Meta-analysis and field synopsis of genetic variants associated with the risk and severity of acute pancreatitis.

BACKGROUND: Genetic risk factors can provide insight into susceptibility for acute pancreatitis (AP) and disease progression towards (infected) necrotizing pancreatitis and persistent organ failure. The aim of the study was to undertake a systematic review of the genetic evidence for AP. METHODS: Online databases (MEDLINE, Embase, BIOSIS, Web of Science, Cochrane Library) were searched to 8 February 2018. Studies that reported on genetic associations with AP susceptibility, severity and/or complications were eligible for inclusion. Meta-analyses were performed of variants that were reported by at least two data sources. Venice criteria and Bayesian false-discovery probability were applied to assess credibility. RESULTS: Ninety-six studies reporting on 181 variants in 79 genes were identified. In agreement with previous meta-analyses, credible associations were established for SPINK1 (odds ratio (OR) 2·87, 95 per cent c.i. 1·89 to 4·34), IL1B (OR 1·23, 1·06 to 1·42) and IL6 (OR 1·64, 1·15 to 2·32) and disease risk. In addition, two novel credible single-nucleotide polymorphisms were identified in Asian populations: ALDH2 (OR 0·48, 0·36 to 0·64) and IL18 (OR 1·47, 1·18 to 1·82). Associations of variants in TNF, GSTP1 and CXCL8 genes with disease severity were identified, but were of low credibility. CONCLUSION: Genetic risk factors in genes related to trypsin activation and innate immunity appear to be associated with susceptibility to and severity of AP.

ANTECEDENTES: Los factores de riesgo genético pueden contribuir a determinar la susceptibilidad para desarrollar una pancreatitis aguda (acute pancreatitis, AP) y de su progresión a pancreatitis necrotizante (infectada) e insuficiencia orgánica crónica. Nuestro objetivo fue revisar de forma sistemática la evidencia genética de la pancreatitis aguda. MÉTODOS: Se revisaron las bases de datos electrónicas (MEDLINE, Embase, BIOSIS, Web of Science, Cochrane Library) hasta febrero de 2018. Se incluyeron estudios que presentaban información de las asociaciones genéticas y la susceptibilidad de AP, gravedad y/o complicaciones. Se realizó un metaanálisis de las variantes genéticas descritas en al menos dos fuentes. Se aplicaron los criterios de Venecia y la probabilidad bayesiana de falsa alarma para la valoración de la credibilidad. RESULTADOS: Se identificaron 96 estudios que analizaron 181 variantes en 79 genes. De acuerdo con un metaanálisis previo, se establecieron asociaciones creibles con el riesgo de enfermedad para SPINK1 (razón de oportunidades, odds ratio, OR 2,87, i.c. del 95% 1,89-4,34), IL1B (OR 1,23, i.c. del 95% 1,06-1,42) e IL6 (OR 1,64, i.c. del 95% 1,15-2,32). Además, en poblaciones asiáticas, se identificaron dos nuevos polimorfismos de nucleótico único (SNP) creibles en ALDH2 (OR 0,48, i.c. del 95% 0,36-0,64) e IL18 (OR 1,47, i.c. del 95% 1,18-1,82). En cuanto a la gravedad de la enfermedad se identificaron variantes en los genes TNF, GSTP1 y CXCL8, pero de baja credibilidad en función de nuestra evaluación. CONCLUSIÓN: Los factores de riesgo genéticos en genes relacionados con la activación de la tripsina y la inmunidad innata parecen ser estar asociados con la susceptibilidad y gravedad de la pancreatitis aguda.

International consensus guidelines for surgery and the timing of intervention in chronic pancreatitis.

