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
AIM: To establish an optimum combination of molecular markers resulting in best overall diagnostic sensitivity and specificity for evaluation of suspicious pancreatic mass. METHODS: Endoscopic ultrasound (EUS)-gui...AIM: To establish an optimum combination of molecular markers resulting in best overall diagnostic sensitivity and specificity for evaluation of suspicious pancreatic mass. METHODS: Endoscopic ultrasound (EUS)-guided fine needle aspiration cytology (FNA) was performed on 101 consecutive patients (63 males, 38 females, 60 ± 12 years; 81 with subsequently diagnosed pancreatic cancer, 20 with chronic pancreatitis) with focal pancreatic mass. Samples were evaluated on-site by an experienced cytopathologist. DNA was extracted from Giemsa stained cells selected by laser microdissection and the presence of K-ras, p53 and p16 somatic mutations was tested by cycling-gradient capillary electrophoresis (CGCE) and single-strand conformation polymorphism (SSCP) techniques. In addition, allelic losses of tumor suppressor genes p16 (INK4, CDKN2A) and DPC4 (MADH4, SMAD4) were detected by monitoring the loss of heterozygosity (LOH) at 9p and 18q, respectively. RESULTS: Sensitivity and specificity of EUS-guided FNA were 75% and 85%, positive and negative predictive value reached 100%. The remaining 26% samples were assigned as inconclusive. Testing of molecular markers revealed sensitivity and specificity of 70% and 100% for K-ras mutations (P 〈 0.001), 24% and 90% for p53 mutations (NS), 13% and 100% for p16 mutations (NS), 85% and 64% for aUelic losses at 9p (P 〈 0.001) and 78% and 57% for allelic losses at 18q (P 〈 0.05). When tests for different molecular markers were combined, the best results were obtained with K-ras + LOH at 9p (92% and 64%, P 〈 0.001), K-ras + LOH at 18q (92% and 57%, P 〈 0.001), and K-ras + LOH 9q + LOH 18q (96% and 43%, P 〈 0.001). When the molecular markers were used as complements to FNA cytology to evaluate inconclusive samples only, the overall sensitivity of cancer detection was 100% in all patients enrolled in the study. CONCLUSION: EUS-guided FNA cytology combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy. Molecular markers may find its use particularly in cases where FNA cytology has been inconclusive.展开更多
AIM:To investigate the markers of pancreatic diseases and provide basic data and experimental methods for the diagnosis of pancreatic diseases.METHODS:There were 15 patients in the present study,among whom 10 had panc...AIM:To investigate the markers of pancreatic diseases and provide basic data and experimental methods for the diagnosis of pancreatic diseases.METHODS:There were 15 patients in the present study,among whom 10 had pancreatic cancer and 5,chronic pancreatitis.In all patients,pancreatic cancer or chronic pancreatitis was located on the head of the p-a-ncrea-s.Pa-thology da-ta-of a-ll p-a-tients wa-s confirmed by biopsy and surgery.Among the 10 patients with pancreatic cancer,3 people had a medical history of longterm alcohol consumption.Of 5 patients with chronic pancreatitis,4 men suffered from alcoholic chronic pancreatitis.Pancreatic juice samples were obtained from patients by endoscopic retrograde cholangiopancreatography.Magnetic resonance spectroscopyn was performed on an 11.7-T scanner (Bruker DRX-500) using Call-Purcell-Meiboom-Gill pulse sequences.The parameters were as follows:spectral width,15 KHz;time domain,64 K;number of scans,512;and acquisition time,2.128 s.RESULTS:The main component of pancreatic juice included leucine,iso-leucine,valine,lactate,alanine,acetate,aspartate,lysine,glycine,threonine,tyrosine,histidine,tryptophan,and phenylalanine.On performing 1D 1H and 2D total correlation spectroscopy,we found a triplet peak at the chemical shift of 1.19 ppm,which only appeared in the spectra of pancreatic juice obtained from patients with alcoholic chronic pancreatitis.This triplet peak was considered the resonance of the methyl of ethoxy group,which may be associated with the metabolism of alcohol in the pancreas.CONCLUSION:The triplet peak,at the chemical shift of 1.19 ppm is likely to be the characteristic metabolite of alcoholic chronic pancreatitis.展开更多
AIM: To investigate c-met expression during early pancreatic carcinogenesis. METHODS: We used 46 bulk tissues and 36 microdissected samples, including normal pancreas, chronic pancreatitis, and pancreatic cancer, fo...AIM: To investigate c-met expression during early pancreatic carcinogenesis. METHODS: We used 46 bulk tissues and 36 microdissected samples, including normal pancreas, chronic pancreatitis, and pancreatic cancer, for quantitative realtime reverse transcription-polymerase chain reaction. RESULTS: In bulk tissue analyses, pancreatic cancer tissues expressed significantly higher levels of c-met than did chronic pancreatitis and normal pancreas tissues. c-met levels did not differ between chronic pancreatitis and normal pancreas tissues. In microdissection-based analyses, c-met was expressed at higher levels in microclissected pancreatic cancer cells and pancreatitisaffected epithelial cells than in normal ductal epithelial cells (both, P 〈 0.01). Interestingly, pancreatitis-affected epithelial cells expressed levels of c-met similar to those of pancreatic cancer cells. CONCLUSION: Overexpression of c-met occurs during the early stage of pancreatic carcinogenesis, and a single alteration of c-met expression is not sufficient for progression of chronic pancreatitis-affected epithelial cells to pancreatic cancer cells.展开更多
