Gut microbiota predicts severity and reveals novel metabolic signatures in acute pancreatitis.

OBJECTIVE: Early disease prediction is challenging in acute pancreatitis (AP). Here, we prospectively investigate whether the microbiome predicts severity of AP (Pancreatitis-Microbiome As Predictor of Severity; P-MAPS) early at hospital admission. DESIGN: Buccal and rectal microbial swabs were collected from 424 patients with AP within 72 hours of hospital admission in 15 European centres. All samples were sequenced by full-length 16S rRNA and metagenomic sequencing using Oxford Nanopore Technologies. Primary endpoint was the association of the orointestinal microbiome with the revised Atlanta classification (RAC). Secondary endpoints were mortality, length of hospital stay and severity (organ failure >48 hours and/or occurrence of pancreatic collections requiring intervention) as post hoc analysis. Multivariate analysis was conducted from normalised microbial and corresponding clinical data to build classifiers for predicting severity. For functional profiling, gene set enrichment analysis (GSEA) was performed and normalised enrichment scores calculated. RESULTS: After data processing, 411 buccal and 391 rectal samples were analysed. The intestinal microbiome significantly differed for the RAC (Bray-Curtis, p value=0.009), mortality (Bray-Curtis, p value 0.006), length of hospital stay (Bray-Curtis, p=0.009) and severity (Bray-Curtis, p value=0.008). A classifier for severity with 16 different species and systemic inflammatory response syndrome achieved an area under the receiving operating characteristic (AUROC) of 85%, a positive predictive value of 67% and a negative predictive value of 94% outperforming established severity scores. GSEA revealed functional pathway units suggesting elevated short-chain fatty acid (SCFA) production in severe AP. CONCLUSIONS: The orointestinal microbiome predicts clinical hallmark features of AP, and SCFAs may be used for future diagnostic and therapeutic concepts. TRIAL REGISTRATION NUMBER: NCT04777812.

Type 1 Autoimmune Pancreatitis in Europe: Clinical Profile and Response to Treatment.

BACKGROUND & AIMS: Autoimmune pancreatitis (AIP) is an immune-mediated disease of the pancreas with distinct pathophysiology and manifestations. Our aims were to characterize type 1 AIP in a large pan-European cohort and study the effectiveness of current treatment regimens. METHODS: We retrospectively analyzed adults diagnosed since 2005 with type 1 or not-otherwise-specified AIP in 42 European university hospitals. Type 1 AIP was uniformly diagnosed using specific diagnostic criteria. Patients with type 2 AIP and those who had undergone pancreatic surgery were excluded. The primary end point was complete remission, defined as the absence of clinical symptoms and resolution of the index radiologic pancreatic abnormalities attributed to AIP. RESULTS: We included 735 individuals with AIP (69% male; median age, 57 years; 85% White). Steroid treatment was started in 634 patients, of whom 9 (1%) were lost to follow-up. The remaining 625 had a 79% (496/625) complete, 18% (111/625) partial, and 97% (607/625) cumulative remission rate, whereas 3% (18/625) did not achieve remission. No treatment was given in 95 patients, who had a 61% complete (58/95), 19% partial (18/95), and 80% cumulative (76/95) spontaneous remission rate. Higher (≥0.4 mg/kg/day) corticosteroid doses were no more effective than lower (<0.4 mg/kg/day) doses (odds ratio, 0.428; 95% confidence interval, 0.054-3.387) and neither was a starting dose duration >2 weeks (odds ratio, 0.908; 95% confidence interval, 0.818-1.009). Elevated IgG4 levels were independently associated with a decreased chance of complete remission (odds ratio, 0.639; 95% confidence interval, 0.427-0.955). Relapse occurred in 30% of patients. Relapses within 6 months of remission induction were independent of the steroid-tapering duration, induction treatment duration, and total cumulative dose. CONCLUSIONS: Patients with type 1 AIP and elevated IgG4 level may need closer monitoring. For remission induction, a starting dose of 0.4 mg/kg/day for 2 weeks followed by a short taper period seems effective. This study provides no evidence to support more aggressive regimens.

The four seasons of pancreatitis - Etiology of acute pancreatitis during the course of the year.

