Acute Pancreatitis Recurrences Augment Long-Term Pancreatic Cancer Risk.

INTRODUCTION: 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). METHODS: 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. RESULTS: 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). DISCUSSION: 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.

Risk of pancreatic cancer in patients with pancreatic cyst.

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.

Increased risk of pancreatic adenocarcinoma after acute pancreatitis.

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 diagnosis of chronic pancreatitis: risk of missing an underlying pancreatic cancer.

OBJECTIVES: Patients with pancreatic cancer (PaCa) sometimes present with symptoms suggestive of chronic pancreatitis (CP). We evaluated the prevalence of undiagnosed PaCa in patients with new CP diagnosis. METHODS: This is a retrospective study with data from Veterans Health Administration national medical care data sets from fiscal year 1998-2007. A 3-year washout period was used to identify patients with preexisting PaCa and preexisting CP diagnosis. RESULTS: Among 471,992 veterans included, 917 (0.19%) had PaCa, 2,557 (0.54%) had a preexisting CP, and 2,175 (0.46%) had a new diagnosis of CP. PaCa was diagnosed ≤2 years following CP diagnosis in 44 patients, comprising 4.80% of patients with PaCa. Following a new diagnosis of CP, the risk of PaCa diagnosis was most marked in the first year (incidence 18.04 per 1,000 person-years (py), relative risk (RR) 63.43) and became similar to risk in patients with preexisting CP in the third year. The first-year incidence of PaCa was 7.33/1,000 py in the fifth decade and reached 36.91/1,000 py after seventh decade of life. Time to PaCa diagnosis following a CP diagnosis was ≤60 days in 14 patients, 3-12 months in 25 patients, and 13-24 months in 5 patients. CONCLUSIONS: Approximately 5% of patients with PaCa are initially misdiagnosed as CP, and in two-thirds of these patients the cancer diagnosis is delayed by >2 months. PaCa should reliably be excluded before making a new CP diagnosis in patients who are >40 years old, especially in those without heavy smoking or alcohol history.

Patients with obstructive jaundice and biliary stricture ± mass lesion on imaging: prevalence of malignancy and potential role of EUS-FNA.

BACKGROUND: In patients with obstructive jaundice and biliary stricture, the role of endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) is debated for fear of missing a potentially resectable pancreatobiliary malignancy (PBM). We evaluated the prevalence of (1) PBM; (2) lesions that do not require a potentially curative cancer surgery; and (3) potentially resectable PBMs in patients with false-negative diagnosis by EUS-FNA. PATIENTS AND METHODS: This is a retrospective analysis of 342 patients who underwent EUS/EUS-FNA from 2002 to 2009 after presenting with obstructive jaundice and a biliary stricture. Of these, 170 patients had no definitive mass on computed tomography and 172 patients had definitive mass on computed tomography without evidence of unresectability. Final diagnosis was based on surgical pathology or definitive cytology and clinical follow-up of ≥ 12 months. RESULTS: The mean age of patients (176 male) was 68.0±12.5 years. A final diagnosis of malignancy was made in only 248 patients (72.5%; 95% confidence interval, 67.7, 77.2). The overall accuracy of EUS-FNA for diagnosing malignancy was 92.4% (89.0, 94.8), with 91.5% sensitivity (87.1, 94.5) and 80.9% negative predictive value (72.0, 87.5). Among 21 patients with false-negative diagnosis, 8 had cholangiocarcinoma (2 resectable), 13 had pancreatic cancer (5 resectable). EUS-FNA provided information to potentially modify surgical management in 116 patients (33.9%; 95% confidence interval, 29.1, 39.0): 89 patients diagnosed as true negatives, 24 with distant malignant lymphadenopathy, and 3 with malignant lymphoma. CONCLUSIONS: In above-defined patient subset, the risk of missing resectable tumors by EUS-FNA has been exaggerated because of artifactually low negative predictive value resulting from a high pretest probability of PBM. The actual miss rate for resectable PBM by EUS-FNA is rather small and was 2% in present cohort. Information from EUS-FNA can potentially modify surgical management in up to one third of patients.

Considerations for the prediction of survival time in pancreatic cancer based on registry data.