Pancreatic ductal adenocarcinoma is an aggressive tumor with poor long-term outcomes.Chronic pancreatitis(CP)is considered a risk factor for the development of pancreatic cancer(PC).Persistent pancreatic inflammation ...Pancreatic ductal adenocarcinoma is an aggressive tumor with poor long-term outcomes.Chronic pancreatitis(CP)is considered a risk factor for the development of pancreatic cancer(PC).Persistent pancreatic inflammation and activation of pancreatic stellate cells play a crucial role in the pathogenesis of CPrelated PC by activating the oncogene pathway.While genetic mutations increase the possibility of recurrent and persistent pancreatic inflammation,they are not directly associated with the development of PC.Recent studies suggest that early surgical intervention for CP might have a protective role in the development of CP-related PC.Hence,the physician faces the clinical question of whether early surgical intervention should be recommended in patients with CP to prevent the development of PC.However,the varying relative risk of PC in different subsets of CP underlines the complex gene-environment interactions in the disease pathogenesis.Hence,it is essential to stratify the risk of PC in each individual patient.This review focuses on the complex relationship between CP and PC and the impact of surgical intervention on PC risk.The proposed risk stratification based on the genetic and environmental factors could guide future research and select patients for prophylactic surgery.展开更多
AIM: To evaluate the contrast-enhanced endosonography as a method of differentiating inflammation from pancreatic carcinoma based on perfusion characteristics of microvessels. METHODS: In 86 patients with suspected ...AIM: To evaluate the contrast-enhanced endosonography as a method of differentiating inflammation from pancreatic carcinoma based on perfusion characteristics of microvessels. METHODS: In 86 patients with suspected chronic pancreatitis (age: 62± 12 years; sex: f/m 38/48), pancreatic lesions were examined by conventional endo- scopic B-mode, power Doppler ultrasound and contrastenhanced power mode (Hitachi EUB 525, SonoVue, 2.4 mL, Bracco) using the following criteria for malignant lesions: no detectable vascularisation using conventional power Doppler scanning, irregular appearance of arterial vessels over a short distance using SonoVue contrastenhanced technique and no detectable venous vessels inside the lesion. A malignant lesion was assumed if all criteria were detectable [gold standard endoscopic ultrasound (EUS)-guided fine needle aspiration cytology, operation]. The criteria of chronic pancreatitis without neoplasia were defined as no detectable vascularisation before injection of SonoVue, regular appearance of vessels over a distance of at least 20 mm after injection of SonoVue and detection of arterial and venous vessels. RESULTS: The sensitivity and specifidty of conventional EUS were 73.2% and 83.3% respectively for pancreatic cancer. The sensitivity of contrast-enhanced EUS increased to 91.1% in 51 of 56 patients with malignant pancreatic lesion and the specificity increased to 93.3% in 28 of 30 patients with chronic inflammatory pancreatic disease.CONCLUSION: Contrast-enhanced endoscopic ultrasound improves the differentiation between chronic pancreatitis and pancreatic carcinoma.展开更多
Pancreatic cancer is a challenging disease for patients,doctors and researchers who for decades have searched for a cure for this deadly malignancy.Although existing mouse models of pancreatic cancer have shed light o...Pancreatic cancer is a challenging disease for patients,doctors and researchers who for decades have searched for a cure for this deadly malignancy.Although existing mouse models of pancreatic cancer have shed light on the mecha-nistic basis of the neoplastic conversion of the pancreas,their impact in terms of offering new diagnostics and therapeu-tic modalities remains limited.Chronic pancreatitis is an inflammatory disease of the pancreas that is associated with a gradual damage of the organ and an increased risk of developing neoplastic lesions.In this review,we propose that detailed studies of chronic inflammatory processes in the pancreas will provide insights into the evolution of pancreatic cancer.This information may prove useful in the design of effective therapeutic strategies to battle the disease.展开更多
AIM To assess the occurrence of autoimmune pancreatitis(AIP) in pancreatic resections performed for focal pancreatic enlargement.METHODS We performed a retrospective analysis of medical records of all patients who und...AIM To assess the occurrence of autoimmune pancreatitis(AIP) in pancreatic resections performed for focal pancreatic enlargement.METHODS We performed a retrospective analysis of medical records of all patients who underwent pancreatic resection for a focal pancreatic enlargement at our tertiary center from January 2000 to July 2013. The indication for surgery was suspicion of a tumor based on clinical presentation, imaging findings and laboratory evaluations. The diagnosis of AIP was based on histology findings. An experienced pathologist specialized in pancreatic disease reviewed all the cases and confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The histological diagnosis of AIP was set according to the international consensus diagnostic criteria.RESULTS Two hundred ninety-five pancreatic resections were performed in 201 men and 94 women. AIP was diagnosed in 15 patients(5.1%, 12 men and 3 women) based on histology of the resected specimen. Six of them had AIP type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma(PC) was also present in six patients with AIP(40%), all six were men. Patients with AIP + PC were significantly older(60.5 vs 49 years of age, P = 0.045), more likely to have been recently diagnosed with diabetes(67% vs 11%, P = 0.09), and had experienced greater weight loss(15.5 kg vs 8.5 kg, P = 0.03) than AIP patients without PC. AIP was not diagnosed in any patients prior to surgery; however, the diagnostic algorithm was not fully completed in every case. CONCLUSION The possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP does not rule out simultaneous presence of PC.展开更多
Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer,whereas such an association with autoimmune pancreatitis(AIP)is widely debated.Due to the rarity of the latter disorder,there are few spe...Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer,whereas such an association with autoimmune pancreatitis(AIP)is widely debated.Due to the rarity of the latter disorder,there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer,which do not seem to support it.However,these studies are affected by several limitations and,therefore,a link between AIP(and,specifically,type 1 AIP)and pancreatic cancer cannot be ruled out definitively on this basis.Moreover,several immunopathological aspects of type 1 AIP and,in general,immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression.In detail,Th2 immunological dominance,type 2 macrophage polarization and basophil infiltration observed in type 1 AIP,may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis,in addition to the immunosuppressive therapies that can be used in these patients.展开更多
