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Neoplasia (New York, N.Y.) Nov 2021Current standard of care imaging, cytology, or cystic fluid analysis cannot reliably differentiate malignant from benign pancreatic cystic neoplasms. This study sought...
OBJECTIVES
Current standard of care imaging, cytology, or cystic fluid analysis cannot reliably differentiate malignant from benign pancreatic cystic neoplasms. This study sought to determine if the metabolic profile of cystic fluid could distinguish benign and malignant lesions, as well as mucinous and non-mucinous lesions.
METHODS
Metabolic profiling by untargeted mass spectrometry and quantitative nuclear magnetic resonance was performed in 24 pancreatic cyst fluid from surgically resected samples with pathological diagnoses and clinicopathological correlation.
RESULTS
(Iso)-butyrylcarnitine distinguished malignant from benign pancreatic cysts, with a diagnostic accuracy of 89%. (Iso)-butyrylcarnitine was 28-fold more abundant in malignant cyst fluid compared with benign cyst fluid (P=.048). Furthermore, 5-oxoproline (P=.01) differentiated mucinous from non-mucinous cysts with a diagnostic accuracy of 90%, better than glucose (82% accuracy), a previously described metabolite that distinguishes mucinous from non-mucinous cysts. Combined analysis of glucose and 5-oxoproline did not improve the diagnostic accuracy. In comparison, standard of care cyst fluid carcinoembryonic antigen (CEA) and cytology had a diagnostic accuracy of 40% and 60% respectively for mucinous cysts. (Iso)-butyrylcarnitine and 5-oxoproline correlated with cyst fluid CEA levels (P<.0001 and P<.05 respectively). For diagnosing malignant pancreatic cysts, the diagnostic accuracies of cyst size > 3 cm, ≥ 1 high-risk features, cyst fluid CEA, and cytology are 38%, 75%, 80%, and 75%, respectively.
CONCLUSIONS
(Iso)-butyrylcarnitine has potential clinical application for accurately distinguishing malignant from benign pancreatic cysts, and 5-oxoproline for distinguishing mucinous from non-mucinous cysts.
Topics: Adenocarcinoma, Mucinous; Adult; Aged; Biomarkers, Tumor; Cyst Fluid; Diagnosis, Differential; Female; Follow-Up Studies; Humans; Male; Metabolome; Middle Aged; Pancreatic Cyst; Pancreatic Neoplasms; Prognosis
PubMed: 34583246
DOI: 10.1016/j.neo.2021.09.004 -
Annals of Surgery Nov 1978The experience with 131 patients with 157 pseudocysts is reported. One hundred and twenty patients with 146 pseudocysts underwent 165 operations. There were ten...
The experience with 131 patients with 157 pseudocysts is reported. One hundred and twenty patients with 146 pseudocysts underwent 165 operations. There were ten operative deaths (8.3%) three of which were not attributable to the pseudocyst or its operative management. Sixteen patients died six months to 14 years after operation. Deaths in six of the 16 patients were in part attributable to pancreatitis or complications of pseudocyst management. The operative mortality was highest in patients undergoing incision and drainage and cystoduodenostomy. Other factors influencing mortality unfavorably included postoperative gastrointestinal hemorrhage from a pseudocyst; rupture or fistulization of the cyst into the gastrointestinal tract if associated with hemorrhage, and evidence of common duct obstruction, or the location of cysts in the head or uncinate process of the pancreas. Visceral angiography should be performed on all patients with pseudocysts. The risk of massive gastrointestinal or intra-abdominal hemorrhage is highest in the 10% of patients having pseudoaneurysms associated with their pseudocysts. Incision and drainage of pseudocysts is associated with a high rate of recurrence of the cyst and continued pain. Incision and drainage should only be used if the cyst is infected, or the cyst wall is not mature enough to hold sutures. Cystogastrostomy and cystojejunostomy are the procedures of choice for mature cysts. The presence of a pseudoaneurysm visualized on preoperative visceral angiography is an indication for an excisional operation as are the presence of multiple cysts, compression of the common duct or duodenum by the cyst, evidence of left sided portal hypertension, recurrent cysts or evidence of chronic pancreatitis.