BACKGROUND/OBJECTIVES: Whether seasonality is a factor that influences the incidence of acute pancreatitis (AP) is an under-investigated area. If seasonal incidence peaks can be detected, specifically with regard to biliary pancreatitis, has so far been answered in contradictory ways in the literature. METHODS: All AP cases from two tertiary German referral centers were identified between 2016 and 2022 based on ICD-10 discharge codes. The χ2 test for goodness of fit was applied to test significant differences in monthly and seasonal distributions of AP admissions. RESULTS: In total, 3597 AP cases were included. We observed significantly more idiopathic and biliary cases in May to July (p-values 0.041 and 0.027, respectively). Furthermore, most drug-induced APs were identified during the winter months (p-value 0.006). Moreover, there was a significant peak of alcohol-induced pancreatitis in summer and fall (p-value 0.038). CONCLUSIONS: Our data indicate a seasonal impact on AP incidences for certain etiologies.

Definition of age-dependent reference values for the diameter of the common bile duct and pancreatic duct on MRCP: a population-based, cross-sectional cohort study.

OBJECTIVE: Changes of the pancreaticobiliary ducts herald disease. Magnetic resonance cholangiopancreatography (MRCP) allows accurate duct visualisation. Data on reliable upper reference ranges are missing. DESIGN: Cross-sectional whole body MRI data from the population-based Study of Health in Pomerania were analysed. The width of the common bile duct (CBD) and the pancreatic duct (PD) was determined. We aimed to describe the distribution of physiological duct diameters on MRCP in a population of healthy subjects and to identify factors influencing duct size. RESULTS: After excluding pre-existing pancreaticobiliary conditions, CBD and PD diameters from 938 and 774 healthy individuals, respectively, showed a significant increase with age (p<0.0001) and exceeded the conventional upper reference limit of normal in 10.9% and 18.2%, respectively. Age-dependent upper reference limits of duct diameters were delineated with non-parametric quantile regression, defined as 95th percentile: for CBD up to 8 mm in subjects <65 years and up to 11 mm in subjects ≥65 years. For the PD reference diameters were up to 3 mm in subjects <65 years and up to 4 mm in subjects ≥65 years. CONCLUSIONS: This is the first population-based study delineating age-adjusted upper reference limits of CBD and PD on MRCP. We showed that up to 18.2% of healthy volunteers would have needed diagnostic workup, if the conventional reference values were used. The utilisation of the adapted reference levels may help to avoid unnecessary investigations and thus to reduce healthcare expenditure and test-related adverse events.

Consensus definition of sludge and microlithiasis as a possible cause of pancreatitis.

OBJECTIVE: In up to 20% of patients, the aetiology of acute pancreatitis (AP) remains elusive and is thus called idiopathic. On more detailed review these cases can often be explained through biliary disease and are amenable to treatment. Findings range from biliary sludge to microlithiasis but their definitions remain fluid and controversial. DESIGN: A systematic literature review (1682 reports, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines) analysed definitions of biliary sludge and microlithiasis, followed by an online international expert survey (30 endoscopic ultrasound/hepatobiliary and pancreatic experts; 36 items) which led to definitions of both. These were consented by Delphi voting and clinically evaluated in a retrospective cohort of patients with presumed biliary pancreatitis. RESULTS: In 13% of original articles and 19.2% of reviews, microlithiasis and biliary sludge were used synonymously. In the survey, 41.7% of experts described the term 'sludge' and 'microlithiasis' as identical findings. As a consequence, three definitions were proposed, agreed on and confirmed by voting to distinctly discriminate between biliary sludge (hyperechoic material without acoustic shadowing) and microlithiasis (echorich calculi of ≤5 mm with acoustic shadowing) as opposed to larger biliary stones, both for location in gallbladder and bile ducts. In an initial attempt to investigate the clinical relevance in a retrospective analysis in 177 confirmed cases in our hospital, there was no difference in severity of AP if caused by sludge, microlithiasis or stones. CONCLUSION: We propose a consensus definition for the localisation, ultrasound morphology and diameter of biliary sludge and microlithiasis as distinct entities. Interestingly, severity of biliary AP was not dependent on the size of concrements warranting prospective randomised studies which treatment options are adequate to prevent recurrence.

