In animal models, inflammation caused by experimental acute pancreatitis (AP) promotes pancreatic carcinogenesis that is preventable by suppressing inflammation. Recent studies noted higher long-term ...risk of pancreatic ductal adenocarcinoma (PDAC) after AP. In this study, we evaluated whether the long-term PDAC risk after AP was influenced by the etiology of AP, number of recurrences, and if it was because of progression to chronic pancreatitis (CP).
This retrospective study used nationwide Veterans Administration database spanning 1999-2015. A 2-year washout period was applied to exclude patients with preexisting AP and PDAC. PDAC risk was estimated in patients with AP without (AP group) and with underlying CP (APCP group) and those with CP alone (CP group) and compared with PDAC risk in patients in a control group, respectively, using cause-specific hazards model.
The final cohort comprised 7,147,859 subjects (AP-35,550 and PDAC-16,475). The cumulative PDAC risk 3-10 years after AP was higher than in controls (0.61% vs 0.18%), adjusted hazard ratio (1.7 1.4-2.0, P < 0.001). Adjusted hazard ratio was 1.5 in AP group, 2.4 in the CP group, and 3.3 in APCP group. PDAC risk increased with the number of AP episodes. Elevated PDAC risk after AP was not influenced by the etiology of AP (gallstones, smoking, or alcohol).
There is a higher PDAC risk 3-10 years after AP irrespective of the etiology of AP, increases with the number of episodes of AP and is additive to higher PDAC risk because of CP.
Background and Aims Certain pancreatic cysts (mucinous cystic neoplasm and side branch intraductal papillary mucinous neoplasm IPMN) have malignant potential and require surveillance. However, ...whether patients with pancreatic cysts have a higher long-term risk of pancreatic cancer (PaCa) has still not been established. Methods This was a retrospective study of Veterans Administration patients. Patients noted to have pancreatic cysts on CT/magnetic resonance imaging (n = 1050) were identified using International Classification of Diseases, Ninth Revision, Clinical Modification codes. Patients aged <15 years (n = 425), patients with <1 year of follow-up (n = 13,259), and patients diagnosed to have PaCa within 1 year of identification of a pancreatic cyst (n = 102) or within 1 year of follow-up in the remaining patients in the database (n = 200) were excluded. Patients with pancreatic cystic lesions (group A, n = 755) and the remaining patients in the database without cysts (group B, n = 520,215) were followed from 1998 to 2007. Results During the study period, in group A and B PaCa was diagnosed in 17 and 1206 patients, respectively, and the incidence rate of PaCa was 5.08 and .32 per 1000 patient-years, respectively. The hazard ratio of PaCa in all patients with cysts was 19.64 (95% CI, 12.12-31.82; P < .0001) when compared with the rest of the patients without cysts. In the subset of patients with cysts, without a history of acute or chronic pancreatitis (n = 241), the hazard ratio of PaCa (n = 5) was 18.80 (95% CI, 7.80-45.31; P < .0001). Conclusion Patients with pancreatic cysts have a significantly higher overall risk of PaCa. The etiologic distribution of cysts in our study patients is not available. Patients with mucinous cystic neoplasm and side branch IPMN are likely to have a higher risk of PaCa than our estimation of risk based on all etiologies.
Background & Aims Acute pancreatitis (AP) is often the initial presentation of pancreatic cancer (pancreatic adenocarcinoma PaCa). We evaluated the risk of PaCa after AP. Methods We performed a ...retrospective study of patients with AP who sought care in the Veterans Health Administration from 1998 through 2007. We excluded patients with pre-existing PaCa or recurrent AP and those who had the first episode of acute pancreatitis, from 1998 through 2000. Results Of 495,504 patients with Veterans Health Administration inpatient and outpatient records, 5720 were diagnosed with AP (1.15%) and 710 were diagnosed with PaCa (0.14%), from 2000 through 2007. Seventy-six patients had AP within 2 years before being diagnosed with PaCa (10.7% of all patients with cancer diagnosed during that period). The risk for PaCa was greatest in the first year after AP (14.5 per 1000 patient-years) and then decreased rapidly. Risk for PaCa was negligible in patients <40 years old. The incidence of PaCa within the first year after AP was 7.69 per 1000 patient-years in fifth decade of life and reached 28.67 after the seventh decade. Time to diagnosis of PaCa after AP was ≤2 months for 34 patients, 3–12 months for 35 patients, 13–24 months for 7 patients, and >24 months for 10 patients. Conclusions A significant number of patients with PaCa initially present with AP; the diagnosis of cancer is often delayed by up to 2 years. We suggest that PaCa be routinely considered as a potential etiology of AP in patients ≥40 years old.
