The 5-year survival rates for colorectal cancer are generally lower in the UK than other European countries. In an attempt to improve prognosis, central government has stipulated that patients with suspicious symptoms ought to be seen within 2 weeks of referral from a primary care physician. In order to evaluate whether symptom duration affects stage at presentation of colorectal cancer, a retrospective analysis of all patients presenting over a 2-year period to a large district general hospital was performed. There was no significant difference (P = 0.885) in Dukes' staging in patients with symptoms lasting less or more than 6 months. Though seeing patients with symptoms suspicious of colorectal cancer in specialist out-patient clinics within 2 weeks of presentation to the primary care physician would probably reduce the number of patients presenting as an emergency, it is unlikely to improve prognosis. Thus funds diverted towards the 2-week wait are probably best utilised for other procedures such as colonoscopy and for improving care once the diagnosis of cancer has been made. Diagnosis of colorectal cancer at an earlier stage is best achieved by screening of the population.

Endoscopic asymmetric inflammation of the pouch may represent an ischemia-associated pouchitis with characteristic clinical, radiographic, and histologic features. Its hemodynamic, cellular, and molecular basis of mechanism warrants further study.

Predicting tumor sensitivity to antineoplastics remains an elusive challenge, with no methods demonstrating predictive power. Joint analysis of tumors-from patients with distinct malignancies who had progressed on multiple lines of therapy-and drug perturbation transcriptional profiles predicted sensitivity to 28 of 350 drugs, 26 of which (93%) were confirmed in low-passage, patient-derived xenograft (PDX) models. Drugs were prioritized based on their ability to either invert the activity of individual Master Regulator proteins, with available high-affinity inhibitors, or of the modules they comprise (Tumor-Checkpoints), based on de novo mechanism of action analysis. Of 138 PDX mice enrolled in 16 single and 18 multi-protein treatment arms, a disease control rate (DCR) of 68% and 91%, and an objective response rate (ORR) of 12% and 17%, were achieved respectively, compared to 6% and 0% in the negative controls arm, with multi-protein drugs achieving significantly more durable responses. Thus, these approaches may effectively complement and expand current precision oncology approaches, as also illustrated by a case study.

Although degree of T-cell infiltration in CRC was shown to correlate with a positive prognosis, the contribution of phenotypically and functionally distinct T cell subtypes within tumors remains unclear. We analyzed 37,931 single T cells with respect to transcriptome, TCR sequence and 23 cell surface proteins, from tumors and adjacent normal colon of 16 patients. Our comprehensive analysis revealed two phenotypically distinct cytotoxic T cell populations within tumors, including positively prognostic effector memory cells and non-prognostic resident memory cells. These cytotoxic T cell infiltrates transitioned from effector memory to resident memory in a stage-dependent manner. We further defined several Treg subpopulations within tumors. While Tregs overall were associated with positive clinical outcomes, CD38+ peripherally-derived Tregs, phenotypically related to Th17 cells, correlated with poor outcomes independent of cancer stage. Thus, our data highlight the diversity of T cells in CRC and demonstrate the prognostic significance of distinct T cell subtypes, which could inform therapeutic strategies.

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