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Background and Aims: Inflammatory head mass of pancreas (IMP) developing in background of chronic pancreatitis (CP) is difficult to distinguish from carcinoma pancreas. We aimed to delineate natural course of IMP and predict their malignancy risk, avoiding unnecessary biopsies., Materials and Methods: In this retrospective single-center study, clinical records of patients with CP with diagnosed pancreatic head mass were reviewed. Clinical, laboratory, imaging, endoscopic findings, and follow-up details were retrieved from prospectively maintained database. A diagnostic nomogram was developed combining serum cancer antigen 19-9 and endoscopic ultrasound (EUS) findings to predict the risk of malignancy., Results: We identified 107 patients with pancreatic head mass with CP of whom 87 (81.3%) were IMP and 20 (18.7%) were malignant. Patients with IMP were more frequently young males with alcohol-related CP and low CA 19-9 in comparison with those with malignancy (age IMP: 41.3 ± 11.3 vs carcinoma: 49.3 ± 14.5 years [ P = 0.009]; males 89.7% vs 65% [ P = 0.011]; alcoholic etiology: 71.3% vs 20% [ P < 0.001]; median CA 19-9: 25.78 [interquartile range, 7.20-120.60] vs 1034.50 [106.65-7808.25] [ P < 0.001]). A diagnostic nomogram combining CA 19-9 and EUS findings could identify malignancy with an optimism-corrected c-statistic of 0.905, which was better than both CA 19-9 (0.80) and EUS alone (0.826). Patients with IMP had relatively benign disease course with 40.2% biliary obstruction, 20.7% portal venous thrombosis, 14.9% gastric outlet obstruction, and 1-, 3-, and 5-year survival being 97.3%, 92.7%, and 92.0%, respectively. Surgery was required in only 12 patients (13.8%) with IMP., Conclusions: Combination of CA 19-9 and EUS best identifies malignancy risk in patients with IMP, who have otherwise benign course., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: The Japan Pancreas Society introduced the concept of early chronic pancreatitis (ECP) in 2009, but its epidemiology remains unclear. This study investigated challenges in ECP diagnosis., Methods: Early chronic pancreatitis was diagnosed in 4 cohorts between April 2019 and November 2021 using the Clinical Diagnostic Criteria for Chronic Pancreatitis 2019. These cohorts included patients with abdominal/back pain, abnormal pancreatic enzyme levels, ECP suspected due to other reasons, and those who underwent endoscopic ultrasonography for other diseases., Results: A total of 2502 cases were analyzed and 150 (40 alcoholic and 110 nonalcoholic) cases with ECP findings on endoscopic ultrasonography were included. Early chronic pancreatitis was confirmed in 14 cases (9%), including 9 (22.5%) alcoholic and 5 (4.5%) nonalcoholic cases. Early chronic pancreatitis was confirmed in 15%, 0%, 2.2%, and 0.13% cases in the 4 cohorts, respectively. Early chronic pancreatitis was confirmed in 10 (48%) of the 21 (14%) cases with pancreatic pain., Conclusions: Early chronic pancreatitis diagnostic rate was low, particularly in nonalcoholic cases, but was slightly higher in cases with pancreatic pain. The diagnostic rate was highest in the abdominal/back pain group. Further studies are required to establish appropriate diagnostic criteria for ECP., Competing Interests: H.I. has received research grant from Fujifilm Co, Ltd, Boston Scientific Japan Co, Ltd, Eisai Co, Ltd, and Gilead Sciences Co, Ltd, and lecture fee from Fujifilm Co, Ltd, and scholarship donation from Taiho Pharmaceutical Co, Ltd, Gadelius Medical Co, Ltd, and Boston Scientific Japan Co, Ltd. The other authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: The concept of early chronic pancreatitis (ECP) and its diagnostic criteria were first proposed by Japan, using endoscopic ultrasonography (EUS) findings for diagnosis. However, these findings have not been supported by pathological findings. We aimed to examine the association between the EUS and pathological findings of the same area of the pancreas., Methods: In 12 patients who underwent pancreaticoduodenectomy for distal bile duct cancer without accompanying pancreatitis, a comparative analysis between preoperative EUS and pathological findings was performed. The part of the pancreas adjoining the portal vein was evaluated., Results: In 7 cases, abnormal EUS findings included in the diagnostic criteria for ECP were seen; the correlation of the accuracy of lobularity seen on EUS compared with the pathological findings of the pancreatic parenchyma (inflammatory cell infiltration, atrophy of acinar cells, and fibrosis) was high (83.3%-91.7%). Pancreatic duct findings revealed that the accuracy of the hyperechoic margin of the pancreatic duct on EUS compared with pathological findings (wall thickness of pancreatic duct) was high (83.3%)., Conclusions: Endoscopic ultrasonography findings for ECP, according to Japan's 2019 revised criteria, lobularity, and the hyperechoic margin of the pancreatic duct may highly correspond to the pathological findings of chronic inflammation., Competing Interests: The authors declare no conflict of interest., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Secretin-stimulated magnetic resonance imaging (s-MRI) is the best validated radiological modality assessing pancreatic exocrine secretion. In this prospective observational study, we compare the diagnostic accuracy of s-MRI for exocrine pancreatic failure due to different pancreatic diseases and healthy controls., Methods: We performed s-MRI in 21 cystic fibrosis (CF) patients, 78 patients with chronic pancreatitis (CP) and 20 healthy controls. Exocrine failure was defined by fecal elastase-1 of less than 200 μg/g or bicarbonate concentration from endoscopic secretin test of less than 80 mmol/L., Results: Eleven CF and 61 CP patients were exocrine insufficient. Insufficient CF patients had lower s-MRI volume output compared with all other groups (P < 0.05). Insufficient CP patients had reduced volume output compared with controls and sufficient CF (P < 0.05). Secretin-stimulated MRI yielded overall accuracy of 0.78 (95% confidence interval [CI], 0.70-0.86) for exocrine failure. When divided according to etiology, the test yielded accuracy of 0.95 (95% CI, 0.90-1) in CF and 0.73 (95% CI, 0.64-0.82) in CP., Conclusions: The accuracy of s-MRI volume output measures to diagnose exocrine failure was higher in CF than in CP. Differences in s-MRI volume output in patients with exocrine failure may be due to different etiological and pathogenic mechanisms in CF and CP.