Independent Validation and Assay Standardization of Improved Metabolic Biomarker Signature to Differentiate Pancreatic Ductal Adenocarcinoma From Chronic Pancreatitis.

BACKGROUND & AIMS: Pancreatic ductal adenocarcinoma cancer (PDAC) is a highly lethal malignancy requiring efficient detection when the primary tumor is still resectable. We previously developed the MxPancreasScore comprising 9 analytes and serum carbohydrate antigen 19-9 (CA19-9), achieving an accuracy of 90.6%. The necessity for 5 different analytical platforms and multiple analytical runs, however, hindered clinical applicability. We therefore aimed to develop a simpler single-analytical run, single-platform diagnostic signature. METHODS: We evaluated 941 patients (PDAC, 356; chronic pancreatitis [CP], 304; nonpancreatic disease, 281) in 3 multicenter independent tests, and identification (ID) and validation cohort 1 (VD1) and 2 (VD2) were evaluated. Targeted quantitative plasma metabolite analysis was performed on a liquid chromatography-tandem mass spectrometry platform. A machine learning-aided algorithm identified an improved (i-Metabolic) and minimalistic metabolic (m-Metabolic) signatures, and compared them for performance. RESULTS: The i-Metabolic Signature, (12 analytes plus CA19-9) distinguished PDAC from CP with area under the curve (95% confidence interval) of 97.2% (97.1%-97.3%), 93.5% (93.4%-93.7%), and 92.2% (92.1%-92.3%) in the ID, VD1, and VD2 cohorts, respectively. In the VD2 cohort, the m-Metabolic signature (4 analytes plus CA19-9) discriminated PDAC from CP with a sensitivity of 77.3% and specificity of 89.6%, with an overall accuracy of 82.4%. For the subset of 45 patients with PDAC with resectable stages IA-IIB tumors, the sensitivity, specificity, and accuracy were 73.2%, 89.6%, and 82.7%, respectively; for those with detectable CA19-9 >2 U/mL, 81.6%, 88.7%, and 84.5%, respectively; and for those with CA19-9 <37 U/mL, 39.7%, 94.1%, and 76.3%, respectively. CONCLUSIONS: The single-platform, single-run, m-Metabolic signature of just 4 metabolites used in combination with serum CA19-9 levels is an innovative accurate diagnostic tool for PDAC at the time of clinical presentation, warranting further large-scale evaluation.

Tumor-Specific Delivery of 5-Fluorouracil-Incorporated Epidermal Growth Factor Receptor-Targeted Aptamers as an Efficient Treatment in Pancreatic Ductal Adenocarcinoma Models.

BACKGROUNDS & AIMS: Fluoropyrimidine c (5-fluorouracil [5FU]) increasingly represents the chemotherapeutic backbone for neoadjuvant, adjuvant, and palliative treatment of pancreatic ductal adenocarcinoma (PDAC). Even in combination with other agents, 5FU efficacy remains transient and limited. One explanation for the inadequate response is insufficient and nonspecific delivery of 5FU to the tumor. METHODS: We designed, generated, and characterized 5FU-incorporated systematic evolution of ligands by exponential enrichment (SELEX)-selected epidermal growth factor receptor (EGFR)-targeted aptamers for tumor-specific delivery of 5FU to PDAC cells and tested their therapeutic efficacy in vitro and in vivo. RESULTS: 5FU-EGFR aptamers reduced proliferation in a concentration-dependent manner in mouse and human pancreatic cancer cell lines. Time-lapsed live imaging showed EGFR-specific uptake of aptamers via clathrin-dependent endocytosis. The 5FU-aptamer treatment was equally effective in 5FU-sensitive and 5FU-refractory PDAC cell lines. Biweekly treatment with 5FU-EGFR aptamers reduced tumor burden in a syngeneic orthotopic transplantation model of PDAC, in an autochthonously growing genetically engineered PDAC model (LSL-KrasG12D/+;LSL-Trp53flox/+;Ptf1a-Cre [KPC]), in an orthotopic cell line-derived xenograft model using human PDAC cells in athymic mice (CDX; Crl:NU-Foxn1nu), and in patient-derived organoids. Tumor growth was significantly attenuated during 5FU-EGFR aptamer treatment in the course of follow-up. CONCLUSIONS: Tumor-specific targeted delivery of 5FU using EGFR aptamers as the carrier achieved high target specificity; overcame 5FU resistance; and proved to be effective in a syngeneic orthotopic transplantation model, in KPC mice, in a CDX model, and in patient-derived organoids and, therefore, represents a promising backbone for pancreatic cancer chemotherapy in patients. Furthermore, our approach has the potential to target virtually any cancer entity sensitive to 5FU treatment by incorporating 5FU into cancer cell-targeting aptamers as the delivery platform.

