Evidence-based guidelines on the management of pancreatic cystic neoplasms (PCN) are lacking. This guideline is a joint initiative of the European Study Group on Cystic Tumours of the Pancreas, United European Gastroenterology, European Pancreatic Club, European-African Hepato-Pancreato-Biliary Association, European Digestive Surgery, and the European Society of Gastrointestinal Endoscopy. It replaces the 2013 European consensus statement guidelines on PCN. European and non-European experts performed systematic reviews and used GRADE methodology to answer relevant clinical questions on nine topics (biomarkers, radiology, endoscopy, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm (MCN), serous cystic neoplasm, rare cysts, (neo)adjuvant treatment, and pathology). Recommendations include conservative management, relative and absolute indications for surgery. A conservative approach is recommended for asymptomatic MCN and IPMN measuring 5 mm, and MPD diameter >10 mm. Lifelong follow-up of IPMN is recommended in patients who are fit for surgery. The European evidence-based guidelines on PCN aim to improve the diagnosis and management of PCN.

Purpose: We investigated the global gene expression in a large panel of pancreatic endocrine tumors (PETs) aimed at identifying new potential targets for therapy and biomarkers to predict patient outcome. Patients and Methods: Using a custom microarray, we analyzed 72 primary PETs, seven matched metastases, and 10 normal pancreatic samples. Relevant differentially expressed genes were validated by either quantitative real-time polymerase chain reaction or immunohistochemistry on tissue microarrays. Results: Our data showed that: tuberous sclerosis 2 (TSC2) and phosphatase and tensin homolog (PTEN) were downregulated in most of the primary tumors, and their low expression was significantly associated with shorter disease-free and overall survival; somatostatin receptor 2 (SSTR2) was absent or very low in insulinomas compared with nonfunctioning tumors; and expression of fibroblast growth factor 13 (FGF13) gene was significantly associated with the occurrence of liver metastasis and shorter disease-free survival. TSC2 and PTEN are two key inhibitors of the Akt/mammalian target of rapamycin (mTOR) pathway and the specific inhibition of mTOR with rapamycin or RAD001 inhibited cell proliferation of PET cell lines. Conclusion: Our results strongly support a role for PI3K/Akt/mTOR pathway in PET, which ties in with the fact that mTOR inhibitors have reached phase III trials in neuroendocrine tumors. The finding of differential SSTR expression raises the potential for SSTR expression to be evaluated as a marker of response to somatostatin analogs. Finally, we identified FGF13 as a new prognostic marker that predicted poorer outcome in patients who were clinically considered free from disease.

Since gastro-entero-pancreatic endocrine tumors are rare and heterogeneous diseases, their prognosis and long-term survival are not well known. This study aimed at identifying prognostic factors and assessing long-term survival in gastro-entero-pancreatic endocrine tumors. A total of 156 patients enrolled. Prognostic factors were determined by univariate/multivariate analysis; survival rates were assessed by the Kaplan–Meier method. The tumors were non-functioning in 59.6% of patients, and originated from the pancreas in 42.9%. At diagnosis, 64.3% of patients had metastases. The tumors were well differentiated in 89.6% of patients. Ki67 was >2% in 39.6% of patients. Primary tumor size was >3 cm in 49.6% of cases studied. For the univariate analysis, the negative prognostic factors were: pancreatic origin (rate ratio 4.64, P = 0.0002), poorly differentiated tumor (rate ratio 7.70, P = 0.0001), primary tumor size >3 cm (rate ratio 4.26, P = 0.0009), presence of distant metastases (liver: rate ratio 5.88, P = 0.01; distant extra-hepatic: rate ratio 13.41, P = 0.0008). The pancreatic site, the poor degree of differentiation and the distant metastases were confirmed as negative prognostic factors at multivariate analysis. Overall 5-year survival rate was 77.5%. Survival rates differed according to: primary tumor site (62% for pancreatic vs 89.9% for gastrointestinal tract, P = 0.0001) and size (65.7% for >3 cm vs 88.8% for ≤ 3 cm, P = 0.0003), degree of differentiation (22% for poor vs 86.8% for good, P 2% vs 90.1% for ≤ 2%, P = 0.003), metastases (96.1, 77, 73.3 and 50.1% for absent, local, liver and distant extra-hepatic metastases respectively), age at diagnosis (85.3% for ≤ 50 years vs 70.3% for > 50 years, P = 0.03). Although 64.3% of gastro-entero-pancreatic endocrine tumors present metastases at diagnosis, the 5-year survival rate is 77.5%. Pancreatic site, a poor degree of tumor cell differentiation and distant extra-hepatic metastases are the major negative prognostic factors.