Semi-parametric and parametric survival models in patients with pancreatic adenocarcinoma (PC) using data from Surveillance, Epidemiology, and End Result (SEER) registry were developed to identify relevant covariates affecting survival, verify against external patient data and predict disease outcome. Data from 82,251 patients was extracted using site and histology codes for PC in the SEER database and refined based on specific cause of death. Predictors affecting survival were selected from SEER database; the analysis dataset included 2,437 patients. Survival models were developed using both semi-parametric and parametric approaches, evaluated using Cox-Snell and deviance residuals, and predictions were assessed using an external dataset from Saint Louis University (SLU). Prediction error curves (PECs) were used to evaluate prediction performance of these models compared to Kaplan-Meier response. Median overall survival time of patients from SEER data was 5 months. Our analysis shows that the PC data from SEER was best fitted by both semi-parametric and the parametric model with log-logistic distribution. Predictors that influence survival included disease stage, grade, histology, tumor size, radiation, chemotherapy, surgery, and lymph node status. Survival time predictions from the SLU dataset were comparable and PECs show that both semi-parametric and parametric models exhibit similar predictive performance. PC survival models constructed from registry data can provide a means to classify patients into risk-based subgroups, to predict disease outcome and aide in the design of future prospective randomized trials. These models can evolve to incorporate predictive biomarker and pharmacogenetic correlates once adequate causal data is established.

EUS/EUS-FNA for suspected pancreatic cancer: influence of chronic pancreatitis and clinical presentation with or without obstructive jaundice on performance characteristics.

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.

Etiologic Distribution of Pancreatic Cystic Lesions Identified on Computed Tomography/Magnetic Resonance Imaging.

OBJECTIVES: This study aimed to determine the distribution of etiology of pancreatic cysts using established criteria/markers from cyst fluid analysis and cytology that have been reported to have high specificity in published literature. METHODS: A retrospective study of pancreatic cysts using an endoscopic database from March 2002 and May 2013 was conducted. Pancreatic cysts <10 mm and cysts with a history of pancreatic cancer were excluded. RESULTS: In our cohort of 758 patients with pancreatic cyst(s), the cyst etiology was as follows: mucinous cyst/side-branch intraductal papillary mucinous neoplasms (SB-IPMNs)/mucinous cystic neoplasms (MCN; 48.2%), pseudocyst (27.6%), serous cystadenoma (11%), simple cysts (6.4%), mucinous cystadenocarcinoma (5.1%), and other (1%). Approximately 41% (n = 310) of the cysts were ≥3 cm in size and included the following: pseudocyst (39.7%), mucinous cysts/SB-IPMN/MCN (28.1%), serous cystadenoma (16.7%), mucinous cyst adenocarcinoma (9.7%), and simple cyst (4.8%). In 118 patients with a known history of acute pancreatitis, the cyst diagnoses included pseudocyst (68.7%), mucinous cyst/SB-IPMN/MCN (18.6%), benign/simple cyst (7.6%), and mucinous cystadenocarcinoma (2.5%). CONCLUSIONS: In patients with cystic pancreatic lesion noted on cross-sectional imaging, approximately half of the patients have lesions without malignancy or malignant potential and therefore not requiring surveillance. Endoscopic ultrasound/endoscopic ultrasound-guided fine-needle aspiration evaluation of the pancreatic cysts can help optimize their further management.

Immunostaining as an adjunct to cytology for diagnosis of pancreatic adenocarcinoma.

BACKGROUND & AIMS: Serial analysis of gene expression has helped identify several proteins that are expressed differentially in pancreatic cancer and are highly sensitive and specific for pancreatic adenocarcinoma. We evaluated if the diagnostic accuracy of pancreatic cancer from endoscopic ultrasound (EUS)-fine-needle aspiration (FNA) can be improved by combined evaluation of cytology and immunostaining with these markers. METHODS: This study involved the use of archived specimens from patients treated at Saint Louis University Hospital from 2002 to 2006. We identified 5 protein markers that appeared most promising from published literature. We sequentially evaluated immunostaining with these markers in (1) surgical resection specimens, (2) cell blocks from EUS-FNA, and (3) direct smears of EUS-FN aspirates. Finally, we performed a combined evaluation of cytology and immunostaining in direct smears that were difficult to interpret and required a second consultative cytologic opinion. RESULTS: In resection specimens, the majority of pancreatic adenocarcinomas expressed all 5 markers but fascin, maspin, and carcinoembryonic antigen-related cell adhesion molecule 6 also were expressed abnormally in normal pancreata and in chronic pancreatitis. Further evaluation therefore was limited to the other 2 markers: mesothelin and 14-3-3sigma. It was feasible and useful to perform immunostaining in cell blocks and direct smear for diagnosing pancreatic cancer. In cases requiring a second cytologic consultation, a combined evaluation of cytologic morphology and immunostaining had 90% accuracy for a pancreatic adenocarcinoma diagnosis. CONCLUSIONS: In conclusion, immunostaining with newer protein markers is feasible in EUS-FNA specimens and can assist cytopathologists in diagnosing pancreatic cancer. Among the currently available protein immunomarkers, a combination of mesothelin and 14-3-3sigma seems most promising, but needs to be validated in prospective studies before routine clinical use.

