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Endoscopic full-thickness resection of gastrointestinal (GI) tumors has been applied to the management of premalignant, early malignant, and indolent tumors of the GI tract to spare morbidity associated with traditional surgical approaches. Increasingly, a combined laparoscopic-endoscopic approach is being used to treat lesions that are not amenable to endoscopic resection alone. Case reports and small case series have demonstrated utility for lesions such as gastric GI stromal tumors, early gastric carcinomas, small duodenal masses, and colonic polyps or masses. Although promising, further research is necessary to determine the best indications for such an approach, and to compare long-term outcomes to those achieved with more traditional approaches. [ABSTRACT FROM AUTHOR]

Tumor-associated macrophages (TAMs) play an important role in tumor immunity and comprise of subsets that have distinct phenotype, function, and ontology. Transcriptomic analyses of human medulloblastoma, the most common malignant pediatric brain cancer, showed that medulloblastomas (MBs) with activated sonic hedgehog signaling (SHH-MB) have significantly more TAMs than other MB subtypes. Therefore, we examined MB-associated TAMs by single-cell RNA sequencing of autochthonous murine SHH-MB at steady state and under two distinct treatment modalities: molecular-targeted inhibitor and radiation. Our analyses reveal significant TAM heterogeneity, identify markers of ontologically distinct TAM subsets, and show the impact of brain microenvironment on the differentiation of tumor-infiltrating monocytes. TAM composition undergoes dramatic changes with treatment and differs significantly between molecular-targeted and radiation therapy. We identify an immunosuppressive monocyte-derived TAM subset that emerges with radiation therapy and demonstrate its role in regulating T cell and neutrophil infiltration in MB. [Display omitted] • Sonic Hedgehog (SHH) subgroup of medulloblastoma (MB) recruits diverse macrophages • Radiation or molecular-targeted therapy alters macrophage distribution in SHH-MB • Radiation recruits immunosuppressive monocyte-derived macrophages (TAMoMacs) in SHH-MB • Radiation-induced TAMoMacs regulate CD8 T cell and neutrophil numbers in SHH-MB Dang et al. show that the sonic hedgehog subgroup of medulloblastoma (SHH-MB) contains macrophages derived from microglia and circulating monocytes. Radiation therapy, but not treatment targeting the SHH pathway, led to recruitment of immunosuppressive monocyte-derived macrophages that reduced T cells and neutrophils in the tumor microenvironment. [ABSTRACT FROM AUTHOR]

Activated macrophages must carefully calibrate their inflammatory responses to balance efficient pathogen control with inflammation-mediated tissue damage, but the molecular underpinnings of this "balancing act" remain unclear. Using genetically engineered mouse models and primary macrophage cultures, we show that Toll-like receptor (TLR) signaling induces the expression of the transcription factor Spic selectively in patrolling monocytes and tissue macrophages by a nuclear factor κB (NF-κB)-dependent mechanism. Functionally, Spic downregulates pro-inflammatory cytokines and promotes iron efflux by regulating ferroportin expression in activated macrophages. Notably, interferon-gamma blocks Spic expression in a STAT1-dependent manner. High levels of interferon-gamma are indicative of ongoing infection, and in its absence, activated macrophages appear to engage a "default" Spic -dependent anti-inflammatory pathway. We also provide evidence for the engagement of this pathway in sterile inflammation. Taken together, our findings uncover a pathway wherein counter-regulation of Spic by NF-κB and STATs attune inflammatory responses and iron metabolism in macrophages. • The transcription factor Spic restrains inflammatory responses in macrophages • Spic promotes the expression of the iron exporter ferroportin in activated macrophages • NF-κB activity is required for the expression of Spic in activated macrophages • Interferon-gamma suppresses Spic expression in activated macrophages Activated macrophages must fine-tune their inflammatory responses to promote host defense while limiting tissue damage. Alam et al. find that the transcription factor Spic restrains inflammatory responses and promotes iron efflux from activated macrophages, thereby calibrating macrophage responses during the resolution of inflammation. [ABSTRACT FROM AUTHOR]

Objective Acute limb ischemia (ALI) is the cause of significant morbidity and mortality. Although ALI after cardiac surgery is associated with high rates of morbidity and mortality, there are no robust, controlled analyses of the risk factors and outcomes of ALI in this setting. We aimed to identify risk factors for and to delineate outcomes after ALI in patients undergoing cardiac surgery. Methods We performed a retrospective review of prospectively collected data on patients undergoing cardiac surgery at our institution between 2002 and 2012. Results Between 2002 and 2012, there were 11,343 patients who underwent major open cardiac surgery, with 156 cases of ALI for an incidence of 1.4%. In a multivariable model, significant risk factors for ALI included body surface area (odds ratio [OR], 0.41; 95% confidence interval [CI], 0.18-0.92), current smoking status (OR, 2.2; 95% CI, 1.3-3.7), peripheral arterial disease (OR, 2.5; 95% CI, 1.6-3.7), nonelective operative status (OR, 1.9-5.0; 95% CI, 1.2-19.7), use of extracorporeal membrane oxygenation (OR, 5.6; 95% CI, 2.5-11.6) or intra-aortic balloon pump (OR, 4.7; 95% CI, 2.9-7.5), and valve operation (OR, 2.1; 95% CI, 1.1-4.0). There were 105 (67%) patients who developed ALI who required an operation, and 27 (17%) required an amputation on the index admission. ALI was associated with a significant reduction in long-term survival (hazard ratio, 3.72; 95% CI, 2.97-4.65; P < .0001). Conclusions ALI is associated with significant morbidity and mortality, and it is also associated with reduced long-term survival. Those patients with the risk factors described require extra vigilance to limit the risk of ALI and should be managed in accordance with the patient's overall clinical condition and goals of care. [ABSTRACT FROM AUTHOR]