The use of ace inhibitors influences the risk of progression of BD-IPMNs under follow-up.

BACKGROUND: Chemoprevention's ability to slow down or prevent the progression of BD-IPMNs is extremely appealing. Aspirin (ASA), Ace Inhibitors/Angiotensin Receptor Blockers (ACEIs/ARBs) and Statins (STATs) are frequently prescribed drugs with a possible beneficial effect on different cancer types. Their effect on IPMNs is largely unknown. AIM: To evaluate the association between the use of ASA, ACEIs/ARBs and STATs and the risk of progression of BD-IPMNs in follow-up. MATERIALS AND METHODS: multicenter, retrospective cohort study on patients with presumed BD-IPMNs without relative or absolute indication for surgery. Pharmacological exposures and risk factors were collected. We identified clinically relevant progression (occurrence of radiological absolute or relative indication for surgery) and any progression (occurrence of clinically relevant progression OR any dimension increase OR the occurrence of new cysts). RESULTS: Overall 594 patients were included. ACEIs were associated with a lower occurrence of any progression (HR = 0.70; 95% CI 0.49-0.98, p = 0.04) and clinically relevant progression, HR = 0.42 (95% CI 0.20-0.88; p = 0.02). No significant effect was shown for factors associated with the occurrence of pancreas cancer such as smoking, alcohol consumption and 1st degree family history of pancreas cancer. Among pharmacological exposures, no convincing effect was shown for the chronic use of ASA, ARB and STAT. CONCLUSIONS: ACEIs might have an effect in slowing the progression of BD-IPMNs. ASA, STAT and ARBs show no convincing effect on the progression of BD-IPMNs. Further, prospective, and long-term multicenter studies are needed to verify such association and to define the potential underlying mechanisms.

Lumen apposing metal stents vs double pigtail plastic stents for the drainage of pancreatic walled-off necrosis.

BACKGROUND: Few studies compared lumen-apposing metal stents (LAMS) and standard double pigtail plastic stents (PS) for the endoscopic drainage of pancreatic walled-off necrosis (WON). Albeit sometimes large, previously described cohorts display considerable heterogeneity and often pooled together data from several centers, involving multiple operators and techniques. Moreover, they often lack a control group for the comparison of outcomes. AIM: to compare clinical efficacy and safety of PS versus LAMS for the endoscopic drainage of infected WON. METHODS: Single-centre, 1:1 case-control study. We compared patients undergoing endoscopic drainages of infected WON through LAMS (cases) or PS (controls). The primary endpoint was the clinical efficacy (resolution of the WON/sepsis), the secondary endpoint was safety (procedure-related complications). RESULTS: Thirty patients were enrolled between 2011 and 2017. Cases and controls were homogeneous in terms of etiology and clinical characteristics. 93% of cases and 86.7% of controls were clinically successfully treated, with no significant differences in rates of post-operative infections, bleedings and stent migrations (respectively 13.3% vs 21.4%; p=0.65; 13.3% vs 0%; p=0.48; 13.3% vs 7.1%; p=1.00). No difference was shown regarding the need for additional percutaneous or surgical treatments (33.3% vs 13.3%; p=0.39). Cases, however, displayed a significantly prolonged mean hospital stay (90.2 days vs 18.5 days; p<0.01) and a higher mean number of endoscopic procedures per patient (4.8 vs 1.5; p<0.01). CONCLUSIONS: PS might be not inferior to LAMS for the treatment WONs. Further prospective RCT is needed to compare clinical efficacy and safety in the two groups.

Development and external validation of a prediction model for survival in patients with resected ampullary adenocarcinoma.

INTRODUCTION: Ampullary adenocarcinoma (AAC) is a rare malignancy with great morphological heterogeneity, which complicates the prediction of survival and, therefore, clinical decision-making. The aim of this study was to develop and externally validate a prediction model for survival after resection of AAC. MATERIALS AND METHODS: An international multicenter cohort study was conducted, including patients who underwent pancreatoduodenectomy for AAC (2006-2017) from 27 centers in 10 countries spanning three continents. A derivation and validation cohort were separately collected. Predictors were selected from the derivation cohort using a LASSO Cox proportional hazards model. A nomogram was created based on shrunk coefficients. Model performance was assessed in the derivation cohort and subsequently in the validation cohort, by calibration plots and Uno's C-statistic. Four risk groups were created based on quartiles of the nomogram score. RESULTS: Overall, 1007 patients were available for development of the model. Predictors in the final Cox model included age, resection margin, tumor differentiation, pathological T stage and N stage (8th AJCC edition). Internal cross-validation demonstrated a C-statistic of 0.75 (95% CI 0.73-0.77). External validation in a cohort of 462 patients demonstrated a C-statistic of 0.77 (95% CI 0.73-0.81). A nomogram for the prediction of 3- and 5-year survival was created. The four risk groups showed significantly different 5-year survival rates (81%, 57%, 22% and 14%, p < 0.001). Only in the very-high risk group was adjuvant chemotherapy associated with an improved overall survival. CONCLUSION: A prediction model for survival after curative resection of AAC was developed and externally validated. The model is easily available online via www.pancreascalculator.com.