Objectives: Deep pancreatic cannulation (DPC) failure during endoscopic retrograde cholangiopancreatography (ERCP) in patients with chronic pancreatitis (CP) can occur in the presence of ductal obstruction due to strictures and/or stones. There are currently no simple preprocedure clinical or laboratory tests that can predict DPC failure during ERCP., Methods: All adult patients with definite CP by M-ANNHEIM criteria referred to the pancreatitis clinic between 2010 and 2017 were evaluated. Serum trypsin levels were obtained to assess the morphologic severity of disease and/or exocrine insufficiency. Univariable and multivariable logistic regression analyses were performed to identify factors associated with DPC failure., Results: There were 346 patients, of whom 100 underwent trypsin measurements and ERCP for symptomatic CP. Deep pancreatic cannulation failure occurred in 32 (32%). There were no significant differences with regard to age, sex, etiology, smoking, and alcohol use. Deep pancreatic cannulation failure was more likely to occur in patients with low trypsin levels (53.1% vs 25%, P = 0.007) compared with those with successful DPC. Low trypsin levels were independently associated with DPC failure in adjusted analysis (odds ratio, 3.7; 95% confidence interval, 1.2-11; P = 0.02)., Conclusions: Low serum trypsin levels independently predict DPC failure during ERCP in patients with symptomatic obstructive CP.

Objectives: Chronic asymptomatic pancreatic hyperenzymemia (CAPH) was described as a benign disease. However, we already described clinically relevant findings requiring surgery or follow-up in half of the subjects. The aim of this study was to evaluate the long-term outcome of CAPH in terms of symptoms and evolution toward chronic pancreatitis., Methods: Subjects previously enrolled in the first phase of the study (from 2005 to 2010) were reinvestigated from December 2013 to January 2017 with a phone call ± magnetic resonance cholangiopancreatography with secretin stimulation., Results: A total of 133 subjects were eligible for the follow-up study (75 males, 58 females; age, 48.4 [standard deviation {SD}, 14] years); 24 (18%) of them dropped out. During a mean follow-up of 9.3 (SD, 5.2) years after the first diagnosis of CAPH, no episode of acute pancreatitis or abdominal pain was reported. Sixty-three subjects (58%) of 109 underwent magnetic resonance cholangiopancreatography with secretin stimulation with a mean follow-up of 5.7 [SD, 3.1] years (range, 1-11 years). Secretin stimulation-MRCP resulted unchanged in 54 (90%) of 60 subjects, worsened in 3 (5%) and improved in 3 (5%). Two subjects died from causes unrelated to pancreatic disease., Conclusions: Excluding subjects with a pancreatic disease at index magnetic resonance imaging, CAPH is a benign condition.

Objective: The aim of this study was to determine the association of the pancreatic steatosis with obesity, chronic pancreatitis (CP), and type 2 diabetes mellitus., Methods: Patients (n = 118) were retrospectively identified and categorized into no CP (n = 60), mild (n = 21), moderate (n = 27), and severe CP (n = 10) groups based on clinical history and magnetic resonance cholangiopancreatography using the Cambridge classification as the diagnostic standard. Visceral and subcutaneous compartments were manually segmented, and fat tissue was quantitatively measured on axial magnetic resonance imaging., Results: Pancreatic fat fraction showed a direct correlation with fat within the visceral compartment (r = 0.54). Patients with CP showed higher visceral fat (P = 0.01) and pancreatic fat fraction (P < 0.001): mild, 24%; moderate, 23%; severe CP, 21%; no CP group, 15%. Patients with type 2 diabetes mellitus showed higher pancreatic steatosis (P = 0.03) and higher visceral (P = 0.007) and subcutaneous fat (P = 0.004). Interobserver variability of measuring fat by magnetic resonance imaging was excellent (r ≥ 0.90-0.99)., Conclusions: Increased visceral adipose tissue has a moderate direct correlation with pancreatic fat fraction. Chronic pancreatitis is associated with higher pancreatic fat fraction and visceral fat. Type 2 diabetes mellitus is associated with higher pancreatic fat fraction and visceral and subcutaneous adiposity.

Objectives: Endoscopic ultrasound (EUS) is a minimally invasive pancreatic imaging modality. We evaluated children with idiopathic acute pancreatitis (IAP) and acute recurrent pancreatitis (ARP) for changes of chronicity (Rosemont criteria) and biliary risk factors. Diagnostic yield of simultaneously performed transabdominal ultrasonography (TUS) was compared with EUS., Methods: This was a prospective observational study. Patients underwent EUS and TUS after 2 months of pancreatitis attack., Results: Forty-five (18 IAP, 27 ARP) patients underwent EUS and TUS. Mean (standard deviation) age and weight were 9.1 (2.6) years and 32.66 (12.43) kg in IAP, whereas these were 12.2 (3.1) years and 44.84 (15.12) kg in ARP, respectively. Endoscopic ultrasound demonstrated morphological abnormality in 33.3% and 40.7% of IAP and ARP, respectively (P = 0.61), whereas 16.6% and 25.9% were abnormal in TUS. Endoscopic ultrasound showed unequivocal changes of chronicity (11.1% vs 0%) and risk factors only among ARP (25.9% vs 0%; P = 0.03) and demonstrated slightly higher odds ratio (95% confidence interval) as compared with TUS to detect abnormalities in both IAP (2.43 [0.49-14.17], P = 0.28) and ARP (1.94 [0.60-6.47], P = 0.26)., Conclusions: Applying EUS, changes of chronicity and risk factors were noted only in ARP. Endoscopic ultrasound performed better than TUS in detecting chronicity.