Clinical and translational markers of severity and prognosis in chronic pancreatitis.

PURPOSE OF REVIEW: The incidence of chronic pancreatitis as a progressive inflammation and fibrosis syndrome is on the rise due to increasing awareness and improved imaging modalities. Numerous classification systems have been suggested in recent years to describe the disease, but only few of them have been used to classify the severity and prognostic significance of the disease. Biomarkers for severity and (early) chronic pancreatitis diagnosis are not yet ready for clinical application. RECENT FINDINGS: In using the M-ANNHEIM and Chronic Pancreatitis Prognosis Score (COPPS) classification system, the severity assessment and short- and medium-term disease progression is available. A prospectively validated biomarker for early chronic pancreatitis diagnosis is not yet available, metabolome-based approaches seem to have the greatest potential for clinical translation. SUMMARY: Currently, due to the lack of universal definition for the early disease stage of chronic pancreatitis, it is difficult to accurately classify these patient cohorts in existing scoring systems. In principle, setting up a suitable scoring system would allow surveillance and establish a therapy approaches flanked by corresponding biomarker panel development. Therapy management of chronic pancreatitis and monitoring by means of scoring systems (such as the COPPS) would make a decisive contribution to improving patient treatment.

HLA-DRB1∗16 and -DQB1∗05 alleles are strongly associated with autoimmune pancreatitis in a cohort of hundred patients.

BACKGROUND/OBJECTIVES: Autoimmune diseases are often associated with human leukocyte antigen (HLA) haplotypes, indicating that changes in major histocompatibility complex (MHC)-dependent self-peptide or antigen presentation contribute to autoimmunity. In our study, we aimed to investigate HLA alleles in a large European cohort of autoimmune pancreatitis (AIP) patients. METHODS: Hundred patients with AIP, diagnosed and classified according to the International Consensus Diagnostic Criteria (ICDC), were prospectively enrolled in the study. Forty-four patients with chronic pancreatitis (CP) and 254 healthy subjects served as control groups. DNA was isolated from blood samples and two-digit HLA typing was performed with sequence-specific primer (SSP-) PCR. HLA allele association strength to AIP was calculated as odds ratio. RESULTS: We uncovered a strong enrichment of HLA-DQB1 homozygosity in type 1 and type 2 AIP patients. Moreover, a significantly increased incidence of the HLA-DRB1∗16 and HLA-DQB1∗05 alleles and a concomitant lack of the HLA-DRB1∗13 allele was detected in AIP type 1 and type 2 patients. In contrast, the HLA-DQB1∗02 allele was underrepresented in the 'not otherwise specified' (NOS) AIP subtype. We detected no significant difference in the HLA-DRB3, HLA-DRB4 and HLA-DRB5 allele frequency in our cohort. CONCLUSIONS: Although AIP type 1 and type 2 are characterized by distinct histopathological characteristics, both subtypes are associated with the same HLA alleles, indicating that the disease might rely on similar immunogenic mechanisms. However, AIP NOS represented another subclass of AIP.

Identification and validation of a multivariable prediction model based on blood plasma and serum metabolomics for the distinction of chronic pancreatitis subjects from non-pancreas disease control subjects.

