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Objectives Pancreatic cancer (PDAC) with localized stage includes resectable (RPC), borderline resectable (BRPC), or locally advanced unresectable (LAPC). Standard of care for RPC is adjuvant chemotherapy. There are no prospective randomized trials for best treatment of BRPC and LAPC. We evaluate the impact of induction chemotherapy on localized PDAC. Methods Charts of PDAC patients treated at Emory University between 2009 and 2016 were reviewed. The primary end point was overall survival (OS). Results A total of 409 localized PDACs were identified. Resectability was prospectively determined at a multidisciplinary tumor conference. Median age was 67 years (range, 30–92 years), 49% were male, 66% were white, 171 had RPC, 131 had BRPC, and 107 had LAPC. Median OSs for RPC, BRPC, and LAPC were 19.5, 16.1, and 12.7 months, respectively. Type of chemotherapy and age were predictors of OS. Induction chemotherapy was used in 106 with BRPC (81%) and 74 with RPC (56.5%); patients with BRPC who received combination chemotherapy and resection had a median OS of 31.5 compared with 19.5 months in patients with RPC (P = 0.0049). Patients with LAPC had a median OS of 12.7 months. Conclusions In patients with BRPC who undergo resection after induction treatment, the OS was significantly better than in patients with RPC. Neoadjuvant treatment should be considered for all localized PDACs.

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Background Alcohol impairs pulmonary innate immune function and is associated with an increased risk of tuberculosis (TB). Toll‐like receptor 2 (TLR2) is a pattern recognition receptor on alveolar macrophages that recognizes Mycobacterium tuberculosis (Mtb). The expression of TLR2 depends, in part, on granulocyte‐macrophage colony‐stimulating factor (GM‐CSF) signaling. Given our prior work demonstrating the suppression of GM‐CSF signaling following chronic alcohol ingestion, we hypothesized that alcohol impairs TLR2 expression via the suppression of GM‐CSF and thereby reduces the ability of the macrophage to recognize and phagocytose Mtb. Methods Primary alveolar macrophages were isolated from control‐fed and alcohol‐fed rats. Prior to cell isolation, some alcohol‐fed rats were treated with intranasal GM‐CSF and then endotracheally inoculated with an attenuated strain of Mtb. Primary macrophages were then isolated and immunofluorescence was used to determine phagocytic efficiency and TLR2 expression in the presence and absence of GM‐CSF treatment and phagocytic efficiency in the presence and absence of TLR2 neutralization. Results TLR2 expression and phagocytosis of Mtb were significantly lower in the alveolar macrophages of alcohol‐fed rats than control‐fed rats. In parallel, blocking TLR2 signaling recapitulated this decreased phagocytosis of Mtb. In contrast, intranasal GM‐CSF treatment restored TLR2 expression and Mtb phagocytosis in the alveolar macrophages of alcohol‐fed rats to levels comparable to those of control‐fed rats. Conclusions Chronic alcohol ingestion reduces TLR2 protein expression and phagocytosis of Mtb, likely due to impaired GM‐CSF signaling. GM‐CSF restores membrane‐bound TLR2 expression and phagocytic function.

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