Objectives: Total pancreatectomy with islet autotransplantation (TPIAT) offers symptom relief to highly selected patients with recurrent acute and/or chronic pancreatitis. However, with variable clinical response, it is important to refine islet manipulation technique and patient selection criteria. This study explores the variables associated with high islet cell yield, a driver of success in TPIAT., Methods: This study evaluated patients who underwent TPIAT at Dartmouth-Hitchcock Medical Center from 2012 to 2016. Odds ratios were calculated for various patient and procedural characteristics. The primary clinical outcome was the number of isolated islet equivalents per kilogram body weight., Results: Thirty-eight patients met inclusion criteria. Patients with no computed tomography or magnetic resonance imaging evidence of chronic pancreatitis, without pancreatic duct stones, and without parenchymal stones were associated with higher odds of success (P = 0.02, P = 0.02, and P = 0.002, respectively). Patients with preoperative glycated hemoglobin greater than 5.6, with islet cell suspensions positive for cultures, and with positive gram stains were associated with lower odds of success (P = 0.02, P = 0.01, and P = 0.02, respectively)., Conclusions: Factors that diminish a successful islet cell harvest during TPIAT include the presence of infected islets, an elevated preoperative glycated hemoglobin, and the presence of pancreatic duct stones.

Objectives: This study aims to compare the M-ANNHEIM, Büchler, and Lüneburg diagnostic tools for chronic pancreatitis (CP)., Methods: A cross-sectional analysis of the development of CP was performed in a prospectively collected multicenter cohort including 669 patients after a first episode of acute pancreatitis. We compared the individual components of the M-ANNHEIM, Büchler, and Lüneburg tools, the agreement between tools, and estimated diagnostic accuracy using Bayesian latent-class analysis., Results: A total of 669 patients with acute pancreatitis followed-up for a median period of 57 (interquartile range, 42-70) months were included. Chronic pancreatitis was diagnosed in 50 patients (7%), 59 patients (9%), and 61 patients (9%) by the M-ANNHEIM, Lüneburg, and Büchler tools, respectively. The overall agreement between these tools was substantial (κ = 0.75). Differences between the tools regarding the following criteria led to significant changes in the total number of diagnoses of CP: abdominal pain, recurrent pancreatitis, moderate to marked ductal lesions, endocrine and exocrine insufficiency, pancreatic calcifications, and pancreatic pseudocysts. The Büchler tool had the highest sensitivity (94%), followed by the M-ANNHEIM (87%), and finally the Lüneburg tool (81%)., Conclusions: Differences between diagnostic tools for CP are mainly attributed to presence of clinical symptoms, endocrine insufficiency, and certain morphological complications.

Objective: We aimed to determine the feasibility and accuracy of a combined endoscopic ultrasonography (EUS) with a shortened pancreatic function testing (sEUS) for structural and functional assessment using a single instrument in patients with suspected chronic pancreatitis (CP)., Methods: We completed a prospective crossover study, enrolling patients with suspected CP. Patients who underwent both traditional 1-hour secretin pancreatic function test (sPFT) and sEUS were included in the analysis. We compared study results for test concordance and for correlation of peak bicarbonate concentrations., Results: Eleven (64.7%) of 17 patients had concordant sPFT and sEUS findings when the cutoff for peak bicarbonate was 80 mEq/L. Six patients had discordant findings with a negative sPFT and positive sEUS. This poor concordance suggests that sEUS is an unreliable functional test. Lowering the sEUS cutoff to 70 mEq/L resulted in improved concordance (64.7% vs 70.6%). Finally, there was no significant correlation between peak bicarbonate concentrations (r = 0.47; 95% confidence interval, -0.02 to 0.79) in these 2 functional tests., Conclusions: We demonstrate poor concordance between sPFT and sEUS suggesting that a combined shortened functional and structural test using a single instrument may not be a feasible test for diagnosis of suspected CP when a cutoff of 80 mEq/L is used.

Objective: The aim of this study was to characterize utilization and benefit of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in children with acute recurrent pancreatitis (ARP) or chronic pancreatitis (CP)., Methods: From August 2012 to February 2015, 301 children with ARP or CP were enrolled in the INSPPIRE (INternational Study group of Pediatric Pancreatitis: In search for a cuRE) study. Physicians reported utilization and benefit of therapeutic ERCP at enrollment. Differences were analyzed using appropriate statistical methods., Results: One hundred seventeen children (38.9%) underwent at least 1 therapeutic ERCP. The procedure was more commonly performed in children with CP compared with those with ARP (65.8% vs 13.5%, P < 0.0001). Utility of therapeutic ERCP was reported to be similar between ARP and CP (53% vs 56%, P = 0.81) and was found to be helpful for at least 1 indication in both groups (53/99 patients [53.5%]). Predictors for undergoing therapeutic ERCP were presence of obstructive factors in ARP and CP, Hispanic ethnicity, or white race in CP., Conclusions: Therapeutic ERCP is frequently utilized in children with ARP or CP and may offer benefit in selected cases, specifically if ductal obstruction is present. Longitudinal studies are needed to clarify the efficacy of therapeutic ERCP and to explore subgroups that might have increased benefit from such intervention.

Objectives: Pancreatic intraepithelial neoplasia lesions can appear as chronic pancreatitis-like changes on endoscopic ultrasound (EUS). The aim of our study was to determine if BRCA2 mutation carriers were more likely than noncarriers to demonstrate chronic pancreatitis-like changes on EUS., Methods: Patients with BRCA2 mutations referred for EUS were identified (cases) from an endoscopy database. Controls were matched with cases in a 2:1 ratio for sex, date EUS was performed, endoscopist, and echoendoscope. Data were extracted from medical records, EUS reports, and EUS images. Rosemont classification was used to categorize chronic pancreatitis-like changes., Results: During the study period, 37 BRCA2 mutation carriers and 92 controls underwent EUS. Compared with controls, BRCA2 mutation carriers had a higher prevalence of solid pancreas lesions (16.2% vs 1.08%; P = 0.005), pancreatic cysts (21.6% vs 6.1%; P = 0.01), Rosemont "consistent with chronic pancreatitis" definition changes (13.5% vs 1%; P = 0.002), and Rosemont "suggestive of chronic pancreatitis" definition changes (16.2% vs 2.1%; P = 0.003). After adjusting for age, alcohol use, and smoking, BRCA2 mutation carriers were almost 25 times more likely to demonstrate chronic pancreatitis-like changes., Conclusions: Chronic pancreatitis-like changes, along with solid and cystic pancreatic lesions, were significantly more common in BRCA2 mutation carriers than in noncarriers.