Topics: Adolescent; Adult; Aged; Biliary Tract Diseases; Child; Chronic Disease; Common Bile Duct; Female; Gastrointestinal Hemorrhage; Humans; Male; Methods; Middle Aged; Pancreas; Pancreatic Cyst; Pancreatitis; Postoperative Complications; Rupture, Spontaneous; Time Factors
PubMed: 309751
DOI: 10.1097/00000658-197811000-00012 -
Clinical Cancer Research : An Official... Sep 2012The diagnosis of pancreatic cystic lesions has increased dramatically. Most are benign, whereas some, such as intraductal papillary mucinous neoplasms (IPMN), represent...
PURPOSE
The diagnosis of pancreatic cystic lesions has increased dramatically. Most are benign, whereas some, such as intraductal papillary mucinous neoplasms (IPMN), represent precursors of pancreatic adenocarcinoma. Therapeutic stratification of IPMNs is challenging without precise information on dysplasia grade and presence of invasion. We assessed the diagnostic benefit of using miRNAs as biomarkers in pancreatic cyst fluid, focusing on IPMNs because of their frequency and malignant potential.
EXPERIMENTAL DESIGN
RNA was extracted from 55 microdissected formalin-fixed, paraffin-embedded (FFPE) IPMN specimens, and 65 cyst fluid specimens aspirated following surgical resection. Expression of 750 miRNAs was evaluated with TaqMan miRNA Arrays using 22 FFPE and 15 cyst fluid specimens. Differential expression of selected miRNA candidates was validated in 33 FFPE and 50 cyst fluid specimens using TaqMan miRNA Assays.
RESULTS
We identified 26 and 37 candidate miRNAs that distinguish low-grade from high-grade IPMNs using FFPE and cyst fluid specimens, respectively. A subset of 18 miRNAs, selected from FFPE and cyst fluid data, separated high-grade IPMNs from low-grade IPMNs, serous cystadenomas (SCA) and uncommon cysts, such as solid pseudopapillary neoplasms (SPN) and cystic pancreatic neuroendocrine tumors (PanNET). A logistic regression model using nine miRNAs allowed prediction of cyst pathology implying resection (high-grade IPMNs, PanNETs, and SPNs) versus conservative management (low-grade IPMNs, SCAs), with a sensitivity of 89%, a specificity of 100%, and area under the curve of 1.
CONCLUSIONS
We found candidate miRNAs that helped identify patients with high-grade IPMN and exclude nonmucinous cysts. These classifiers will require validation in a prospective setting to ultimately confirm their clinical usefulness.
Topics: Adenocarcinoma; Biomarkers, Tumor; Cyst Fluid; Cystadenoma, Serous; Diagnosis, Differential; Gene Expression Regulation, Neoplastic; Humans; MicroRNAs; Neoplasm Grading; Pancreatic Cyst; Pancreatic Neoplasms; Prospective Studies
PubMed: 22723372
DOI: 10.1158/1078-0432.CCR-12-0035 -
Gastroenterology Nov 2019Obesity is a risk factor for pancreatic cancer. In mice, a high-fat diet (HFD) and expression of oncogenic KRAS lead to development of invasive pancreatic ductal...
BACKGROUND & AIMS
Obesity is a risk factor for pancreatic cancer. In mice, a high-fat diet (HFD) and expression of oncogenic KRAS lead to development of invasive pancreatic ductal adenocarcinoma (PDAC) by unknown mechanisms. We investigated how oncogenic KRAS regulates the expression of fibroblast growth factor 21, FGF21, a metabolic regulator that prevents obesity, and the effects of recombinant human FGF21 (rhFGF21) on pancreatic tumorigenesis.
METHODS
We performed immunohistochemical analyses of FGF21 levels in human pancreatic tissue arrays, comprising 59 PDAC specimens and 45 nontumor tissues. We also studied mice with tamoxifen-inducible expression of oncogenic KRAS in acinar cells (Kras mice) and fElas mice (controls). Kras mice were placed on an HFD or regular chow diet (control) and given injections of rhFGF21 or vehicle; pancreata were collected and analyzed by histology, immunoblots, quantitative polymerase chain reaction, and immunohistochemistry. We measured markers of inflammation in the pancreas, liver, and adipose tissue. Activity of RAS was measured based on the amount of bound guanosine triphosphate.
