AIMTo describe magnetic resonance(MR)imaging features of pancreatic neuroendocrine neoplasms(PanNENs)according to their grade and tumor-nodes-metastases stage by comparing them to histopathology and to determine the a...AIMTo describe magnetic resonance(MR)imaging features of pancreatic neuroendocrine neoplasms(PanNENs)according to their grade and tumor-nodes-metastases stage by comparing them to histopathology and to determine the accuracy of MR imaging features in predicting their biological behavior.METHODSThis study was approved by our institutional review board;requirement for informed patient consent was waived due to the retrospective nature of the study.Preoperative MR examinations of 55 PanNEN patients(29 men,26 women;mean age of 57.6 years,range 21-83 years)performed between June 2013 and December 2015 were reviewed.Qualitative and quantitative features were compared between tumor grades and stages determined by histopathological analysis.RESULTSIll defined margins were more common in G2-3 and stage III-IV PanNENs than in G1 and low-stage tumors(P<0.001);this feature had high specificity in the identification of G2-3 and stage III-IV tumors(90.3%and 96%,95%CI:73.1-97.5 and 77.7-99.8).The mean apparent diffusion coefficient value was significantly lower in G2-3 and stage III-IV lesions compared to well differentiated and low-stage tumors(1.09×10<sup>-3</sup>mm<sup>2</sup>/s vs 1.45×10<sup>-3</sup>mm<sup>2</sup>/s and 1.10×10<sup>-3</sup>mm<sup>2</sup>/s vs 1.53×10<sup>-3</sup>mm<sup>2</sup>/s,P=0.003 and 0.001).Receiving operator characteristic analysis determined optimal cut-offs of 1.21 and 1.28×10<sup>-3</sup>mm<sup>2</sup>/s for the identification of G2-3 and stage III-IV tumors,with sensitivity and specificity values of 70.8/80.7%and 64.5/64%(95%CI:48.7-86.6/60-92.7 and 45.4-80.2/42.6-81.3).CONCLUSIONMR features of PanNENs vary according to their grade of differentiation and their stage at diagnosis and could predict the biological behavior of these tumors.展开更多
Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity...Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity to understand the comparative biology of all periampullary malignancies. These neoplasms can exhibit intestinal, pancreaticobiliary or mixed features, whereas the subclassification based on morphology and immunohistochemical features failed in demonstrating a robust prognostic reliability. In the last few years, the molecular landscape of this tumor entity has been uncovered, identifying alterations that may serve as prognostic and predictive biomarkers. In this review, the histological and genetic characteristics of ampullary carcinomas are discussed, taking into account the main clinical and therapeutic implications related to this tumor type as well.展开更多
Due to extremely poor prognosis,pancreatic cancer(PDAC)represents the fourth leading cause of cancerrelated death in Western countries.For more than a decade,gemcitabine(Gem)has been the mainstay of first-line PDAC tr...Due to extremely poor prognosis,pancreatic cancer(PDAC)represents the fourth leading cause of cancerrelated death in Western countries.For more than a decade,gemcitabine(Gem)has been the mainstay of first-line PDAC treatment.Many efforts aimed at improving single-agent Gem efficacy by either combining it with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation provided disappointing results.Recently,the field of systemic therapy of advanced PDAC is finally moving forward.Polychemotherapy has shown promise over single-agent Gem:regimens like PEFG-PEXG-PDXG and GTX provide significant potential advantages in terms of survival and/or disease control,although sometimes at the cost of poor tolerability.The PRODIGE 4/ACCORD 11 was the first phaseⅢtrial to provide unequivocal benefit using the polychemotherapy regimen FOLFIRINOX;however the less favorable safety profile and the characteristics of the enrolled population,restrict the use of FOLFIRINOX to young and fit PDAC patients.The nanoparticle albumin-bound paclitaxel(nab-Paclitaxel)formulation was developed to overcome resistance due to the desmoplastic stroma surrounding pancreatic cancer cells.Regardless of whether or not this is its main mechanisms of action,the combination of nabPaclitaxel plus Gem showed a statistically and clinically significant survival advantage over single agent Gem and significantly improved all the secondary endpoints.Furthermore,recent findings on maintenance therapy are opening up potential new avenues in the treatment of advanced PDAC,particularly in a new era in which highly effective first-line regimens allow patients to experience prolonged disease control.Here,we provide an overview of recent advances in the systemic treatment of advanced PDAC,mostly focusing on recent findings that have set new standards in metastatic disease.Potential avenues for further development in the metastatic setting and current efforts to integratenew effective chemotherapy regimens in earlier stages of disease(neoadjuvant,adjuvant,and multimodal approaches in both resectable and unresectable patients)are also briefly discussed.展开更多
Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To bet...Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To better understand the biology of pancreatic cancer,it is fundamental to know its precursors and to study the mechanisms of carcinogenesis.Each of these precursors displays peculiar histological features,as well as specific molecular alterations.Starting from such pre-invasive lesions,this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer,with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.展开更多
Tumour cells have exquisite flexibility in reprogramming their metabolism in order to support tumour initiation, progression,metastasis and resistance to therapies. These reprogrammed activities include a complete rew...Tumour cells have exquisite flexibility in reprogramming their metabolism in order to support tumour initiation, progression,metastasis and resistance to therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosyntheticand redox status to sustain the increased energetic demand of the cells. Over the last decades, the cancer metabolism field hasseen an explosion of new biochemical technologies giving more tools than ever before to navigate this complexity. Within a cell ora tissue, the metabolites constitute the direct signature of the molecular phenotype and thus their profiling has concrete clinicalapplications in oncology. Metabolomics and fluxomics, are key technological approaches that mainly revolutionized the fieldenabling researchers to have both a qualitative and mechanistic model of the biochemical activities in cancer. Furthermore, theupgrade from bulk to single-cell analysis technologies provided unprecedented opportunity to investigate cancer biology at cellularresolution allowing an in depth quantitative analysis of complex and heterogenous diseases. More recently, the advent offunctional genomic screening allowed the identification of molecular pathways, cellular processes, biomarkers and noveltherapeutic targets that in concert with other technologies allow patient stratification and identification of new treatmentregimens. This review is intended to be a guide for researchers to cancer metabolism, highlighting current and emergingtechnologies, emphasizing advantages, disadvantages and applications with the potential of leading the development ofinnovative anti-cancer therapies.展开更多
文摘AIMTo describe magnetic resonance(MR)imaging features of pancreatic neuroendocrine neoplasms(PanNENs)according to their grade and tumor-nodes-metastases stage by comparing them to histopathology and to determine the accuracy of MR imaging features in predicting their biological behavior.METHODSThis study was approved by our institutional review board;requirement for informed patient consent was waived due to the retrospective nature of the study.Preoperative MR examinations of 55 PanNEN patients(29 men,26 women;mean age of 57.6 years,range 21-83 years)performed between June 2013 and December 2015 were reviewed.Qualitative and quantitative features were compared between tumor grades and stages determined by histopathological analysis.RESULTSIll defined margins were more common in G2-3 and stage III-IV PanNENs than in G1 and low-stage tumors(P<0.001);this feature had high specificity in the identification of G2-3 and stage III-IV tumors(90.3%and 96%,95%CI:73.1-97.5 and 77.7-99.8).The mean apparent diffusion coefficient value was significantly lower in G2-3 and stage III-IV lesions compared to well differentiated and low-stage tumors(1.09×10<sup>-3</sup>mm<sup>2</sup>/s vs 1.45×10<sup>-3</sup>mm<sup>2</sup>/s and 1.10×10<sup>-3</sup>mm<sup>2</sup>/s vs 1.53×10<sup>-3</sup>mm<sup>2</sup>/s,P=0.003 and 0.001).Receiving operator characteristic analysis determined optimal cut-offs of 1.21 and 1.28×10<sup>-3</sup>mm<sup>2</sup>/s for the identification of G2-3 and stage III-IV tumors,with sensitivity and specificity values of 70.8/80.7%and 64.5/64%(95%CI:48.7-86.6/60-92.7 and 45.4-80.2/42.6-81.3).CONCLUSIONMR features of PanNENs vary according to their grade of differentiation and their stage at diagnosis and could predict the biological behavior of these tumors.
基金Supported by the Italian Association for Cancer Research,No.12182
文摘Ampulla of Vater is a peculiar anatomical structure, characterized by the crossroad of three distinct epithelia: Intestinal, ductal pancreatic and biliary. Adenocarcinomas arising in this area represent an opportunity to understand the comparative biology of all periampullary malignancies. These neoplasms can exhibit intestinal, pancreaticobiliary or mixed features, whereas the subclassification based on morphology and immunohistochemical features failed in demonstrating a robust prognostic reliability. In the last few years, the molecular landscape of this tumor entity has been uncovered, identifying alterations that may serve as prognostic and predictive biomarkers. In this review, the histological and genetic characteristics of ampullary carcinomas are discussed, taking into account the main clinical and therapeutic implications related to this tumor type as well.