New-onset diabetes mellitus (NODM) in adults is often an early manifestation of pancreatic cancer (PaCa), but the incidence of PaCa in this cohort is rather low. We evaluated whether combining other ...patient factors such as age, smoking history, the absence of obesity, the presence of chronic pancreatitis (CP), and gallstone disease can result in a more enriched cohort.
After a washout period of 2 years to exclude pre-existing PaCa or DM, 507,378 non-diabetic patients in the veterans' administration healthcare system were identified. Patients <40 years (n=54,465) and those with PaCa diagnosed before the diagnosis of diabetes (n=22) were excluded. A total of 452,804 veterans were followed for development of DM or PaCa.
73,811 patients (16.3%) developed NODM during the follow-up period. One hundred and eighty-three NODM patients (0.25%) were diagnosed with PaCa within 3 years. In comparison, 434 of 378,993 remaining patients (0.11%) developed PaCa in 3 years following inclusion into the study relative risk (RR)=2.27, 95% confidence intervals (CI) 1.96, 2.63; P<0.0001. The risk of PaCa diagnosis was higher among patients who were non-obese (RR=1.51), were ≥65 years old (RR=2.01), were heavy smokers (RR=1.55), and had a history of CP (RR=4.72) or gallstone disease (RR=2.02). Using a combination of these risk factors in NODM patients resulted in up to 0.72% three-year risk of PaCa but captured only 17% of patients with PaCa.
Based on our findings, the likelihood of PaCa in adults with NODM even after adjusting for other potential risk factors for PaCa including age, body mass index, smoking, gallstones, and CP is probably not high enough to recommend routine evaluation for all these patients for underlying PaCa.
Endoscopic ultrasound (EUS) is now established as a valuable imaging test for diagnosing and staging pancreatic cancer. But, with significant recent improvements in spiral CT scanners, particularly ...higher resolution and ability to reconstruct 3D images, spiral CT is now increasingly accepted as being better for pancreatic cancer staging. The debate continues, however, about the best diagnostic test or combination of tests in patients with suspected pancreatic cancer. Spiral CT is more readily available than EUS-FNA and, therefore, more frequently used. In this study, we evaluated the use of EUS-FNA in conjunction with spiral CT for suspected pancreatic cancer.
We retrospectively evaluated 81 consecutive patients who underwent EUS and EUS-FNA for clinical suspicion of a pancreatic cancer from November 2000 to November 2001. All patients had spiral CT with a multiphasic pancreatic protocol using multidetector spiral CT scanners. In all patients, EUS-FNA and spiral CT examinations were performed less than 3 wk apart.
Overall, the accuracy of spiral CT, EUS, and EUS-FNA was 74% (n = 60/81, CI 63-83%), 94% (n = 76/81, CI 87-98%), and 88% (n = 73/81, CI 81-96%), respectively, for diagnosing pancreatic cancer. In patients without an identifiable mass on spiral CT, the diagnostic accuracy of EUS and EUS-FNA for pancreatic tumors was 92% (n = 23/25, CI 74-99%). Absence of a focal "mass" lesion on EUS reliably excluded pancreatic cancer irrespective of clinical presentation (NPV 100% n = 5/5, CI 48-100%). The negative predictive value of EUS-FNA was only 22% (n = 2/9, CI 3-60%) in patients with obstructive jaundice and biliary stricture. However, in patients without obstructive jaundice at initial presentation, EUS-FNA was highly accurate (accuracy 97%, n = 33/34, CI 85-100%) and was reliable for ruling out malignancy (NPV 89%, n = 8/9, CI 52-100%). Cytologic assessment of EUS-FNA specimens was 89% accurate for identifying malignancy in suspicious lesions visualized on EUS.
The EUS with FNA can be a valuable adjunct to newer high-resolution multidetector spiral CT for diagnostic evaluation of patients with suspected pancreatic cancer.