BACKGROUND Epidemiological studies of chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC)are limited.Understanding demographic and ethno-racial factors may help identify patients at...BACKGROUND Epidemiological studies of chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC)are limited.Understanding demographic and ethno-racial factors may help identify patients at the highest risk for CP and PDAC.AIM To evaluate the ethno-racial risk factors for CP and its association with PDAC.The secondary aim was to evaluate hospitalization outcomes in patients admitted with CP and PDAC.METHODS This retrospective cohort study used the 2016 and 2017 National Inpatient Sample databases.Patients included in the study had ICD-10 codes for CP and PDAC.The ethnic,socioeconomic,and racial backgrounds of patients with CP and PDAC were analyzed.RESULTS Hospital admissions for CP was 29 per 100000,and 2890(0.78%)had PDAC.Blacks[adjusted odds ratio(aOR)1.13],men(aOR 1.35),age 40 to 59(aOR 2.60),and being overweight(aOR 1.34)were significantly associated with CP(all with P<0.01).In patients with CP,Whites(aOR 1.23),higher income,older age(aOR 1.05),and being overweight(aOR 2.40)were all significantly associated with PDAC(all with P<0.01).Men(aOR 1.81)and Asians(aOR 15.19)had significantly increased mortality(P<0.05).Hispanics had significantly increased hospital length of stay(aOR 5.24)(P<0.05).CONCLUSION Based on this large,nationwide analysis,black men between 40-59 years old and overweight are at significantly increased risk for admission with CP.White men older than 40 years old and overweight with higher income were found to have significant associations with CP and PDAC.This discrepancy may reflect underlying differences in healthcare access and utilization among different socioeconomic and ethno-racial groups.展开更多
Pancreatic cancer(PC)is often associated with a poor prognosis.Long-standing diabetes mellitus is considered as an important risk factor for its development.This risk can be modified by the use of certain antidiabetic...Pancreatic cancer(PC)is often associated with a poor prognosis.Long-standing diabetes mellitus is considered as an important risk factor for its development.This risk can be modified by the use of certain antidiabetic medications.On the other hand,new-onset diabetes can signal towards an underlying PC in the elderly population.Recently,several attempts have been made to develop an effective clinical tool for PC screening using a combination of history of new-onset diabetes and several other clinical and biochemical markers.On the contrary,diabetes affects the survival after treatment for PC.We describe this intimate and complex two-way relationship of diabetes and PC in this review by exploring the underlying pathogenesis.展开更多
OBJECTIVE: To assess the diagnostic value of endoscopic pancreatic duct brushing in detecting mutation of the K-ras gene at codon 12 in cytologic specimens from patients with pancreatic cancer. METHODS: Thirty-five pa...OBJECTIVE: To assess the diagnostic value of endoscopic pancreatic duct brushing in detecting mutation of the K-ras gene at codon 12 in cytologic specimens from patients with pancreatic cancer. METHODS: Thirty-five patients treated at Changhai Hospital, Shanghai between 1999 and 2001 were enrolled. Their cells obtained by pancreatic duct brushing during endoscopic retrograde tholangiopancreatography (ERCP) were suspended with phosphate buffer solution (PBS). DNA of the cells was extracted and mutation of the K-ras gene at codon 12 detected by means of PCR-SSCP. RESULTS: The K-ras gene mutation rate of pancreatic cancer was 70%, which was higher than that of chronic pancreatitis (14%, P<0.05). K-ras gene mutation was not found in patients with pancreatic cystorcarcinoma and duodenum carcinoma. As to the location of pancreatic cancer, no significant difference was observed between the head, the body and tail. The sensitivity, specificity, accuracy of pancreatic duct brushing in detecting pancreatic cancer was 70%, 94%, and 83%, respectively. CONCLUSION: K-ras analysis of pancreatic brushing samples is helpful in the diagnosis of patients with early pancreatic cancer.展开更多
Activated pancreatic stellate cells(PSCs)have been widely accepted as a key precursor of excessive pancreatic fibrosis,which is a crucial hallmark of chronic pancreatitis(CP)and its formidable associated disease,pancr...Activated pancreatic stellate cells(PSCs)have been widely accepted as a key precursor of excessive pancreatic fibrosis,which is a crucial hallmark of chronic pancreatitis(CP)and its formidable associated disease,pancreatic cancer(PC).Hence,anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs.Most of the anti-fibrotic agents have been limited to phaseⅠ/Ⅱclinical trials involving vitamin analogs,which are abundant in medicinal plants and have proved to be promising for clinical application.The use of phytomedicines,as new anti-fibrotic agents,has been applied to a variety of complementary and alternative approaches.The aim of this review was to present a focused update on the selective new potential anti-fibrotic agents,including curcumin,resveratrol,rhein,emodin,green tea catechin derivatives,metformin,eruberin A,and ellagic acid,in combating PSC in CP and PC models.It aimed to describe the mechanism(s)of the phytochemicals used,either alone or in combination,and the associated molecular targets.Most of them were tested in PC models with similar mechanism of actions,and curcumin was tested intensively.Future research may explore the issues of bioavailability,drug design,and nano-formulation,in order to achieve successful clinical outcomes with promising activity and tolerability.展开更多
