In spite of advances made in the management of the other more common cancers of the gastrointestinal tract,significant progress in the treatment of pancreatic cancer remains elusive.Nearly as many deaths occur from pa...In spite of advances made in the management of the other more common cancers of the gastrointestinal tract,significant progress in the treatment of pancreatic cancer remains elusive.Nearly as many deaths occur from pancreatic cancer as are diagnosed each year reflecting the poor prognosis typically associated with this disease.Until recently,the only treatment with an impact on survival was surgery.In the palliative setting,gemcitabine(Gem) has been a standard treatment for advanced pancreatic cancer since it was shown a decade ago to result in a superior clinical benefit response and survival compared with bolus 5-fluorouracil.Since then,clinical trials have explored the pharmacokinetic modulation of Gem by fixed dose administration and the combination of Gem with other cytotoxic or the biologically"targeted"agents.However,promising trial results in small phaseⅡtrials have not translated into survival improvements in larger phaseⅢrandomized trials in the advanced disease setting.Two trials have recently reported modest survival improvements with the use of combination treatment with Gem and capecitabine(United Kingdom National Cancer Research GEMCAP trial) or erlotinib(National Cancer Institute of CanadaClinical Trials Group PA.3 trial) .This review will focus on the use of systemic therapy for advanced and metastatic pancreatic cancer,summarizing the results of several recent clinical trials and discuss their implications for clinical practice.We will also discuss briefly the second-line chemotherapy options for advanced pancreatic cancer.展开更多
Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal malignancies and is developing into the 2nd leading cause of cancer-related death.Often,the clinical and radiological presentation of PDAC may be mirrore...Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal malignancies and is developing into the 2nd leading cause of cancer-related death.Often,the clinical and radiological presentation of PDAC may be mirrored by other inflammatory pancreatic masses,such as autoimmune pancreatitis(AIP)and massforming chronic pancreatitis(MFCP),making its diagnosis challenging.Differentiating AIP and MFCP from PDAC is vital due to significant therapeutic and prognostic implications.Current diagnostic criteria and tools allow the precise differentiation of benign from malignant masses;however,the diagnostic accuracy is imperfect.Major pancreatic resections have been performed in AIP cases under initial suspicion of PDAC after a diagnostic approach failed to provide an accurate diagnosis.It is not unusual that after a thorough diagnostic evaluation,the clinician is confronted with a pancreatic mass with uncertain diagnosis.In those cases,a re-evaluation must be entertained,preferably by an experienced multispecialty team including radiologists,pathologists,gastroenterologists,and surgeons,looking for disease-specific clinical,imaging,and histological hallmarks or collateral evidence that could favor a specific diagnosis.Our aim is to describe current diagnostic limitations that hinder our ability to reach an accurate diagnosis among AIP,PDAC,and MFCP and to highlight those disease-specific clinical,radiological,serological,and histological characteristics that could support the presence of any of these three disorders when facing a pancreatic mass with uncertain diagnosis after an initial diagnostic approach has been unsuccessful.展开更多
BACKGROUND Currently,perioperative complications of classic Whipple surgery occur at a rate of approximately 40%.Common complications include delayed gastric emptying,pancreatic fistula,and bile leakage,whereas gastro...BACKGROUND Currently,perioperative complications of classic Whipple surgery occur at a rate of approximately 40%.Common complications include delayed gastric emptying,pancreatic fistula,and bile leakage,whereas gastrojejunostomy(GJ)leakage is rare.CASE SUMMARY This case report will assess the management of a GJ leak in a 71-year-old male patient following the Whipple procedure.After surgery,the patient was trans-ferred to the clinic after four days of intensive care,where vacuum therapy was used to handle a developing subcutaneous collection.The patient,who had bile in the drains and incision during follow-up,underwent endoscopic examination on the 21st day after the operation.An opening of approximately 4 mm was observed in the GJ anastomosis during endoscopy.Five titanium clips were used to close the openings.The drainage of bile decreased to less than 50 mL on the first day after the procedure,and the patient's oral intake was opened.CONCLUSION Current literature reports a GJ leakage rate of 0.54%following Whipple surgery,with clinical findings lasting on average between 4-34 days.Surgery was the main form of therapy for this case,with a success rate of 84%,and percutaneous drai-nage was also utilized as a treatment option.This case report is the first to docu-ment endoscopic treatment of GJ leaks following the classic Whipple procedure.展开更多
Pancreatic cancer is the 4<sup>th</sup> leading cause of cancer-related death in Western countries. Considering the low incidence of pancreatic cancer, population-based screening is not feasible. However, ...Pancreatic cancer is the 4<sup>th</sup> leading cause of cancer-related death in Western countries. Considering the low incidence of pancreatic cancer, population-based screening is not feasible. However, the existence of a group of individuals with an increased risk to develop pancreatic cancer has been well established. In particular, individuals suffering from a somatic or genetic condition associated with an increased relative risk of more than 5- to 10-fold seem to be suitable for enrollment in a surveillance program for prevention or early detection of pancreatic cancer. The aim of such a program is to reduce pancreatic cancer mortality through early or preemptive surgery. Considering the risk associated with pancreatic surgery, the concept of preemptive surgery cannot consist of a prophylactic removal of the pancreas in high-risk healthy individuals, but must instead aim at treating precancerous lesions such as intraductal papillary mucinous neoplasms or pancreatic intraepithelial neoplasms, or early cancer. Currently, results from clinical trials do not convincingly demonstrate the efficacy of this approach in terms of identification of precancerous lesions, nor do they define the outcome of the surgical treatment of these lesions. For this reason, surveillance programs for individuals at risk of pancreatic cancer are thus far generally limited to the setting of a clinical trial. However, the acquisition of a deeper understanding of this complex area, together with the increasing request for screening and treatment by individuals at risk, will usher pancreatologists into a new era of preemptive pancreatic surgery. Along with the growing demand to treat individuals with precancerous lesions, the need for low-risk investigation, low-morbidity operation and a minimally invasive approach becomes increasingly pressing. All of these considerations are reasons for preemptive pancreatic surgery programs to be undertaken in specialized centers only.展开更多
Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these...Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.展开更多
A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been activel...A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells(Tregs) and myeloid-derived suppressor cells. With the better understanding of the cell components in the tumor microenvironment and the effect of chemotherapy to improve tumor microenvironment, it has been gradually clear that the chemotherapeutic agents is two-edged sword to have both immune promoting and suppressing effects. The cellular components of the tumor microenvironment include infiltrating T lymphocytes, dendritic cells, regulatory T cells, tumor associated macrophages, myeloid derived suppressor cells and cancer associated fibroblasts. Based on the better understanding of tumor microenvironment following chemotherapy, the treatment protocol could be modified as personalized medicine and the prognosis of pancreas cancer would be more improved utilizing multimodal chemotherapy. Here we review the recent advances of chemotherapy to improve tumor microenvironment of pancreatic cancer, introducing the unique feature of tumor microenvironment of pancreatic cancer, interaction between anti-cancer reagents and these constituting cells and future prospects.展开更多
TT virus (TTV) was first isolated in 1997 from the patient with acute post-transfusion hepatitis. This fact led to the conclusion that the virus was hepatotropic and could be one of the causative agents of acute hepat...TT virus (TTV) was first isolated in 1997 from the patient with acute post-transfusion hepatitis. This fact led to the conclusion that the virus was hepatotropic and could be one of the causative agents of acute hepatitis. Afterwards, however, the virus was found in other human tissues and serological studies revealed that it was widespread. Multiple tropisms of TTV and the fact of its high incidence in general population are considered to indicate no medical significance of TTV in human pathology. Here we present a report of two cases of TTV infection in patients who developed pancreas cancer. The patients were hospitalized at the Department of Infectious Diseases due to hepatitis of unknown origin. Since serological and virological markers of common primary and secondary hepatotropic viruses were negative, TTV-DNA was found in serum and was believed to be the only causative agent with probable hepatotropic action. The patients later developed pancreas cancer and they underwent operation. The relationship is difficult to confirm, however the cases we present should be treated as a preliminary report and a comment on the real role of TTV in human pathology.展开更多
Pancreatic cancer ranks tenth in terms of newly diagnosed cases, but just 10%–15% of these patients can undergo resection. Survival after curative surgery is dismal, as recurrences occur either locally or in the live...Pancreatic cancer ranks tenth in terms of newly diagnosed cases, but just 10%–15% of these patients can undergo resection. Survival after curative surgery is dismal, as recurrences occur either locally or in the liver. Adjuvant treatment with either chemotherapy or chemoradiation (with or without maintenance chemotherapy) has been employed, to improve the poor prognosis. Justification for the use of chemoradiation, with follow on chemotherapy, is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. There has been no survival advantage demonstrated in the one randomized controlled trial that examined chemoradiation compared to chemotherapy. There is a clear cut survival advantage however with chemotherapy compared to observation, based on the results from two large randomized controlled trials, and supported by an individual patient data meta-analysis. The standard of care for adjuvant therapy based on level I evidence (from the ESPAC-1 trial) is post operative chemotherapy using 5-Fluorouracil with folinic acid providing a best estimate of 29% five years survival.展开更多
The present study investigates the contribution of AMPK response and mTOR (mammalian target of rapamycin) pathways through high protein diet to the pancreas cancer susceptibility. The hypothalamic modulation of the ...The present study investigates the contribution of AMPK response and mTOR (mammalian target of rapamycin) pathways through high protein diet to the pancreas cancer susceptibility. The hypothalamic modulation of the AMPK/ACC and mTOR signaling pathways induce by HPD and are followed by assaying the tumorigenicity. The results demonstrate that AMPK and mTOR cooperated in the hypothalamus during HPD and resulted in reducing AMPK activity, and increasing mTOR activity.展开更多
The majority of patients with localized pancreatic cancer (PC) who undergo surgery followed by adjuvant therapy will develop metastatic disease, suggesting that surgery alone is not sufficient for cure and micrometast...The majority of patients with localized pancreatic cancer (PC) who undergo surgery followed by adjuvant therapy will develop metastatic disease, suggesting that surgery alone is not sufficient for cure and micrometastases are present even when are not clinically detected. As such, the delivery of early systemic therapy may be a rational alternative to a surgery-first approach, in an effort to provide oncologic therapies which are commensurate with the disease stage, and improve surgical selection. This review details the rationale for a neoadjuvant approach to localized PC and provides specific recommendations for both pretreatment staging and treatment sequencing for patients with resectable and borderline resectable PC.展开更多