RESULTS
Pancreatic tissues of mice expressed high levels of FGF21 compared with liver tissues. FGF21 and its receptor proteins were expressed by acinar cells. Acinar cells that expressed Kras had significantly lower expression of Fgf21 messenger RNA compared with acinar cells from control mice, partly due to down-regulation of PPARG expression-a transcription factor that activates Fgf21 transcription. Pancreata from Kras mice on a control diet and given injections of rhFGF21 had reduced pancreatic inflammation, infiltration by immune cells, and acinar-to-ductal metaplasia compared with mice given injections of vehicle. HFD-fed Kras mice given injections of vehicle accumulated abdominal fat, developed extensive inflammation, pancreatic cysts, and high-grade pancreatic intraepithelial neoplasias (PanINs); half the mice developed PDAC with liver metastases. HFD-fed Kras mice given injections of rhFGF21 had reduced accumulation of abdominal fat and pancreatic triglycerides, fewer pancreatic cysts, reduced systemic and pancreatic markers of inflammation, fewer PanINs, and longer survival-only approximately 12% of the mice developed PDACs, and none of the mice had metastases. Pancreata from HFD-fed Kras mice given injections of rhFGF21 had lower levels of active RAS than from mice given vehicle.
CONCLUSIONS
Normal acinar cells from mice and humans express high levels of FGF21. In mice, acinar expression of oncogenic KRAS significantly reduces FGF21 expression. When these mice are placed on an HFD, they develop extensive inflammation, pancreatic cysts, PanINs, and PDACs, which are reduced by injection of FGF21. FGF21 also reduces the guanosine triphosphate binding capacity of RAS. FGF21 might be used in the prevention or treatment of pancreatic cancer.
Topics: Acinar Cells; Animals; Carcinoma, Pancreatic Ductal; Cell Transformation, Neoplastic; Diet, High-Fat; Down-Regulation; Fibroblast Growth Factors; Gene Expression Regulation, Neoplastic; Humans; Klotho Proteins; Membrane Proteins; Mice, Transgenic; Mutation; PPAR gamma; Pancreatic Cyst; Pancreatic Intraductal Neoplasms; Pancreatic Neoplasms; Pancreatitis; Proto-Oncogene Proteins p21(ras); Receptor, Fibroblast Growth Factor, Type 1; Signal Transduction; Transcription Factors; Tumor Suppressor Protein p53
PubMed: 31352001
DOI: 10.1053/j.gastro.2019.07.030 -
HPB : the Official Journal of the... Jun 2015To assess the accuracy of pre-operative staging in patients with peripheral pancreatic cystic neoplasms (pPCNs). (Comparative Study)
Comparative Study
OBJECTIVE
To assess the accuracy of pre-operative staging in patients with peripheral pancreatic cystic neoplasms (pPCNs).
METHODS
From 2005 to 2011, 148 patients underwent a pancreatectomy for pPCNs. The pre-operative examination methods of computed tomography (CT), magnetic resonance imaging (MRI), endoscopic ultrasonography (EUS) were compared for their ability to predict the suggested diagnosis accurately, and the definitive diagnosis was affirmed by pathological examination.
RESULTS
A mural nodule was detected in 34 patients (23%): only 1 patient (3%) had an invasive pPCN at the final histological examination. A biopsy was performed in 79 patients (53%) during EUS: in 55 patients (70%), the biopsy could not conclude a diagnosis; the biopsy provided the correct and wrong diagnosis in 19 patients (24%) and 5 patients (6%), respectively. A correct diagnosis was affirmed by CT, EUS and pancreatic MRI in 60 (41%), 103 (74%) and 80 (86%) patients (when comparing EUS and MRI; P = 0.03), respectively. The positive predictive values (PPVs) of CT, EUS and MRI were 70%, 75% and 87%, respectively.
CONCLUSIONS
Pancreatic MRI appears to be the most appropriate examination to diagnose pPCNs accurately. EUS alone had a poor PPV. Mural nodules in a PCN should not be considered an indisputable sign of pPCN invasiveness.
