The Modified Pancreatitis Activity Scoring System Shows Distinct Trajectories in Acute Pancreatitis: An International Study.

BACKGROUND & AIMS: The aims of this study were to: (1) assess the performance of the Pancreatitis Activity Scoring System (PASS) in a large intercontinental cohort of patients with acute pancreatitis (AP); and (2) investigate whether a modified PASS (mPASS) yields a similar predictive accuracy and produces distinct early trajectories between severity subgroups. METHODS: Data was prospectively collected through the Acute Pancreatitis Patient Registry to Examine Novel Therapies In Clinical Experience (APPRENTICE) consortium (2015-2018) involving 22 centers from 4 continents. AP severity was categorized per the revised Atlanta classification. PASS trajectories were compared between the three severity groups using the generalized estimating equations model. Four mPASS models were generated by modifying the morphine equivalent dose (MED), and their trajectories were compared. RESULTS: A total of 1393 subjects were enrolled (median age, 49 years; 51% males). The study cohort included 950 mild (68.2%), 315 (22.6%) moderately severe, and 128 (9.2%) severe AP. Mild cases had the lowest PASS at each study time point (all P < .001). A subset of patients with outlier admission PASS values was identified. In the outlier group, 70% of the PASS variation was attributed to the MED, and 66% of these patients were from the United States centers. Among the 4 modified models, the mPASS-1 (excluding MED from PASS) demonstrated high performance in predicting severe AP with an area under the receiver operating characteristic curve of 0.88 (vs area under the receiver operating characteristic of 0.83 in conventional PASS) and produced distinct trajectories with distinct slopes between severity subgroups (all P < .001). CONCLUSION: We propose a modified model by removing the MED component, which is easier to calculate, predicts accurately severe AP, and maintains significantly distinct early trajectories.

The relationship between pre-existing diabetes mellitus and the severity of acute pancreatitis: Report from a large international registry.

BACKGROUND/OBJECTIVES: The relationship between pre-existing diabetes mellitus (DM) and acute pancreatitis (AP) severity has not been established. We assessed the impact of pre-existing DM on AP severity in an international, prospectively ascertained registry. METHODS: APPRENTICE registry prospectively enrolled 1543 AP patients from 22 centers across 4 continents (8 US, 6 Europe, 5 Latin America, 3 India) between 2015 and 2018, and collected detailed clinical information. Pre-existing DM was defined a diagnosis of DM prior to AP admission. The primary outcome was AP severity defined by the Revised Atlanta Classification (RAC). Secondary outcomes were development of systemic inflammatory response syndrome (SIRS) or intensive care unit (ICU) admission. RESULTS: Pre-existing DM was present in 270 (17.5%) AP patients, of whom 252 (93.3%) had type 2 DM. Patients with pre-existing DM were significantly (p < 0.05) older (55.8 ± 16 vs. 48.3 ± 18.7 years), more likely to be overweight (BMI 29.5 ± 7 vs. 27.2 ± 6.2), have hypertriglyceridemia as the etiology (15% vs. 2%) and prior AP (33 vs. 24%). Mild, moderate, and severe AP were noted in 66%, 23%, and 11% of patients, respectively. On multivariable analysis, pre-existing DM did not significantly impact AP severity assessed by the RAC (moderate-severe vs. mild AP, OR = 0.86, 95% CI 0.63-1.18; severe vs. mild-moderate AP, OR = 1.05, 95% CI, 0.67-1.63), development of SIRS, or the need for ICU admission. No interaction was noted between DM status and continent. CONCLUSION: About one in 5 patients with AP have pre-existing DM. Once confounding risk factors are considered, pre-existing DM per se is not a risk factor for severe AP.

Mortality in acute pancreatitis with persistent organ failure is determined by the number, type, and sequence of organ systems affected.