Solid pseudopapillary neoplasms are rare.This article reviews the clinical and pathologic features of solid pseudopapillary neoplasm of the pancreas,including the epidemiology,cytology,molecular pathology,differential...Solid pseudopapillary neoplasms are rare.This article reviews the clinical and pathologic features of solid pseudopapillary neoplasm of the pancreas,including the epidemiology,cytology,molecular pathology,differential diagnosis,treatment,and prognosis.Solid pseudopapillary neoplasms are low-grade malignant tumours of the pancreas characterized by poorly cohesive epithelial cells with solid and pseudopapillary patterns.Solid pseudopapillary neoplasms occur predominantly in young women.Although solid pseudopapillary neoplasms can occur throughout the pancreas,they arise slightly more frequently in the tail of the pancreas.The aetiology is unknown.Extremely rare cases have been reported in the setting of familial adenomatous polyposis.There are no symptoms unique to solid pseudopapillary neoplasms,however,the most common symptom is abdominal pain or discomfort.The features of solid pseudopapillary neoplasms on computed tomography imaging are indicative of the pathologic changes within the tumour.Typically,well-demarcated masses with variably solid and cystic appearances.Microscopically,these tumours are composed of epithelial cells forming solid and pseudopapillary structures,frequently undergoing haemorrhagic cystic degeneration.Typically,these tumours express nuclear and/or cytoplasmicβ-catenin.Almost all solid pseudopapillary neoplasms harbour mutations in exon 3 of CTNNB1,the gene encodingβ-catenin.The overall prognosis is excellent,and most patients are cured by complete surgical resection.展开更多
AIM:To evaluate safety and feasibility of microcoil embolization of the common hepatic artery under proper or distal balloon inflation in preoperative preparation for en bloc celiac axis resection for pancreatic body ...AIM:To evaluate safety and feasibility of microcoil embolization of the common hepatic artery under proper or distal balloon inflation in preoperative preparation for en bloc celiac axis resection for pancreatic body cancer.METHODS:Fifteen patients(11 males,4 females;median age,67 years) with pancreatic body cancer involving the nerve plexus surrounding the celiac artery underwent microcoil embolization.To alter the total hepatic blood flow from superior mesenteric artery(SMA),microcoil embolization of the common hepatic artery(CHA) was conducted in 2 cases under balloon inflation at the proximal end of the CHA and in 13 cases under distal microballoon inflation at the distal end of the CHA.RESULTS:Of the first two cases of microcoil embolization with proximal balloon inflation,the first was successful,but there was microcoil migration to the proper hepatic artery in the second.The migrated microcoil was withdrawn to the CHA by an inflated microballoon catheter.Microcoil embolization was successful in the other 13 cases with distal microballoon inflation,with no microcoil migration.Compact microcoil embolization under distal microballoon inflation created sufficient resistance against the vascular wall to prevent migration.Distal balloon inflation achieved the requisite 1 cm patency at the CHA end for vascular clamping.All patients underwent en bloc celiac axis resection without arterial reconstruction or liver ischemia.CONCLUSION:To impede microcoil migration to the proper hepatic artery during CHA microcoil embolization,distal microballoon inflation is preferable to proximal balloon inflation.展开更多
AIM: To provide appropriate treatment, it is crucial to share the clinical status of pancreas head cancer among multidisciplinary treatment members.METHODS: A retrospective analysis of the medical records of 113 patie...AIM: To provide appropriate treatment, it is crucial to share the clinical status of pancreas head cancer among multidisciplinary treatment members.METHODS: A retrospective analysis of the medical records of 113 patients who underwent surgery for pancreas head cancer from January 2008 to December 2012 was performed. We developed preoperative defining system of pancreatic head cancer by describing “resectability - tumor location - vascular relationship - adjacent organ involvement - preoperative CA19-9 (initial bilirubin level) - vascular anomaly”. The oncologic correlations with this reporting system were evaluated.RESULTS: Among 113 patients, there were 75 patients (66.4%) with resectable, 34 patients (30.1%) with borderline resectable, and 4 patients (3.5%) with locally advanced pancreatic cancer. Mean disease-free survival was 24.8 mo (95%CI: 19.6-30.1) with a 5-year disease-free survival rate of 13.5%. Pretreatment tumor size ≥ 2.4 cm [Exp(B) = 3.608, 95%CI: 1.512-8.609, P = 0.044] and radiologic vascular invasion [Exp(B) = 5.553, 95%CI: 2.269-14.589, P = 0.002] were independent predictive factors for neoadjuvant treatment. Borderline resectability [Exp(B) = 0.222, P = 0.008], pancreatic head cancer involving the pancreatic neck [Exp(B) = 9.461, P = 0.001] and arterial invasion [Exp(B) = 6.208, P = 0.010], and adjusted CA19-9 ≥ 50 [Exp(B) = 1.972 P = 0.019] were identified as prognostic clinical factors to predict tumor recurrence.CONCLUSION: The suggested preoperative defining system can help with designing treatment plans and also predict oncologic outcomes.展开更多
BACKGROUND Presence of liver metastatic disease in pancreatic ductal adenocarcinoma(PDAC),either synchronous or metachronous after pancreatic resection,is a terminal diagnosis that warrants management with palliative ...BACKGROUND Presence of liver metastatic disease in pancreatic ductal adenocarcinoma(PDAC),either synchronous or metachronous after pancreatic resection,is a terminal diagnosis that warrants management with palliative intent as per all international practice guidelines.However,there is an increasing interest on any potential value of surgical treatment of isolated oligometastatic disease in selected cases.AIM To present the published evidence on surgical management of PDAC liver metastases,synchronous and metachronous,and compare the outcomes of these treatments to the current standard of care.METHODS A systematic review was performed in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to compare the outcomes of both synchronous and metachronous liver metastases resection to standard care.RESULTS 356 studies were identified,31 studies underwent full-text review and of these 10 were suitable for inclusion.When synchronous resection of liver metastases was compared to standard care,most studies did not demonstrate a survival benefit with the exception of one study that utilised neoadjuvant treatment.However,resection of metachronous disease appeared to confer a survival advantage when compared to treatment with chemotherapy alone.CONCLUSION A survival benefit may exist in resection of selected cases of metachronous liver oligometastatic PDAC disease,after disease biology has been tested with time and systemic treatment.Any survival benefit is less clear in synchronous cases;however an approach with neoadjuvant treatment and consideration of resection in some selected cases may confer some benefit.Future studies should focus on pathways for selection of cases that may benefit from an aggressive approach.展开更多
Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on ou...Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several largevolume centers have initiated such screening protocols, and consensus-based guidelines for screening high-riskgroups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields.展开更多
AIM: To evaluate the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic solid tumors larger or smaller than 3 cm, and cystic lesions.METHODS: From January/1997 to D...AIM: To evaluate the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic solid tumors larger or smaller than 3 cm, and cystic lesions.METHODS: From January/1997 to December/2006, 611 patients with pancreatic tumors were subjected to EUSFNA. The final diagnosis was obtained either by surgery (356 cases) or after a mean clinical follow-up of 11.8 mo in the remaining patients.RESULTS: There were 405 solid tumors, 189 cystic lesions and 17 mixed. Pancreatic specimens for cytological assessment were successfully obtained by EUS-FNA in 595 (97.4%) cases. There were 352 (57.6%) malignancies and 259 (42.4%) benign tumors. Among the malignancies, pancreatic adenocarcinomas accounted for 67% of the lesions. Overall, the sensitivity, specificity, positive and negative predictive values, and accuracy of EUS-FNA were, respectively, 78.4%, 99.2%, 99.3%, 77.2% and 87.2%. Specifically for solid tumors, the same parameters for neoplasms larger and smaller than 3 cm were, respectively, 78.8% ys 82.4%, 100% ys 98.4%, 100% vs 99%, 54.8% vs 74.1% and 83.1% vs 87.8%. For cystic lesions, the values were, respectively, 72.2%, 99.3%, 97.5%, 91% and 92.2%.CONCLUSION: EUS-FNA can be used to sample pancreatic tumors in most patients. Even though the negative predictive value is inadequate for large solid tumors, the results are rather good for small solid tumors, especially concerning the sensitivity, negative predictive value and diagnostic accuracy. Among all pancreatic lesions, EUS-FNA for cystic lesions can reveal the best negative predictive value and diagnostic accuracy, both higher than 90%.展开更多
The role of whole-body FDG [(~(18)F)2-fluoro-2-deoxy-glucose] positron emission tomography(PET)scan-ning as an imaging modality in the management of patients with malignancy has evolved enormously over the past two d...The role of whole-body FDG [(~(18)F)2-fluoro-2-deoxy-glucose] positron emission tomography(PET)scan-ning as an imaging modality in the management of patients with malignancy has evolved enormously over the past two decades.FDG-PET has demonstrated signifi cant effi cacy in the staging,prognostication and detection of occult metastatic disease in malignancies of the gastrointestinal tract,in addition to assessment of the response to cytotoxic chemotherapy in a more timely manner than has traditionally been possible by more conventional imaging tools.The sensitivity and specif icity of FDG-PET for the detection and staging of malignancy depend not only on the site and size of the primary tumor and metastases,but also on histologi-cal cell type,reflecting underlying disparities in glucose metabolism.The metabolic response to neo-adjuvant chemotherapy or to chemo-radiotherapy in cancers of the gastro-esophageal junction or stomach has been demonstrated in several prospective studies to correlate signifi cantly with both the histological tumor response to treatment and with consequent improvements in overall survival.This may offer a future paradigm ofpersonalized treatment based on the PET response to chemotherapy.FDG-PET has been less successful in efforts to screen for and detect recurrent upper gastro-intestinal malignancies,and in the detection of low vol-ume metastatic peritoneal disease.Efforts to improve the accuracy of PET include the use of novel radiotrac-ers such as(~(18)F)FLT(3-deoxy-3-fluorothymidine)or 11C-choline,or fusion PET-CT with concurrent high-res-olution computed tomography.This review focuses on the role of FDG-PET scanning in staging and response assessment in malignancies of the upper gastrointesti-nal tract,specif ically gastric,esophageal and pancreas carcinoma.展开更多
This is a case of a pancreatic tumor with invasion of the celiac stem treated using the modified Appleby operation.Preoperatively,routine B-ultrasound,computed tomography,and magnetic resonance imaging were performed....This is a case of a pancreatic tumor with invasion of the celiac stem treated using the modified Appleby operation.Preoperatively,routine B-ultrasound,computed tomography,and magnetic resonance imaging were performed.In the perioperative period,the combined gallbladder was excised;the duration of the operation was 5 h and volume of blood loss was approximately 500 ml.Postoperatively,the liver function temporarily returned and after a liver protection treatment,it returned to normal within 2 weeks.The liver had normal arterial blood supply,and the postoperative course was uneventful.It is safe and feasible to resect the whole pancreatic body and tail tumor combined with celiac stem resection.It can improve the resection rate of tumor and relieve pain.展开更多
文摘In spite of advances made in the management of the other more common cancers of the gastrointestinal tract,significant progress in the treatment of pancreatic cancer remains elusive.Nearly as many deaths occur from pancreatic cancer as are diagnosed each year reflecting the poor prognosis typically associated with this disease.Until recently,the only treatment with an impact on survival was surgery.In the palliative setting,gemcitabine(Gem) has been a standard treatment for advanced pancreatic cancer since it was shown a decade ago to result in a superior clinical benefit response and survival compared with bolus 5-fluorouracil.Since then,clinical trials have explored the pharmacokinetic modulation of Gem by fixed dose administration and the combination of Gem with other cytotoxic or the biologically"targeted"agents.However,promising trial results in small phaseⅡtrials have not translated into survival improvements in larger phaseⅢrandomized trials in the advanced disease setting.Two trials have recently reported modest survival improvements with the use of combination treatment with Gem and capecitabine(United Kingdom National Cancer Research GEMCAP trial) or erlotinib(National Cancer Institute of CanadaClinical Trials Group PA.3 trial) .This review will focus on the use of systemic therapy for advanced and metastatic pancreatic cancer,summarizing the results of several recent clinical trials and discuss their implications for clinical practice.We will also discuss briefly the second-line chemotherapy options for advanced pancreatic cancer.
