This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas(AISP).We covered the main diseases a...This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas(AISP).We covered the main diseases associated with exocrine pancreatic insufficiency(EPI)which are of common interest to internists/gastroenterologists,oncologists and surgeons,fully aware that EPI may also occur together with many other diseases,but less frequently.A preliminary manuscript based on an extended literature search(Medline/PubMed,Cochrane Library and Google Scholar)of published reports was prepared,and key recommendations were proposed.The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012.Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached.The final draft of the manuscript was then sent to the AISP Council for approval and/or modification.All concerned parties approved the final version of the manuscript in June 2013.展开更多
Ampullary neoplasms,although rare,present distinctive clinical and pathological features from other neoplastic lesions of the periampullary region.No specific guidelines about their management are available,and they a...Ampullary neoplasms,although rare,present distinctive clinical and pathological features from other neoplastic lesions of the periampullary region.No specific guidelines about their management are available,and they are often assimilated either to biliary tract or to pancreatic carcinomas.Due to their location,they tend to become symptomatic at an earlier stage compared to pancreatic malignancies.This behaviour results in a higher resectability rate at diagnosis.From a pathological point of view they arise in a zone of transition between two different epithelia,and,according to their origin,may be divided into pancreatobiliary or intestinal type.This classification has a substantial impact on prognosis.In most cases,pancreaticoduodenectomy represents the treatment of choice when there is an overt or highly suspicious malignant behaviour.The rate of potentially curative resection is as high as 90% and in high-volume centres an acceptable rate of complications is reported.In selected situations less invasive approaches,such as ampullectomy,have been advocated,although there are some concerns mainly because of a higher recurrence rate associated with limited resections for invasive carcinomas.Importantly,these methods have the drawback of not including an appropriate lymphadenectomy,while nodal involvement has been shown to be frequently present also in apparently lowrisk carcinomas.Endoscopic ampullectomy is now the procedure of choice in case of low up to high-grade dysplasia providing a proper assessment of the T status by endoscopic ultrasound.In the present paper the evidence currently available is reviewed,with the aim of offering an updated framework for diagnosis and management of this specific type of disease.展开更多
We here report a case of a 18-year-old man with a history of recurrent abdominal pain and a previous episode of severe acute pancreatitis. Abdominal ultrasonography, contrast enhanced multislice computer tomography, e...We here report a case of a 18-year-old man with a history of recurrent abdominal pain and a previous episode of severe acute pancreatitis. Abdominal ultrasonography, contrast enhanced multislice computer tomography, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography and magnetic resonance imaging demonstrated a cystic mass lesion. Only on delayed phase magnetic resonance images after GadoliniumBOPTA injection, it was possible to demonstrate the lesion's relationship with the biliary tree, differentiating the lesion from intraluminal duodenal diverticulum, and to achieve the diagnosis of duodenal duplication cyst, a recognized rare cause of acute pancreatitis. The diagnosis was confirmed by histology.展开更多
Intraductal papillary mucinous neoplasms(IPMNs) can involve the main pancreatic duct(MD-IPMNs) or its secondary branches(BD-IPMNs) in a segmental of multifocal/diffuse fashion.Growing evidence indicates that BDIPMNs a...Intraductal papillary mucinous neoplasms(IPMNs) can involve the main pancreatic duct(MD-IPMNs) or its secondary branches(BD-IPMNs) in a segmental of multifocal/diffuse fashion.Growing evidence indicates that BDIPMNs are less likely to harbour cancer and in selected cases these lesions can be managed non operatively.For surgery,clarification is required on:(1) when to resect an IPMN;(2) which type of resection should be performed;and(3) how much pancreas should be resected.In recent years parenchyma-sparing resections as well as laparoscopic procedures have being performed more frequently by pancreatic surgeons in order to decrease the rate of postoperative pancreatic insufficiency and to minimize the surgical impact of these operations.However,oncological radicality is of paramount importance,and extended resections up to total pancreatectomy may be necessary in the setting of IPMNs.In this article the type and extension of surgical resections in patients with MD-IPMNs and BD-IPMNs are analyzed,evaluating perioperative and long-term outcomes.The role of standard and parenchyma-sparing resections is discussed as well as different strategies in the case of multifocal neoplasms.展开更多
