Metabolomics is an emerging scientific field focusing on compounds, also known as metabolomes that are produced by biologic systems. Metabolomes represent phenotypic end-products of living entities, and are of particular interest as they represent a novel group of biomarkers that can be used for diagnosis, monitoring response to treatments, and more recently as potential therapeutic agents for benign but more so for malignant diseases. One of the main factors associated with improved survival of patients affected by malignancies is early diagnosis, particularly for those tumors with poor prognosis such as pancreatic cancer. Currently, there are no diagnostic tests for the screening of pancreatic cancer, and although novel biomarkers continue to be discovered, none has yet to be proven useful for this purpose. The main aims of this paper are to review the current literature and to summarize the most relevant advances in the field of metabolomics applied to pancreatic adenocarcinoma. Image: Dalhousie University. Halifax, Nova Scotia, Canada.
{"title":"Advances in Pancreatic Cancer: The Role of Metabolomics","authors":"V. Nguyen, S. Hurton, S. Ayloo, M. Molinari","doi":"10.6092/1590-8577/2990","DOIUrl":"https://doi.org/10.6092/1590-8577/2990","url":null,"abstract":"Metabolomics is an emerging scientific field focusing on compounds, also known as metabolomes that are produced by biologic systems. Metabolomes represent phenotypic end-products of living entities, and are of particular interest as they represent a novel group of biomarkers that can be used for diagnosis, monitoring response to treatments, and more recently as potential therapeutic agents for benign but more so for malignant diseases. One of the main factors associated with improved survival of patients affected by malignancies is early diagnosis, particularly for those tumors with poor prognosis such as pancreatic cancer. Currently, there are no diagnostic tests for the screening of pancreatic cancer, and although novel biomarkers continue to be discovered, none has yet to be proven useful for this purpose. The main aims of this paper are to review the current literature and to summarize the most relevant advances in the field of metabolomics applied to pancreatic adenocarcinoma. Image: Dalhousie University. Halifax, Nova Scotia, Canada.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"16 1","pages":"244-248"},"PeriodicalIF":0.2,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234534","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. Schober, R. Jesenofsky, R. Faissner, S. Krug, C. Weidenauer, W. Hagmann, S. Haas, R. Heuchel, M. Löhr
Context Pancreatic ductal adenocarcinoma is a dismal disease with one of the worst prognoses amongst solid tumors. Its ability to develop chemoresistance mechanisms towards cytotoxic drugs is the main cause of treatment failure. Objective Here, we have established a drug-resistance model for pancreatic cancer in which Capan-1 pancreatic carcinoma cells (designated Capan-1 5-FU2000) acquired 5-fluorouracil (5-FU) resistance and were used as a paradigm to reveal alterations in intracellular signaling cascades that. Those alterations may contribute to the circumvention of apoptosis during the course of the disease, culminating in treatment failure. Methods We made use of 2-D-gelelectrophoresis, mass-spectrometry, sandwich-ELISA and western blotting to compare the proteomic expression patterns of respective mediators involved in pro- and antiapoptotic as well as inflammatory processes in both cell lines. An ATP-based chemosensitivity assay validated the chemoresistant phenotype of the Capan-1 5-FU2000 clones. Results We detected specific changes in our resistant cell clones in particular a decreased expression of S100A4. We also found a decreased basal phosphorylation of SAPK/JNK and P38. The expression of the pro-apoptotic mediators Bok and Bad was down- and up-regulated in these cells, respectively. In case of NfkB p65 and IkB-alpha treatment with 5-FU (2,000 µg/mL for 96 h) markedly induced phosphorylation in native Capan-1 cells. In contrast in resistant clones it decreased phosphorylation of NfkB p65 and did not affect IkB-alpha phosphorylation. Basal phosphorylation of S6-ribosomal-protein was markedly increased in resistant clones, treatment with 5-FU decreased this phosphorylation, while in native Capan-1 cells it was vice versa. Conclusion Thus we can conclude that several pathways were found to be altered in chemoresistant Capan-1 5-FU2000 cells. Moreover these alterations are most likely the consequence of a multistep adaption towards gradual cytotoxic exposure finally culminating in a chemoresistant phenotype. Interfering with these pathways may possibly reverse the phenotype and thus open up alternative treatment options. Image: Effect of 5-FU treatment on NfkB p65 phosphorylation in native and 5-FU resistant cells.