AIM: To study the patients with main pancreatic duct dilation on computed tomography (CT) and thereby to provide the predictive criteria to identify patients at high risk of significant diseases, such as pancreatic ca...AIM: To study the patients with main pancreatic duct dilation on computed tomography (CT) and thereby to provide the predictive criteria to identify patients at high risk of significant diseases, such as pancreatic cancer, and to avoid unnecessary work up for patients at low risk of such diseases. METHODS: Patients with dilation of the main pancreatic duct on CT at Emory University Hospital in 2002 were identified by computer search. Clinical course and ultimate diagnosis were obtained in all the identified patients by abstraction of their computer database records. RESULTS: Seventy-seven patients were identified in this study. Chronic pancreatitis and pancreatic cancer were the most common causes of the main pancreatic duct dilation on CT. Although the majority of patients with isolated dilation of the main pancreatic duct (single duct dilation) had chronic pancreatitis, one-third of patients with single duct dilation but without chronic pancreatitis had pancreatic malignancies, whereas most of patients with concomitant biliary duct dilation (double duct dilation) had pancreatic cancer. CONCLUSION: Patients with pancreatic double duct dilation need extensive work up and careful followup since a majority of these patients are ultimately diagnosed with pancreatic cancer. Patients with single duct dilation, especially such patients without any evidence of chronic pancreatitis, also need careful follow-up since the possibility of pancreatic malignancy, including adenocarcinoma and intraductal papillary mucinous tumors, is still high.展开更多
Although the association between alcohol and pancreatic diseases has been recognized for a long time,the impact of alcohol consumption on pancreatitis and pancreatic cancer(PC)remains poorly defined.Nowadays there is ...Although the association between alcohol and pancreatic diseases has been recognized for a long time,the impact of alcohol consumption on pancreatitis and pancreatic cancer(PC)remains poorly defined.Nowadays there is not consensus about the epidemiology and the beverage type,dose and duration of alcohol consumption causing these diseases.The objective of this study was to review the epidemiology described in the literature for pancreatic diseases as a consequence of alcoholic behavior trying to understand the association between dose,type and frequency of alcohol consumption and risk of pancreatitis and PC.The majority of the studies conclude that high alcohol intake was associated with a higher risk of pancreatitis(around 2.5%-3% between heavy drinkers and 1.3%between non drinkers).About 70%of pancreatitis are due to chronic heavy alcohol consumption.Although this incidence rate differs between countries,it is clear that the risk of developing pancreatitis increases with increasing doses of alcohol and the average of alcohol consumption vary since 80 to 150 g/d for 10-15 years.With regard to PC, the role of alcohol consumption remains less clear,and low to moderate alcohol consumption do not appear to be associated with PC risk,and only chronic heavy drinking increase the risk compared with lightly drinkers.In a population of 10%-15%of heavy drinkers, 2%-5%of all PC cases could be attributed to alcohol consumption.However,as only a minority(less than 10%for pancreatitis and 5%for PC)of heavily drinkers develops these pancreatic diseases,there are other predisposing factors besides alcohol involved.Genetic variability and environmental exposures such as smoking and diet modify the risk and should be considered for further investigations.展开更多
The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency ...The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency (PEI). Systematic searches of the literature were performed using the PubMed database. Articles were selected for inclusion if they reported findings from trials assessing the effects of PERT on quality of life, survival, malabsorption, growth parameters (such as height, body weight and body mass index), or gastrointestinal symptoms (such as abdominal pain, stool consistency and flatulence). PERT improved PEI-related malabsorption and weight maintenance in patients with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and post-surgical states. In patients with chronic pancreatitis, PERT improved PEI-related symptoms and quality of life measures. Several small retrospective studies have also suggested that PERT may have a positive impact on survival, but long-term studies assessing this effect were not identified. PERT is effective for treating malnutrition and supporting weight maintenance, and it is associated with improved quality of life and possibly with enhanced survival in patients with PEI. However, there is evidence that not all patients with PEI receive adequate PERT. Future work should aim to assess the long-term effects of PERT on the survival of patients with PEI.展开更多
Elastography is one of technologies assisting diagnosis ofsolid pancreatic lesions(SPL). This technology has been previously used for measuring the stiffness of various organs based on a principle of "harder the ...Elastography is one of technologies assisting diagnosis ofsolid pancreatic lesions(SPL). This technology has been previously used for measuring the stiffness of various organs based on a principle of "harder the lesions, higher chance for malignancy". Two elastography techniques; strain and shear wave elastography, are available. For endoscopic ultrasound(EUS), only the former is existing. To interpret results of EUS elastography for SPL, 3 methods are used:(1) pattern recognition;(2) strain ratio; and (3) strain histogram. Based on results of existing studies, these 3 techniques provide high sensitivity but low to moderate specificity and accuracy rate. This review will summarize all available information in order to update current situation of using elastography for an evaluation of SPLs to readers.展开更多
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.