Neuroendocrine carcinomas(NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated...Neuroendocrine carcinomas(NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.展开更多
Since the first description of intraductal papillary mucinous neoplasms(IPMNs)of the pancreas in the eighties,their identification has dramatically increased in the last decades,hand to hand with the improvements in d...Since the first description of intraductal papillary mucinous neoplasms(IPMNs)of the pancreas in the eighties,their identification has dramatically increased in the last decades,hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases.However,the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions.The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed.We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms,identifying some genes,molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy.The knowledge of molecular biology of IPMNs has impressively developed over the last few years.A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified,in pancreatic juice or in blood or in the samples from the pancreatic resections,but further researches are required to use these informations for clinical intent,in order to better define the natural history of these diseases and to improve their management.展开更多
Gastro-entero-pancreatic neuroendocrine neoplasms(GEPNENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many oth...Gastro-entero-pancreatic neuroendocrine neoplasms(GEPNENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor(VEGF), basic-fibroblastic growth factor, transforming growth factor(TGF-α and-β), platelet derived growth factor(PDGF), insulin-like growth factor-1(IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit(stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing.展开更多
Pancreatic surgery is being offered to an increasing number of patients every year. Although postoperative outcomes have significantly improved in the last decades, even in high-volume centers patients still experienc...Pancreatic surgery is being offered to an increasing number of patients every year. Although postoperative outcomes have significantly improved in the last decades, even in high-volume centers patients still experience significant postoperative morbidity and full recovery after surgery takes longer than we think. In recent years, enhanced recovery pathways incorporating a large number of evidence-based perioperative interventions have proved to be beneficial i n t e r m s o f i m p rove d p o s t o p e ra t i ve o u t c o m e s, and accelerated patient recovery in the context of gastrointestinal, genitourinary and orthopedic surgery. The role of these pathways for pancreatic surgery is still unclear as high-quality randomized controlled trials are lacking. To date, non-randomized studies have shown that care pathways for pancreaticoduodenectomy and distal pancreatectomy are safe with no difference in postoperative morbidity, leading to early discharge and no increase in hospital readmissions. Hospital costs are reduced due to better organization of care and resource utilization. However, further research is needed to clarify the effect of enhanced recovery pathways on patient recovery and post-discharge outcomes following pancreatic resection. Future studies should be prospective and follow recent recommendations for the design and reporting of enhanced recovery pathways.展开更多
Von Recklinghausen＇s disease is an autosomal dominant hereditary disease associated with a wide number of neoplasms. We report a case of a 47-year-old Caucasian male affected by Von Recklinghausen＇s disease who deve...Von Recklinghausen＇s disease is an autosomal dominant hereditary disease associated with a wide number of neoplasms. We report a case of a 47-year-old Caucasian male affected by Von Recklinghausen＇s disease who developed a malignant somatostatinoma of the papilla major and minor associated with jejunal gastrointestinal stromal tumour with uncertain behaviour. At laparotomy, multiple hepatic metastases were evident. Whipple pancreaticoduodenectomy, jejunal resection, extensive lymphadenectomy and multiple hepatic wedge resections were performed. The patient was alive without recurrence after 24 mo. This is the fourth case reported in the world literature of a patient with Von Recklinghausen＇s disease associated with periampuUary somatostatinomas and jejunal stromal tumor. In patients with Von Recklinghausen＇s disease who complain of gastrointestinal symptoms, a high suspicion index for periampullary endocrine tumours and/or gastrointestinal stromal tumour is required. An aggressive surgical approach seems to give long term survival also in metastatic patients.展开更多