{"title":"Acquired 5-Fluorouracil Resistance in Human Pancreatic Carcinoma Cells. A Paradigm for Chemoresistance Mechanisms in Pancreatic Cancer","authors":"M. Schober, R. Jesenofsky, R. Faissner, S. Krug, C. Weidenauer, W. Hagmann, S. Haas, R. Heuchel, M. Löhr","doi":"10.6092/1590-8577/2992","DOIUrl":"https://doi.org/10.6092/1590-8577/2992","url":null,"abstract":"Context Pancreatic ductal adenocarcinoma is a dismal disease with one of the worst prognoses amongst solid tumors. Its ability to develop chemoresistance mechanisms towards cytotoxic drugs is the main cause of treatment failure. Objective Here, we have established a drug-resistance model for pancreatic cancer in which Capan-1 pancreatic carcinoma cells (designated Capan-1 5-FU2000) acquired 5-fluorouracil (5-FU) resistance and were used as a paradigm to reveal alterations in intracellular signaling cascades that. Those alterations may contribute to the circumvention of apoptosis during the course of the disease, culminating in treatment failure. Methods We made use of 2-D-gelelectrophoresis, mass-spectrometry, sandwich-ELISA and western blotting to compare the proteomic expression patterns of respective mediators involved in pro- and antiapoptotic as well as inflammatory processes in both cell lines. An ATP-based chemosensitivity assay validated the chemoresistant phenotype of the Capan-1 5-FU2000 clones. Results We detected specific changes in our resistant cell clones in particular a decreased expression of S100A4. We also found a decreased basal phosphorylation of SAPK/JNK and P38. The expression of the pro-apoptotic mediators Bok and Bad was down- and up-regulated in these cells, respectively. In case of NfkB p65 and IkB-alpha treatment with 5-FU (2,000 µg/mL for 96 h) markedly induced phosphorylation in native Capan-1 cells. In contrast in resistant clones it decreased phosphorylation of NfkB p65 and did not affect IkB-alpha phosphorylation. Basal phosphorylation of S6-ribosomal-protein was markedly increased in resistant clones, treatment with 5-FU decreased this phosphorylation, while in native Capan-1 cells it was vice versa. Conclusion Thus we can conclude that several pathways were found to be altered in chemoresistant Capan-1 5-FU2000 cells. Moreover these alterations are most likely the consequence of a multistep adaption towards gradual cytotoxic exposure finally culminating in a chemoresistant phenotype. Interfering with these pathways may possibly reverse the phenotype and thus open up alternative treatment options. Image: Effect of 5-FU treatment on NfkB p65 phosphorylation in native and 5-FU resistant cells.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"219 1","pages":"256-265"},"PeriodicalIF":0.2,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234557","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}
Context Laparoscopic distal pancreatectomy is a widely accepted treatment for non-malignant lesions of the left pancreas. However, the role of laparoscopy in more complex procedures such as pancreaticoduodenectomy or treatment of pancreatic adenocarcinoma remains controversial. Case report A seventy-seven-year-old woman underwent surgery twice: first for a PADC of the tail infiltrating the spleen and left kidney, and then for a second PADC of the neck and head of the pancreas diagnosed during follow-up (11 months) of the first tumor. In both procedures a totally laparoscopic approach was applied. The first procedure was an en-bloc resection including the left kidney, spleen and left pancreas. Final diagnosis showed a PADC (49x42x40 mm) involving one of the 17 lymph nodes harvested (R0). Postoperative course was uneventful, and lasted five days. Later, due to the appearance of a new tumor in the right pancreas, an extended pylorus-preserving PD was performed with the patient in supine position with the legs apart. In the postoperative period she presented chylous ascites and required hospitalization for 17 days. Definitive biopsy showed a 2 cm PADC (PanIn 2 and 3 lesions in the rest of the gland). Two out of 21 nodes isolated were found to be affected (R0). No chemotherapy was administered after the second operation. Conclusions Our report may help to redefine the limits of laparoscopy in pancreatic oncologic surgery. It describes several features of added technical difficulty, and may prompt further reflection on the current limits and indications of laparoscopic pancreatectomy. Image: Positioning of the trocars and incision.