OBJECTIVE: Chronic pancreatitis (CP) is a fibroinflammatory syndrome leading to organ dysfunction, chronic pain, an increased risk for pancreatic cancer and considerable morbidity. Due to a lack of specific biomarkers, diagnosis is based on symptoms and specific but insensitive imaging features, preventing an early diagnosis and appropriate management. DESIGN: We conducted a type 3 study for multivariable prediction for individual prognosis according to the TRIPOD guidelines. A signature to distinguish CP from controls (n=160) was identified using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry on ethylenediaminetetraacetic acid (EDTA)-plasma and validated in independent cohorts. RESULTS: A Naive Bayes algorithm identified eight metabolites of six ontology classes. After algorithm training and computation of optimal cut-offs, classification according to the metabolic signature detected CP with an area under the curve (AUC) of 0.85 ((95% CI 0.79 to 0.91). External validation in two independent cohorts (total n=502) resulted in similar accuracy for detection of CP compared with non-pancreatic controls in EDTA-plasma (AUC 0.85 (95% CI 0.81 to 0.89)) and serum (AUC 0.87 (95% CI 0.81 to 0.95)). CONCLUSIONS: This is the first study that identifies and independently validates a metabolomic signature in plasma and serum for the diagnosis of CP in large, prospective cohorts. The results could provide the basis for the development of the first routine laboratory test for CP.

Chronic pancreatitis.

Chronic pancreatitis is a multifactorial, fibroinflammatory syndrome in which repetitive episodes of pancreatic inflammation lead to extensive fibrotic tissue replacement, resulting in chronic pain, exocrine and endocrine pancreatic insufficiency, reduced quality of life, and a shorter life expectancy. The incidence and prevalence of chronic pancreatitis is rising and no curative treatment is available. Using novel diagnostic algorithms, definitive chronic pancreatitis can be diagnosed by imaging criteria alone, whereas probable chronic pancreatitis requires clinical features and imaging criteria. Criteria for the diagnosis of early chronic pancreatitis are still under discussion and need prospective validation in clinical trials. Cross-sectional imaging should be used first; endoscopic ultrasound is needed only when CT or MRI are inconclusive or to plan therapeutic interventions. Management of chronic pancreatitis requires an interdisciplinary approach including primary care practitioners, gastroenterologists, surgeons, radiologists, pain specialists, and nutritional therapists. Patients with chronic pancreatitis should be seen at least once a year and re-evaluated for causal risk factors, symptom control, and complications such as malnutrition, pancreatic exocrine insufficiency, and diabetes; refer to a specialised centre if symptoms are poorly controlled or there is risk of deterioration. Scoring systems to monitor disease progression have been developed and validated internationally. Interventional treatments for pain or cholestasis should be done by specialists only, and early discussion of treatment approaches should include all medical disciplines involved in care. Throughout this Seminar, we address research needs such as staging of pancreatitis, aspects of malnutrition and pain, and cancer surveillance, to help improve the care of patients.

[Conservative or surgical treatment of chronic pancreatitis?] / Konservative oder chirurgische Therapie der chronischen Pankreatitis?

The cardinal symptom of chronic pancreatitis is severe belt-like upper abdominal pain, which requires immediate and adequate treatment. Furthermore, advanced stage chronic pancreatitis is often associated with complications, such as pancreatic pseudocysts, pancreatic duct stones and stenosis as well as biliary stenosis. The various endoscopic and surgical treatment options for chronic pancreatitis patients have been controversially discussed for decades. The new German S3 guidelines on pancreatitis now clearly define the best treatment options depending on the indications for treatment. For the treatment of pain in chronic pancreatitis it has been known for a long time that a surgical intervention is superior to endoscopic intervention concerning long-term pain relief. The recently published ESCAPE study has further underlined this by showing that early surgical intervention was superior to a step-up approach with initial endoscopic treatment. For the treatment of pancreatic pain, an initial endoscopic treatment attempt is therefore justified for short-term pain relief but in the midterm and long term, surgical intervention is the treatment of choice. In contrast, pancreatic pseudocysts, solitary proximally situated pancreatic duct stones and benign biliary strictures (except in calcifying pancreatitis) can nowadays generally be managed endoscopically. For distal pancreatic duct stones and symptomatic pancreatic duct stenosis surgical treatment is again the method of choice. This review article discusses these indication-related procedures in detail and explains them in relation to the recently published S3 guidelines on pancreatitis of the German Society for Gastroenterology, Digestive and Metabolic Diseases (DGVS).