With recent advances in molecular pathology and the development of new chemotherapy regimens,the knowledge of the molecular alterations of pancreatic ductal adenocarcinoma(PDAC)is becoming appealing for stratifying pa...With recent advances in molecular pathology and the development of new chemotherapy regimens,the knowledge of the molecular alterations of pancreatic ductal adenocarcinoma(PDAC)is becoming appealing for stratifying patients for prognosis and response to a defined treatment.Archival formalin-fixed,paraffinembedded samples are a useful source of genomic deoxyribonucleic acid;nevertheless,most studies employed formalin-fixed,paraffin-embedded samples deriving from surgical specimens,which are therefore representative of<20%of PDAC patients.Indeed,the development of a reliable methodology for endoscopic ultrasound-guided tissue acquisition,stabilization,and analysis is crucial for the development of molecular markers for clinical use in order to achieve“personalized medicine”.With the development of new needles,this technique is able to retrieve a high quantity and quality of PDAC tissue that can be used not only for diagnosis but also for mutational and transcriptome evaluations and for the development of primary cell or tissue cultures.In the present editorial,we discuss the current knowledge regarding the use of endoscopic ultrasound as a tool to obtain samples for molecular analyses,its possible pitfalls,and its use for the development of disease models such as xenografts or organoids.展开更多
Pancreatic ductal adenocarcinoma(PDA) remains one of the most aggressive tumors with a low rate of survival. Surgery is the only curative treatment for PDA, although only 20% of patients are resectable at diagnosis. D...Pancreatic ductal adenocarcinoma(PDA) remains one of the most aggressive tumors with a low rate of survival. Surgery is the only curative treatment for PDA, although only 20% of patients are resectable at diagnosis. During the last decade there was an improvement in survival in patients affected by PDA, possibly explained by the advances in cancer therapy and by improve patient selection by pancreatic surgeons. It is necessary to select patients not only on the basis of surgical resectability, but also on the basis of the biological nature of the tumor. Specific preoperative criteria can be identified in order to select patients who will benefit from surgical resection. Duration of symptoms and level of carbohydrate antigen 19.9 in resectable disease should be considered to avoid R1 resection and early relapse. Radiological assessment can help surgeons to distinguish resectable disease from borderline resectable disease and locally advanced pancreatic cancer. Better patient selection can increase survival rate and neoadjuvant treatment can help surgeons select patients who will benefit from surgery.展开更多
Upfront resection is becoming a rarer indication for pancreatic ductal adenocarcinoma,as biologic behavior and natural history of the disease has boosted indications for neoadjuvant treatments.Jaundice,gastric outlet ...Upfront resection is becoming a rarer indication for pancreatic ductal adenocarcinoma,as biologic behavior and natural history of the disease has boosted indications for neoadjuvant treatments.Jaundice,gastric outlet obstruction and acute cholecystitis can frequently complicate this window of opportunity,resulting in potentially deleterious chemotherapy discontinuation,whose resumption relies on effective,prompt and long-lasting management of these complications.Although therapeutic endoscopic ultrasound(t-EUS)can potentially offer some advantages over comparators,its use in potentially resectable patients is primal and has unfairly been restricted for fear of potential technical difficulties during subsequent surgery.This is a narrative review of available evidence regarding EUS-guided choledochoduodenostomy,gastrojejunostomy and gallbladder drainage in the bridge-to-surgery scenario.Proof-ofconcept evidence suggests no influence of t-EUS procedures on outcomes of eventual subsequent surgery.Moreover,the very high efficacy-invasiveness ratio over comparators in managing pancreatic cancer-related symptoms or complications can provide a powerful weapon against chemotherapy discontinuation,potentially resulting in higher subsequent resectability.Available evidence is discussed in this short paper,together with technical notes that might be useful for endoscopists and surgeons operating in this scenario.No published evidence supports restricting t-EUS in potential surgical candidates,especially in the setting of pancreatic cancer patients undergoing neoadjuvant chemotherapy.Bridge-to-surgery tEUS deserves further prospective evaluation.展开更多
BACKGROUND Endoscopic ultrasound(EUS)-guided radiofrequency ablation(RFA)has recently been proposed as a local treatment for functional pancreatic neuroendocrine neoplasms in patients unfit for surgery,in order to obt...BACKGROUND Endoscopic ultrasound(EUS)-guided radiofrequency ablation(RFA)has recently been proposed as a local treatment for functional pancreatic neuroendocrine neoplasms in patients unfit for surgery,in order to obtain clinical syndrome regression.Data on the safety and long-term effectiveness of this approach are scarce,and EUS-RFA procedures are not standardized.CASE SUMMARY The present case series reports 3 elderly patients with a pancreatic insulinoma and comorbidities,locally treated by EUS-guided RFA with clinical success in terms of hypoglycemic symptoms.RFA procedures were performed during deep sedation,under EUS control with a 19 G needle,an electrode 5-mm in size at a power of 30 W and multiple RFA applications during the same session in order to treat the whole area of the lesions.Immediate relief of symptoms was evident in 2 patients after the first EUS-RFA,while in the third patient a second endoscopic treatment was needed.All 3 patients are symptom-free without need of medications after 24 mo of follow-up with imaging follow-up showing no disease recurrence.A single adverse event of intraprocedural bleeding occurred,which was successfully treated endoscopically.CONCLUSION EUS-RFA represents an effective and safe alternative to surgery for the treatment of insulinomas in elderly patients at high surgical risk.However,larger multicenter studies withlonger follow-up are needed in order to better assess its safety and clinical success.展开更多
