Perineural invasion and immunosuppressive tumor microenvironment are the distinct features of pancreatic ductal adenocarcinoma (PDAC). Heterogeneous myeloid-derived suppressor cells (MDSCs) are potent suppressors of antitumor immunity, posing obstacles for cancer immunotherapy. Increasing evidences have demonstrated the accumulation of MDSCs in PDAC patients. However, the role of MDSCs in perineural invasion of PDAC and the existence of novel MDSC subsets during PDAC remain unclear. This study found that lymphocytic perineural cuffs were frequently present in chronic pancreatitis (CP) tissues and adjacent non-neoplastic pancreatic tissues (ANPTs), but not in PDAC with perineural invasion. Meanwhile, we found that neutrophil-like MDSCs (nMDSCs), but not monocyte-like MDSCs (mMDSCs), were significantly increased in PBMCs and tumor tissues of PDAC patients. Further observation identified two distinct subsets of nMDSCs, CD13 and CD13 nMDSCs in PDAC patients, which have not been reported previously. Despite a similar morphology, CD13 nMDSCs expressed higher levels of CD11b, CD33, CD16 and arginase 1 but lower levels of CD66b than CD13 nMDSCs. Importantly, CD13 MDSCs, compared with CD13 nMDSCs, more effectively suppressed alloreactive T cell responses via an arginase-1-related mechanism. After tumor resection, the circulating CD13 nMDSCs were decreased markedly. PDAC patients with more CD13 nMDSCs had a shorter overall survival than those with less CD13 nMDSCs. To conclude, we identified two novel MDSC subsets with different characteristics and functions in PDAC, demonstrated the association of the two MDSC subsets with cancer progression, and explored their roles in perineural invasion and immune escape of PDAC.

Constipation, mainly manifesting as abdominal discomfort and painful defecation, is considered as a chronic disorder. Due to a lack of effective therapy, it imposes a significant economic burden and greatly impacts patients’ quality of life which prompt searches for new, original approaches. Based on the research of vibrating capsule (VC) carried out by Ron et al., we investigated the safety and efficacy of an innovative, multi-mode VC in terms of its effect on defecation in animal studies. The parameters associated with different operation modes of VCs can be detected and adjusted by smartphone controlled external configuration device (ECD). The results of blood tests, physiological parameters, CT scan and pathological examination showed no significant abnormality, which undoubtedly confirmed the safety of VCs. For efficacy studies, defecation frequency of beagles increased after administration of these capsules without influence on stool characters. Meanwhile, the mean time of capsule evacuation tended to be reduced while showing no significant difference between different modes. In summary, this study elucidates the safety and effectiveness of VC in prompting the passage of gastrointestinal walls thus greatly increasing the defecation frequency. This study innovatively displays the promising application of VC in the treatment of constipation.

BackgroundTo explore the impact of distant metastases on cancer-specific survival in patients with intraductal papillary mucinous neoplasm (IPMN) with associated invasive carcinoma and identify the risk factor of distant metastases in IPMN with associated invasive carcinoma.MethodsPatients with IPMN with associated invasive carcinoma between 2010 and 2015 were retrospectively selected from the Surveillance, Epidemiology, and End Results (SEER) database. The survival analyses were assessed by Kaplan-Meier analyses and log-rank test. The impact of distant metastases was evaluated by Cox regression model and the risk factors of distant metastases were identified by logistic regression analyses, respectively.ResultsThe median cancer-specific survival time of patients with no metastases, isolated liver, isolated lung, and multiple site metastases were 19 months, 4 months, 7 months, and 3 months, respectively. In patients with isolated liver metastases, multivariate analysis after adjustment indicated that chemotherapy (Hazard Ratio [HR]=0.351, 95% confidence interval [CI]=0.256-0.481, P<0.001) was a protective prognostic factor for cancer-specific survival (CSS) in patients with isolated liver metastases. In isolated lung metastases subgroup, old age (HR=1.715, 95% CI=1.037-2.838, P=0.036) and chemotherapy (HR=0.242, 95% CI=0.134-0.435, P<0.001) were related to CSS in multivariable Cox regression analysis(P<0.05). Tumor located in the pancreatic body/tail (HR=2.239, 95% CI=1.140-4.400, P=0.019) and chemotherapy (HR=0.191, 95% CI=0.108-0.340, P<0.001) were independent prognostic factors for CSS in patients with multiple metastases. Finally, a nomogram was constructed for cancer-specific survival and the predicted C-index was 0.780 (95% CI=0.762-0.798).ConclusionThe liver is the most common site of distant metastases in IPMN with associated invasive carcinoma. Tumor located in the pancreatic body/tail and chemotherapy are independent prognostic factors for CSS in patients with multiple metastases. Further, tumor located in body/tail is identified as a risk factor of distant metastases.