{"title":"Consecutive Laparoscopic En-Block Left Pancreato-Nephro-Splenectomy and Later Pancreaticoduodenectomy: Pushing Back the Limits of Laparoscopic Pancreatic Resections","authors":"I. Poves, F. Burdío, A. Francés, L. Grande","doi":"10.6092/1590-8577/3004","DOIUrl":"https://doi.org/10.6092/1590-8577/3004","url":null,"abstract":"Context Laparoscopic distal pancreatectomy is a widely accepted treatment for non-malignant lesions of the left pancreas. However, the role of laparoscopy in more complex procedures such as pancreaticoduodenectomy or treatment of pancreatic adenocarcinoma remains controversial. Case report A seventy-seven-year-old woman underwent surgery twice: first for a PADC of the tail infiltrating the spleen and left kidney, and then for a second PADC of the neck and head of the pancreas diagnosed during follow-up (11 months) of the first tumor. In both procedures a totally laparoscopic approach was applied. The first procedure was an en-bloc resection including the left kidney, spleen and left pancreas. Final diagnosis showed a PADC (49x42x40 mm) involving one of the 17 lymph nodes harvested (R0). Postoperative course was uneventful, and lasted five days. Later, due to the appearance of a new tumor in the right pancreas, an extended pylorus-preserving PD was performed with the patient in supine position with the legs apart. In the postoperative period she presented chylous ascites and required hospitalization for 17 days. Definitive biopsy showed a 2 cm PADC (PanIn 2 and 3 lesions in the rest of the gland). Two out of 21 nodes isolated were found to be affected (R0). No chemotherapy was administered after the second operation. Conclusions Our report may help to redefine the limits of laparoscopy in pancreatic oncologic surgery. It describes several features of added technical difficulty, and may prompt further reflection on the current limits and indications of laparoscopic pancreatectomy. Image: Positioning of the trocars and incision.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"201 1","pages":"313-315"},"PeriodicalIF":0.2,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71235140","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}
K. Ånonsen, T. Buanes, B. Røsok, T. Hauge, B. Edwin
Context Recent guidelines for the management of cystic lesions of the pancreas recommend observation for selected neoplasms using imaging criteria. However, current imaging modalities lack diagnostic accuracy, and the indication for surgery is debated. Objective In this study we have explored the outcome of laparoscopic distal pancreatic resections in all patients referred with potential pancreatic cystic neoplasms, with histological diagnosis as endpoint. Methods Between 1997 and 2009 all patients referred to our tertiary referral centre having a cystic neoplasm of the distal pancreas accepted for surgery were included in the present observational study. Results A total of 69 patients were included. Sixty-two patients underwent distal pancreatectomies, in whom 19 were spleen-preserving, and 7 enucleations were performed. Two procedures were converted to open technique. The lesions removed in 27 patients (39%) were either malignant or premalignant. The final diagnoses were serous cystic neoplasm (n=29), mucinous cystic neoplasm (n=12), pseudocyst (n=11), solid pseudopapillary neoplasm (n=10), intraductal papillary mucinous neoplasm (n=5) and other (n=2). Overall morbidity was 33%; 56% of the complications were classified as mild. Fistula rate was 10%. One patient died postoperatively from a cerebral haemorrhage. Conclusion Most complications after laparoscopic distal resection of cystic pancreatic lesions are mild, but the proportion of patients with benign lesions (61%) has to be reduced by focused preoperative investigations. Endoscopic ultrasound examination (EUS), enabling aspiration of cyst fluid and fine needle aspiration is an additional option for the preoperative workup. Image: Histological diagnosis of the resected specimens.