Objective:The aim of the current review is to summarize the available evidence to aid clinicians in the surveillance,treatment and follow-up of the different primary tumors developed by patients diagnosed with von Hip...Objective:The aim of the current review is to summarize the available evidence to aid clinicians in the surveillance,treatment and follow-up of the different primary tumors developed by patients diagnosed with von Hippel-Lindau(VHL)syndrome.Methods:A non-systematic narrative review of original articles,meta-analyses,and random-ized trials was conducted,including articles in the pre-clinical setting to support relevant find-ings.Results:VHL disease is the most common rare hereditary disorder associated with clear cell renal cell carcinoma.Affected individuals inherit a germline mutation in one VHL allele,and any somatic event that disrupt the other allele can trigger mutations,chromosomal rearrange-ments,or epigenetic regulations leading to oncogenesis.From a clinical perspective,patients continuously develop multiple primary tumors.Conclusion:Because VHL is considered a rare disease,very limited evidence is available for diagnosis,surveillance,active treatment with local or systemic therapy and follow-up.展开更多
In neuroendocrine tumors(NETs),liver metastases(LM)represent the most crucial prognostic factor,irrespective of the primary tumor site.At diagnosis,about 65-95%of gastroenteropancreatic neuroendocrine tumors(GEP-NETs)...In neuroendocrine tumors(NETs),liver metastases(LM)represent the most crucial prognostic factor,irrespective of the primary tumor site.At diagnosis,about 65-95%of gastroenteropancreatic neuroendocrine tumors(GEP-NETs)show hepatic metastasis.Management strategies of LM are heterogeneous and range from systemic therapy to liver-directed procedures.The type of systemic therapy used is dependent on the grade and proliferation of the tumor and includes somatostatin analogues,interferon,m-Tor and tyrosine kinase inhibitors,and chemotherapy.Angiographic liver-directed techniques,such as transarterial embolization/chemoembolization and selective internal radiation therapy,offer excellent palliation for patients with liver-predominant disease.In highly selected cases,liver transplantation and peptide receptor radionuclide therapy are considered.The relatively low disease incidence and the diversity of presentation have led to a lack of well-conducted randomized controlled trials comparing the efficacy of different treatment options.Experience indicates that surgery is the only treatment that offers potential for cure.For unresectable lesions,the absence of data from rigorous trials limits the validity of many publications that detail management.In this review we will discuss the existing approaches for hepatic metastases from GEP-NETs.展开更多
Efficacy of pancreatic cancer surveillance programs The publication of the American Gastroenterology Association(AGA)Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals(HRIs)underlines the i...Efficacy of pancreatic cancer surveillance programs The publication of the American Gastroenterology Association(AGA)Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals(HRIs)underlines the increasing attention for this topic(1).Secondary prevention(surveillance)for pancreatic ductal adenocarcinoma(PDAC),however,remains a challenge with many unsolved questions(Table 1).展开更多
基金Supported by An unrestricted grant from Abbott Italia s.r.l
文摘This is a medical position statement developed by the Exocrine Pancreatic Insufficiency collaborative group which is a part of the Italian Association for the Study of the Pancreas(AISP).We covered the main diseases associated with exocrine pancreatic insufficiency(EPI)which are of common interest to internists/gastroenterologists,oncologists and surgeons,fully aware that EPI may also occur together with many other diseases,but less frequently.A preliminary manuscript based on an extended literature search(Medline/PubMed,Cochrane Library and Google Scholar)of published reports was prepared,and key recommendations were proposed.The evidence was discussed at a dedicated meeting in Bologna during the National Meeting of the Association in October 2012.Each of the proposed recommendations and algorithms was discussed and an initial consensus was reached.The final draft of the manuscript was then sent to the AISP Council for approval and/or modification.All concerned parties approved the final version of the manuscript in June 2013.
