Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection prov...Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.展开更多
BACKGROUND Cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)for peritoneal carcinomatosis can be performed in two ways:Open or closed abdominal technique.AIM To evaluate the impact of HIP...BACKGROUND Cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)for peritoneal carcinomatosis can be performed in two ways:Open or closed abdominal technique.AIM To evaluate the impact of HIPEC method on post-operative and long-term survival outcomes.METHODS Patients undergoing CRS with HIPEC from 2000-2017 were identified in the United States HIPEC collaborative database.Post-operative,recurrence,and overall survival outcomes were compared between those who received open vs closed HIPEC.RESULTS Of the 1812 patients undergoing curative-intent CRS and HIPEC,372(21%)patients underwent open HIPEC and 1440(79%)underwent closed HIPEC.There was no difference in re-operation or severe complications between the two groups.Closed HIPEC had higher rates of 90-d readmission while open HIPEC had a higher rate of 90-d mortalities.On multi-variable analysis,closed HIPEC technique was not a significant predictor for overall survival(hazards ratio:0.75,95%confidence interval:0.51-1.10,P=0.14)or recurrence-free survival(hazards ratio:1.39,95%confidence interval:1.00-1.93,P=0.05)in the entire cohort.These findings remained consistent in the appendiceal and the colorectal subgroups.CONCLUSION In this multi-institutional analysis,the HIPEC method was not independently associated with relevant post-operative or long-term outcomes.HIPEC technique may be left to the discretion of the operating surgeon.展开更多
Translational research is a broad field of medicine with several key phases moving from scientific discovery to bench research and the hospital bedside,followed by evidence-based practice and population-level policy a...Translational research is a broad field of medicine with several key phases moving from scientific discovery to bench research and the hospital bedside,followed by evidence-based practice and population-level policy and programming. Understanding these phases is crucial when it comes to preventing and treating illness,especially in global health. Communities around the world struggle with a variety of health problems that are at some times similar and at others quite different. Three major world health issues help to outline the phases of translational research:vaccines,human immunodeficiency virus and acquired immunodeficiencysyndrome,and non-communicable diseases. Laboratory research has excelled in many of these areas and is struggling in a few. Where successful therapies have been discovered there are often problems with appropriate use or dissemination to groups in need. Also,many diseases would be better prevented from a population health approach. This review highlights successes and struggles in the arena of global health,from smallpox eradication to the impending epidemic of cardiovascular disease,in an attempt to illustrate of the various phases of translational research.展开更多
文摘Pancreatic adenocarcinoma remains a most deadly malignancy, with an overall 5-year survival of 5%. A subset of patients will be diagnosed with potentially resectable disease, and while complete surgical resection provides the only chance at cure, data from trials of postoperative chemoradiation and/or chemotherapy demonstrate a modest survival advantage over those patients who undergo resection alone. As such, most practitioners believe that completion of multimodality therapy is the optimal treatment. However, the sequence of surgery, chemotherapy and radiation therapy is frequently debated, as patients may benefit from a neoadjuvant approach by initiating chemotherapy and/or chemoradiation prior to resection. Here we review the rationale for neoadjuvant therapy, which includes a higher rate of completion of multimodality therapy, minimizing the risk of unnecessary surgical resection for patients who develop early metastatic disease, improved surgical outcomes and the potential for longer overall survival. However, there are no prospective, randomized studies of the neoadjuvant approach compared to a surgeryfirst strategy; the established and ongoing investigations of neoadjuvant therapy for pancreatic cancer are discussed in detail. Lastly, as the future of therapeutic regimens is likely to entail patient-specific genetic and molecular analyses, and the treatment that is best applied based on those data, a review of clinically relevant biomarkers in pancreatic cancer is also presented.
基金the National Center for Advancing Translational SciencesNo.UL1TR002377。
文摘BACKGROUND Cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)for peritoneal carcinomatosis can be performed in two ways:Open or closed abdominal technique.AIM To evaluate the impact of HIPEC method on post-operative and long-term survival outcomes.METHODS Patients undergoing CRS with HIPEC from 2000-2017 were identified in the United States HIPEC collaborative database.Post-operative,recurrence,and overall survival outcomes were compared between those who received open vs closed HIPEC.RESULTS Of the 1812 patients undergoing curative-intent CRS and HIPEC,372(21%)patients underwent open HIPEC and 1440(79%)underwent closed HIPEC.There was no difference in re-operation or severe complications between the two groups.Closed HIPEC had higher rates of 90-d readmission while open HIPEC had a higher rate of 90-d mortalities.On multi-variable analysis,closed HIPEC technique was not a significant predictor for overall survival(hazards ratio:0.75,95%confidence interval:0.51-1.10,P=0.14)or recurrence-free survival(hazards ratio:1.39,95%confidence interval:1.00-1.93,P=0.05)in the entire cohort.These findings remained consistent in the appendiceal and the colorectal subgroups.CONCLUSION In this multi-institutional analysis,the HIPEC method was not independently associated with relevant post-operative or long-term outcomes.HIPEC technique may be left to the discretion of the operating surgeon.
文摘Translational research is a broad field of medicine with several key phases moving from scientific discovery to bench research and the hospital bedside,followed by evidence-based practice and population-level policy and programming. Understanding these phases is crucial when it comes to preventing and treating illness,especially in global health. Communities around the world struggle with a variety of health problems that are at some times similar and at others quite different. Three major world health issues help to outline the phases of translational research:vaccines,human immunodeficiency virus and acquired immunodeficiencysyndrome,and non-communicable diseases. Laboratory research has excelled in many of these areas and is struggling in a few. Where successful therapies have been discovered there are often problems with appropriate use or dissemination to groups in need. Also,many diseases would be better prevented from a population health approach. This review highlights successes and struggles in the arena of global health,from smallpox eradication to the impending epidemic of cardiovascular disease,in an attempt to illustrate of the various phases of translational research.
