In rectal cancer patients with a cCR following neoadjuvant chemoradiotherapy, a Watch and Wait policy appears feasible and safe. Robust surveillance with early detection of regrowths allows a high rate of successful salvage surgery, without an increase in the risk of systemic disease, or adverse survival outcomes.

mutation is a common canonical mutation in colorectal cancer, found at differing frequencies in all consensus molecular subtypes (CMS). The independent immunobiological impacts of RAS mutation and CMS are unknown. Thus, we explored the immunobiological effects of mutation across the CMS spectrum. Expression analysis of immune genes/signatures was performed using The Cancer Genome Atlas (TCGA) RNA-seq and the KFSYSCC microarray datasets. Multivariate analysis included status, CMS, tumor location, MSI status, and neoantigen load. Protein expression of STAT1, HLA-class II, and CXCL10 was analyzed by digital IHC. The Th1-centric co-ordinate immune response cluster (CIRC) was significantly, albeit modestly, reduced in -mutant colorectal cancer in both datasets. Cytotoxic T cells, neutrophils, and the IFNγ pathway were suppressed in-mutant samples. The expressions of STAT1 and CXCL10 were reduced at the mRNA and protein levels. In multivariate analysis, mutation, CMS2, and CMS3 were independently predictive of reduced CIRC expression. Immune response was heterogeneous across-mutant colorectal cancer: -mutant CMS2 samples have the lowest CIRC expression, reduced expression of the IFNγ pathway, and , and reduced infiltration of cytotoxic cells and neutrophils relative to CMS1 and CMS4 and to wild-type CMS2 samples in the TCGA. These trends held in the KFSYSCC dataset. mutation is associated with suppressed Th1/cytotoxic immunity in colorectal cancer, the extent of the effect being modulated by CMS subtype. These results add a novel immunobiological dimension to the biological heterogeneity of colorectal cancer. .

The overall incidence of LAGB erosions in our series was 1.96%. This incidence fell with increasing experience to 0.5% after the initial 300 bands were excluded from the analysis (3 band erosions in the last 565 band insertions). However, further increases in incidence are likely with a longer follow-up period. The most common presentation was abdominal pain followed by weight regain and port-site sepsis. In the authors' hands, laparoscopic omental plugging and band removal through a separate anterior gastrotomy appear to be effective methods for dealing with band erosions. Band erosion is a significant source of morbidity, with at least one-third of the erosion patients in our series not achieving their final goal of weight loss despite appropriate treatment. This study highlights the need for a future prospective randomized study to clarify the apparent strong influence of band design and construction on the etiopathogenesis of band erosion.

Omental plugging is a way of managing LAGB erosion, which in our hands has led to an uneventful postoperative course and future rebanding without undue delay. It is suited patients with incomplete erosion when the endoscopic option is difficult, thereby removing the need for a surveillance period awaiting complete band erosion.

<p>CIRC is largely non-overlapping with immune cell type signatures.</p>

<p>KRAS mutation is associated with reduced expression of STAT1 and CXCL10.</p>

<p>Supp Fig 5: CIRC is significantly correlated with all immune cell subpopulations. Pairwise correlations of CIRC and immune cell signatures in (A) TCGA and (B) KFSYSCC data sets.</p>

<div>Abstract<p><b>Purpose:</b> <i>KRAS</i> mutation is a common canonical mutation in colorectal cancer, found at differing frequencies in all consensus molecular subtypes (CMS). The independent immunobiological impacts of RAS mutation and CMS are unknown. Thus, we explored the immunobiological effects of <i>KRAS</i> mutation across the CMS spectrum.</p><p><b>Experimental Design:</b> Expression analysis of immune genes/signatures was performed using The Cancer Genome Atlas (TCGA) RNA-seq and the KFSYSCC microarray datasets. Multivariate analysis included <i>KRAS</i> status, CMS, tumor location, MSI status, and neoantigen load. Protein expression of STAT1, HLA-class II, and CXCL10 was analyzed by digital IHC.</p><p><b>Results:</b> The Th1-centric co-ordinate immune response cluster (CIRC) was significantly, albeit modestly, reduced in <i>KRAS</i>-mutant colorectal cancer in both datasets. Cytotoxic T cells, neutrophils, and the IFNγ pathway were suppressed in <i>KRAS</i>-mutant samples. The expressions of STAT1 and CXCL10 were reduced at the mRNA and protein levels. In multivariate analysis, <i>KRAS</i> mutation, CMS2, and CMS3 were independently predictive of reduced CIRC expression. Immune response was heterogeneous across <i>KRAS</i>-mutant colorectal cancer: <i>KRAS</i>-mutant CMS2 samples have the lowest CIRC expression, reduced expression of the IFNγ pathway, <i>STAT1</i> and <i>CXCL10</i>, and reduced infiltration of cytotoxic cells and neutrophils relative to CMS1 and CMS4 and to <i>KRAS</i> wild-type CMS2 samples in the TCGA. These trends held in the KFSYSCC dataset.</p><p><b>Conclusions:</b> <i>KRAS</i> mutation is associated with suppressed Th1/cytotoxic immunity in colorectal cancer, the extent of the effect being modulated by CMS subtype. These results add a novel immunobiological dimension to the biological heterogeneity of colorectal cancer. <i>Clin Cancer Res; 24(1); 224–33. ©2017 AACR</i>.</p></div>