文摘Ampullary neoplasms,although rare,present distinctive clinical and pathological features from other neoplastic lesions of the periampullary region.No specific guidelines about their management are available,and they are often assimilated either to biliary tract or to pancreatic carcinomas.Due to their location,they tend to become symptomatic at an earlier stage compared to pancreatic malignancies.This behaviour results in a higher resectability rate at diagnosis.From a pathological point of view they arise in a zone of transition between two different epithelia,and,according to their origin,may be divided into pancreatobiliary or intestinal type.This classification has a substantial impact on prognosis.In most cases,pancreaticoduodenectomy represents the treatment of choice when there is an overt or highly suspicious malignant behaviour.The rate of potentially curative resection is as high as 90% and in high-volume centres an acceptable rate of complications is reported.In selected situations less invasive approaches,such as ampullectomy,have been advocated,although there are some concerns mainly because of a higher recurrence rate associated with limited resections for invasive carcinomas.Importantly,these methods have the drawback of not including an appropriate lymphadenectomy,while nodal involvement has been shown to be frequently present also in apparently lowrisk carcinomas.Endoscopic ampullectomy is now the procedure of choice in case of low up to high-grade dysplasia providing a proper assessment of the T status by endoscopic ultrasound.In the present paper the evidence currently available is reviewed,with the aim of offering an updated framework for diagnosis and management of this specific type of disease.
文摘We here report a case of a 18-year-old man with a history of recurrent abdominal pain and a previous episode of severe acute pancreatitis. Abdominal ultrasonography, contrast enhanced multislice computer tomography, endoscopic retrograde cholangiopancreatography, endoscopic ultrasonography and magnetic resonance imaging demonstrated a cystic mass lesion. Only on delayed phase magnetic resonance images after GadoliniumBOPTA injection, it was possible to demonstrate the lesion's relationship with the biliary tree, differentiating the lesion from intraluminal duodenal diverticulum, and to achieve the diagnosis of duodenal duplication cyst, a recognized rare cause of acute pancreatitis. The diagnosis was confirmed by histology.
文摘Intraductal papillary mucinous neoplasms(IPMNs) can involve the main pancreatic duct(MD-IPMNs) or its secondary branches(BD-IPMNs) in a segmental of multifocal/diffuse fashion.Growing evidence indicates that BDIPMNs are less likely to harbour cancer and in selected cases these lesions can be managed non operatively.For surgery,clarification is required on:(1) when to resect an IPMN;(2) which type of resection should be performed;and(3) how much pancreas should be resected.In recent years parenchyma-sparing resections as well as laparoscopic procedures have being performed more frequently by pancreatic surgeons in order to decrease the rate of postoperative pancreatic insufficiency and to minimize the surgical impact of these operations.However,oncological radicality is of paramount importance,and extended resections up to total pancreatectomy may be necessary in the setting of IPMNs.In this article the type and extension of surgical resections in patients with MD-IPMNs and BD-IPMNs are analyzed,evaluating perioperative and long-term outcomes.The role of standard and parenchyma-sparing resections is discussed as well as different strategies in the case of multifocal neoplasms.
