoing PD for periampullary cancer between 2002-2013 at “Campus Bio-Medico” University of Rome. In all case a meticulous para-aortic lymph node dissection was performed. We analyzed the incidence rate of para-aortic lymph-nodes involvement. Moreover, we evaluated the difference in terms of overall survival between patients with (M+) and withouth (M-) involvement of para-aortic lymphnodes. Results Considering all 127 patients that underwent PD for cancer: 74 patients (58%) were affected by adenocarcinoma of the head of the pancreas; 8 patients (6.3%) were affected by distal cholangiocarcinoma; 17 patients (13.4%) were affected by carcinoma of the ampulla of Vater; and 2 patients (1.6%) were affected by carcinoma of the duodenum. The incidence rate of involvement of para-aortic lymph-nodes was 11.0%. Particularly, the involvement of para-aortic lymph-nodes was found in 14.9% of patients affected by adenocarcinoma of the head of the pancreas and in 37.5% of patients affected by distal cholangiocarcinoma. On the opposite, an involvement of para-aortic lymph-nodes was not found in patients affected by adenocarcinoma of the ampulla or by carcinoma of the duodenum. The overall survival of all 127 patients was 13 months (range: 0-132 months). The overall survival was 5.5 months (range: 0-27 months) in patients with involvement of para-aortic lymph-nodes (M+) and 15 months (range: 0-132 months) in patients without involvement of para-aortic lymph-nodes (P<0.05). Conclusions PD associated with lymphadenectomy is the gold-standard treatment for patients with periampullary cancer. The para-aortic lymph node dissection is not routinely performed during PD. Our data showed that the rate of neoplastic involvement of para-aortic lymph nodes was about 10%. Particularly, para-aortic lymph-nodes involvement was more frequent in patients affected by distal cholangiocarcinoma (37% of cases) and by adenocarcinoma of the head of the pancreatic (15% of cases). Moreover, our results showed that the involvement of para-aortic lymph-nodes negatively affected the prognosis: overall survival was 5.5 months in patients with lymph-nodes metastases and 15 months in patients without lymph-nodes metastases.
{"title":"The Dissection of Para-Aortic Lymph-Nodes During Pancreaticoduodenectomy for Cancer and Its Prognostic Value","authors":"G. Nappo, D. Borzomati, S. Valeri, G. Mascianá, R. Coppola","doi":"10.6092/1590-8577/1702","DOIUrl":"https://doi.org/10.6092/1590-8577/1702","url":null,"abstract":"Context Pancreaticoduodenectomy (PD) is the treatment of choice for patients affected by peri-ampullary cancer. Para-aortic nodes dissection during PD for cancer is not routinely performed, even in high volume pancreatic hospitals. However, according to the American Joint Committee on Cancer (AJCC), the neoplastic involvement of para-aortic lymph-nodes is considered expression of metastatic disease (M1). Objective The aims of this prospective analysis were to evaluate the incidence of para-aortic lymph-nodes involvement in patients undergoing PD for periampullary cancer and its prognostic value. Materials and methods We evaluated 127 consecutive patients undergoing PD for periampullary cancer between 2002-2013 at “Campus Bio-Medico” University of Rome. In all case a meticulous para-aortic lymph node dissection was performed. We analyzed the incidence rate of para-aortic lymph-nodes involvement. Moreover, we evaluated the difference in terms of overall survival between patients with (M+) and withouth (M-) involvement of para-aortic lymphnodes. Results Considering all 127 patients that underwent PD for cancer: 74 patients (58%) were affected by adenocarcinoma of the head of the pancreas; 8 patients (6.3%) were affected by distal cholangiocarcinoma; 17 patients (13.4%) were affected by carcinoma of the ampulla of Vater; and 2 patients (1.6%) were affected by carcinoma of the duodenum. The incidence rate of involvement of para-aortic lymph-nodes was 11.0%. Particularly, the involvement of para-aortic lymph-nodes was found in 14.9% of patients affected by adenocarcinoma of the head of the pancreas and in 37.5% of patients affected by distal cholangiocarcinoma. On the opposite, an involvement of para-aortic lymph-nodes was not found in patients affected by adenocarcinoma of the ampulla or by carcinoma of the duodenum. The overall survival of all 127 patients was 13 months (range: 0-132 months). The overall survival was 5.5 months (range: 0-27 months) in patients with involvement of para-aortic lymph-nodes (M+) and 15 months (range: 0-132 months) in patients without involvement of para-aortic lymph-nodes (P<0.05). Conclusions PD associated with lymphadenectomy is the gold-standard treatment for patients with periampullary cancer. The para-aortic lymph node dissection is not routinely performed during PD. Our data showed that the rate of neoplastic involvement of para-aortic lymph nodes was about 10%. Particularly, para-aortic lymph-nodes involvement was more frequent in patients affected by distal cholangiocarcinoma (37% of cases) and by adenocarcinoma of the head of the pancreatic (15% of cases). Moreover, our results showed that the involvement of para-aortic lymph-nodes negatively affected the prognosis: overall survival was 5.5 months in patients with lymph-nodes metastases and 15 months in patients without lymph-nodes metastases.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"584-584"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71232144","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}