基金Internal Grant Agency of the Ministry of Health, Czech Republic, No. 8027-3
文摘AIM: To establish an optimum combination of molecular markers resulting in best overall diagnostic sensitivity and specificity for evaluation of suspicious pancreatic mass. METHODS: Endoscopic ultrasound (EUS)-guided fine needle aspiration cytology (FNA) was performed on 101 consecutive patients (63 males, 38 females, 60 ± 12 years; 81 with subsequently diagnosed pancreatic cancer, 20 with chronic pancreatitis) with focal pancreatic mass. Samples were evaluated on-site by an experienced cytopathologist. DNA was extracted from Giemsa stained cells selected by laser microdissection and the presence of K-ras, p53 and p16 somatic mutations was tested by cycling-gradient capillary electrophoresis (CGCE) and single-strand conformation polymorphism (SSCP) techniques. In addition, allelic losses of tumor suppressor genes p16 (INK4, CDKN2A) and DPC4 (MADH4, SMAD4) were detected by monitoring the loss of heterozygosity (LOH) at 9p and 18q, respectively. RESULTS: Sensitivity and specificity of EUS-guided FNA were 75% and 85%, positive and negative predictive value reached 100%. The remaining 26% samples were assigned as inconclusive. Testing of molecular markers revealed sensitivity and specificity of 70% and 100% for K-ras mutations (P 〈 0.001), 24% and 90% for p53 mutations (NS), 13% and 100% for p16 mutations (NS), 85% and 64% for aUelic losses at 9p (P 〈 0.001) and 78% and 57% for allelic losses at 18q (P 〈 0.05). When tests for different molecular markers were combined, the best results were obtained with K-ras + LOH at 9p (92% and 64%, P 〈 0.001), K-ras + LOH at 18q (92% and 57%, P 〈 0.001), and K-ras + LOH 9q + LOH 18q (96% and 43%, P 〈 0.001). When the molecular markers were used as complements to FNA cytology to evaluate inconclusive samples only, the overall sensitivity of cancer detection was 100% in all patients enrolled in the study. CONCLUSION: EUS-guided FNA cytology combined with screening of K-ras mutations and allelic losses of tumor suppressors p16 and DPC4 represents a very sensitive approach in screening for pancreatic malignancy. Molecular markers may find its use particularly in cases where FNA cytology has been inconclusive.
基金Supported by Grants from the National Natural Science Foundation of China,No. 30870709the Program of Shanghai Subject Chief Scientist,No. 08XD14002(A)
文摘AIM:To investigate the markers of pancreatic diseases and provide basic data and experimental methods for the diagnosis of pancreatic diseases.METHODS:There were 15 patients in the present study,among whom 10 had pancreatic cancer and 5,chronic pancreatitis.In all patients,pancreatic cancer or chronic pancreatitis was located on the head of the p-a-ncrea-s.Pa-thology da-ta-of a-ll p-a-tients wa-s confirmed by biopsy and surgery.Among the 10 patients with pancreatic cancer,3 people had a medical history of longterm alcohol consumption.Of 5 patients with chronic pancreatitis,4 men suffered from alcoholic chronic pancreatitis.Pancreatic juice samples were obtained from patients by endoscopic retrograde cholangiopancreatography.Magnetic resonance spectroscopyn was performed on an 11.7-T scanner (Bruker DRX-500) using Call-Purcell-Meiboom-Gill pulse sequences.The parameters were as follows:spectral width,15 KHz;time domain,64 K;number of scans,512;and acquisition time,2.128 s.RESULTS:The main component of pancreatic juice included leucine,iso-leucine,valine,lactate,alanine,acetate,aspartate,lysine,glycine,threonine,tyrosine,histidine,tryptophan,and phenylalanine.On performing 1D 1H and 2D total correlation spectroscopy,we found a triplet peak at the chemical shift of 1.19 ppm,which only appeared in the spectra of pancreatic juice obtained from patients with alcoholic chronic pancreatitis.This triplet peak was considered the resonance of the methyl of ethoxy group,which may be associated with the metabolism of alcohol in the pancreas.CONCLUSION:The triplet peak,at the chemical shift of 1.19 ppm is likely to be the characteristic metabolite of alcoholic chronic pancreatitis.