文摘Neuroendocrine carcinomas(NEC) of the pancreas are defined by a mitotic count > 20 mitoses/10 high power fields and/or Ki67 index > 20%, and included all the tumors previously classified as poorly differentiated endocrine carcinomas. These latter are aggressive malignancies with a high propensity for distant metastases and poor prognosis, and they can be further divided into small- and large-cell subtypes. However in the NEC category are included also neuroendocrine tumors with a well differentiated morphology but ki67 index > 20%. This category is associated with better prognosis and does not significantly respond to cisplatin-based chemotherapy, which represents the gold standard therapeutic approach for poorly differentiated NEC. In this review, the differences between well differentiated and poorly differentiated NEC are discussed considering both pathology, imaging features, treatment and prognostic implications. Diagnostic and therapeutic flowcharts are proposed. The need for a revision of current classification system is stressed being well differentiated NEC a more indolent disease compared to poorly differentiated tumors.
文摘Since the first description of intraductal papillary mucinous neoplasms(IPMNs)of the pancreas in the eighties,their identification has dramatically increased in the last decades,hand to hand with the improvements in diagnostic imaging and sampling techniques for the study of pancreatic diseases.However,the heterogeneity of IPMNs and their malignant potential make difficult the management of these lesions.The objective of this review is to identify the molecular characteristics of IPMNs in order to recognize potential markers for the discrimination of more aggressive IPMNs requiring surgical resection from benign IPMNs that could be observed.We briefly summarize recent research findings on the genetics and epigenetics of intraductal papillary mucinous neoplasms,identifying some genes,molecular mechanisms and cellular signaling pathways correlated to the pathogenesis of IPMNs and their progression to malignancy.The knowledge of molecular biology of IPMNs has impressively developed over the last few years.A great amount of genes functioning as oncogenes or tumor suppressor genes have been identified,in pancreatic juice or in blood or in the samples from the pancreatic resections,but further researches are required to use these informations for clinical intent,in order to better define the natural history of these diseases and to improve their management.
文摘Gastro-entero-pancreatic neuroendocrine neoplasms(GEPNENs) represents a various family of rare tumours. Surgery is the first choice in GEP-NENs patients with localized disease whilst in the metastatic setting many other treatment options are available. Somatostatin analogues are indicated for symptoms control in functioning tumours. Furthermore they may be effective to inhibit tumour progression. GEP-NENs pathogenesis has been extensively studied in the last years therefore several driver mutations pathway genes have been identified as crucial factors in their tumourigenesis. GEP-NENs can over-express vascular endothelial growth factor(VEGF), basic-fibroblastic growth factor, transforming growth factor(TGF-α and-β), platelet derived growth factor(PDGF), insulin-like growth factor-1(IGF-1) and their receptors PDGF receptor, IGF-1 receptor, epidermal growth factor receptor, VEGF receptor, and c-kit(stem cell factor receptor) that can be considered as potential targets. The availability of new targeted agents, such as everolimus and sunitinib that are effective in advanced and metastatic pancreatic neuroendocrine tumours, has provided new treatment opportunities. Many trials combing new drugs are ongoing.
文摘Pancreatic surgery is being offered to an increasing number of patients every year. Although postoperative outcomes have significantly improved in the last decades, even in high-volume centers patients still experience significant postoperative morbidity and full recovery after surgery takes longer than we think. In recent years, enhanced recovery pathways incorporating a large number of evidence-based perioperative interventions have proved to be beneficial i n t e r m s o f i m p rove d p o s t o p e ra t i ve o u t c o m e s, and accelerated patient recovery in the context of gastrointestinal, genitourinary and orthopedic surgery. The role of these pathways for pancreatic surgery is still unclear as high-quality randomized controlled trials are lacking. To date, non-randomized studies have shown that care pathways for pancreaticoduodenectomy and distal pancreatectomy are safe with no difference in postoperative morbidity, leading to early discharge and no increase in hospital readmissions. Hospital costs are reduced due to better organization of care and resource utilization. However, further research is needed to clarify the effect of enhanced recovery pathways on patient recovery and post-discharge outcomes following pancreatic resection. Future studies should be prospective and follow recent recommendations for the design and reporting of enhanced recovery pathways.
