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The consensus molecular subtype (CMS) classification of colorectal cancer is based on bulk transcriptomics. The underlying epithelial cell diversity remains unclear. We analyzed 373,058 single-cell transcriptomes from 63 patients, focusing on 49,155 epithelial cells. We identified a pervasive genetic and transcriptomic dichotomy of malignant cells, based on distinct gene expression, DNA copy number and gene regulatory network. We recapitulated these subtypes in bulk transcriptomes from 3,614 patients. The two intrinsic subtypes, iCMS2 and iCMS3, refine CMS. iCMS3 comprises microsatellite unstable (MSI-H) cancers and one-third of microsatellite-stable (MSS) tumors. iCMS3 MSS cancers are transcriptomically more similar to MSI-H cancers than to other MSS cancers. CMS4 cancers had either iCMS2 or iCMS3 epithelium; the latter had the worst prognosis. We defined the intrinsic epithelial axis of colorectal cancer and propose a refined ‘IMF’ classification with five subtypes, combining intrinsic epithelial subtype (I), microsatellite instability status (M) and fibrosis (F).

LR should be the procedure of choice for duodenal GIST whenever technically feasible, because it is associated with good oncologic outcomes and lower morbidity compared with PD. The oncologic outcome of GIST is more likely to be dependent on tumor biology rather that the type of surgical resection. The use of Imatinib in patients with duodenal GIST may potentially allow a proportion of patients who would otherwise require a PD to undergo LR instead.

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Laparoscopic wedge resection for gastric GIST can be safely adopted. It is associated with a more favorable perioperative outcome than the open approach. Its introduction as a surgical option has resulted in an improvement in perioperative outcomes without compromising oncologic safety at our institution.

IPMN(INV) were significantly more likely to present at an earlier stage and were less likely to demonstrate nodal involvement, perineural invasion and vascular invasion. When controlled for stage, IPMN(INV) had an improved OS when compared with PDAC in the early stages.

The MSKCC nomogram slightly underestimated the probability of RFS after surgical resection of GISTs. It was associated with a significantly better predictive accuracy compared to the NIH and Joensuu. This study suggests that there is a wider than expected prognostic divergence between gastric GISTs versus GISTs arising from the small intestine.