文摘Pancreatic ductal adenocarcinoma(PDAC)is one of the most lethal malignancies and is developing into the 2nd leading cause of cancer-related death.Often,the clinical and radiological presentation of PDAC may be mirrored by other inflammatory pancreatic masses,such as autoimmune pancreatitis(AIP)and massforming chronic pancreatitis(MFCP),making its diagnosis challenging.Differentiating AIP and MFCP from PDAC is vital due to significant therapeutic and prognostic implications.Current diagnostic criteria and tools allow the precise differentiation of benign from malignant masses;however,the diagnostic accuracy is imperfect.Major pancreatic resections have been performed in AIP cases under initial suspicion of PDAC after a diagnostic approach failed to provide an accurate diagnosis.It is not unusual that after a thorough diagnostic evaluation,the clinician is confronted with a pancreatic mass with uncertain diagnosis.In those cases,a re-evaluation must be entertained,preferably by an experienced multispecialty team including radiologists,pathologists,gastroenterologists,and surgeons,looking for disease-specific clinical,imaging,and histological hallmarks or collateral evidence that could favor a specific diagnosis.Our aim is to describe current diagnostic limitations that hinder our ability to reach an accurate diagnosis among AIP,PDAC,and MFCP and to highlight those disease-specific clinical,radiological,serological,and histological characteristics that could support the presence of any of these three disorders when facing a pancreatic mass with uncertain diagnosis after an initial diagnostic approach has been unsuccessful.
文摘BACKGROUND Currently,perioperative complications of classic Whipple surgery occur at a rate of approximately 40%.Common complications include delayed gastric emptying,pancreatic fistula,and bile leakage,whereas gastrojejunostomy(GJ)leakage is rare.CASE SUMMARY This case report will assess the management of a GJ leak in a 71-year-old male patient following the Whipple procedure.After surgery,the patient was trans-ferred to the clinic after four days of intensive care,where vacuum therapy was used to handle a developing subcutaneous collection.The patient,who had bile in the drains and incision during follow-up,underwent endoscopic examination on the 21st day after the operation.An opening of approximately 4 mm was observed in the GJ anastomosis during endoscopy.Five titanium clips were used to close the openings.The drainage of bile decreased to less than 50 mL on the first day after the procedure,and the patient's oral intake was opened.CONCLUSION Current literature reports a GJ leakage rate of 0.54%following Whipple surgery,with clinical findings lasting on average between 4-34 days.Surgery was the main form of therapy for this case,with a success rate of 84%,and percutaneous drai-nage was also utilized as a treatment option.This case report is the first to docu-ment endoscopic treatment of GJ leaks following the classic Whipple procedure.
文摘Pancreatic cancer is the 4<sup>th</sup> leading cause of cancer-related death in Western countries. Considering the low incidence of pancreatic cancer, population-based screening is not feasible. However, the existence of a group of individuals with an increased risk to develop pancreatic cancer has been well established. In particular, individuals suffering from a somatic or genetic condition associated with an increased relative risk of more than 5- to 10-fold seem to be suitable for enrollment in a surveillance program for prevention or early detection of pancreatic cancer. The aim of such a program is to reduce pancreatic cancer mortality through early or preemptive surgery. Considering the risk associated with pancreatic surgery, the concept of preemptive surgery cannot consist of a prophylactic removal of the pancreas in high-risk healthy individuals, but must instead aim at treating precancerous lesions such as intraductal papillary mucinous neoplasms or pancreatic intraepithelial neoplasms, or early cancer. Currently, results from clinical trials do not convincingly demonstrate the efficacy of this approach in terms of identification of precancerous lesions, nor do they define the outcome of the surgical treatment of these lesions. For this reason, surveillance programs for individuals at risk of pancreatic cancer are thus far generally limited to the setting of a clinical trial. However, the acquisition of a deeper understanding of this complex area, together with the increasing request for screening and treatment by individuals at risk, will usher pancreatologists into a new era of preemptive pancreatic surgery. Along with the growing demand to treat individuals with precancerous lesions, the need for low-risk investigation, low-morbidity operation and a minimally invasive approach becomes increasingly pressing. All of these considerations are reasons for preemptive pancreatic surgery programs to be undertaken in specialized centers only.