基金Supported by Fondazione Cariverona 2005, Verona (Italy) Ministero della Salute, Regione Marche e Ministero dell’Università No. PRIN 2005069205
文摘Von Recklinghausen＇s disease is an autosomal dominant hereditary disease associated with a wide number of neoplasms. We report a case of a 47-year-old Caucasian male affected by Von Recklinghausen＇s disease who developed a malignant somatostatinoma of the papilla major and minor associated with jejunal gastrointestinal stromal tumour with uncertain behaviour. At laparotomy, multiple hepatic metastases were evident. Whipple pancreaticoduodenectomy, jejunal resection, extensive lymphadenectomy and multiple hepatic wedge resections were performed. The patient was alive without recurrence after 24 mo. This is the fourth case reported in the world literature of a patient with Von Recklinghausen＇s disease associated with periampuUary somatostatinomas and jejunal stromal tumor. In patients with Von Recklinghausen＇s disease who complain of gastrointestinal symptoms, a high suspicion index for periampullary endocrine tumours and/or gastrointestinal stromal tumour is required. An aggressive surgical approach seems to give long term survival also in metastatic patients.
基金Supported by Associazione Italiana Ricerca sul Cancro(AIRC), No.IG17177
文摘With recent advances in molecular pathology and the development of new chemotherapy regimens,the knowledge of the molecular alterations of pancreatic ductal adenocarcinoma(PDAC)is becoming appealing for stratifying patients for prognosis and response to a defined treatment.Archival formalin-fixed,paraffinembedded samples are a useful source of genomic deoxyribonucleic acid;nevertheless,most studies employed formalin-fixed,paraffin-embedded samples deriving from surgical specimens,which are therefore representative of<20%of PDAC patients.Indeed,the development of a reliable methodology for endoscopic ultrasound-guided tissue acquisition,stabilization,and analysis is crucial for the development of molecular markers for clinical use in order to achieve“personalized medicine”.With the development of new needles,this technique is able to retrieve a high quantity and quality of PDAC tissue that can be used not only for diagnosis but also for mutational and transcriptome evaluations and for the development of primary cell or tissue cultures.In the present editorial,we discuss the current knowledge regarding the use of endoscopic ultrasound as a tool to obtain samples for molecular analyses,its possible pitfalls,and its use for the development of disease models such as xenografts or organoids.
文摘Pancreatic ductal adenocarcinoma(PDA) remains one of the most aggressive tumors with a low rate of survival. Surgery is the only curative treatment for PDA, although only 20% of patients are resectable at diagnosis. During the last decade there was an improvement in survival in patients affected by PDA, possibly explained by the advances in cancer therapy and by improve patient selection by pancreatic surgeons. It is necessary to select patients not only on the basis of surgical resectability, but also on the basis of the biological nature of the tumor. Specific preoperative criteria can be identified in order to select patients who will benefit from surgical resection. Duration of symptoms and level of carbohydrate antigen 19.9 in resectable disease should be considered to avoid R1 resection and early relapse. Radiological assessment can help surgeons to distinguish resectable disease from borderline resectable disease and locally advanced pancreatic cancer. Better patient selection can increase survival rate and neoadjuvant treatment can help surgeons select patients who will benefit from surgery.
文摘Upfront resection is becoming a rarer indication for pancreatic ductal adenocarcinoma,as biologic behavior and natural history of the disease has boosted indications for neoadjuvant treatments.Jaundice,gastric outlet obstruction and acute cholecystitis can frequently complicate this window of opportunity,resulting in potentially deleterious chemotherapy discontinuation,whose resumption relies on effective,prompt and long-lasting management of these complications.Although therapeutic endoscopic ultrasound(t-EUS)can potentially offer some advantages over comparators,its use in potentially resectable patients is primal and has unfairly been restricted for fear of potential technical difficulties during subsequent surgery.This is a narrative review of available evidence regarding EUS-guided choledochoduodenostomy,gastrojejunostomy and gallbladder drainage in the bridge-to-surgery scenario.Proof-ofconcept evidence suggests no influence of t-EUS procedures on outcomes of eventual subsequent surgery.Moreover,the very high efficacy-invasiveness ratio over comparators in managing pancreatic cancer-related symptoms or complications can provide a powerful weapon against chemotherapy discontinuation,potentially resulting in higher subsequent resectability.Available evidence is discussed in this short paper,together with technical notes that might be useful for endoscopists and surgeons operating in this scenario.No published evidence supports restricting t-EUS in potential surgical candidates,especially in the setting of pancreatic cancer patients undergoing neoadjuvant chemotherapy.Bridge-to-surgery tEUS deserves further prospective evaluation.