{"title":"Outcome of Laparoscopic Surgery in Patients with Cystic Lesions in the Distal Pancreas","authors":"K. Ånonsen, T. Buanes, B. Røsok, T. Hauge, B. Edwin","doi":"10.6092/1590-8577/2993","DOIUrl":"https://doi.org/10.6092/1590-8577/2993","url":null,"abstract":"Context Recent guidelines for the management of cystic lesions of the pancreas recommend observation for selected neoplasms using imaging criteria. However, current imaging modalities lack diagnostic accuracy, and the indication for surgery is debated. Objective In this study we have explored the outcome of laparoscopic distal pancreatic resections in all patients referred with potential pancreatic cystic neoplasms, with histological diagnosis as endpoint. Methods Between 1997 and 2009 all patients referred to our tertiary referral centre having a cystic neoplasm of the distal pancreas accepted for surgery were included in the present observational study. Results A total of 69 patients were included. Sixty-two patients underwent distal pancreatectomies, in whom 19 were spleen-preserving, and 7 enucleations were performed. Two procedures were converted to open technique. The lesions removed in 27 patients (39%) were either malignant or premalignant. The final diagnoses were serous cystic neoplasm (n=29), mucinous cystic neoplasm (n=12), pseudocyst (n=11), solid pseudopapillary neoplasm (n=10), intraductal papillary mucinous neoplasm (n=5) and other (n=2). Overall morbidity was 33%; 56% of the complications were classified as mild. Fistula rate was 10%. One patient died postoperatively from a cerebral haemorrhage. Conclusion Most complications after laparoscopic distal resection of cystic pancreatic lesions are mild, but the proportion of patients with benign lesions (61%) has to be reduced by focused preoperative investigations. Endoscopic ultrasound examination (EUS), enabling aspiration of cyst fluid and fine needle aspiration is an additional option for the preoperative workup. Image: Histological diagnosis of the resected specimens.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"16 1","pages":"266-270"},"PeriodicalIF":0.2,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234592","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}
D. Dell’Edera, D. Salvatore, M. Benedetto, Antonio Lovaglio, Manuela Leo, A. Epifania
Context Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasian population. Extending knowledge about the molecular pathology on the one hand allows better delineation of the mutations in the cystic fibrosis transmembrane regulator gene and the other to dramatically increase the predictive power of molecular testing. Case report This study wants to underline that the identification of individuals with atypical cystic fibrosis can sometimes present particular difficulties of interpretation. Conclusion On that ground, if there is a strong clinical suspicion, it is always advisable the biochemical study by performing the sweat test, followed by sequencing of the cystic fibrosis transmembrane regulator gene. Image: Madonna delle Grazie Hospital. Matera, Italy.
{"title":"Mild Cystic Fibrosis. A Case Report","authors":"D. Dell’Edera, D. Salvatore, M. Benedetto, Antonio Lovaglio, Manuela Leo, A. Epifania","doi":"10.6092/1590-8577/3005","DOIUrl":"https://doi.org/10.6092/1590-8577/3005","url":null,"abstract":"Context Cystic fibrosis is the most common autosomal recessive genetic disease in Caucasian population. Extending knowledge about the molecular pathology on the one hand allows better delineation of the mutations in the cystic fibrosis transmembrane regulator gene and the other to dramatically increase the predictive power of molecular testing. Case report This study wants to underline that the identification of individuals with atypical cystic fibrosis can sometimes present particular difficulties of interpretation. Conclusion On that ground, if there is a strong clinical suspicion, it is always advisable the biochemical study by performing the sweat test, followed by sequencing of the cystic fibrosis transmembrane regulator gene. Image: Madonna delle Grazie Hospital. Matera, Italy.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"16 1","pages":"316-317"},"PeriodicalIF":0.2,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71235294","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}
When hyperechoic pancreatic parenchyma is observed on endoscopic or transabdominal ultrasound, fat infiltration of the pancreas is suspected. This condition was first reported by Ogilvie in 1993 and is termed fatty pancreas, pancreatic lipomatosis, non-alcoholic fatty pancreas, or pancreatic steatosis. Diagnosis of this condition mostly relies on imaging tools such as magnetic resonance imaging, computed tomography, or ultrasonography rather than histology. Although the condition is rare, it has clinical significance. There are multiple hypotheses regarded the etiology of this condition, listing factors such as viral infections, toxins, and congenital syndromes as possible causes. Metabolic syndrome and diabetes mellitus correlated with this condition. However, other etiologies should also be considered to aid specific treatment. In addition to a correlation between pancreatic steatosis and metabolic syndrome, relationships between pancreatic steatosis and worsened severity and prognosis of pancreatic cancer, increased complications after pancreatic surgery, and acute pancreatitis were reported. Gastroenterologists should be well informed about this condition for better care of these patients. Image: Siriraj Hospital. Bangkok, Thailand.