基金Supported by a Grant-in-Aid from the Ministry of Education,Culture, Sports, ScienceTechnology of Japan, Research Fellowships of the Japan Society for the Promotion of Science for Young Scientistsa grant from the Japanese Foundation for Research and Promotion of Endoscopy
文摘AIM: To investigate c-met expression during early pancreatic carcinogenesis. METHODS: We used 46 bulk tissues and 36 microdissected samples, including normal pancreas, chronic pancreatitis, and pancreatic cancer, for quantitative realtime reverse transcription-polymerase chain reaction. RESULTS: In bulk tissue analyses, pancreatic cancer tissues expressed significantly higher levels of c-met than did chronic pancreatitis and normal pancreas tissues. c-met levels did not differ between chronic pancreatitis and normal pancreas tissues. In microdissection-based analyses, c-met was expressed at higher levels in microclissected pancreatic cancer cells and pancreatitisaffected epithelial cells than in normal ductal epithelial cells (both, P 〈 0.01). Interestingly, pancreatitis-affected epithelial cells expressed levels of c-met similar to those of pancreatic cancer cells. CONCLUSION: Overexpression of c-met occurs during the early stage of pancreatic carcinogenesis, and a single alteration of c-met expression is not sufficient for progression of chronic pancreatitis-affected epithelial cells to pancreatic cancer cells.
文摘Pancreatic ductal adenocarcinoma is an aggressive tumor with poor long-term outcomes.Chronic pancreatitis(CP)is considered a risk factor for the development of pancreatic cancer(PC).Persistent pancreatic inflammation and activation of pancreatic stellate cells play a crucial role in the pathogenesis of CPrelated PC by activating the oncogene pathway.While genetic mutations increase the possibility of recurrent and persistent pancreatic inflammation,they are not directly associated with the development of PC.Recent studies suggest that early surgical intervention for CP might have a protective role in the development of CP-related PC.Hence,the physician faces the clinical question of whether early surgical intervention should be recommended in patients with CP to prevent the development of PC.However,the varying relative risk of PC in different subsets of CP underlines the complex gene-environment interactions in the disease pathogenesis.Hence,it is essential to stratify the risk of PC in each individual patient.This review focuses on the complex relationship between CP and PC and the impact of surgical intervention on PC risk.The proposed risk stratification based on the genetic and environmental factors could guide future research and select patients for prophylactic surgery.
文摘AIM: To evaluate the contrast-enhanced endosonography as a method of differentiating inflammation from pancreatic carcinoma based on perfusion characteristics of microvessels. METHODS: In 86 patients with suspected chronic pancreatitis (age: 62± 12 years; sex: f/m 38/48), pancreatic lesions were examined by conventional endo- scopic B-mode, power Doppler ultrasound and contrastenhanced power mode (Hitachi EUB 525, SonoVue, 2.4 mL, Bracco) using the following criteria for malignant lesions: no detectable vascularisation using conventional power Doppler scanning, irregular appearance of arterial vessels over a short distance using SonoVue contrastenhanced technique and no detectable venous vessels inside the lesion. A malignant lesion was assumed if all criteria were detectable [gold standard endoscopic ultrasound (EUS)-guided fine needle aspiration cytology, operation]. The criteria of chronic pancreatitis without neoplasia were defined as no detectable vascularisation before injection of SonoVue, regular appearance of vessels over a distance of at least 20 mm after injection of SonoVue and detection of arterial and venous vessels. RESULTS: The sensitivity and specifidty of conventional EUS were 73.2% and 83.3% respectively for pancreatic cancer. The sensitivity of contrast-enhanced EUS increased to 91.1% in 51 of 56 patients with malignant pancreatic lesion and the specificity increased to 93.3% in 28 of 30 patients with chronic inflammatory pancreatic disease.CONCLUSION: Contrast-enhanced endoscopic ultrasound improves the differentiation between chronic pancreatitis and pancreatic carcinoma.
文摘Pancreatic cancer is a challenging disease for patients,doctors and researchers who for decades have searched for a cure for this deadly malignancy.Although existing mouse models of pancreatic cancer have shed light on the mecha-nistic basis of the neoplastic conversion of the pancreas,their impact in terms of offering new diagnostics and therapeu-tic modalities remains limited.Chronic pancreatitis is an inflammatory disease of the pancreas that is associated with a gradual damage of the organ and an increased risk of developing neoplastic lesions.In this review,we propose that detailed studies of chronic inflammatory processes in the pancreas will provide insights into the evolution of pancreatic cancer.This information may prove useful in the design of effective therapeutic strategies to battle the disease.
文摘AIM To assess the occurrence of autoimmune pancreatitis(AIP) in pancreatic resections performed for focal pancreatic enlargement.METHODS We performed a retrospective analysis of medical records of all patients who underwent pancreatic resection for a focal pancreatic enlargement at our tertiary center from January 2000 to July 2013. The indication for surgery was suspicion of a tumor based on clinical presentation, imaging findings and laboratory evaluations. The diagnosis of AIP was based on histology findings. An experienced pathologist specialized in pancreatic disease reviewed all the cases and confirmed the diagnosis in pancreatic resection specimens suggestive of AIP. The histological diagnosis of AIP was set according to the international consensus diagnostic criteria.RESULTS Two hundred ninety-five pancreatic resections were performed in 201 men and 94 women. AIP was diagnosed in 15 patients(5.1%, 12 men and 3 women) based on histology of the resected specimen. Six of them had AIP type 1, nine were diagnosed with AIP type 2. Pancreatic adenocarcinoma(PC) was also present in six patients with AIP(40%), all six were men. Patients with AIP + PC were significantly older(60.5 vs 49 years of age, P = 0.045), more likely to have been recently diagnosed with diabetes(67% vs 11%, P = 0.09), and had experienced greater weight loss(15.5 kg vs 8.5 kg, P = 0.03) than AIP patients without PC. AIP was not diagnosed in any patients prior to surgery; however, the diagnostic algorithm was not fully completed in every case. CONCLUSION The possible co-occurrence of PC and AIP suggests that preoperative diagnosis of AIP does not rule out simultaneous presence of PC.