International validation and update of the Amsterdam model for prediction of survival after pancreatoduodenectomy for pancreatic cancer.

BACKGROUND: The objective of this study was to validate and update the Amsterdam prediction model including tumor grade, lymph node ratio, margin status and adjuvant therapy, for prediction of overall survival (OS) after pancreatoduodenectomy for pancreatic cancer. METHODS: We included consecutive patients who underwent pancreatoduodenectomy for pancreatic cancer between 2000 and 2017 at 11 tertiary centers in 8 countries (USA, UK, Germany, Italy, Sweden, the Netherlands, Korea, Australia). Model performance for prediction of OS was evaluated by calibration statistics and Uno's C-statistic for discrimination. Validation followed the TRIPOD statement. RESULTS: Overall, 3081 patients (53% male, median age 66 years) were included with a median OS of 24 months, of whom 38% had N2 disease and 77% received adjuvant chemotherapy. Predictions of 3-year OS were fairly similar to observed OS with a calibration slope of 0.72. Statistical updating of the model resulted in an increase of the C-statistic from 0.63 to 0.65 (95% CI 0.64-0.65), ranging from 0.62 to 0.67 across different countries. The area under the curve for the prediction of 3-year OS was 0.71 after updating. Median OS was 36, 25 and 15 months for the low, intermediate and high risk group, respectively (P < 0.001). CONCLUSIONS: This large international study validated and updated the Amsterdam model for survival prediction after pancreatoduodenectomy for pancreatic cancer. The model incorporates readily available variables with a fairly accurate model performance and robustness across different countries, while novel markers may be added in the future. The risk groups and web-based calculator www.pancreascalculator.com may facilitate use in daily practice and future trials.

The role of adipose stem cells in inflammatory bowel disease: From biology to novel therapeutic strategies.

Inflammatory bowel diseases are an increasing phenomenon in western countries and in growing populations. The physiopathology of these conditions is linked to intestinal stem cells homeostasis and regenerative potential in a chronic inflammatory microenvironment. Patients with IBD present an increased risk of developing colorectal cancer (CRC), or colitis associated cancer (CAC). Conventional treatment for IBD target the inflammatory process (and include anti-inflammatory and immunosuppressive drugs) with biological agents emerging as a therapeutic approach for non-responders to traditional therapy. Conventional treatment provides scarce results and present severe complications. The intestinal environment may host incoming stem cells, able to engraft in the epithelial damaged sites and differentiate. Therefore, stem cell therapies represent an emerging alternative in inflammatory bowel diseases, with current investigations on the use of haematopoietic and mesenchymal stem cells, in particular adipose stem cells, apparently fundamental as regenerators and as immune-modulators. Here, we discuss stem cells in intestinal homeostasis and as therapeutic agents for the treatment of inflammatory bowel diseases.

From Inflammation to Cancer in Inflammatory Bowel Disease: Molecular Perspectives.

Inflammatory bowel diseases (IBD) are associated with an increased risk of colitis-associated colorectal carcinoma (CAC). CAC is one of the most important causes of morbidity and mortality in patients with Crohn's disease and ulcerative colitis. The aim of the present review was to discuss the most important signaling pathways and genetic alterations involved in carcinogenesis related to IBD, focusing on the molecular aspects of cancer stem cell physiology and the impact of the inflammatory microenvironment. Molecular mechanisms involved in CAC development differ from those in sporadic colorectal cancer, reflecting the prominent role of inflammation-induced carcinogenesis in the development of CAC. The alteration of the physiological microenvironment is thought to be responsible for the initiation of carcinogenesis in IBD. Furthermore, cancer stem cells seem to have a fundamental role in the generation and growth of CAC. We also address prevention and treatment modalities of CAC and its involvement in IBD.