Objectives: We have previously shown that at least 50% of patients with asymptomatic chronic pancreatic hyperenzymemia (ACPH) may develop morphological pancreatic alterations. Endoscopic ultrasonography (EUS) may detect small lesions, and its sensitivity seems to be higher than other imaging techniques. The aim of this study was to evaluate whether EUS may modify the management of patients having ACPH., Methods: In 2 referral centers for pancreatic disease, a retrospective analysis of prospectively enrolled patients with ACPH was conducted., Results: Seventy-three patients with ACPH were enrolled for the purpose of this study. Endoscopic ultrasonography was performed as the last examination in 45 subjects who resulted negative at previous imaging studies (abdominal ultrasound, computed tomography, magnetic resonance imaging associated with cholangiopancreatography). Using EUS in 7 subjects, abnormalities were found in the following: 3 branch-duct intraductal papillary mucinous neoplasms, 1 duodenal diverticulum, 1 annular pancreas, 1 findings suggestive of chronic pancreatitis, and 1 undefined cyst (<5 mm)., Conclusions: Endoscopic ultrasonography is able to detect alteration not found by other imaging technique in 15.5% of patients with ACPH and may be useful to select those patients who require a more strict follow-up.

Objectives: Hereditary pancreatitis (HP) is characterized by recurrent episodes of inflammation of the pancreas. Radiological imaging is used to diagnose HP and to monitor complications. The aim of this study was to describe specific imaging findings in HP., Methods: We retrospectively collected data of HP patients with serial imaging and reviewed all radiological imaging studies (transabdominal ultrasonography, computed tomography, and magnetic resonance imaging)., Results: We included 15 HP patients, with a mean age of 32.5 years (range, 9-61 years) and mean disease duration of 24.1 years (range, 6-42 years). In total, 152 imaging studies were reviewed. Seventy-three percent of patients had a dilated main pancreatic duct (MPD) (width 3.5-18 mm). The MPD varied in size during disease course, with temporary reduction in diameter after drainage procedures. A severe dilated MPD (>10 mm) often coincided with presence of intraductal calcifications (size, 1-12 mm). In 73% of patients, pancreatic parenchyma atrophy occurred, which did not correlate with presence of exocrine or endocrine insufficiency., Conclusions: In HP, the MPD diameter increases with time, mostly without dilated side branches, and is often accompanied by large intraductal calcifications. The size of the MPD is independent of disease state. Atrophy of pancreatic parenchyma is not correlated with exocrine or endocrine insufficiency.

Objectives: Diagnosing chronic pancreatitis remains challenging. Endoscopic ultrasound (EUS) is utilized to evaluate pancreatic disease. Abnormal pancreas function test is considered the "nonhistologic" criterion standard for chronic pancreatitis. We derived a prediction model for abnormal endoscopic pancreatic function test (ePFT) by enriching EUS findings with patient demographic and pancreatitis behavioral risk characteristics., Methods: Demographics, behavioral risk characteristics, EUS findings, and peak bicarbonate results were collected from patients evaluated for pancreatic disease. Abnormal ePFT was defined as peak bicarbonate of less than 75 mEq/L. We fit a logistic regression model and converted it to a risk score system. The risk score was validated using 1000 bootstrap simulations., Results: A total of 176 patients were included; 61% were female with median age of 48 years (interquartile range, 38-57 years). Abnormal ePFT rate was 39.2% (69/176). Four variables formulated the risk score: alcohol or smoking status, number of parenchymal abnormalities, number of ductal abnormalities, and calcifications. Abnormal ePFT occurred in 10.7% with scores 4 or less versus 92.0% scoring 20 or greater. The model C-statistic was 0.78 (95% confidence interval, 0.71-0.85)., Conclusions: Number of EUS pancreatic duct and parenchymal abnormalities, presence of calcification, and smoking/alcohol status were predictive of abnormal ePFT. This simple model has good discrimination for ePFT results.

Objectives: The aim of this study was to investigate the contribution of smoking and alcohol intake and pancreas divisum on the risk of developing chronic pancreatitis (CP)., Methods: Consecutive patients with CP who underwent secretin-enhanced magnetic resonance cholangiopancreatography were compared with consecutive patients without pancreatic disease who underwent secretin-enhanced magnetic resonance cholangiopancreatography for irritable bowel syndrome., Results: We enrolled 145 consecutive CP patients and 103 irritable bowel syndrome patients from 2010 to 2014. In a univariate analysis, statistically significant differences in sex, mean age, and the duration and amount of cigarette and alcohol use were found. Per a receiver operating characteristic curve analysis, thresholds for cigarette and alcohol consumption were, respectively, 5.5 cigarettes and 13.5 g daily. In a multivariate analysis, independent risk factors for CP were male sex (odds ratio [OR], 2.05), smoking more than 5.5 cigarettes per day (OR, 2.72), and drinking more than 13.5 g/d (OR, 6.35)., Conclusions: In an Italian population, we confirmed smoking and alcohol as cofactors in the development of CP. This study shows that alcohol intake and smoking habits are 2 of the most important risk factors for the development of CP.