Ilaria Passacantilli, Sara Calabretta, P. Bielli, G. Capurso, G. Fave, C. Sette
Context Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease, characterised by limited response to chemotherapeutic treatment and early metastasis, leading to very poor prognosis. Epithelial to mesenchymal transition (EMT), a process finely regulated both at transcription and splicing level, contributes to PDAC invasion and affects the response to chemotherapeutic drugs. The expression of the EMT transcription factor ZEB1 is inversely related to sensitivity cells to gemcitabine treatment. Notably, ZEB1 encodes multiple splice variants that mainly differ in the 5’ untranslated region (UTR). However, the biological role of these splice variants in EMT and drug resistance is currently unknown. Objective Characterization of the molecular events involved in the acquisition of gemcitabine resistance in PDAC cells. Methods PCR analysis of EMT genes; Western blot analysis of proteins of the mTOR pathway; 7-mGTP cap assay of cap-dependent translation; polysomal-RNPs fractioning for analysis of mRNA translation. Results PDAC cells exposed to gemcitabine for 72 hours up-regulated mesenchymal genes, including ZEB1, which is known to confer chemoresistance. This response is accompanied by inhibition of mTOR pathway and cap-dependent translation, as confirmed by reduced assembly of the translation initiation complex eIF4F. Conversely, cap-independent translation is not impaired by the drug. In this context, ZEB1 splice variants containing different 5’ UTRs are differentially loaded on polysomes, suggesting that expression of specific variants allows ZEB1 translation during drug treatment. Conclusion Our results show that treatment with gemcitabine alters the expression of EMT genes and that these events are concomitant to important alteration in the translational program. Together, these processes can drive to different translational patterns in presence of gemcitabine, as shown for the ZEB1 variants, which may take part to the mechanisms leading to chemoresistance of PDAC cells.
{"title":"Gemcitabine Treatment Causes Deregulation of Epithelial to Mesenchymal Transition Transcription Factors Transcription and Translation in Pancreatic Ductal Adenocarcinoma Cells","authors":"Ilaria Passacantilli, Sara Calabretta, P. Bielli, G. Capurso, G. Fave, C. Sette","doi":"10.6092/1590-8577/1736","DOIUrl":"https://doi.org/10.6092/1590-8577/1736","url":null,"abstract":"Context Pancreatic ductal adenocarcinoma (PDAC) is an aggressive disease, characterised by limited response to chemotherapeutic treatment and early metastasis, leading to very poor prognosis. Epithelial to mesenchymal transition (EMT), a process finely regulated both at transcription and splicing level, contributes to PDAC invasion and affects the response to chemotherapeutic drugs. The expression of the EMT transcription factor ZEB1 is inversely related to sensitivity cells to gemcitabine treatment. Notably, ZEB1 encodes multiple splice variants that mainly differ in the 5’ untranslated region (UTR). However, the biological role of these splice variants in EMT and drug resistance is currently unknown. Objective Characterization of the molecular events involved in the acquisition of gemcitabine resistance in PDAC cells. Methods PCR analysis of EMT genes; Western blot analysis of proteins of the mTOR pathway; 7-mGTP cap assay of cap-dependent translation; polysomal-RNPs fractioning for analysis of mRNA translation. Results PDAC cells exposed to gemcitabine for 72 hours up-regulated mesenchymal genes, including ZEB1, which is known to confer chemoresistance. This response is accompanied by inhibition of mTOR pathway and cap-dependent translation, as confirmed by reduced assembly of the translation initiation complex eIF4F. Conversely, cap-independent translation is not impaired by the drug. In this context, ZEB1 splice variants containing different 5’ UTRs are differentially loaded on polysomes, suggesting that expression of specific variants allows ZEB1 translation during drug treatment. Conclusion Our results show that treatment with gemcitabine alters the expression of EMT genes and that these events are concomitant to important alteration in the translational program. Together, these processes can drive to different translational patterns in presence of gemcitabine, as shown for the ZEB1 variants, which may take part to the mechanisms leading to chemoresistance of PDAC cells.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"14 1","pages":"588-588"},"PeriodicalIF":0.2,"publicationDate":"2013-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71232824","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}
京公网安备 11010802042870号
京ICP备2023020795号-1
扫码关注我们
求助内容：
应助结果提醒方式：