Genetics, Cell Biology, and Pathophysiology of Pancreatitis.

Since the discovery of the first trypsinogen mutation in families with hereditary pancreatitis, pancreatic genetics has made rapid progress. The identification of mutations in genes involved in the digestive protease-antiprotease pathway has lent additional support to the notion that pancreatitis is a disease of autodigestion. Clinical and experimental observations have provided compelling evidence that premature intrapancreatic activation of digestive proteases is critical in pancreatitis onset. However, disease course and severity are mostly governed by inflammatory cells that drive local and systemic immune responses. In this article, we review the genetics, cell biology, and immunology of pancreatitis with a focus on protease activation pathways and other early events.

Immune Cell and Stromal Signature Associated With Progression-Free Survival of Patients With Resected Pancreatic Ductal Adenocarcinoma.

BACKGROUND & AIMS: Changes to the microenvironment of pancreatic ductal adenocarcinomas (PDACs) have been associated with poor outcomes of patients. We studied the associations between composition of the pancreatic stroma (fibrogenic, inert, dormant, or fibrolytic stroma) and infiltration by inflammatory cells and times of progression-free survival (PFS) of patients with PDACs after resection. METHODS: We obtained 1824 tissue microarray specimens from 385 patients included in the European Study Group for Pancreatic Cancer trial 1 and 3 and performed immunohistochemistry to detect alpha smooth muscle actin, type 1 collagen, CD3, CD4, CD8, CD68, CD206, and neutrophils. Tumors that expressed high and low levels of these markers were compared with patient outcomes using Kaplan-Meier curves and multivariable recursive partitioning for discrete-time survival tree analysis. Prognostic index was delineated by a multivariable Cox proportional hazards model of immune cell and stromal markers and PFS. Findings were validated using 279 tissue microarray specimens from 93 patients in a separate cohort. RESULTS: Levels of CD3, CD4, CD8, CD68, and CD206 were independently associated with tumor recurrence. Recursive partitioning for discrete-time survival tree analysis identified a high level of CD3 as the strongest independent predictor for longer PFS. Tumors with levels of CD3 and high levels of CD206 associated with a median PFS time of 16.6 months and a median prognostic index of -0.32 (95% confidence interval [CI] -0.35 to -0.31), whereas tumors with low level of CD3 cell and low level of CD8 and high level of CD68 associated with a median PFS time of 7.9 months and a prognostic index of 0.32 (95% CI 0.050-0.32); we called these patterns histologic signatures. Stroma composition, when unassociated with inflammatory cell markers, did not associate significantly with PFS. In the validation cohort, the histologic signature resulted in an error matrix accuracy of predicted response of 0.75 (95% CI 0.64-0.83; accuracy P < .001). CONCLUSIONS: In an analysis of PDAC tissue microarray specimens, we identified and validated a histologic signature, based on leukocyte and stromal factors, that associates with PFS times of patients with resected PDACs. Immune cells might affect the composition of the pancreatic stroma to affect progression of PDAC. These findings provide new insights into the immune response to PDAC.

Impact of intensified chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) in clinical routine in Europe.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is associated with poor prognosis. Gemcitabine is the standard chemotherapy for patients with metastatic pancreatic adenocarcinoma (MPA). Randomized clinical trials evaluating intensified chemotherapies including FOLFIRINOX and nab-paclitaxel plus gemcitabine (NAB+GEM) have shown improvement in survival. Here, we have evaluated the efficacy of intensified chemotherapy versus gemcitabine monotherapy in real-life settings across Europe. METHODS: A retrospective multi-center study including 1056 MPA patients, between 2012 and 2015, from nine centers in UK, Germany, Italy, Hungary and the Swedish registry was performed. Follow-up was at least 12 months. Cox proportional Harzards regression was used for uni- and multivariable evaluation of prognostic factors. RESULTS: Of 1056 MPA patients, 1030 (98.7%) were assessable for survival analysis. Gemcitabine monotherapy was the most commonly used regimen (41.3%), compared to FOLFIRINOX (n = 204, 19.3%), NAB+GEM (n = 81, 7.7%) and other gemcitabine- or 5-FU-based regimens (n = 335, 31.7%). The median overall survival (OS) was: FOLFIRINOX 9.9 months (95%CI 8.4-12.6), NAB+GEM 7.9 months (95%CI 6.2-10.0), other combinations 8.5 months (95%CI 7.7-9.3) and gemcitabine monotherapy 4.9 months (95%CI 4.4-5.6). Compared to gemcitabine monotherapy, any combination of chemotherapeutics improved the survival with no significant difference between the intensified regimens. Multivariable analysis showed an association between treatment center, male gender, inoperability at diagnosis and performance status (ECOG 1-3) with poor prognosis. CONCLUSION: Gemcitabine monotherapy was predominantly used in 2012-2015. Intensified chemotherapy improved OS in comparison to gemcitabine monotherapy. In real-life settings, the OS rates of different treatment approaches are lower than shown in randomized phase III trials.