Objectives: Previous studies have shown changes in the pancreas of type 1 diabetic (T1-DM) patients, similar to those present in patients with chronic pancreatitis. Our aim was to analyze the prevalence of endoscopic ultrasound (EUS) criteria for chronic pancreatitis in T1-DM, to determine the association with factors related to the diabetes and to define its clinical significance., Methods: Eighty-six T1-DM patients were prospectively included. All of them underwent EUS. Standard criteria were used. Patients were divided into 3 groups according to the number of EUS criteria they met: group A, 0 to 2 criteria; group B, 3 to 4; and group C, more than 4. Association between EUS findings and demographic or clinical factors was studied as well as the relationship between EUS abnormalities and the presence of gastrointestinal symptoms or nutritional deficiencies., Results: Fifty-three patients (61.6%) showed at least 1 morphologic abnormality. Fifty-eight patients were included in group A, 21 in group B, and 7 in Group C. No significant differences were found when comparing the 3 groups., Conclusions: Chronic pancreatitis-like changes are frequent in the pancreas of T1-DM patients. These changes are not associated with demographic or clinical data. Therefore, the clinical relevance seems to be scarce.

Objectives: Approximately two thirds of patients will remain on insulin therapy after total pancreatectomy with islet autotransplant (TPIAT) for chronic pancreatitis. We investigated the relationship between measured pancreas volume on computerized tomography or magnetic resonance imaging and features of chronic pancreatitis on imaging, with subsequent islet isolation and diabetes outcomes., Methods: Computerized tomography or magnetic resonance imaging was reviewed for pancreas volume (Vitrea software) and presence or absence of calcifications, atrophy, and dilated pancreatic duct in 97 patients undergoing TPIAT. Relationship between these features and (1) islet mass isolated and (2) diabetes status at 1-year post-TPIAT were evaluated., Results: Pancreas volume correlated with islet mass measured as total islet equivalents (r = 0.50, P < 0.0001). Mean islet equivalents were reduced by more than half if any one of calcifications, atrophy, or ductal dilatation were observed. Pancreatic calcifications increased the odds of insulin dependence 4.0 fold (1.1, 15). Collectively, the pancreas volume and 3 imaging features strongly associated with 1-year insulin use (P = 0.07), islet graft failure (P = 0.003), hemoglobin A1c (P = 0.0004), fasting glucose (P = 0.027), and fasting C-peptide level (P = 0.008)., Conclusions: Measures of pancreatic parenchymal destruction on imaging, including smaller pancreas volume and calcifications, associate strongly with impaired islet mass and 1-year diabetes outcomes.

On May 16, 2015 at the invitation of the American Gastroenterological Association Institute Council E.P.D. presented a state-of-the-art lecture at Digestive Disease Week 2015. The aims were to discuss a selection of landmark papers in chronic pancreatitis (CP) that influence modern management and to conclude by suggesting some future directions. This is based on that presentation. We will specifically review the following: duct anatomy and pancreas divisum, description of chronic relapsing pancreatitis and its differentiation from recurrent acute pancreatitis and established CP (ECP), natural histories and gene discoveries of alcoholic, idiopathic and hereditary pancreatitis, development of pancreatic cancer in CP, exocrine pancreatic insufficiency and calculation of dose and delivery of enzymes, endoscopic ultrasonography, and autoimmune pancreatitis. With some exceptions, we exclude basic science and surgery.

Objectives: Patients with chronic pancreatitis are managed by extracorporeal shock wave lithotripsy (ESWL) for pancreatic stones. Stone density on noncontrast computed tomography (NCCT) is used to predict stone composition and fragility, but no report investigating the pancreatic stone density has been documented. We aimed to assess the usefulness of pancreatic stone density on NCCT in predicting the ESWL outcome., Methods: We evaluated 128 consecutive patients with pancreatic stones who underwent ESWL. Pancreatic stone density on NCCT was measured in Hounsfield units. Patients with complete stone removal were compared with those with incomplete stone removal. Patient characteristics; imaging findings, including stone density; and interventions were evaluated as potential predictors. The optimal cutoff value of variables to differentiate complete removal from incomplete removal was determined by receiver operating characteristic analysis., Results: Complete stone removal was achieved in 66 patients (51.6%). When the density threshold was set at 820.5 Hounsfield units, complete stone removal was achieved in 52 patients (78.8%) with lower-density stones. In multivariate analysis, single stone (P = 0.007) and lower-density stone (P < 0.001) revealed significant association with complete stone removal., Conclusions: The measurement of pancreatic stone density before therapy can help predict therapeutic outcomes.

Objectives: Knowledge of risk factors for development of pancreatic ductal adenocarcinoma (PDAC) is limited. To clarify the background condition of the pancreas for the development of PDAC, we analyzed pancreatic histological changes in noncancerous lesion specimens after pancreatectomy in PDAC patients., Methods: Seventy-six patients with PDAC were enrolled in this study. The PDAC was in the pancreatic head in 37 patients, in the body in 31, and in the tail in 8. No patients had a history of clinical chronic pancreatitis. As controls, 98 patients without PDAC were enrolled. The following parameters were examined: fibrosis, fatty degeneration, and inflammatory cell infiltration. More than 5% of fatty degeneration in the specimen, more than 10% of fibrosis, and more than 5% of inflammatory cell infiltration were considered positive changes., Results: Pancreatectomy specimens showed a higher ratio of positive change in fibrosis (86% vs 42%), fatty degeneration (72% vs 44%), and inflammatory cell infiltration (14% vs 3%) than control samples. Multivariate analyses demonstrated that each histological change was a significant, independent determinant for PDAC., Conclusions: Our study demonstrated that cryptogenic pancreatic inflammation with fatty changes represents an important predisposing factor for PDAC. Screening for subclinical chronic pancreatitis in healthy populations may enable the detection of PDAC at an early stage.