Endoscopic diagnosis and staging of mucosa-associated lymphoid tissue lymphoma.

PURPOSE OF REVIEW: The role of endoscopy, including endoscopic ultrasound, in the diagnosis and management of mucosa-associated lymphoid tissue lymphomas of the stomach has evolved steadily in the last two decades. The present review summarizes recent findings and puts them in context with studies on the diagnosis and management of mucosa-associated lymphoid tissue lymphoma published earlier. RECENT FINDINGS: Several recent studies have emphasized the crucial role of endoscopic ultrasound in treatment planning in patients with gastric mucosa-associated lymphoid tissue lymphoma. This is important as early-stage gastric mucosa-associated lymphoid tissue lymphomas can be managed just by the eradication of Helicobacter pylori by appropriate antibiotic regimens. However, the more advanced lesions are treated with much more invasive treatment regimens involving radical gastrectomy, chemotherapy or radiation, or all. SUMMARY: Endoscopic ultrasound staging is highly accurate in predicting response to Helicobacter pylori eradication in patients with gastric mucosa-associated lymphoid tissue lymphoma. Normalization of gastric wall thickness and architecture can be used to monitor tumor regression following treatment. Endoscopic ultrasound findings can also be used to identify treatment failures and relapses and can help identify patients who need more aggressive therapy.

EUS and/or EUS-guided FNA in patients with CT and/or magnetic resonance imaging findings of enlarged pancreatic head or dilated pancreatic duct with or without a dilated common bile duct.

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 echoendoscopy followed by a linear echoendoscopy, 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.

EUS Morphology Is Reliable in Selecting Patients with Mucinous Pancreatic Cyst(s) Most Likely to Benefit from Surgical Resection.

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.

Chronic Pancreatitis and Fracture: A Retrospective, Population-Based Veterans Administration Study.

OBJECTIVES: There is increasing evidence that chronic pancreatitis (CP) is a risk factor for osteoporotic fracture, but data on males with CP and fracture prevalence are sparse. We determined the association of sex and age using a large Veterans Administration database. METHODS: This was a retrospective analysis (1998-2007). Patients with CP (International Classification of Diseases code 577.1) and control subjects (without CP) were identified after exclusions and fracture prevalence (vertebral, hip, and wrist) were recorded. RESULTS: 453,912 Veterans Administration patients were identified (control subjects: 450,655 and patients with CP: 3257). Mean ages of control subjects and CP were 53.6 and 54.2 years (P < 0.014). Patients with CP had higher odds ratios of total fractures (2.35; 95% confidence interval [CI], 2.00-2.77), vertebral fracture 2.11 (95% CI, 1.44-3.01), hip fracture 3.49 (95% CI, 2.78-4.38), and wrist fracture 1.68 (95% CI, 1.29-2.18) when compared with control subjects. After adjusting for age group and etiology, patients with CP had increased odds of total fractures, vertebral fractures, and hip fractures (P < 0.05). CONCLUSIONS: In this male-predominate Veterans Administration study, patients with CP were at increased risk of osteoporotic fractures. The risk was higher for hip fracture (>3 times) in patients with CP compared with control subjects. All patients with CP older than 45 years, irrespective of sex, should be screened for bone mineral density loss.

Biliary strictures: diagnostic considerations and approach.

Biliary strictures present a diagnostic challenge, especially when no etiology can be ascertained after laboratory evaluation, abdominal imaging and endoscopic retrograde cholangiopancreatography (ERCP) sampling. These strictures were traditionally classified as indeterminate strictures, although with advances in endoscopic techniques and better understanding of hepato-biliary pathology, more are being correctly diagnosed. The implications of missing a malignancy in patients with biliary strictures-and hence delaying surgery-are grave but a significant number of patients (up to 20%) undergoing surgery for suspected biliary malignancy can have benign pathology. The diagnostic approach to these patients involves detailed history and physical examination and depends on the presence or absence of jaundice, level of obstruction, and presence or absence of a mass lesion. While abdominal imaging helps to find the level of obstruction and provides a 'road map' for further endoscopic investigations, tissue diagnosis is usually needed to make decisions on management. Initially ERCP was the only modality to investigate these strictures but now, with the development of endoscopic ultrasound with fine needle aspiration and the availability of newer techniques such as intraductal ultrasound, single-operator cholangioscopy and confocal laser endomicroscopy, the diagnostic approach to biliary strictures has changed significantly. In this review, we will focus on the decision-making process for patients with biliary strictures and discuss the key decision points that should dictate further diagnostic investigations at each step.