Topics: Adult; Aged; Biopsy; Endosonography; Female; France; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasm Staging; Neoplasms, Cystic, Mucinous, and Serous; Pancreatectomy; Pancreatic Cyst; Pancreatic Neoplasms; Predictive Value of Tests; Reproducibility of Results; Tomography, X-Ray Computed
PubMed: 25691074
DOI: 10.1111/hpb.12388 -
Journal of Gastrointestinal and Liver... Dec 2019Pancreatic cystic lesions are very prevalent, especially in elderly patients and are increasingly being diagnosed because of the massive use of cross sectional imaging.... (Review)
Review
Pancreatic cystic lesions are very prevalent, especially in elderly patients and are increasingly being diagnosed because of the massive use of cross sectional imaging. Our knowledge about the natural history of these lesions is limited, especially in the case of intraductal papillary mucinous neoplasms. This fact explains why scientific societies guidelines statements are based on evidence graded as very low quality and helps the understanding of some of the different guidelines recommendations. Several guidelines have been recently revised to incorporate the new evidence published in the literature with the aim to help clinicians make the best decisions. American Gastroenterological Association guidelines, a revision of the International Consensus Guidelines, the American College of Gastroenterology and the European Study Group guidelines are the most recent. Herein we review the current guidelines on pancreatic cysts and focus our discussion on controversies and updates about the best imaging modalities, the indications for endoscopic ultrasound guided fine needle aspiration, cyst fluid analysis, indications for resection and surveillance strategies.
Topics: Biomarkers; Cyst Fluid; Diagnosis, Differential; Endoscopic Ultrasound-Guided Fine Needle Aspiration; Humans; Pancreatic Cyst; Pancreatic Neoplasms; Population Surveillance; Practice Guidelines as Topic
PubMed: 31826053
DOI: 10.15403/jgld-341 -
Journal of Zhejiang University.... Mar 2013Pancreatic cystic neoplasms (PCNs) are a diverse group of neoplasms in the pancreas, and are more increasingly encountered with widespread abdominal screening and... (Review)
Review
Pancreatic cystic neoplasms (PCNs) are a diverse group of neoplasms in the pancreas, and are more increasingly encountered with widespread abdominal screening and improved imaging techniques. The most common types of PCNs are serous cystic neoplasms (SCNs), mucinous cystic neoplasms (MCNs), and intraductal papillary mucinous neoplasms (IPMNs). Clinicians frequently feel bewildered in the differential diagnosis and subsequent management among the various types of lesions in the pancreas, which may lead to overtreatment or delayed treatment. The current review provides recent developments in the understanding of the three most common types of PCNs, the latest modalities used in preoperative diagnosis and differential diagnosis, as well as the most up to date management. Suggestions for diagnosis and differential diagnosis of SCNs, MCNs, and IPMNs are also provided for young surgeons. Better understanding of these neoplasms is essential for clinicians to make accurate diagnosis and to provide the best management for patients.
Topics: Disease Management; Humans; Pancreatectomy; Pancreatic Cyst; Pancreatic Neoplasms; Preoperative Care
PubMed: 23463761
DOI: 10.1631/jzus.B1200283 -
Annals of Surgery Dec 1984Cystoduodenostomy for internal drainage of pancreatic pseudocysts has been both condemned and condoned. The current study reports the largest personal experience with a...
Cystoduodenostomy for internal drainage of pancreatic pseudocysts has been both condemned and condoned. The current study reports the largest personal experience with a single method of cystoduodenostomy. Transduodenal cystoduodenostomy was performed in 14 cases followed an average of 39 months without mortality, fistula formation, abscess, or hemorrhage. Recurrent pseudocysts developed in two patients, neither in the pancreatic head. In a 15-year combined review of surgical procedures for pancreatic pseudocyst, transduodenal cystoduodenostomy evidenced mortality rates similar to other forms of internal drainage. In direct contrast, laterolateral cystoduodenostomy by suture anastomosis resulted in a 70% mortality rate and should rarely, if ever, be performed.