Objective: This study aimed to evaluate associations between endoscopic ultrasound (EUS) criteria for chronic pancreatitis (CP) and coexisting pancreatic intraepithelial neoplasia (PanIN) lesions., Methods: Patients with known or suspected CP who underwent pancreatic resection within a year of EUS were selected. Histology slides and EUS images were reviewed for evidence of pancreatic fibrosis., Results: Ninety-seven (51 men; mean age, 53 [12] years) underwent EUS within a 1 year or less of EUS. Pancreatic intraepithelial neoplasia lesions were found in 84 (87%) patients. Pancreatic intraepithelial neoplasia 1, 2, and 3 lesions were seen in 71 (83%), 10 (14%), and 1 (2%), respectively. Two patients had more than 1 PanIN grade (one had PanIN 1 and 2 and the other had PanIN 1 and 3). The mean number of EUS criteria for PanIN 1, 2, and 3 lesions were 3.9, 4.5, and 5.5, respectively. The odds ratio for the association between PanIN 2 and hyperechoic foci without shadowing in the pancreas head was 8.5 (P = 0.05). The odds ratio for the association between PanIN 2 and lobularity with honeycombing was 2.7 (P = ns). Advanced PanIN lesions had greater than or equal to 4 EUS criteria for CP., Conclusions: Pancreatic intraepithelial neoplasia lesions were highly prevalent in CP resections. Increasing PanIN grade is observed with increasing fibrosis score and increasing number of EUS criteria for CP.

Objectives: This study aimed to correlate endoscopic ultrasound (EUS) criteria and pathology in patients with chronic pancreatitis (CP)., Methods: Endoscopic ultrasound reports and pathology specimens were reviewed from patients with known or suspected CP who underwent surgery within 1 year of EUS. The following information was abstracted: EUS criteria for CP, corresponding pathology results, and histologic features. The EUS and pathology results were correlated., Results: One hundred patients (55 men; mean age, 54 years) underwent a pancreatic resection, median of 50 days (range, 1-363 days). The mean (SD) fibrosis scores in the head and body/tail specimens were 7.9 (3.0) and 6.4 (3.8), respectively (P = 0.02). The main pancreatic duct (MPD) dilation and irregularity were associated with moderate and severe fibrosis. Lobularity with honeycombing was associated with intralobular and interlobular fibrosis. Severe CP was associated with the following: lobularity with honeycombing, hyperechoic foci with shadowing, hyperechoic foci without shadowing, MPD dilation, MPD irregularity, and dilated side branches., Conclusions: Endoscopic ultrasound of the pancreas head may be considered in the evaluation of CP. The EUS criteria that were associated with severe CP included the following: lobularity with honeycombing, hyperechoic foci with shadowing, dilated MPD, irregular MPD, and dilated side branches. The importance of pancreatic ductal changes should not be minimized in the evaluation of CP.

Objectives: Endoscopic ultrasound (EUS) quality benchmarks for pancreatic disease previously focused on maintaining thresholds of diagnostic accuracy for fine-needle aspiration and measuring complications. We aimed to evaluate quality indicators when performing EUS specifically for the diagnosis of chronic pancreatitis (CP)., Methods: Using a single-center EUS database, we identified patients who underwent an EUS since 2001 specifically for the indication of (1) suspected CP, (2) exclusion of CP, or (3) established CP. Each EUS report was evaluated for the number of parenchymal and ductal criteria as per minimal standards terminology criteria., Results: Two hundred eighty-six EUS examinations performed by 4 endosonographers were included. The mean number of reported evaluated parenchymal criteria was 2.44 (median, 2), and that of ductal criteria was 2.41 (median, 2). There was a difference among endosonographers in terms of mean number of total criteria reported evaluated (P < 0.001): endosonographer 1 = 3.9 (n = 174 examinations), endosonographer 2 = 6.8 (n = 86 examinations), endosonographer 3 = 6.2 (n = 13 examinations), and endosonographer 4 = 2.5 (n = 11 examinations). However, there was no difference between endosonographers in the number of total (parenchymal and ductal) criteria found., Conclusions: There was a discrepancy among endosonographers when reporting which EUS findings were evaluated in patients undergoing EUS specifically to diagnose CP.

Objectives: This study aimed to determine whether (1) a pancreatic duct (PD) diameter to pancreatic gland width (G) ratio (PDG) by endoscopic ultrasonography (EUS) predicts pancreatic cancer (PC) and (2) whether this ratio better indicates PC compared to PD dilation alone., Methods: Patients presenting for EUS were classified into the following 4 categories: (1) normal, (2) noncalcific chronic pancreatitis (NCCP), (3) calcific CP (CCP), and (4) PC., Results: There were 198 patients enrolled. Final diagnoses were PC (n = 34), CCP (n = 16), and normal/NCCP (n = 148). The median PD diameter (8, 5, and 2 mm, respectively; P = <0.001), G (16, 20, and 17 mm, respectively; P = 0.002), and PDG ratio were significantly different among groups (0.54, 0.25, and 0.12, respectively; P < 0.001). Patients with PC were more likely to have a PDG ratio of greater than or equal to 0.34 compared to CCP, and normal/NCCP groups (94%, 19%, 1.3%, respectively; P < 0.001). The positive predictive value, negative predictive value, sensitivity, specificity, and accuracy of PDG greater than or equal to 0.34 for detecting cancer were 87%, 99%, 94%, 97%, and 97%, respectively. The accuracy and positive predictive value of PD dilation alone for diagnosing PC were 83% and 50%, respectively., Conclusions: A PDG ratio is a good predictor of PC and is better than PD dilation. This sign should be routinely used by endosonographers to improve EUS diagnostic capability of PC.

Objectives: Endoscopic ultrasound (EUS) evaluation of pancreatic duct compliance after secretin stimulation (sEUS) along with EUS morphologic examination (EUS) and duodenal fluid [HCO3] measurement (endoscopic pancreatic function test, ePFT) in 1 endoscopic session has not been reported as a means of evaluating for chronic pancreatitis (CP). We evaluated the feasibility of the combined examination and compared EUS measurements of pancreatic ductal compliance with duodenal fluid [HCO3] for diagnosing CP., Methods: The study is a prospective case series of patients with suspected CP who underwent a combined EUS, sEUS, and ePFT examination in 1 endoscopic session. The main outcome measures were the feasibility of performing the combination examination and the correlation between ductal compliance and ePFT., Results: All examinations were completed in 1 endoscopic session, and there were no complications in 35 patients. Although there was a trend toward less change from baseline head and body ductal diameter in patients with CP, only the percent change from baseline in the tail was significant (CP 144.3% vs healthy patients 240.9%, P < 0.01). Regression analysis demonstrated fair correlation between maximum change in ductal diameter and duodenal fluid [HCO3] (r = 0.27)., Conclusions: Combined EUS, sEUS, and ePFTs are feasible and safe, with preliminary results demonstrating a positive correlation between pancreatic ductal compliance and duodenal fluid [HCO3].