Predictors for Pancreatic Cancer Diagnosis Following New-Onset Diabetes Mellitus.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Heavy Smoking Is Associated With Lower Age at First Episode of Acute Pancreatitis and a Higher Risk of Recurrence.

OBJECTIVE: There is limited data on cigarette smoking and the risk of acute pancreatitis (AP). We evaluated the influence of cigarette smoking on AP risk and clinical presentation in a large cohort of Veteran's Administration (VA) patients. METHODS: Retrospective study of VA patients from 1998 to 2007. Exclusion criteria included (1) history of chronic pancreatitis (n = 3222) or gallstones (n = 14,574) and (2) age younger than 15 years (n = 270). A 2-year washout period was used to exclude patients with pre-existing recurrent AP. RESULTS: The study included 484,624 patients. From 2001 to 2007, a total of 6799 (1.4%) patients had AP. Alcohol (risk ratio, 4.20) and smoking (risk ratio, 1.78) were independent significant risk factors of AP on multiple regression analysis. Smoking increased the risk of AP in both nonalcoholics (0.57% vs 1.1%) and alcoholics (2.6% vs 4.1%). Smoking was associated with younger mean age at first episode of AP and higher likelihood of recurrent AP (≥4 episodes) in both nonalcoholics and alcoholics. The interval between recurrent episodes was not altered by alcohol or smoking. CONCLUSIONS: In a large cohort of VA patients, smoking is an independent risk factor for AP and augmented the effect of alcohol on the risk, age of onset, and recurrence of AP.

Dramatic Survival Benefit Related to R0 Resection of Pancreatic Adenocarcinoma in Patients With Tumor ≤25 mm in Size and ≤1 Involved Lymph Nodes.

OBJECTIVES: To evaluate i) the relative importance of R0 resection, tumor size and peripancreatic lymph node (LN) status are significant determinants of survival benefit following upfront surgery for pancreatic adenocarcinoma (PaCa), ii) whether R0 resection confers survival benefit in all patients or a patient subset with certain favorable prognostic factors. METHODS: Retrospective analysis of patients (2001-2010) who underwent planned potentially curative surgical resection without neoadjuvant therapy for PaCa. RESULTS: Among 154 patients, median survival following R0 (n=105) and R1 resections was 26.8 and 17.7 months, respectively (P=0.010). Tumor size and LN status were significant determinants of survival following R0 resection. There were no differences in survival based on tumor size and LN in patients with R1 resection. Median survival was 17.7 months following R1 resection and was 70.9 months (P<0.001) and 22.2 months (P=0.44) in patients with tumor ≤25 mm in size and ≤1 involved LN and in the remaining patients in the cohort respectively following R0 resection. CONCLUSIONS: R0 resection is associated with dramatic survival benefit over R1 resection in a subset of patients with tumor size ≤25 mm and ≤1 involved LN. These findings underscore the importance of R0 resection and careful patient selection for upfront surgery in patients with PaCa.

Clinical predictors of pancreatic carcinoma causing acute pancreatitis.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Dilation of both pancreatic duct and the common bile duct on computed tomography and magnetic resonance imaging scans in patients with or without obstructive jaundice.

OBJECTIVES: "Double-duct sign" (strictures in both common bile duct [CBD] and pancreatic duct [PD] with proximal dilation) on endoscopic retrograde cholangiopancreatography is considered suggestive of pancreatic malignancy. Dilation of CBD and PD is frequently noted on computed tomography/magnetic resonance imaging scans, sometimes found incidentally in patients without jaundice. The prevalence of malignancy in these patients is not established. METHODS: In this retrospective analysis, consecutive patients who underwent endoscopic ultrasound (EUS) at a tertiary care hospital from 2002 to 2006 for suspected pancreatic malignancy and had double-duct sign on imaging were included. We evaluated (1) prevalence of malignancy in patients with or without obstructive jaundice and (2) performance characteristics of EUS-fine-needle aspiration (FNA) in diagnosing malignancy in this setting. RESULTS: A final diagnosis of pancreatic malignancy was made in 142 (85.5%) of 166 patients with and 4 (5.9%) of 68 without obstructive jaundice (P < 0.005). The accuracy of EUS-FNA for diagnosing malignancy in patients with or without obstructive jaundice was 92.8% versus 98.5%. CONCLUSIONS: Dilation of both PD and CBD on computed tomography/magnetic resonance imaging scans is suggestive of pancreatic malignancy. The prevalence of malignancy, however, is markedly lower in patients without obstructive jaundice but is clinically significant and merits further diagnostic evaluation. Endoscopic ultrasound-FNA is highly accurate for diagnosing malignancy in this setting.