文摘BACKGROUND Endoscopic ultrasound(EUS)-guided radiofrequency ablation(RFA)has recently been proposed as a local treatment for functional pancreatic neuroendocrine neoplasms in patients unfit for surgery,in order to obtain clinical syndrome regression.Data on the safety and long-term effectiveness of this approach are scarce,and EUS-RFA procedures are not standardized.CASE SUMMARY The present case series reports 3 elderly patients with a pancreatic insulinoma and comorbidities,locally treated by EUS-guided RFA with clinical success in terms of hypoglycemic symptoms.RFA procedures were performed during deep sedation,under EUS control with a 19 G needle,an electrode 5-mm in size at a power of 30 W and multiple RFA applications during the same session in order to treat the whole area of the lesions.Immediate relief of symptoms was evident in 2 patients after the first EUS-RFA,while in the third patient a second endoscopic treatment was needed.All 3 patients are symptom-free without need of medications after 24 mo of follow-up with imaging follow-up showing no disease recurrence.A single adverse event of intraprocedural bleeding occurred,which was successfully treated endoscopically.CONCLUSION EUS-RFA represents an effective and safe alternative to surgery for the treatment of insulinomas in elderly patients at high surgical risk.However,larger multicenter studies withlonger follow-up are needed in order to better assess its safety and clinical success.
文摘Objective:The aim of the current review is to summarize the available evidence to aid clinicians in the surveillance,treatment and follow-up of the different primary tumors developed by patients diagnosed with von Hippel-Lindau(VHL)syndrome.Methods:A non-systematic narrative review of original articles,meta-analyses,and random-ized trials was conducted,including articles in the pre-clinical setting to support relevant find-ings.Results:VHL disease is the most common rare hereditary disorder associated with clear cell renal cell carcinoma.Affected individuals inherit a germline mutation in one VHL allele,and any somatic event that disrupt the other allele can trigger mutations,chromosomal rearrange-ments,or epigenetic regulations leading to oncogenesis.From a clinical perspective,patients continuously develop multiple primary tumors.Conclusion:Because VHL is considered a rare disease,very limited evidence is available for diagnosis,surveillance,active treatment with local or systemic therapy and follow-up.
文摘In neuroendocrine tumors(NETs),liver metastases(LM)represent the most crucial prognostic factor,irrespective of the primary tumor site.At diagnosis,about 65-95%of gastroenteropancreatic neuroendocrine tumors(GEP-NETs)show hepatic metastasis.Management strategies of LM are heterogeneous and range from systemic therapy to liver-directed procedures.The type of systemic therapy used is dependent on the grade and proliferation of the tumor and includes somatostatin analogues,interferon,m-Tor and tyrosine kinase inhibitors,and chemotherapy.Angiographic liver-directed techniques,such as transarterial embolization/chemoembolization and selective internal radiation therapy,offer excellent palliation for patients with liver-predominant disease.In highly selected cases,liver transplantation and peptide receptor radionuclide therapy are considered.The relatively low disease incidence and the diversity of presentation have led to a lack of well-conducted randomized controlled trials comparing the efficacy of different treatment options.Experience indicates that surgery is the only treatment that offers potential for cure.For unresectable lesions,the absence of data from rigorous trials limits the validity of many publications that detail management.In this review we will discuss the existing approaches for hepatic metastases from GEP-NETs.
文摘Efficacy of pancreatic cancer surveillance programs The publication of the American Gastroenterology Association(AGA)Clinical Practice Update on Pancreas Cancer Screening in High-Risk Individuals(HRIs)underlines the increasing attention for this topic(1).Secondary prevention(surveillance)for pancreatic ductal adenocarcinoma(PDAC),however,remains a challenge with many unsolved questions(Table 1).
