Lucas Ilzarbe

Valoración y tratamiento de la pancreatitis aguda. Documento de posicionamiento de la Societat Catalana de Digestologia, Societat Catalana de Cirurgia y Societat Catalana de Pàncrees

The incidence of acute pancreatitis (AP) is increasing. AP is one of the gastrointestinal diseases that most frequently requires hospital admission in affected individuals. In the last few years, considerable scientific evidence has led to substantial changes in the medical and surgical treatment of this disease. New knowledge of the physiopathology of AP indicates that its severity is influenced by its systemic effects (organ failure), especially if the disease is persistent, and also by local complications (fluid collections or necrosis), especially if these become infected. Treatment should be personalized and depends on the patients clinical status, the location of the necrosis, and disease stage.

Risk of pancreatic cancer associated with family history of cancer and other medical conditions by accounting for smoking among relatives

Background Family history (FH) of pancreatic cancer (PC) has been associated with an increased risk of PC, but little is known regarding the role of inherited/environmental factors or that of FH of other comorbidities in PC risk. We aimed to address these issues using multiple methodological approaches. Methods Case-control study including 1431 PC cases and 1090 controls and a reconstructed-cohort study (N = 16 747) made up of their first-degree relatives (FDR). Logistic regression was used to evaluate PC risk associated with FH of cancer, diabetes, allergies, asthma, cystic fibrosis and chronic pancreatitis by relative type and number of affected relatives, by smoking status and other potential effect modifiers, and by tumour stage and location. Familial aggregation of cancer was assessed within the cohort using Cox proportional hazard regression. Results FH of PC was associated with an increased PC risk [odds ratio (OR) = 2.68; 95% confidence interval (CI): 2.27-4.06] when compared with cancer-free FH, the risk being greater when ≥ 2 FDRs suffered PC (OR = 3.88; 95% CI: 2.96-9.73) and among current smokers (OR = 3.16; 95% CI: 2.56-5.78, interaction FHPC*smoking P-value = 0.04). PC cumulative risk by age 75 was 2.2% among FDRs of cases and 0.7% in those of controls [hazard ratio (HR) = 2.42; 95% CI: 2.16-2.71]. PC risk was significantly associated with FH of cancer (OR = 1.30; 95% CI: 1.13-1.54) and diabetes (OR = 1.24; 95% CI: 1.01-1.52), but not with FH of other diseases. Conclusions The concordant findings using both approaches strengthen the notion that FH of cancer, PC or diabetes confers a higher PC risk. Smoking notably increases PC risk associated with FH of PC. Further evaluation of these associations should be undertaken to guide PC prevention strategies.

A systems approach identifies time-dependent associations of multimorbidities with pancreatic cancer risk

Background Pancreatic ductal adenocarcinoma (PDAC) is usually diagnosed in late adulthood; therefore, many patients suffer or have suffered from other diseases. Identifying disease patterns associated with PDAC risk may enable a better characterization of high-risk patients. Methods Multimorbidity patterns (MPs) were assessed from 17 self-reported conditions using hierarchical clustering, principal component, and factor analyses in 1705 PDAC cases and 1084 controls from a European population. Their association with PDAC was evaluated using adjusted logistic regression models. Time since diagnosis of morbidities to PDAC diagnosis/recruitment was stratified into recent (<3 years) and long term (≥3 years). The MPs and PDAC genetic networks were explored with DisGeNET bioinformatics-tool which focuses on gene-diseases associations available in curated databases. Results Three MPs were observed: gastric (heartburn, acid regurgitation, Helicobacter pylori infection, and ulcer), metabolic syndrome (obesity, type-2 diabetes, hypercholesterolemia, and hypertension), and atopic (nasal allergies, skin allergies, and asthma). Strong associations with PDAC were observed for ≥2 recently diagnosed gastric conditions [odds ratio (OR), 6.13; 95% confidence interval CI 3.01-12.5)] and for ≥3 recently diagnosed metabolic syndrome conditions (OR, 1.61; 95% CI 1.11-2.35). Atopic conditions were negatively associated with PDAC (high adherence score OR for tertile III, 0.45; 95% CI, 0.36-0.55). Combining type-2 diabetes with gastric MP resulted in higher PDAC risk for recent (OR, 7.89; 95% CI 3.9-16.1) and long-term diagnosed conditions (OR, 1.86; 95% CI 1.29-2.67). A common genetic basis between MPs and PDAC was observed in the bioinformatics analysis. Conclusions Specific multimorbidities aggregate and associate with PDAC in a time-dependent manner. A better characterization of a high-risk population for PDAC may help in the early diagnosis of this cancer. The common genetic basis between MP and PDAC points to a mechanistic link between these conditions.