文摘Management of cancers of the digestive system has progressed rapidly into the molecular era. Despite the significant recent achievements in the diagnosis and treatment of these patients, the number of deaths for these tumors has currently plateaued. Many investigations have assessed the role of HER2 in tumors of the digestive system in both prognostic and therapeutic settings, with heterogeneous results. Novel testing and treatment guidelines are emerging, in particular in gastric and colorectal cancers. However, further advances are needed. In this review we provide a comprehensive overview of the current state-ofknowledge of HER2 alterations in the most common tumors of the digestive system and discuss the operational implications of HER2 testing.
文摘A perioperative multimodal strategy including combination chemotherapy and radiotherapy, in addition to surgical resection, has been acknowledged to improve patient prognosis. However chemotherapy has not been actively applied as an immunomodulating modality because of concerns about various immunosuppressive effects. It has recently been shown that certain chemotherapeutic agents could modify tumor microenvironment and host immune responses through several underlying mechanisms such as immunogenic cell death, local T-cell infiltration and also the eradication of immune-suppressing regulatory cells such as regulatory T cells(Tregs) and myeloid-derived suppressor cells. With the better understanding of the cell components in the tumor microenvironment and the effect of chemotherapy to improve tumor microenvironment, it has been gradually clear that the chemotherapeutic agents is two-edged sword to have both immune promoting and suppressing effects. The cellular components of the tumor microenvironment include infiltrating T lymphocytes, dendritic cells, regulatory T cells, tumor associated macrophages, myeloid derived suppressor cells and cancer associated fibroblasts. Based on the better understanding of tumor microenvironment following chemotherapy, the treatment protocol could be modified as personalized medicine and the prognosis of pancreas cancer would be more improved utilizing multimodal chemotherapy. Here we review the recent advances of chemotherapy to improve tumor microenvironment of pancreatic cancer, introducing the unique feature of tumor microenvironment of pancreatic cancer, interaction between anti-cancer reagents and these constituting cells and future prospects.
文摘TT virus (TTV) was first isolated in 1997 from the patient with acute post-transfusion hepatitis. This fact led to the conclusion that the virus was hepatotropic and could be one of the causative agents of acute hepatitis. Afterwards, however, the virus was found in other human tissues and serological studies revealed that it was widespread. Multiple tropisms of TTV and the fact of its high incidence in general population are considered to indicate no medical significance of TTV in human pathology. Here we present a report of two cases of TTV infection in patients who developed pancreas cancer. The patients were hospitalized at the Department of Infectious Diseases due to hepatitis of unknown origin. Since serological and virological markers of common primary and secondary hepatotropic viruses were negative, TTV-DNA was found in serum and was believed to be the only causative agent with probable hepatotropic action. The patients later developed pancreas cancer and they underwent operation. The relationship is difficult to confirm, however the cases we present should be treated as a preliminary report and a comment on the real role of TTV in human pathology.
文摘Pancreatic cancer ranks tenth in terms of newly diagnosed cases, but just 10%–15% of these patients can undergo resection. Survival after curative surgery is dismal, as recurrences occur either locally or in the liver. Adjuvant treatment with either chemotherapy or chemoradiation (with or without maintenance chemotherapy) has been employed, to improve the poor prognosis. Justification for the use of chemoradiation, with follow on chemotherapy, is based on the results of an underpowered 1987 GITSG study, which closed prematurely and compared intervention to observation. There has been no survival advantage demonstrated in the one randomized controlled trial that examined chemoradiation compared to chemotherapy. There is a clear cut survival advantage however with chemotherapy compared to observation, based on the results from two large randomized controlled trials, and supported by an individual patient data meta-analysis. The standard of care for adjuvant therapy based on level I evidence (from the ESPAC-1 trial) is post operative chemotherapy using 5-Fluorouracil with folinic acid providing a best estimate of 29% five years survival.
文摘The present study investigates the contribution of AMPK response and mTOR (mammalian target of rapamycin) pathways through high protein diet to the pancreas cancer susceptibility. The hypothalamic modulation of the AMPK/ACC and mTOR signaling pathways induce by HPD and are followed by assaying the tumorigenicity. The results demonstrate that AMPK and mTOR cooperated in the hypothalamus during HPD and resulted in reducing AMPK activity, and increasing mTOR activity.
文摘The majority of patients with localized pancreatic cancer (PC) who undergo surgery followed by adjuvant therapy will develop metastatic disease, suggesting that surgery alone is not sufficient for cure and micrometastases are present even when are not clinically detected. As such, the delivery of early systemic therapy may be a rational alternative to a surgery-first approach, in an effort to provide oncologic therapies which are commensurate with the disease stage, and improve surgical selection. This review details the rationale for a neoadjuvant approach to localized PC and provides specific recommendations for both pretreatment staging and treatment sequencing for patients with resectable and borderline resectable PC.