文摘Ordinary chronic pancreatitis is a well-known risk factor for pancreatic cancer,whereas such an association with autoimmune pancreatitis(AIP)is widely debated.Due to the rarity of the latter disorder,there are few specific clinical and epidemiological studies investigating the relation between AIP and pancreatic cancer,which do not seem to support it.However,these studies are affected by several limitations and,therefore,a link between AIP(and,specifically,type 1 AIP)and pancreatic cancer cannot be ruled out definitively on this basis.Moreover,several immunopathological aspects of type 1 AIP and,in general,immunoglobulin G4-related disease can create an immunological context that may impair the tumoral immunosurveillance and promote the pancreatic carcinogenesis and its progression.In detail,Th2 immunological dominance,type 2 macrophage polarization and basophil infiltration observed in type 1 AIP,may play a permissive role in creating a favorable immunological environment for pancreatic carcinogenesis,in addition to the immunosuppressive therapies that can be used in these patients.
文摘BACKGROUND Epidemiological studies of chronic pancreatitis(CP)and its association with pancreatic ductal adenocarcinoma(PDAC)are limited.Understanding demographic and ethno-racial factors may help identify patients at the highest risk for CP and PDAC.AIM To evaluate the ethno-racial risk factors for CP and its association with PDAC.The secondary aim was to evaluate hospitalization outcomes in patients admitted with CP and PDAC.METHODS This retrospective cohort study used the 2016 and 2017 National Inpatient Sample databases.Patients included in the study had ICD-10 codes for CP and PDAC.The ethnic,socioeconomic,and racial backgrounds of patients with CP and PDAC were analyzed.RESULTS Hospital admissions for CP was 29 per 100000,and 2890(0.78%)had PDAC.Blacks[adjusted odds ratio(aOR)1.13],men(aOR 1.35),age 40 to 59(aOR 2.60),and being overweight(aOR 1.34)were significantly associated with CP(all with P<0.01).In patients with CP,Whites(aOR 1.23),higher income,older age(aOR 1.05),and being overweight(aOR 2.40)were all significantly associated with PDAC(all with P<0.01).Men(aOR 1.81)and Asians(aOR 15.19)had significantly increased mortality(P<0.05).Hispanics had significantly increased hospital length of stay(aOR 5.24)(P<0.05).CONCLUSION Based on this large,nationwide analysis,black men between 40-59 years old and overweight are at significantly increased risk for admission with CP.White men older than 40 years old and overweight with higher income were found to have significant associations with CP and PDAC.This discrepancy may reflect underlying differences in healthcare access and utilization among different socioeconomic and ethno-racial groups.
文摘Pancreatic cancer(PC)is often associated with a poor prognosis.Long-standing diabetes mellitus is considered as an important risk factor for its development.This risk can be modified by the use of certain antidiabetic medications.On the other hand,new-onset diabetes can signal towards an underlying PC in the elderly population.Recently,several attempts have been made to develop an effective clinical tool for PC screening using a combination of history of new-onset diabetes and several other clinical and biochemical markers.On the contrary,diabetes affects the survival after treatment for PC.We describe this intimate and complex two-way relationship of diabetes and PC in this review by exploring the underlying pathogenesis.
文摘OBJECTIVE: To assess the diagnostic value of endoscopic pancreatic duct brushing in detecting mutation of the K-ras gene at codon 12 in cytologic specimens from patients with pancreatic cancer. METHODS: Thirty-five patients treated at Changhai Hospital, Shanghai between 1999 and 2001 were enrolled. Their cells obtained by pancreatic duct brushing during endoscopic retrograde tholangiopancreatography (ERCP) were suspended with phosphate buffer solution (PBS). DNA of the cells was extracted and mutation of the K-ras gene at codon 12 detected by means of PCR-SSCP. RESULTS: The K-ras gene mutation rate of pancreatic cancer was 70%, which was higher than that of chronic pancreatitis (14%, P<0.05). K-ras gene mutation was not found in patients with pancreatic cystorcarcinoma and duodenum carcinoma. As to the location of pancreatic cancer, no significant difference was observed between the head, the body and tail. The sensitivity, specificity, accuracy of pancreatic duct brushing in detecting pancreatic cancer was 70%, 94%, and 83%, respectively. CONCLUSION: K-ras analysis of pancreatic brushing samples is helpful in the diagnosis of patients with early pancreatic cancer.
基金supported by two research university grants,from University of Malaya(grant No.GPF002C-2018,Malaysia)MAHSA University(grant No.RP165-05/19,Malaysia).