Background The clinical utility of EUS-FNA is debated in patients with obstructive jaundice (ObJ) because of a very high pretest probability of pancreatobiliary malignancy (PBM) and biliary ...stent-induced inflammation that can potentially confound EUS-FNA diagnosis. EUS-FNA also has lower accuracy in patients with underlying chronic pancreatitis (CP). Objective Our purpose was to determine the clinical value of EUS-FNA for PBM diagnosis based on clinical presentation and presence of CP. Design Retrospective analysis of prospective database. Setting University hospital. Patients Patients who underwent EUS-FNA from 2002 to 2006 for suspected PBM based on (1) ObJ with biliary stricture or a mass lesion or (2) abnormal pancreatic imaging by CT/MRI: a focal pancreatic “mass” lesion; dilated pancreatic duct ± common bile duct; or an enlarged head of pancreas. Interventions EUS was performed with a radial echoendoscope followed by a linear echoendoscope if a focal pancreatic lesion was identified. Fine-needle aspirates were assessed immediately by an attending cytopathologist. Main outcome measurements (1) Prevalence of cancer and (2) performance characteristics of EUS-FNA. Results PBM was diagnosed in 73.9% of patients with ObJ and biliary stricture or pancreatic mass, in 49.6% of patients with pancreatic mass, and in 7.0% of patients with an enlarged head of pancreas or dilated pancreatic duct ± common bile duct. The prevalence of PBM was lower in all 3 presentations with associated CP. Both CP and presentation with ObJ lowered performance characteristics of EUS-FNA, but CP did so only in the subset of patients with ObJ. All except 1 false-negative diagnoses were due to cytologic misinterpretation. Limitation Retrospective design. Conclusion Among patients with suspected PBM, the accuracy of EUS-FNA is significantly lower only in a subset of patients with ObJ with underlying CP, largely as a result of difficulty in cytologic interpretation.
Background and Study Aims. Endoscopic ultrasound (EUS) surveillance of patients with mucinous pancreatic cysts relies on the assessment of morphologic features suggestive of malignant transformation. ...These criteria were derived from the evaluation of surgical pathology in patients with pancreatic cysts who underwent surgery. Reliability of these criteria when evaluated by EUS in identifying lesions which require surgery has still not been established. Patients and Methods. This retrospective cohort study included seventy-eight patients who underwent surgical resection of pancreatic cysts based on EUS-FNA (fine-needle aspiration) findings suggestive of mucinous pancreatic cysts with concern for malignancy. Results. Final surgical pathology diagnoses of patients were the following: adenocarcinoma (19), intraductal papillary mucinous neoplasm (IPMN) (39), mucinous cystic neoplasm (MCN) (13), serous cystadenoma (2), pseudocyst (3), mucinous solid-cystic lesion of indeterminate type (1), and mesenteric cyst (1). Cysts with focal wall thickening ≥ 3 mm (p=0.0008), dilation of pancreatic duct (PD) (p=0.0067), and cyst size ≥ 3 cm (p=0.016) had significantly higher risk of adenocarcinoma. None of the patients without any of these morphologic features had cancer. Conclusions. In patients with mucinous pancreatic cyst(s), focal wall thickening, cyst size ≥ 3 cm, and PD dilation as assessed by EUS can help identify advanced mucinous cysts which require surgery and should routinely be evaluated during EUS surveillance.
Acute pancreatitis may be the first presentation of pancreatic carcinoma (PaCa). The present study was designed to identify clinical findings suggestive of PaCa in patients with nonalcoholic ...nongallstone-related (NANG) acute pancreatitis and evaluate accuracy of endoscopic ultrasound for diagnosing PaCa in this setting.
This is a retrospective analysis of 332 consecutive patients who underwent endoscopic ultrasound-fine-needle aspiration after acute pancreatitis. Patients with gallstones or common bile duct stones, who were heavy or binge alcohol drinkers, or who had post-endoscopic retrograde cholangiopancreatography pancreatitis were excluded.
Among 218 patients with NANG acute pancreatitis, 38 patients had PaCa. Age more than 50 years (P = 0.008), history of smoking (P < 0.001), weight loss of 10 lb or greater (P = 0.003), serum bilirubin levels of higher than 2 mg/dL (P = 0.035) or serum alkaline phosphatase level of higher than 165 U/mL (in patients with normal serum bilirubin levels) (P = 0.003), and radiological findings of an identifiable pancreatic mass (P = 0.001) or distal pancreatic atrophy (P = 0.006) had significant association with an underlying PaCa on multivariate analysis. Of the 38 patients with PaCa in this cohort, 37 had 2 or more of these findings. Endoscopic ultrasound-fine-needle aspiration had 99.5% accuracy (98.6, 100%) for diagnosing carcinoma in this clinical setting.