文摘Solid pseudopapillary neoplasms are rare.This article reviews the clinical and pathologic features of solid pseudopapillary neoplasm of the pancreas,including the epidemiology,cytology,molecular pathology,differential diagnosis,treatment,and prognosis.Solid pseudopapillary neoplasms are low-grade malignant tumours of the pancreas characterized by poorly cohesive epithelial cells with solid and pseudopapillary patterns.Solid pseudopapillary neoplasms occur predominantly in young women.Although solid pseudopapillary neoplasms can occur throughout the pancreas,they arise slightly more frequently in the tail of the pancreas.The aetiology is unknown.Extremely rare cases have been reported in the setting of familial adenomatous polyposis.There are no symptoms unique to solid pseudopapillary neoplasms,however,the most common symptom is abdominal pain or discomfort.The features of solid pseudopapillary neoplasms on computed tomography imaging are indicative of the pathologic changes within the tumour.Typically,well-demarcated masses with variably solid and cystic appearances.Microscopically,these tumours are composed of epithelial cells forming solid and pseudopapillary structures,frequently undergoing haemorrhagic cystic degeneration.Typically,these tumours express nuclear and/or cytoplasmicβ-catenin.Almost all solid pseudopapillary neoplasms harbour mutations in exon 3 of CTNNB1,the gene encodingβ-catenin.The overall prognosis is excellent,and most patients are cured by complete surgical resection.
文摘AIM:To evaluate safety and feasibility of microcoil embolization of the common hepatic artery under proper or distal balloon inflation in preoperative preparation for en bloc celiac axis resection for pancreatic body cancer.METHODS:Fifteen patients(11 males,4 females;median age,67 years) with pancreatic body cancer involving the nerve plexus surrounding the celiac artery underwent microcoil embolization.To alter the total hepatic blood flow from superior mesenteric artery(SMA),microcoil embolization of the common hepatic artery(CHA) was conducted in 2 cases under balloon inflation at the proximal end of the CHA and in 13 cases under distal microballoon inflation at the distal end of the CHA.RESULTS:Of the first two cases of microcoil embolization with proximal balloon inflation,the first was successful,but there was microcoil migration to the proper hepatic artery in the second.The migrated microcoil was withdrawn to the CHA by an inflated microballoon catheter.Microcoil embolization was successful in the other 13 cases with distal microballoon inflation,with no microcoil migration.Compact microcoil embolization under distal microballoon inflation created sufficient resistance against the vascular wall to prevent migration.Distal balloon inflation achieved the requisite 1 cm patency at the CHA end for vascular clamping.All patients underwent en bloc celiac axis resection without arterial reconstruction or liver ischemia.CONCLUSION:To impede microcoil migration to the proper hepatic artery during CHA microcoil embolization,distal microballoon inflation is preferable to proximal balloon inflation.
文摘AIM: To provide appropriate treatment, it is crucial to share the clinical status of pancreas head cancer among multidisciplinary treatment members.METHODS: A retrospective analysis of the medical records of 113 patients who underwent surgery for pancreas head cancer from January 2008 to December 2012 was performed. We developed preoperative defining system of pancreatic head cancer by describing “resectability - tumor location - vascular relationship - adjacent organ involvement - preoperative CA19-9 (initial bilirubin level) - vascular anomaly”. The oncologic correlations with this reporting system were evaluated.RESULTS: Among 113 patients, there were 75 patients (66.4%) with resectable, 34 patients (30.1%) with borderline resectable, and 4 patients (3.5%) with locally advanced pancreatic cancer. Mean disease-free survival was 24.8 mo (95%CI: 19.6-30.1) with a 5-year disease-free survival rate of 13.5%. Pretreatment tumor size ≥ 2.4 cm [Exp(B) = 3.608, 95%CI: 1.512-8.609, P = 0.044] and radiologic vascular invasion [Exp(B) = 5.553, 95%CI: 2.269-14.589, P = 0.002] were independent predictive factors for neoadjuvant treatment. Borderline resectability [Exp(B) = 0.222, P = 0.008], pancreatic head cancer involving the pancreatic neck [Exp(B) = 9.461, P = 0.001] and arterial invasion [Exp(B) = 6.208, P = 0.010], and adjusted CA19-9 ≥ 50 [Exp(B) = 1.972 P = 0.019] were identified as prognostic clinical factors to predict tumor recurrence.CONCLUSION: The suggested preoperative defining system can help with designing treatment plans and also predict oncologic outcomes.
文摘BACKGROUND Presence of liver metastatic disease in pancreatic ductal adenocarcinoma(PDAC),either synchronous or metachronous after pancreatic resection,is a terminal diagnosis that warrants management with palliative intent as per all international practice guidelines.However,there is an increasing interest on any potential value of surgical treatment of isolated oligometastatic disease in selected cases.AIM To present the published evidence on surgical management of PDAC liver metastases,synchronous and metachronous,and compare the outcomes of these treatments to the current standard of care.METHODS A systematic review was performed in line with the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines to compare the outcomes of both synchronous and metachronous liver metastases resection to standard care.RESULTS 356 studies were identified,31 studies underwent full-text review and of these 10 were suitable for inclusion.When synchronous resection of liver metastases was compared to standard care,most studies did not demonstrate a survival benefit with the exception of one study that utilised neoadjuvant treatment.However,resection of metachronous disease appeared to confer a survival advantage when compared to treatment with chemotherapy alone.CONCLUSION A survival benefit may exist in resection of selected cases of metachronous liver oligometastatic PDAC disease,after disease biology has been tested with time and systemic treatment.Any survival benefit is less clear in synchronous cases;however an approach with neoadjuvant treatment and consideration of resection in some selected cases may confer some benefit.Future studies should focus on pathways for selection of cases that may benefit from an aggressive approach.