BACKGROUND: Persistent organ failure (POF) is the strongest determinant of mortality in acute pancreatitis (AP). There is a paucity of data regarding the impact of different POF attributes on mortality and the role of different characteristics of systemic inflammatory response syndrome (SIRS) in the risk of developing POF. OBJECTIVE: We aimed to assess the association of POF dynamic features with mortality and SIRS characteristics with POF. METHODS: We studied 1544 AP subjects prospectively enrolled at 22 international centers (APPRENTICE consortium). First, we estimated the association of onset, duration, and maximal score of SIRS with POF. Then, we evaluated the risk of mortality based on POF onset, duration, number, type, and sequence of organs affected. Analyses were adjusted for potential confounders. RESULTS: 58% had SIRS, 11% developed POF, and 2.5% died. Early SIRS, persistent SIRS, and maximal SIRS score ≥ 3 were independently associated with higher risk of POF (p < 0.05). Mortality risk in POF was higher with two (33%, odds ratio [OR] = 10.8, 3.3-34.9) and three (48%, OR = 20.2, 5.9-68.6) organs failing, in comparison to single POF (4%). In subjects with multiple POF, mortality was higher when the cardiovascular and respiratory systems failed first or concurrently as compared to when the renal system failed first or concurrently with other organ (p < 0.05). In multivariate regression model, the number and sequence of organs affected in POF were associated with mortality (p < 0.05). Onset and duration of POF had no impact mortality. CONCLUSION: In AP patients with POF, the risk of mortality is influenced by the number, type, and sequence of organs affected. These results are useful for future revisions of AP severity classification systems.

Incidence and risk factors of oral feeding intolerance in acute pancreatitis: Results from an international, multicenter, prospective cohort study.

BACKGROUND: Inability to advance to an oral diet, or oral feeding intolerance, is a common complication in patients with acute pancreatitis associated with worse clinical outcomes. The factors related to oral feeding intolerance are not well studied. OBJECTIVE: We aimed to determine the incidence and risk factors of oral feeding intolerance in acute pancreatitis. METHODS: Patients were prospectively enrolled in the Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience, an international acute pancreatitis registry, between 2015 and 2018. Oral feeding intolerance was defined as worsening abdominal pain and/or vomiting after resumption of oral diet. The timing of the initial feeding attempt was stratified based on the day of hospitalization. Multivariable logistic regression was performed to assess for independent risk factors/predictors of oral feeding intolerance. RESULTS: Of 1233 acute pancreatitis patients included in the study, 160 (13%) experienced oral feeding intolerance. The incidence of oral feeding intolerance was similar irrespective of the timing of the initial feeding attempt relative to hospital admission day (p = 0.41). Patients with oral feeding intolerance were more likely to be younger (45 vs. 50 years of age), men (61% vs. 49%), and active alcohol users (44% vs. 36%). They also had higher blood urea nitrogen (20 vs. 15 mg/dl; p < 0.001) and hematocrit levels (41.7% vs. 40.5%; p = 0.017) on admission; were more likely to have a nonbiliary acute pancreatitis etiology (69% vs. 51%), systemic inflammatory response syndrome of 2 or greater on admission (49% vs. 35%) and at 48 h (50% vs. 26%), develop pancreatic necrosis (29% vs. 13%), moderate to severe acute pancreatitis (41% vs. 24%), and have a longer hospital stay (10 vs. 6 days; all p < 0.04). The adjusted analysis showed that systemic inflammatory response syndrome of 2 or greater at 48 h (odds ratio 3.10; 95% confidence interval 1.83-5.25) and a nonbiliary acute pancreatitis etiology (odds ratio 1.65; 95% confidence interval 1.01-2.69) were independent risk factors for oral feeding intolerance. CONCLUSION: Oral feeding intolerance occurs in 13% of acute pancreatitis patients and is independently associated with systemic inflammatory response syndrome at 48 h and a nonbiliary etiology.

Design and validation of a patient-reported outcome measure scale in acute pancreatitis: the PAN-PROMISE study.

OBJECTIVE: This study aimed to develop and validate a patient-reported outcome measure (PROM) in acute pancreatitis (AP) as an endpoint centred on the patient. DESIGN: A PROM instrument (PAtieNt-rePoRted OutcoMe scale in acute pancreatItis, an international proSpEctive cohort study, PAN-PROMISE scale) was designed based on the opinion of patients, professionals and an expert panel. The scale was validated in an international multicentre prospective cohort study, describing the severity of AP and quality of life at 15 days after discharge as the main variables for validation. The COSMIN (COnsensus-based Standards for the selection of health status Measurement INstruments) methodology was applied. Both the design and validation stages considered the content and face validity of this new instrument; the metric properties of the different items, reliability (reproducibility and internal consistence), the construct, structural and criterion validity, responsiveness and interpretability of this scale. RESULTS: PAN-PROMISE consists of a seven-item scale based on the symptoms that cause the most discomfort and concern to patients with AP. The validation cohort involved 15 countries, 524 patients. The intensity of symptoms changed from higher values during the first 24 hours to lower values at discharge and 15 days thereafter. Items converged into a unidimensional ordinal scale with good fit indices. Internal consistency and split-half reliability at discharge were adequate. Reproducibility was confirmed using test-retest reliability and comparing the PAN-PROMISE score at discharge and 15 days after discharge. Evidence is also provided for the convergent-discriminant and empirical validity of the scale. CONCLUSION: The PAN-PROMISE scale is a useful tool to be used as an endpoint in clinical trials, and to quantify patient well-being during the hospital admission and follow-up. TRIAL REGISTRATION NUMBER: NCT03650062.