Objective: Assess intraobserver agreement among endosonographers for endoscopic ultrasound (EUS) features of chronic pancreatitis (CP)., Methods: Thirty EUS images from patients with suspected CP were shown twice in random order to 5 blinded endosonographers. The following accepted features of CP were assessed: (1) hyperechoic foci, (2) hyperechoic strands, (3) lobularity, (4) cysts, (5) stones, (6) main pancreatic duct dilatation, (7) pancreatic duct irregularity, (8) hyperechoic duct margins, (9) visible side branches, and (10) overall assessment for CP. Intraobserver κ statistics were calculated for each endosonographer and for each feature. Interobserver κ was also calculated., Results: The mean intraobserver κ values were 0.82, 0.65, 0.71, 0.59, and 0.86 for the 5 endosonographers. The mean intraobserver κ values for each feature were (1) 0.66, (2) 0.67, (3) 0.70, (4) not calculable, (5) 0.96, (6) 0.81, (7) 0.77, (8) 0.69, (9) 0.51, and (10) 0.73. The mean interobserver κ values were 0.19, 0.07, 0.53, not calculable, 0.77, 0.77, 0.60, 0.34, 0.11, and 0.39, respectively., Conclusions: There was good intraobserver agreement in the interpretation of EUS features of CP. The intraobserver agreement seems better than the published interobserver agreement for EUS features of CP and better than the published intraobserver agreement for endoscopic retrograde cholangiopancreatography imaging for CP.

Objective: To clarify the implication of pancreatic findings on transabdominal ultrasound and/or abdominal computed tomographic scan on outcomes of islet isolation and endocrine function after total pancreatectomy (TP) with islet autotransplantation (IAT)., Methods: Retrospective review of islet isolations and graft functions in a cohort of patients with chronic pancreatitis who received TP with IAT from December 2007 to September 2009. Patients were categorized into the following 2 groups on the basis of their transabdominal ultrasound or computed tomographic findings before IAT: early group (normal or equivocal of Cambridge classification) and advanced group (mild to marked)., Results: A total of 12 patients (early group, n=6; advanced group, n=6) were included. Total islet yield per pancreas weight and per patient body weight in the early group was significantly higher compared with that in the advanced group (6989±659 vs 3567±615 islet equivalents per gram, P<0.01; 8556±953 vs 3847±739 islet equivalents per kilogram, P<0.01, respectively). Four patients (67%) in the early group became insulin-free, whereas 2 patients (33%) in the advanced group obtained insulin independence. However, both groups maintained islet graft function and similar glycated hemoglobin levels after transplantation., Conclusions: Excellent glycemic control was observed in both groups of patients who received TP with IAT, although the early group showed a significantly better outcome of islet isolation.

Objectives: To provide histologic correlation of endoscopic ultrasound (EUS) findings believed to represent chronic pancreatitis (CP)., Methods: Eighteen postmortem pancreatic specimens in patients dying of all causes were examined in vitro by EUS for features of CP: (1) echogenic foci, (2) hypoechoic foci, (3) echogenic main pancreatic duct (MPD), (4) accentuated lobular pattern, (5) cysts, (6) irregular MPD, (7) dilated MPD, (8) side branch dilation, and (9) calculi. The pancreata were then examined by 2 pathologists (blinded to the EUS/clinical findings) for histopathologic features of CP., Results: Six specimens were autolyzed, and in 1 specimen, MPD could not be seen by EUS. In the other 11 patients, 10 had evidence of CP by EUS (> or =3 features) and by histopathologic examination (> or =2 features). One patient did not have CP by both EUS and histologic examination., Conclusions: Endoscopic ultrasound accurately detected CP, when compared with histopathologic examination. The presence of 3 or more features of CP correlates with the histologic diagnosis of CP, however, up to 3 features are frequently present in elderly patients dying of all causes. Future studies should address the clinical relevance and the specificity of EUS findings of CP in the older population.

Objectives: We investigated the feasibility of using real-time tissue elastography (EG) with transcutaneous ultrasonography (EG-US) for pancreatic diseases., Methods: A preliminary study (phase I) and a prospective (phase II) study were conducted. Phase I: subjects were 10 volunteers, 5 with cancer, 2 with endocrine tumor, 5 with chronic pancreatitis, 14 with intraductal papillary-mucinous neoplasm. To determine the characteristic EG images (diagnostic criteria for phase II), B-mode images were compared with EG images and histopathologic findings. Phase II: 53 consecutive patients were enrolled. The visualization rate by EG-US in lesions visualized by B mode was assessed, and the correct diagnosis rate by B mode alone (B diagnosis) or in combination with EG-US was evaluated., Results: Phase I: normal parenchyma was a homogeneous color. In cancer, EG-US showed a markedly hard area with soft spots inside. Endocrine tumor was uniform and soft comparable to parenchyma. Chronic pancreatitis showed a mixture of various colors. Phase II: we identified 77.4% (41/53) of the lesions and observed 60.0% (15/25) of the cancers, 100% (3/3) of the endocrine tumor, 92.0% (23/25) of the cases of chronic pancreatitis cases on EG-US. The B-diagnosis rates ranged from about 70% to 80%. The diagnosis rates of the combination were more than 90% of lesions of each type., Conclusions: The EG-US is feasible in the diagnosis of pancreatic diseases.