{"title":"Pancreatic Steatosis: What Should Gastroenterologists Know?","authors":"V. Prachayakul, P. Aswakul","doi":"10.6092/1590-8577/2987","DOIUrl":"https://doi.org/10.6092/1590-8577/2987","url":null,"abstract":"When hyperechoic pancreatic parenchyma is observed on endoscopic or transabdominal ultrasound, fat infiltration of the pancreas is suspected. This condition was first reported by Ogilvie in 1993 and is termed fatty pancreas, pancreatic lipomatosis, non-alcoholic fatty pancreas, or pancreatic steatosis. Diagnosis of this condition mostly relies on imaging tools such as magnetic resonance imaging, computed tomography, or ultrasonography rather than histology. Although the condition is rare, it has clinical significance. There are multiple hypotheses regarded the etiology of this condition, listing factors such as viral infections, toxins, and congenital syndromes as possible causes. Metabolic syndrome and diabetes mellitus correlated with this condition. However, other etiologies should also be considered to aid specific treatment. In addition to a correlation between pancreatic steatosis and metabolic syndrome, relationships between pancreatic steatosis and worsened severity and prognosis of pancreatic cancer, increased complications after pancreatic surgery, and acute pancreatitis were reported. Gastroenterologists should be well informed about this condition for better care of these patients. Image: Siriraj Hospital. Bangkok, Thailand.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"21 1","pages":"227-231"},"PeriodicalIF":0.2,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234476","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}
Pancreatic tuberculosis is a rare occurrence in either immune-competent or immune-suppressed host. Pancreatic tuberculosis most commonly afflicts the region of the head and the uncinate process of the pancreas. It is often misdiagnosed due to low index of suspicion and masquerading of its symptoms as more common pancreatic conditions such as pancreatic malignancy. However, Endoscopic ultrasound fine needle aspiration sampling with an acid-fast smear is essential for establishing the diagnosis of pancreatic tuberculosis. If the diagnosis is delayed, pancreatic tuberculosis can be fatal. Pancreatic tuberculosis responds well to standard anti-tuberculous drugs. Image: Taleghani Hospital. Tehran, Iran.
{"title":"Pancreatic Tuberculosis: An Overview","authors":"M. Miri, M. Safari, A. Alizadeh","doi":"10.6092/1590-8577/2988","DOIUrl":"https://doi.org/10.6092/1590-8577/2988","url":null,"abstract":"Pancreatic tuberculosis is a rare occurrence in either immune-competent or immune-suppressed host. Pancreatic tuberculosis most commonly afflicts the region of the head and the uncinate process of the pancreas. It is often misdiagnosed due to low index of suspicion and masquerading of its symptoms as more common pancreatic conditions such as pancreatic malignancy. However, Endoscopic ultrasound fine needle aspiration sampling with an acid-fast smear is essential for establishing the diagnosis of pancreatic tuberculosis. If the diagnosis is delayed, pancreatic tuberculosis can be fatal. Pancreatic tuberculosis responds well to standard anti-tuberculous drugs. Image: Taleghani Hospital. Tehran, Iran.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"16 1","pages":"232-238"},"PeriodicalIF":0.2,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234485","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}
Pancreatic cancer is a major disease burden that is essentially incurable at present. However significant understanding of the molecular basis of pancreatic cancer has been achieved through sequencing. This is allowing the rational design of therapeutics. The purpose of this review is to introduce the molecular basis of pancreatic cancer, explain the current state of molecular therapy and provide examples of the ongoing developments. These include improvements in chemotherapy, small molecule inhibitors, vaccines, immune checkpoint antibodies, and oncolytics. Image: University of Leeds. Leeds, UK.
{"title":"Future Directions in Pancreatic Cancer Therapy","authors":"David J Orchard-Webb","doi":"10.6092/1590-8577/2991","DOIUrl":"https://doi.org/10.6092/1590-8577/2991","url":null,"abstract":"Pancreatic cancer is a major disease burden that is essentially incurable at present. However significant understanding of the molecular basis of pancreatic cancer has been achieved through sequencing. This is allowing the rational design of therapeutics. The purpose of this review is to introduce the molecular basis of pancreatic cancer, explain the current state of molecular therapy and provide examples of the ongoing developments. These include improvements in chemotherapy, small molecule inhibitors, vaccines, immune checkpoint antibodies, and oncolytics. Image: University of Leeds. Leeds, UK.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"16 1","pages":"249-255"},"PeriodicalIF":0.2,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234540","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}
N. Gubergrits, Alexander Klochkov, G. Lukashevich, P. Maisonneuve
Context Pulmonary tuberculosis and especially multi-drug-resistant tuberculosis remain a pressing health problem. Objective The aim of this study was to establish how often standard preparations for the treatment of tuberculosis, such as isoniazid and rifampicin, lead to acute pancreatitis. Methods Two hundred and eighty patients with pulmonary tuberculosis were investigated by clinical chemistry and ultrasonography to determine in how many cases the use of isoniazid and rifampicin was followed by elevation of pancreatic isoamylase or lipase or by sonographic signs of acute pancreatitis with and without occurrence of acute upper abdominal symptoms. Results Acute pancreatitis definitely occurred in 22 (8%) and probably in 36 (13%) of the patients. In 21 (8%) there was merely an asymptomatic serum elevation of pancreatic enzymes and no pathologic sonographic signs in the pancreas. Conclusions Acute pancreatitis is a frequent occurrence after administration of isoniazid and rifampicin and must be considered whenever upper abdominal symptoms are found in patients treated with these drugs. Image: Donetsk National Medical University. Donetsk, Ukraine.