Introduction and Validation of a Novel Acute Pancreatitis Digital Tool: Interrogating Large Pooled Data From 2 Prospectively Ascertained Cohorts.

OBJECTIVES: Acute pancreatitis (AP) is a sudden onset, rapidly evolving inflammatory response with systemic inflammation and multiorgan failure (MOF) in a subset of patients. New highly accurate clinical decision support tools are needed to allow local doctors to provide expert care. METHODS: Ariel Dynamic Acute Pancreatitis Tracker (ADAPT) is a digital tool to guide physicians in ordering standard tests, evaluate test results and model progression using available data, propose emergent therapies. The accuracy of the severity score calculators was tested using 2 prospectively ascertained Acute Pancreatitis Patient Registry to Examine Novel Therapies in Clinical Experience cohorts (pilot University of Pittsburgh Medical Center, n = 163; international, n = 1544). RESULTS: The ADAPT and post hoc expert-calculated AP severity scores were 100% concordant in both pilot and international cohorts. High-risk criteria of all 4 severity scores at admission were associated with moderately-severe or severe AP and MOF (both P < 0.0001) and prediction of no MOF was 97.8% to 98.9%. The positive predictive value for MOF was 7.5% to 14.9%. CONCLUSIONS: The ADAPT tool showed 100% accuracy with AP predictive metrics. Prospective evaluation of ADAPT features is needed to determine if additional data can accurately predict and mitigate severe AP and MOF.

Clinical features of hypertriglyceridemia-induced acute pancreatitis in an international, multicenter, prospective cohort (APPRENTICE consortium).

BACKGROUND: The clinical features and outcomes of hypertriglyceridemia-induced acute pancreatitis (HTG-AP) are not well-established. OBJECTIVE: To evaluate the clinical characteristics of HTG-AP in an international, multicenter prospective cohort. METHODS: Data collection was conducted prospectively through APPRENTICE between 2015 and 2018. HTG-AP was defined as serum TG levels >500 mg/dl in the absence of other common etiologies of AP. Three multivariate logistic regression models were performed to assess whether HTG-AP is associated with SIRS positive status, ICU admission and/or moderately-severe/severe AP. RESULTS: 1,478 patients were included in the study; 69 subjects (4.7%) were diagnosed with HTG-AP. HTG-AP patients were more likely to be younger (mean 40 vs 50 years; p < 0.001), male (67% vs 52%; p = 0.018), and with a higher BMI (mean 30.4 vs 27.5 kg/m2; p = 0.0002). HTG-AP subjects reported more frequent active alcohol use (71% vs 49%; p < 0.001), and diabetes mellitus (59% vs 15%; p < 0.001). None of the above risk factors/variables was found to be independently associated with SIRS positive status, ICU admission, or severity in the multivariate logistic regression models. These results were similar when including only the 785 subjects with TG levels measured within 48 h from admission. CONCLUSION: HTG-AP was found to be the 4th most common etiology of AP. HTG-AP patients had distinct baseline characteristics, but their clinical outcomes were similar compared to other etiologies of AP.

Worldwide Variations in Demographics, Management, and Outcomes of Acute Pancreatitis.

BACKGROUND & AIMS: Few studies have compared regional differences in acute pancreatitis. We analyzed data from an international registry of patients with acute pancreatitis to evaluate geographic variations in patient characteristics, management, and outcomes. METHODS: We collected data from the APPRENTICE registry of patients with acute pancreatitis, which obtains information from patients in Europe (6 centers), India (3 centers), Latin America (5 centers), and North America (8 centers) using standardized questionnaires. Our final analysis included 1612 patients with acute pancreatitis (median age, 49 years; 53% male, 62% white) enrolled from August 2015 through January 2018. RESULTS: Biliary (45%) and alcoholic acute pancreatitis (21%) were the most common etiologies. Based on the revised Atlanta classification, 65% of patients developed mild disease, 23% moderate, and 12% severe. The mean age of patients in Europe (58 years) was older than mean age for all 4 regions (46 years) and a higher proportion of patients in Europe had comorbid conditions (73% vs 50% overall). The predominant etiology of acute pancreatitis in Latin America was biliary (78%), whereas alcohol-associated pancreatitis accounted for the highest proportion of acute pancreatitis cases in India (45%). Pain was managed with opioid analgesics in 93% of patients in North America versus 27% of patients in the other 3 regions. Cholecystectomies were performed at the time of hospital admission for most patients in Latin America (60% vs 15% overall). A higher proportion of European patients with severe acute pancreatitis died during the original hospital stay (44%) compared with the other 3 regions (15%). CONCLUSIONS: We found significant variation in demographics, etiologies, management practices, and outcomes of acute pancreatitis worldwide. ClinicalTrials.gov number: NCT03075618.