Rachael Stolzenberg-Solomon, Laufey Amundadottir and colleagues report a genome-wide association study of pancreatic cancer. They identify four new susceptibility loci. We performed a multistage genome-wide association study including 7,683 individuals with pancreatic cancer and 14,397 controls of European descent. Four new loci reached genome-wide significance: rs6971499 at 7q32.3 (LINC-PINT, per-allele odds ratio (OR) = 0.79, 95% confidence interval (CI) 0.74–0.84, P = 3.0 × 10−12), rs7190458 at 16q23.1 (BCAR1/CTRB1/CTRB2, OR = 1.46, 95% CI 1.30–1.65, P = 1.1 × 10−10), rs9581943 at 13q12.2 (PDX1, OR = 1.15, 95% CI 1.10–1.20, P = 2.4 × 10−9) and rs16986825 at 22q12.1 (ZNRF3, OR = 1.18, 95% CI 1.12–1.25, P = 1.2 × 10−8). We identified an independent signal in exon 2 of TERT at the established region 5p15.33 (rs2736098, OR = 0.80, 95% CI 0.76–0.85, P = 9.8 × 10−14). We also identified a locus at 8q24.21 (rs1561927, P = 1.3 × 10−7) that approached genome-wide significance located 455 kb telomeric of PVT1. Our study identified multiple new susceptibility alleles for pancreatic cancer that are worthy of follow-up studies.

Breath tests represent a valid and non-invasive diagnostic tool in many gastroenterological conditions. The rationale of hydrogen-breath tests is based on the concept that part of the gas produced by colonic bacterial fermentation diffuses into the blood and is excreted by breath, where it can be quantified easily. There are many differences in the methodology, and the tests are increasingly popular. The Rome Consensus Conference was convened to offer recommendations for clinical practice about the indications and methods of H2-breath testing in gastrointestinal diseases. Experts were selected on the basis of a proven knowledge/expertise in H2-breath testing and divided into Working Groups (methodology; sugar malabsorption; small intestine bacterial overgrowth; oro-coecal transit time and other gas-related syndromes). They performed a systematic review of the literature, and then formulated statements on the basis of the scientific evidence, which were debated and voted by a multidisciplinary Jury. Recommendations were then modified on the basis of the decisions of the Jury by the members of the Expert Group. The final statements, graded according to the level of evidence and strength of recommendation, are presented in this document; they identify the indications for the use of H2-breath testing in the clinical practice and methods to be used for performing the tests.

Purpose: Knowledge of clinical course of pancreatic endocrine carcinomas (PECs) is poor. This study aimed to determine the time to progression of advanced PECs, and to identify predictors capable of selecting subgroups with higher risk of progression. Patients and Methods: In this multicenter retrospective analysis, patients with advanced PECs were enrolled. Staging was according to European Neuroendocrine Tumors Society guidelines. Grading was based on proliferation index using Ki67 immunohistochemistry. The primary end point was progression-free survival (PFS), which was assessed using the Kaplan-Meier method. The Cox regression proportional hazard model was used to identify predictors for tumor progression. Results: Two hundred two patients with PECs were enrolled, including 172 with well-differentiated and 30 with poorly differentiated endocrine carcinomas. There were 34 patients with stage III and 168 with stage IV tumors. G1 tumors were present in 19.7% of patients, whereas 60.1% of patients had G2 tumors, and the remaining 20.2% had G3 tumors. Disease progression occurred in 166 patients (82.2%), at a median interval of 10 months (interquartile range, 5 to 22) from diagnosis. Median PFS was 14 months. Different PFS were observed depending on G grade (P < .001) and tumor differentiation (P < .001) and in patients who did not receive any antitumor treatment (P = .002). The major risk factor for progression was the proliferation index Ki67 (hazard ratio, 1.02 for each increasing unit; P < .001). Overall 5-year survival was 44.1%. Conclusion: The vast majority of patients with advanced PECs undergo disease progression. The major risk factor for progression is Ki67 index, which should lead physicians dealing with PECs to plan appropriate follow-up programs and therapeutic strategies.