A biliary immune landscape map of primary sclerosing cholangitis reveals a dominant network of neutrophils and tissue-resident T cells.

The human biliary system, a mucosal barrier tissue connecting the liver and intestine, is an organ often affected by serious inflammatory and malignant diseases. Although these diseases are linked to immunological processes, the biliary system represents an unexplored immunological niche. By combining endoscopy-guided sampling of the biliary tree with a high-dimensional analysis approach, comprehensive mapping of the human biliary immunological landscape in patients with primary sclerosing cholangitis (PSC), a severe biliary inflammatory disease, was conducted. Major differences in immune cell composition in bile ducts compared to blood were revealed. Furthermore, biliary inflammation in patients with PSC was characterized by high presence of neutrophils and T cells as compared to control individuals without PSC. The biliary T cells displayed a CD103+CD69+ effector memory phenotype, a combined gut and liver homing profile, and produced interleukin-17 (IL-17) and IL-22. Biliary neutrophil infiltration in PSC associated with CXCL8, possibly produced by resident T cells, and CXCL16 was linked to the enrichment of T cells. This study uncovers the immunological niche of human bile ducts, defines a local immune network between neutrophils and biliary-resident T cells in PSC, and provides a resource for future studies of the immune responses in biliary disorders.

Survival Analysis and Risk for Progression of Intraductal Papillary Mucinous Neoplasia of the Pancreas (IPMN) Under Surveillance: A Single-Institution Experience.

PURPOSE: While surveillance of the majority of patients with IPMN is considered best practice, consensus regarding the duration of follow-up is lacking. This study assessed the survival rate and risk for progression of IPMN under surveillance. METHODS: All patients diagnosed with and surveyed for IPMN between January 2008 and December 2013 were identified and assigned to two groups: patients without indication for surgery (Group 1), and patients whose IPMN required surgery but were inoperable for general reasons (Group 2). Disease progression and survival data were compared between both groups. RESULTS: In total 503 patients were identified, of whom 444 (88.3%) were followed up. Group 1 included 395 patients, and Group 2 had 49. In Group 1, IPMN-specific 1-, 5-, and 10-year survival rates were 100, 100, and 94.2%, respectively. Four patients died of associated or concomitant pancreatic cancer, and 230 patients (58.2%) experienced disease progression. The 1-, 4-, 10-year cumulative risk for progression and for surgery was 11.2, 70.6, 97.5, and 2.9, 26.2, 72.1%, respectively. In Group 2, the 1-, 5-, 10-year IPMN-specific survival rate was 90.7, 74.8, and 74.8%, respectively. CONCLUSIONS: This study confirmed the safety of surveillance for patients with IPMN who do not require surgery. However, the risk for disease progression and for surgery increases significantly over time. The study results support International and European guidelines not to discontinue IPMN surveillance and validate the European recommendation to intensify follow-up after 5 years. The fairly good prognosis of patients whose IPMN requires surgery but cannot undergo resection suggests a relatively indolent disease biology.