文摘Activated pancreatic stellate cells(PSCs)have been widely accepted as a key precursor of excessive pancreatic fibrosis,which is a crucial hallmark of chronic pancreatitis(CP)and its formidable associated disease,pancreatic cancer(PC).Hence,anti-fibrotic therapy has been identified as a novel therapeutic strategy for treating CP and PC by targeting PSCs.Most of the anti-fibrotic agents have been limited to phaseⅠ/Ⅱclinical trials involving vitamin analogs,which are abundant in medicinal plants and have proved to be promising for clinical application.The use of phytomedicines,as new anti-fibrotic agents,has been applied to a variety of complementary and alternative approaches.The aim of this review was to present a focused update on the selective new potential anti-fibrotic agents,including curcumin,resveratrol,rhein,emodin,green tea catechin derivatives,metformin,eruberin A,and ellagic acid,in combating PSC in CP and PC models.It aimed to describe the mechanism(s)of the phytochemicals used,either alone or in combination,and the associated molecular targets.Most of them were tested in PC models with similar mechanism of actions,and curcumin was tested intensively.Future research may explore the issues of bioavailability,drug design,and nano-formulation,in order to achieve successful clinical outcomes with promising activity and tolerability.
文摘AIM: To study the patients with main pancreatic duct dilation on computed tomography (CT) and thereby to provide the predictive criteria to identify patients at high risk of significant diseases, such as pancreatic cancer, and to avoid unnecessary work up for patients at low risk of such diseases. METHODS: Patients with dilation of the main pancreatic duct on CT at Emory University Hospital in 2002 were identified by computer search. Clinical course and ultimate diagnosis were obtained in all the identified patients by abstraction of their computer database records. RESULTS: Seventy-seven patients were identified in this study. Chronic pancreatitis and pancreatic cancer were the most common causes of the main pancreatic duct dilation on CT. Although the majority of patients with isolated dilation of the main pancreatic duct (single duct dilation) had chronic pancreatitis, one-third of patients with single duct dilation but without chronic pancreatitis had pancreatic malignancies, whereas most of patients with concomitant biliary duct dilation (double duct dilation) had pancreatic cancer. CONCLUSION: Patients with pancreatic double duct dilation need extensive work up and careful followup since a majority of these patients are ultimately diagnosed with pancreatic cancer. Patients with single duct dilation, especially such patients without any evidence of chronic pancreatitis, also need careful follow-up since the possibility of pancreatic malignancy, including adenocarcinoma and intraductal papillary mucinous tumors, is still high.
基金Supported by CIBERehd Funded by the Health Institute of Carlos Ⅲ
文摘Although the association between alcohol and pancreatic diseases has been recognized for a long time,the impact of alcohol consumption on pancreatitis and pancreatic cancer(PC)remains poorly defined.Nowadays there is not consensus about the epidemiology and the beverage type,dose and duration of alcohol consumption causing these diseases.The objective of this study was to review the epidemiology described in the literature for pancreatic diseases as a consequence of alcoholic behavior trying to understand the association between dose,type and frequency of alcohol consumption and risk of pancreatitis and PC.The majority of the studies conclude that high alcohol intake was associated with a higher risk of pancreatitis(around 2.5%-3% between heavy drinkers and 1.3%between non drinkers).About 70%of pancreatitis are due to chronic heavy alcohol consumption.Although this incidence rate differs between countries,it is clear that the risk of developing pancreatitis increases with increasing doses of alcohol and the average of alcohol consumption vary since 80 to 150 g/d for 10-15 years.With regard to PC, the role of alcohol consumption remains less clear,and low to moderate alcohol consumption do not appear to be associated with PC risk,and only chronic heavy drinking increase the risk compared with lightly drinkers.In a population of 10%-15%of heavy drinkers, 2%-5%of all PC cases could be attributed to alcohol consumption.However,as only a minority(less than 10%for pancreatitis and 5%for PC)of heavily drinkers develops these pancreatic diseases,there are other predisposing factors besides alcohol involved.Genetic variability and environmental exposures such as smoking and diet modify the risk and should be considered for further investigations.
文摘The objective of this study was to analyze the current evidence for the use of pancreatic enzyme replacement therapy (PERT) in affecting survival and quality of life in patients with pancreatic exocrine insufficiency (PEI). Systematic searches of the literature were performed using the PubMed database. Articles were selected for inclusion if they reported findings from trials assessing the effects of PERT on quality of life, survival, malabsorption, growth parameters (such as height, body weight and body mass index), or gastrointestinal symptoms (such as abdominal pain, stool consistency and flatulence). PERT improved PEI-related malabsorption and weight maintenance in patients with cystic fibrosis, chronic pancreatitis, pancreatic cancer, and post-surgical states. In patients with chronic pancreatitis, PERT improved PEI-related symptoms and quality of life measures. Several small retrospective studies have also suggested that PERT may have a positive impact on survival, but long-term studies assessing this effect were not identified. PERT is effective for treating malnutrition and supporting weight maintenance, and it is associated with improved quality of life and possibly with enhanced survival in patients with PEI. However, there is evidence that not all patients with PEI receive adequate PERT. Future work should aim to assess the long-term effects of PERT on the survival of patients with PEI.
文摘Elastography is one of technologies assisting diagnosis ofsolid pancreatic lesions(SPL). This technology has been previously used for measuring the stiffness of various organs based on a principle of "harder the lesions, higher chance for malignancy". Two elastography techniques; strain and shear wave elastography, are available. For endoscopic ultrasound(EUS), only the former is existing. To interpret results of EUS elastography for SPL, 3 methods are used:(1) pattern recognition;(2) strain ratio; and (3) strain histogram. Based on results of existing studies, these 3 techniques provide high sensitivity but low to moderate specificity and accuracy rate. This review will summarize all available information in order to update current situation of using elastography for an evaluation of SPLs to readers.