The clinical criteria defined previously potentially can help select patients with NANG acute pancreatitis with a higher likelihood of an underlying pancreatic neoplasm for further imaging.
Background and Objective The clinical utility of intraductal US (IDUS) for evaluating biliary strictures has been limited because of a lack of easily recognized morphologic criteria to distinguish ...benign and malignant strictures. We studied the clinical value of 2 easily assessed IDUS findings: wall thickness and extrinsic compression at the stricture site. Design and Setting A retrospective, single-center study. Patients and Methods Forty-five patients without an identifiable mass on CT/magnetic resonance imaging, who underwent ERCP/IDUS for evaluation of biliary strictures were studied. IDUS pictures were reviewed specifically to measure wall thickness and to look for extrinsic compression at the stricture site. Main Outcome Measurements and Results The mean age of the patients was 64.2 ± 13.3 years. Thirty patients had jaundice at presentation, and in 15 patients a stricture was suspected on imaging. The mean length of biliary strictures was 15.1 ± 7.8 mm. Strictures were distal (distal common bile duct) in 25 patients and proximal (mid/proximal common bile duct or common hepatic duct) in 20 patients. Fourteen strictures were finally diagnosed to be malignant. Strictures in 20 patients were caused by extrinsic compression, and tissue diagnosis was readily obtained by EUS-FNA in all these patients. Of 25 strictures without extrinsic compression, 6 were malignant (wall thickness 9-16 mm) and 19 were benign (wall thickness ≤9 mm). Bile duct wall thickness ≤7 mm at the stricture site, in the absence of extrinsic compression, had a negative predictive value of 100% for excluding malignancy in this cohort. Limitations Retrospective study and relatively small number of patients. Conclusions Evaluation of wall thickness and the presence of extrinsic compression at the site of biliary strictures by IDUS can help in further management of these patients.
Background Incidental findings of an enlarged head of pancreas (HOP) or dilated pancreatic duct (PD) with or without a dilated common bile duct (CBD) on CT or magnetic resonance imaging (MRI), in ...patients without obstructive jaundice, raise suspicion for a pancreatic neoplasm, but their clinical significance has not been established. Objective To determine the prevalence of pancreatic neoplasm in this patient group. Design Retrospective analysis of a prospective database. Setting Tertiary-care university hospital. Patients Patients without obstructive jaundice at initial presentation, who underwent EUS and/or EUS-guided FNA (EUS-FNA) for an abnormal CT and/or MRI with an enlarged HOP (n = 67) or a PD with or without a dilated CBD (n = 43). The final diagnosis was based on definitive cytology, surgical pathology, and clinical follow-up. Interventions An EUS examination was performed by using a radial echoendoscope followed by a linear echoendoscope, if a focal pancreatic lesion was identified. Fine-needle aspirates were stained with Diff-Quik and Papanicolaou's methods, and were immediately assessed by an attending cytopathologist. Main Outcome Measurements (1) The prevalence of pancreatic neoplasms and (2) performance characteristics of EUS-FNA for identifying malignant neoplasm, in this patient group. Results In 110 study patients, the final diagnosis included adenocarcinoma (n = 7), pancreatic intraepithelial neoplasia (n = 1), neuroendocrine tumor (n = 1), tumor metastasis (n = 1), and benign cyst (n = 3). Thirty-two patients had EUS evidence of chronic pancreatitis, and, in the remaining 65 patients, the pancreas was normal. The accuracy of EUS and EUS-FNA for diagnosing pancreatic neoplasm in these patients was 99.1%, with 88.8% sensitivity, 100% specificity, 99% negative predicative value, and 100% positive predictive value. Limitation A retrospective design and surgical confirmation in only a small number of study patients. Conclusion A pancreatic neoplasm is seen in a clinically significant number of patients with “enlarged HOP” or “dilated PD with or without a dilated CBD” but without obstructive jaundice. EUS-FNA seems highly accurate for diagnosing pancreatic neoplasm in these patients.
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