文摘Pancreatic cancer is the fourth most common cause of cancer-related deaths in the United States, with over 38000 deaths in 2013. The opportunity to detect pancreatic cancer while it is still curable is dependent on our ability to identify and screen high-risk populations before their symptoms arise. Risk factors for developing pancreatic cancer include multiple genetic syndromes as well as modifiable risk factors. Genetic conditions include hereditary breast and ovarian cancer syndrome, Lynch Syndrome, familial adenomatous polyposis, Peutz-Jeghers Syndrome, familial atypical multiple mole melanoma syndrome, hereditary pancreatitis, cystic fibrosis, and ataxia-telangiectasia; having a genetic predisposition can raise the risk of developing pancreatic cancer up to 132-fold over the general population. Modifiable risk factors, which include tobacco exposure, alcohol use, chronic pancreatitis, diet, obesity, diabetes mellitus, as well as certain abdominal surgeries and infections, have also been shown to increase the risk of pancreatic cancer development. Several largevolume centers have initiated such screening protocols, and consensus-based guidelines for screening high-riskgroups have recently been published. The focus of this review will be both the genetic and modifiable risk factors implicated in pancreatic cancer, as well as a review of screening strategies and their diagnostic yields.
文摘AIM: To evaluate the diagnostic accuracy of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) for pancreatic solid tumors larger or smaller than 3 cm, and cystic lesions.METHODS: From January/1997 to December/2006, 611 patients with pancreatic tumors were subjected to EUSFNA. The final diagnosis was obtained either by surgery (356 cases) or after a mean clinical follow-up of 11.8 mo in the remaining patients.RESULTS: There were 405 solid tumors, 189 cystic lesions and 17 mixed. Pancreatic specimens for cytological assessment were successfully obtained by EUS-FNA in 595 (97.4%) cases. There were 352 (57.6%) malignancies and 259 (42.4%) benign tumors. Among the malignancies, pancreatic adenocarcinomas accounted for 67% of the lesions. Overall, the sensitivity, specificity, positive and negative predictive values, and accuracy of EUS-FNA were, respectively, 78.4%, 99.2%, 99.3%, 77.2% and 87.2%. Specifically for solid tumors, the same parameters for neoplasms larger and smaller than 3 cm were, respectively, 78.8% ys 82.4%, 100% ys 98.4%, 100% vs 99%, 54.8% vs 74.1% and 83.1% vs 87.8%. For cystic lesions, the values were, respectively, 72.2%, 99.3%, 97.5%, 91% and 92.2%.CONCLUSION: EUS-FNA can be used to sample pancreatic tumors in most patients. Even though the negative predictive value is inadequate for large solid tumors, the results are rather good for small solid tumors, especially concerning the sensitivity, negative predictive value and diagnostic accuracy. Among all pancreatic lesions, EUS-FNA for cystic lesions can reveal the best negative predictive value and diagnostic accuracy, both higher than 90%.
文摘The role of whole-body FDG [(~(18)F)2-fluoro-2-deoxy-glucose] positron emission tomography(PET)scan-ning as an imaging modality in the management of patients with malignancy has evolved enormously over the past two decades.FDG-PET has demonstrated signifi cant effi cacy in the staging,prognostication and detection of occult metastatic disease in malignancies of the gastrointestinal tract,in addition to assessment of the response to cytotoxic chemotherapy in a more timely manner than has traditionally been possible by more conventional imaging tools.The sensitivity and specif icity of FDG-PET for the detection and staging of malignancy depend not only on the site and size of the primary tumor and metastases,but also on histologi-cal cell type,reflecting underlying disparities in glucose metabolism.The metabolic response to neo-adjuvant chemotherapy or to chemo-radiotherapy in cancers of the gastro-esophageal junction or stomach has been demonstrated in several prospective studies to correlate signifi cantly with both the histological tumor response to treatment and with consequent improvements in overall survival.This may offer a future paradigm ofpersonalized treatment based on the PET response to chemotherapy.FDG-PET has been less successful in efforts to screen for and detect recurrent upper gastro-intestinal malignancies,and in the detection of low vol-ume metastatic peritoneal disease.Efforts to improve the accuracy of PET include the use of novel radiotrac-ers such as(~(18)F)FLT(3-deoxy-3-fluorothymidine)or 11C-choline,or fusion PET-CT with concurrent high-res-olution computed tomography.This review focuses on the role of FDG-PET scanning in staging and response assessment in malignancies of the upper gastrointesti-nal tract,specif ically gastric,esophageal and pancreas carcinoma.
文摘This is a case of a pancreatic tumor with invasion of the celiac stem treated using the modified Appleby operation.Preoperatively,routine B-ultrasound,computed tomography,and magnetic resonance imaging were performed.In the perioperative period,the combined gallbladder was excised;the duration of the operation was 5 h and volume of blood loss was approximately 500 ml.Postoperatively,the liver function temporarily returned and after a liver protection treatment,it returned to normal within 2 weeks.The liver had normal arterial blood supply,and the postoperative course was uneventful.It is safe and feasible to resect the whole pancreatic body and tail tumor combined with celiac stem resection.It can improve the resection rate of tumor and relieve pain.