Cystic Dystrophy of the Duodenal Wall in Heterotopic Pancreas with Groove Pancreatitis: A Diagnostic and Therapeutic Challenge.

Background: Cystic dystrophy of heterotopic pancreas is a benign, rare disease characterized by development of true cysts into the duodenal wall. Non-specific clinical manifestations and difficult to interpret imaging provide a diagnostic challenge, especially when pancreatic cancer is suspected. Surgical treatment (pancreatoduodenectomy) offer best outcomes. CASE REPORT: A 48 years-old man, chronic alcohol consumer, with a history of recurrent mild acute pancreatitis episodes, was diagnosed in 2010 with segmental chronic pancreatitis complicated by a 4cm pseudocyst in the pancreatic head. He stopped drinking, but acute episodes continued to reoccur, while the pseudocyst disappeared. In 2012 the patient was admitted to our department with painful chronic pancreatitis and a new acute episode. EUS diagnosed a cystic dystrophy of the duodenal wall with groove pancreatitis, and endoscopic opening of the cysts into the duodenum was performed. Laparoscopic cholecystectomy was imposed by small gallbladder stones seen at EUS. After 6 months of silence, pain and acute episodes reappeared, imposing pancreatoduodenectomy. Patient is now well, without symptoms during 5 years of follow-up. Conclusions: Cystic dystrophy of heterotopic pancreas can be thought of in case of recurrent idiopathic acute pancreatitis. EUS is the best diagnosis tool, and can provide opening of the cysts into the duodenum. Surgery - pancreatoduodenectomy - offer best results.

Acute pancreatitis patient registry to examine novel therapies in clinical experience (APPRENTICE): an international, multicenter consortium for the study of acute pancreatitis.

BACKGROUND: We have established a multicenter international consortium to better understand the natural history of acute pancreatitis (AP) worldwide and to develop a platform for future randomized clinical trials. METHODS: The AP patient registry to examine novel therapies in clinical experience (APPRENTICE) was formed in July 2014. Detailed web-based questionnaires were then developed to prospectively capture information on demographics, etiology, pancreatitis history, comorbidities, risk factors, severity biomarkers, severity indices, health-care utilization, management strategies, and outcomes of AP patients. RESULTS: Between November 2015 and September 2016, a total of 20 sites (8 in the United States, 5 in Europe, 3 in South America, 2 in Mexico and 2 in India) prospectively enrolled 509 AP patients. All data were entered into the REDCap (Research Electronic Data Capture) database by participating centers and systematically reviewed by the coordinating site (University of Pittsburgh). The approaches and methodology are described in detail, along with an interim report on the demographic results. CONCLUSION: APPRENTICE, an international collaboration of tertiary AP centers throughout the world, has demonstrated the feasibility of building a large, prospective, multicenter patient registry to study AP. Analysis of the collected data may provide a greater understanding of AP and APPRENTICE will serve as a future platform for randomized clinical trials.

Risk factors for surgical complications after central pancreatectomy.

BACKGROUND/AIMS: Central pancreatectomy is a pancreas-sparing alternative to standard pancreatic resections in selected cases. Although associated with high morbidity, the risk factors for surgical complications of this procedure are not yet defined. METHODOLOGY: The clinicopathological and perioperative data of 24 patients who underwent central pancreatectomies (2002-2010) were correlated with surgical complications. RESULTS: The overall morbidity rate was 54% (pancreatic fistula, 40%). In a univariate analysis, age over 40 years, body mass index ≥30kg/m2, smoking and American Society of Anesthesiologists III scores were significantly correlated with increased morbidity. In a multivariate analysis, a significant correlation with the development of complications was found for body mass index ≥30kg/m2 and age over 40 years. CONCLUSIONS: Certain patient-related factors (older age, obesity and smoking) appear to have a negative impact on early postoperative outcome after central pancreatectomy. For patients with these factors, an alternative distal pancreatectomy should be considered. Central pancreatectomy should be tailored not only to the pathology but also to the patient profile.