{"title":"The Risk of Contracting Drug-Induced Pancreatitis during Treatment for Pulmonary Tuberculosis","authors":"N. Gubergrits, Alexander Klochkov, G. Lukashevich, P. Maisonneuve","doi":"10.6092/1590-8577/2995","DOIUrl":"https://doi.org/10.6092/1590-8577/2995","url":null,"abstract":"Context Pulmonary tuberculosis and especially multi-drug-resistant tuberculosis remain a pressing health problem. Objective The aim of this study was to establish how often standard preparations for the treatment of tuberculosis, such as isoniazid and rifampicin, lead to acute pancreatitis. Methods Two hundred and eighty patients with pulmonary tuberculosis were investigated by clinical chemistry and ultrasonography to determine in how many cases the use of isoniazid and rifampicin was followed by elevation of pancreatic isoamylase or lipase or by sonographic signs of acute pancreatitis with and without occurrence of acute upper abdominal symptoms. Results Acute pancreatitis definitely occurred in 22 (8%) and probably in 36 (13%) of the patients. In 21 (8%) there was merely an asymptomatic serum elevation of pancreatic enzymes and no pathologic sonographic signs in the pancreas. Conclusions Acute pancreatitis is a frequent occurrence after administration of isoniazid and rifampicin and must be considered whenever upper abdominal symptoms are found in patients treated with these drugs. Image: Donetsk National Medical University. Donetsk, Ukraine.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"16 1","pages":"278-282"},"PeriodicalIF":0.2,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71234944","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}
Context The B islets isolated from 3-5 day old chick respond well to glucose challenge in a similar fashion to those isolated from mouse pancreas. Objective To compare insulin secretory response of chick B islets with that of human islet equivalents generated from stem cells. Methods Human umbilical cord mesenchymal stem cells were differentiated into hIEqs employing three step sequential serum free protocols. Results Immunofluorescence staining demonstrated insulin, C peptide and Glut 2 positivity of both these islets. Static insulin stimulation of these islets in response to glucose, metformin and gamma amino butyric acid resulted in increased insulin secretion as compared to basal glucose stimulation. Our results demonstrate that insulin secretory response of Chick B islets to metformin and gama amino butyric acid is comparable to those of hIEqs. Moreover, both chick and hIEqs could be successfully cryopreserved and revived in a commercially available cryomix (Cryostore 5 ® ), indicating resemblance in their behavior at sub-zero temperatures. Conclusion Present study advocates Chick islets as an alternative source for diabetes research and islet banking. Image: Isolated Chick B islets.
{"title":"Response of Chick B Islets to Insulin Secretagogues is Comparable to those of Human Islet Equivalents","authors":"Bhawna Chandravanshi, S. Datar, R. Bhonde","doi":"10.6092/1590-8577/3006","DOIUrl":"https://doi.org/10.6092/1590-8577/3006","url":null,"abstract":"Context The B islets isolated from 3-5 day old chick respond well to glucose challenge in a similar fashion to those isolated from mouse pancreas. Objective To compare insulin secretory response of chick B islets with that of human islet equivalents generated from stem cells. Methods Human umbilical cord mesenchymal stem cells were differentiated into hIEqs employing three step sequential serum free protocols. Results Immunofluorescence staining demonstrated insulin, C peptide and Glut 2 positivity of both these islets. Static insulin stimulation of these islets in response to glucose, metformin and gamma amino butyric acid resulted in increased insulin secretion as compared to basal glucose stimulation. Our results demonstrate that insulin secretory response of Chick B islets to metformin and gama amino butyric acid is comparable to those of hIEqs. Moreover, both chick and hIEqs could be successfully cryopreserved and revived in a commercially available cryomix (Cryostore 5 ® ), indicating resemblance in their behavior at sub-zero temperatures. Conclusion Present study advocates Chick islets as an alternative source for diabetes research and islet banking. Image: Isolated Chick B islets.","PeriodicalId":47280,"journal":{"name":"Journal of the Pancreas","volume":"16 1","pages":"318-323"},"PeriodicalIF":0.2,"publicationDate":"2015-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71235201","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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