BACKGROUND/OBJECTIVES: Chronic pancreatitis (CP) is a complex inflammatory disease with pain as the predominant symptom. Pain relief can be achieved using invasive interventions such as endoscopy and surgery. This paper is part of the international consensus guidelines on CP and presents the consensus guideline for surgery and timing of intervention in CP. METHODS: An international working group with 15 experts on CP surgery from the major pancreas societies (IAP, APA, JPS, and EPC) evaluated 20 statements generated from evidence on 5 questions deemed to be the most clinically relevant in CP. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to evaluate the level of evidence available for each statement. To determine the level of agreement, the working group voted on the 20 statements for strength of agreement, using a nine-point Likert scale in order to calculate Cronbach's alpha reliability coefficient. RESULTS: Strong consensus was obtained for the following statements: Surgery in CP is indicated as treatment of intractable pain and local complications of adjacent organs, and in case of suspicion of malignant (cystic) lesion; Early surgery is favored over surgery in a more advanced stage of disease to achieve optimal long-term pain relief; In patients with an enlarged pancreatic head, a combined drainage and resection procedure, such as the Frey, Beger, and Berne procedure, may be the treatment of choice; Pancreaticoduodenectomy is the most suitable surgical option for patients with groove pancreatitis; The risk of pancreatic carcinoma in patients with CP is too low (2% in 10 year) to recommend active screening or prophylactic surgery; Patients with hereditary CP have such a high risk of pancreatic cancer that prophylactic resection can be considered (lifetime risk of 40-55%). Weak agreement for procedure choice in patients with dilated duct and normal size pancreatic head: both the extended lateral pancreaticojejunostomy and Frey procedure seems to provide equivalent pain control in patients. CONCLUSIONS: This international expert consensus guideline provides evidenced-based statements concerning key aspects in surgery and timing of intervention in CP. It is meant to guide clinical practitioners and surgeons in the treatment of patients with CP.

[Multidisciplinary treatment of chronic pancreatitis: an overview of current step-up approach and new options]. / Multidisciplinaire behandeling van chronische pancreatitis.

- Chronic pancreatitis is a progressive inflammatory disease, which leads to a severe decrease in quality of life and reduced life expectancy.- 85-90% of patients with chronic pancreatitis consult the doctor because of pain.- Pain in chronic pancreatitis has a multifactorial aetiology, with nociceptive and neuropathological components.- Current treatment of chronic pancreatitis uses a step-up approach, starting with lifestyle interventions and medication, followed by endoscopic or surgical treatment or a combination of these two.- Surgical drainage or resection is more effective than repeated endoscopic treatment for patients with advanced chronic pancreatitis who use opiates.- There are indications that early surgical intervention in painful chronic pancreatitis and a dilated pancreatic duct provides better results than the current step-up approach; this is currently being investigated in the ESCAPE trial.

Diagnostic performance of imaging modalities in chronic pancreatitis: a systematic review and meta-analysis.

OBJECTIVES: Obtain summary estimates of sensitivity and specificity for imaging modalities for chronic pancreatitis (CP) assessment. METHODS: A systematic search was performed in Cochrane Library, MEDLINE, Embase and CINAHL databases for studies evaluating imaging modalities for the diagnosis of CP up to September 2016. A bivariate random-effects modeling was used to obtain summary estimates of sensitivity and specificity. RESULTS: We included 43 studies evaluating 3460 patients. Sensitivity of endoscopic retrograde cholangiopancreatography (ERCP) (82%; 95%CI: 76%-87%) was significant higher than that of abdominal ultrasonography (US) (67%; 95%CI: 53%-78%; P=0.018). The sensitivity estimates of endoscopic ultrasonography (EUS), magnetic resonance imaging (MRI), and computed tomography (CT) were 81% (95%CI: 70%-89%), 78% (95%CI: 69%-85%), and 75% (95%CI: 66%-83%), respectively, and did not differ significantly from each other. Estimates of specificity were comparable for EUS (90%; 95%CI: 82%-95%), ERCP (94%; 95%CI: 87%-98%), CT (91%; 95% CI: 81%-96%), MRI (96%; 95%CI: 90%-98%), and US (98%; 95%CI: 89%-100%). CONCLUSIONS: EUS, ERCP, MRI and CT all have comparable high diagnostic accuracy in the initial diagnosis of CP. EUS and ERCP are outperformers and US has the lowest accuracy. The choice of imaging modality can therefore be made based on invasiveness, local availability, experience and costs. KEY POINTS: • EUS, ERCP, MRI and CT have high diagnostic sensitivity for chronic pancreatitis • Diagnostic specificity is comparable for all imaging modalities • EUS and ERCP are outperformers and US has the lowest accuracy • The choice of imaging can be made based on clinical considerations.