Objectives: Cystic fibrosis transmembrane conductance regulator (CFTR), cationic trypsinogen gene (PRSS1), and serine protease inhibitor kazal type 1 (SPINK1) gene mutations have been associated with chronic pancreatitis (CP). The aim of this study was to compare clinical and radiological findings in sporadic CP with (CPgm) and without (CPwt) gene mutations., Methods: Data from patients observed between 2001 and 2006 were collected. All patients were tested for 25 CFTR gene mutations, for R122H and N29I on the PRSS1 gene, and for N34S mutation on the SPINK1 gene., Results: We found 34 (17.2%) of 198 patients with CPgm, 23 (11.6%) of them on the CFTR gene, 11 (5.6%) on the SPINK1, and none on the PRSS1 gene. The age at clinical onset was younger in CPgm (36.2 +/- 17.2 years) than in CPwt (44 +/- 12.6 years; P = 0.005). There were more heavy drinkers among CPwt (33%) than among CPgm (9%; P = 0.003), and the same applied to smokers (69% vs 33%, respectively; P < 0.0001). In CPgm group, the onset of pancreatic calcifications was observed more frequently in drinkers and/or smokers. Exocrine and endocrine insufficiency occurred less frequently and later in CPgm than in CPwt patients., Conclusions: Clinical and radiological outcome differ in CPgm compared with CPwt. Alcohol, even in small quantities, and cigarette smoking influence the onset of pancreatic calcifications.

Objective: To correlate cross-sectional imaging findings with histological results in patients with histopathologically proven lymphoplasmacytic sclerosing pancreatitis (LSP) after surgery., Methods: Four cases of resectable pancreatic lesions that were proven to represent LSP are presented in our study. All patients were thought to harbor malignancy. A detailed research in patients' records was retrospectively done concerning clinical presentation and imaging studies., Results: Characteristic imaging findings consistent with fibrotic changes were evident in only one case on magnetic resonance imaging. A discrete mass was evident on imaging in 2 patients that correlated well with pathology results. In the other patients, the extent of inflammatory changes on microscopic examination correlated well with the degree of pancreatic head enlargement on imaging studies., Conclusions: Lymphoplasmacytic sclerosing pancreatitis is a particular form of benign inflammatory pancreatic disease that is extremely difficult to diagnose preoperatively. Familiarization with the variable imaging findings is essential and may result in the reduction of the number of patients with LSP who undergo surgical resection.

Objectives: Despite the advances in pancreatic imaging, there continues to be a need to measure exocrine function to determine which patient requires enzyme supplementation. To evaluate the potential use of a rapid endoscopic test that can be conducted by nonacademic centers, we investigated whether concentration of trypsin in food-stimulated secretion is related to trypsin synthesis and secretion., Methods: Subjects include 22 chronic pancreatitis patients (10 mild, 5 moderate, and 7 severe radiological disease) and 11 healthy controls. During upper gastrointestinal endoscopy, pancreatic secretion was stimulated by a single 30-mL duodenal injection of an enteral diet, followed 5 minutes later by periampullary juice aspiration (endoscopic pancreatic function test [ePFT]). This was followed by a conventional 2-hour marker-perfusion diet-stimulated pancreatic trypsin secretion and synthesis study (2-hour PFT [2hPFT])., Results: Severity of radiological disease was associated with a progressive loss of enzyme secretion measured by the 2hPFT. The endoscopic PFT correlated positively with 2hPFT (r2 = 0.48; P < 0.0001) and an activity of less than 5% of the average normal had a 96% specificity and 75% sensitivity for the detection of pancreatic insufficiency as defined by a loss of greater than 90% of pancreatic secretion., Conclusions: The diagnostic power of endoscopy may be enhanced by the collection of a pancreatic juice sample after enteral feed stimulation because measurement of the trypsin content will identify chronic pancreatitis patients who will be benefited by enzyme supplementation.

Autoimmune chronic pancreatitis (AIP) is increasingly being recognized as a worldwide entity. In 2002, the Japan Pancreas Society published diagnostic criteria for AIP. Since then, increased attention toward this relatively new disease entity has enabled more cases of AIP to be correctly diagnosed, allowing for proper management and avoidance of surgery. Retrospective inclusion of previously unrecognized or misdiagnosed cases of AIP has revealed an increasing number of cases that are not in full accordance with the Japanese diagnostic criteria. As a result, some groups have developed and cited their own criteria in the reporting of AIP, and the Japan Pancreas Society criteria have also undergone revision recently. The absence of consistent and uniform criteria has made the comparison of different cases diagnosed under various guidelines difficult. In this review, we discuss and compare the 4 current diagnostic criteria, focusing on their own strength and weakness with the aim of providing a framework for the development of unified criteria that represent an international consensus.

Gastrointestinal manifestations are common in systemic lupus erythematous (SLE), occurring in 35% to 40% of patients at some stage of their illness. SLE is an uncommon etiology of pancreatic disease. Only 3 cases of chronic pancreatitis associated with SLE have been reported in adults. We report the case of a 59-year-old white woman with a history of mechanic aortic valve replacement and SLE presented to the emergency unit for acute pancreatitis with no other identifiable etiology.

Although fluorine-18 deoxyglucose-positron emission tomography (FDG-PET) is a sensitive diagnostic modality in detecting malignant tumors, differential diagnosis of malignant tumors from inflammatory lesion is challenging. We experienced a case of acute degenerative necrosis superimposed on chronic pancreatitis, which was difficult to distinguish from pancreatic cancer. The patient was a 66-year-old man with a complaint of upper abdominal pain. Abdominal computed tomography revealed low-density masses in the head and body of the pancreas. FDG-PET revealed intense accumulations at the head and body of the pancreas (mean standard uptake value for the head and body pancreatic tumors was 4.1 and 6.7, respectively) corresponding to the 2 tumors detected by computed tomography. Because of a possible malignant pancreatic tumor, the patient underwent pylorus-preserving pancreatoduodenectomy. Histologic examination of the resected specimen revealed a characteristic of chronic pancreatitis in a nontumorous area. Two tumors detected by FDG-PET consisted of degenerative necrosis surrounded by granulation tissue. The amount of granulation tissue was correlated to the levels of standard uptake value. No malignant tumors were observed. This case suggests a limitation of FDG-PET in distinguishing malignant neoplastic lesions in the pancreas, especially from acute degenerative changes in chronic pancreatitis. Repetitive PET examination is recommended for the accurate diagnosis.