Pancreatic cyst surveillance imposes low psychological burden.

BACKGROUND/OBJECTIVES: For the currently recommended pancreatic cyst surveillance to be feasible, participant adherence is a prerequisite. Our objective was to evaluate the psychological burden of pancreatic cyst surveillance from a participant's perspective. METHODS: The present participant survey is part of an international cohort study (PACYFIC study, www.pacyfic.net), which prospectively records the outcome of surveillance of asymptomatic pancreatic cysts. Participants are invited to complete questionnaires before and during cyst surveillance. RESULTS: 109 participants, 31 enrolled before and 78 during surveillance (median time since cyst diagnosis 16.5 (IQR 36) months), returned a total of 179 questionnaires. The majority indicated that surveillance reduces concerns of developing pancreatic cancer (82%), gives a sense of certainty (81%) and is a good method to detect cancer (91%). Participants already undergoing surveillance reported more negative aspects than those still to commence, like sleeping worse (30% vs 13%, P = 0.035), postponing plans (32% vs 13%, P = 0.031), and finding the follow-up burdensome (33% vs 13%, P = 0.044). Overall, the vast majority (94%) deemed advantages to outweigh disadvantages. Anxiety and depression scores were low (median Hospital Anxiety and Depression Scale 4 for anxiety (IQR 6), 2 for depression (IQR 5)). CONCLUSION: The psychological burden of pancreatic cyst surveillance is low. Therefore, participant adherence is expected to be high and annual surveillance seems feasible.

Development and Validation of a Chronic Pancreatitis Prognosis Score in 2 Independent Cohorts.

BACKGROUND & AIMS: The clinical course of chronic pancreatitis is unpredictable. There is no model to assess disease severity or progression or predict patient outcomes. METHODS: We performed a prospective study of 91 patients with chronic pancreatitis; data were collected from patients seen at academic centers in Europe from January 2011 through April 2014. We analyzed correlations between clinical, laboratory, and imaging data with number of hospital readmissions and in-hospital days over the next 12 months; the parameters with the highest degree of correlation were used to develop a 3-stage chronic pancreatitis prognosis score (COPPS). The predictive strength was validated in 129 independent subjects identified from 2 prospective databases. RESULTS: The mean number of hospital admissions was 1.9 (95% confidence interval [CI], 1.39-2.44) and 15.2 for hospital days (95% CI, 10.76-19.71) for the development cohort and 10.9 for the validation cohort (95% CI, 7.54-14.30) (P = .08). Based on bivariate correlations, pain (numeric rating scale), level of glycated hemoglobin A1c, level of C-reactive protein, body mass index, and platelet count were used to develop the COPPS system. The patients' median COPPS was 8.9 points (range, 5-14). The system accurately discriminated stages of disease severity (low to high): A (5-6 points), B (7-9), and C (10-15). In Pearson correlation analysis of the development cohort, the COPPS correlated with hospital admissions (0.39; P < .01) and number of hospital days (0.33; P < .01). The correlation was validated in the validation set (Pearson correlation values of 0.36 and 0.44; P < .01). COPPS did not correlate with results from the Cambridge classification system. CONCLUSIONS: We developed and validated an easy to use dynamic multivariate scoring system, similar to the Child-Pugh-Score for liver cirrhosis. The COPPS allows objective monitoring of patients with chronic pancreatitis, determining risk for readmission to hospital and potential length of hospital stay.