Topics: Adult; Drainage; Duodenum; Female; Humans; Male; Pancreatic Cyst; Pancreatic Pseudocyst; Recurrence
PubMed: 6508397
DOI: 10.1097/00000658-198412000-00004 -
Saudi Journal of Gastroenterology :... 2022The purpose of this study is to assess patients' compliance to recommendations after evaluation of pancreatic cystic neoplasm (PCN) with EUS and investigate how the...
BACKGROUND
The purpose of this study is to assess patients' compliance to recommendations after evaluation of pancreatic cystic neoplasm (PCN) with EUS and investigate how the presence of "worrisome" characteristics including cyst's size, main pancreatic duct dilation and presence of mural nodules might affect the adherence rates of management recommendations.
METHODS
We performed a retrospective cohort study of patients at a private tertiary hospital who were referred for evaluation with EUS over a 5-year period (2015-2019), after the diagnosis of pancreatic cystic neoplasm during radiological imaging.
RESULTS
We included 111 patients (mean age 64.1 years, SD = 13.9) with PCN. After the EUS examination, 16 patients were referred for surgical resection, 4 patients needed no further follow up and 91 patients were recommended to follow imaging surveillance. In total, 70 (63.1%) subjects adhered to surveillance recommendations. In the group of subjects who adhered to surveillance, cyst size ≥3cm was found in 27 (38.6%) patients, main pancreatic duct diameter ≥5mm in 12 (17.1%) subjects and only 3 (4.3%) pancreatic cysts demonstrated mural nodules. However, none of the aforementioned cystic "worrisome features" was significantly correlated with increased adherence to follow up (p = 0.709, P = 0.642 and P = 0.630, respectively).
CONCLUSIONS
Although the majority of patients with PCN adhered to given recommendations after EUS examination, the number of noncompliant subjects was noticeable. The presence of cystic "worrisome" features did not correlate with an increased compliance rate to suggested management plan. Further prospective studies are needed to elucidate the factors that may enhance patients' adherence.
Topics: Humans; Middle Aged; Endosonography; Pancreatic Cyst; Pancreatic Neoplasms; Retrospective Studies
PubMed: 35142657
DOI: 10.4103/sjg.sjg_505_21 -
Digestive Diseases and Sciences Mar 2022Pancreatic cancer incidence and mortality among patients with pancreas cysts are unclear. The aims of this study are to evaluate incidence of pancreatic cancer and...
BACKGROUND AND AIMS
Pancreatic cancer incidence and mortality among patients with pancreas cysts are unclear. The aims of this study are to evaluate incidence of pancreatic cancer and cause-specific mortality among patients with pancreatic cysts using a large national cohort over a long follow-up period.
METHODS
We conducted a retrospective cohort study of US Veterans diagnosed with a pancreatic cyst 1999-2013, based on International Classification of Diseases, 9th edition (ICD9) coding within national Department of Veterans Affairs (VA) data. Pancreatic cancer incidence was ascertained using VA cancer registry data, ICD-9 codes, and the National Death Index, a national centralized database of death records, including cause-specific mortality.
RESULTS
Among 7211 Veterans with pancreatic cysts contributing 31,501 person-years of follow-up (median follow-up 4.4 years), 79 (1.1%) developed pancreatic cancer. A total of 1982 patients (27.5%) died during the study follow-up period. Sixty-three patients (3.2% of deaths; 0.9% of pancreas cyst cohort) died from pancreatic cancer, but the leading causes of death in the cohort were non-pancreatic cancer (n = 498, 25% of deaths) and cardiovascular disease (n = 398, 20% of deaths).
CONCLUSIONS
Pancreas cancer incidence and pancreatic cancer-associated mortality are very low in a large national cohort of VA pancreatic cyst patients with long-term follow-up. Most deaths were from non-pancreas cancers and cardiovascular causes, and only a minority (3.2%) were attributable to pancreas cancer. Given death from pancreas cancer is rare, future research should focus on identifying criteria for selecting individuals at high risk for death from pancreatic cancer for pancreatic cyst surveillance.
Topics: Cohort Studies; Humans; Incidence; Pancreas; Pancreatic Cyst; Pancreatic Neoplasms; Retrospective Studies
PubMed: 33783688
DOI: 10.1007/s10620-021-06923-5