Minimally invasive surgery in the era of step-up approach for treatment of severe acute pancreatitis

OBJECTIVES To assess the minimally invasive surgery into the step-up approach procedures as a standard treatment for severe acute pancreatitis and comparing its results with those obtained by classical management. METHODS Retrospective cohort study comparative with two groups treated over two consecutive, equal periods of time were defined: group A, classic management with open necrosectomy from January 2006 to June 2010; and group B, management with the step-up approach with minimally invasive surgery from July 2010 to December 2014. RESULTS In group A, 83 patients with severe acute pancreatitis were treated, of whom 19 underwent at least one laparotomy, and in 5 any minimally invasive surgery. In group B, 81 patients were treated: minimally invasive surgery was necessary in 17 cases and laparotomy in 3. Among operated patients, the time from admission to first interventional procedures was significantly longer in group B (9 days vs. 18.5 days; p = 0.042). There were no significant differences in Intensive Care Unit stay or overall stay: 9.5 and 27 days (group A) vs. 8.5 and 21 days (group B). Mortality in operated patients and mortality overall were 50% and 18.1% in group A vs 0% and 6.2% in group B (p < 0.001 and p = 0.030). CONCLUSIONS The combination of the step-up approach and minimally invasive surgery algorithm is feasible and could be considered as the standard of treatment for severe acute pancreatitis. The mortality rate deliberately descends when it is used.

Pancreatic cancer and autoimmune diseases: An association sustained by computational and epidemiological case-control approaches: Autoimmune diseases and pancreatic cancer risk

Deciphering the underlying genetic basis behind pancreatic cancer (PC) and its associated multimorbidities will enhance our knowledge toward PC control. The study investigated the common genetic background of PC and different morbidities through a computational approach and further evaluated the less explored association between PC and autoimmune diseases (AIDs) through an epidemiological analysis. Gene‐disease associations (GDAs) of 26 morbidities of interest and PC were obtained using the DisGeNET public discovery platform. The association between AIDs and PC pointed by the computational analysis was confirmed through multivariable logistic regression models in the PanGen European case–control study population of 1,705 PC cases and 1,084 controls. Fifteen morbidities shared at least one gene with PC in the DisGeNET database. Based on common genes, several AIDs were genetically associated with PC pointing to a potential link between them. An epidemiologic analysis confirmed that having any of the nine AIDs studied was significantly associated with a reduced risk of PC (Odds Ratio (OR) = 0.74, 95% confidence interval (CI) 0.58–0.93) which decreased in subjects having ≥2 AIDs (OR = 0.39, 95%CI 0.21–0.73). In independent analyses, polymyalgia rheumatica, and rheumatoid arthritis were significantly associated with low PC risk (OR = 0.40, 95%CI 0.19–0.89, and OR = 0.73, 95%CI 0.53–1.00, respectively). Several inflammatory‐related morbidities shared a common genetic component with PC based on public databases. These molecular links could shed light into the molecular mechanisms underlying PC development and simultaneously generate novel hypotheses. In our study, we report sound findings pointing to an association between AIDs and a reduced risk of PC.

Short article : Presence, extent and location of pancreatic necrosis are independent of aetiology in acute pancreatitis

Objective The most common aetiologies of acute pancreatitis (AP) are gallstones, alcohol and idiopathic. The impact of the aetiology of AP on the extent and morphology of pancreatic and extrapancreatic necrosis (EXPN) has not been clearly established. The aim of the present study was to assess the influence of aetiology on the presence and location of pancreatic necrosis in patients with AP. Patients and methods We carried out a post-hoc analysis of a previously established multicentre cohort of patients with AP in whom a computed tomography was available for review. Clinical data were obtained from the medical records. All computed tomographies were revised by the same expert radiologist. The impact of aetiology on pancreatic and EXPN was calculated. Results In total, 159 patients with necrotizing pancreatitis were identified from a cohort of 285 patients. The most frequent aetiologies were biliary (105 patients, 37%), followed by alcohol (102 patients, 36%) and other aetiologies including idiopathic (78 patients, 27%). No relationship was found between the aetiology and the presence of pancreatic necrosis, EXPN, location of pancreatic necrosis or presence of collections. Conclusion We found no association between the aetiology of AP and the presence, extent and anatomical location of pancreatic necrosis.