文摘Due to extremely poor prognosis,pancreatic cancer(PDAC)represents the fourth leading cause of cancerrelated death in Western countries.For more than a decade,gemcitabine(Gem)has been the mainstay of first-line PDAC treatment.Many efforts aimed at improving single-agent Gem efficacy by either combining it with a second cytotoxic/molecularly targeted agent or pharmacokinetic modulation provided disappointing results.Recently,the field of systemic therapy of advanced PDAC is finally moving forward.Polychemotherapy has shown promise over single-agent Gem:regimens like PEFG-PEXG-PDXG and GTX provide significant potential advantages in terms of survival and/or disease control,although sometimes at the cost of poor tolerability.The PRODIGE 4/ACCORD 11 was the first phaseⅢtrial to provide unequivocal benefit using the polychemotherapy regimen FOLFIRINOX;however the less favorable safety profile and the characteristics of the enrolled population,restrict the use of FOLFIRINOX to young and fit PDAC patients.The nanoparticle albumin-bound paclitaxel(nab-Paclitaxel)formulation was developed to overcome resistance due to the desmoplastic stroma surrounding pancreatic cancer cells.Regardless of whether or not this is its main mechanisms of action,the combination of nabPaclitaxel plus Gem showed a statistically and clinically significant survival advantage over single agent Gem and significantly improved all the secondary endpoints.Furthermore,recent findings on maintenance therapy are opening up potential new avenues in the treatment of advanced PDAC,particularly in a new era in which highly effective first-line regimens allow patients to experience prolonged disease control.Here,we provide an overview of recent advances in the systemic treatment of advanced PDAC,mostly focusing on recent findings that have set new standards in metastatic disease.Potential avenues for further development in the metastatic setting and current efforts to integratenew effective chemotherapy regimens in earlier stages of disease(neoadjuvant,adjuvant,and multimodal approaches in both resectable and unresectable patients)are also briefly discussed.
基金Supported by the Associazione Italiana Ricerca sul Cancro,No.12182Cassini Project
文摘Pancreatic cancer is a lethal malignancy,whose precursor lesions are pancreatic intraepithelial neoplasm,intraductal papillary mucinous neoplasm,intraductal tubulopapillary neoplasm,and mucinous cystic neoplasm.To better understand the biology of pancreatic cancer,it is fundamental to know its precursors and to study the mechanisms of carcinogenesis.Each of these precursors displays peculiar histological features,as well as specific molecular alterations.Starting from such pre-invasive lesions,this review aims at summarizing the most important aspects of carcinogenesis of pancreatic cancer,with a specific focus on the recent advances and the future perspectives of the research on this lethal tumor type.
基金the Associazione Italiana per la Ricerca sul Cancro(AIRC,Project:27080)NextGenerationEU(PNRR“HEAL ITALIA-Health Extended Alliance for Innovative Therapies,Advanced Lab-research,and Integrated Approaches of Precision Medicine”,project:PE00000019,CUP:B33C22001030006)Directorial Decree No.1559 of 11 October 2022 and by Italian Ministry of Health,HUB Diagnostica Avanzata PNC-E3-2022-23683266 PNCHLS-DA.
文摘Tumour cells have exquisite flexibility in reprogramming their metabolism in order to support tumour initiation, progression,metastasis and resistance to therapies. These reprogrammed activities include a complete rewiring of the bioenergetic, biosyntheticand redox status to sustain the increased energetic demand of the cells. Over the last decades, the cancer metabolism field hasseen an explosion of new biochemical technologies giving more tools than ever before to navigate this complexity. Within a cell ora tissue, the metabolites constitute the direct signature of the molecular phenotype and thus their profiling has concrete clinicalapplications in oncology. Metabolomics and fluxomics, are key technological approaches that mainly revolutionized the fieldenabling researchers to have both a qualitative and mechanistic model of the biochemical activities in cancer. Furthermore, theupgrade from bulk to single-cell analysis technologies provided unprecedented opportunity to investigate cancer biology at cellularresolution allowing an in depth quantitative analysis of complex and heterogenous diseases. More recently, the advent offunctional genomic screening allowed the identification of molecular pathways, cellular processes, biomarkers and noveltherapeutic targets that in concert with other technologies allow patient stratification and identification of new treatmentregimens. This review is intended to be a guide for researchers to cancer metabolism, highlighting current and emergingtechnologies, emphasizing advantages, disadvantages and applications with the potential of leading the development ofinnovative anti-cancer therapies.
