Only two of 49 cats undergoing surgical ligation of congenital extra- and intrahepatic portosystemic shunts died perioperatively, a mortality rate comparable with the mortality rates of dogs undergoing surgical attenuation of congenital portosystemic shunts and cats in which the shunts are attenuated with an ameroid ring constrictor. Thirty (83 per cent) of the 36 cats for which long-term information was available were still alive at a median follow-up period of 47 months (range six to 105 months); the outcome was excellent (no clinical signs) in 20 of them (median follow-up 37 months, range six to 105 months) and good (minimal clinical signs) in seven (median follow-up 39 months, range 10 to 73 months) and none of these 27 cats was on any long-term medication or special diet. The only major cause of morbidity was the development of neurological signs in 18 (37 per cent) of the cats. These included seizures and a wide variety of other neurological signs, and their development and persistence was not affected by the presence of preoperative seizures, the type of shunt, the degree of shunt attenuation or the age of the cat. The serum concentrations of ammonia and preprandial bile acids were normal or significantly below normal in the cats with neurological signs. Liver histopathology was similar in the cats with and without neurological signs. Ten (56 per cent) of the 18 cats that developed neurological signs recovered normal neurological function long term.

The advantages of an accurate assessment of a patient's risk include, on an individual level, the opportunity to give a more accurate prognosis and choose the most appropriate treatment. If the risk of an adverse outcome is known for a group of patients, the actual outcome can be compared with the predicted outcome, and comparison can be made between groups in different surgical units for the purposes of audit or research. The Physiological and Operative Severity Score for enUmeration of Mortality and morbidity (POSSUM) is the most appropriate of the currently available scores for general surgical practice.

ObjectivePathological Wnt pathway activation is a conserved hallmark of colorectal cancer. Wnt-activating mutations can be divided into: i) ligand-independent (LI) alterations in intracellular signal transduction proteins (Adenomatous polyposis coli, β-catenin), causing constitutive pathway activation and ii) ligand-dependent (LD) mutations affecting the synergistic R-Spondin axis (RNF43, RSPO-fusions) acting through amplification of endogenous Wnt signal transmembrane transduction. Our aim was to exploit differential Wnt target gene expression to generate a mutation-agnostic biomarker for LD tumours.DesignWe undertook harmonised multi-omic analysis of discovery (n=684) and validation cohorts (n=578) of colorectal tumours collated from publicly available data and the Stratification in Colorectal Cancer Consortium. We used mutation data to establish molecular ground truth and subdivide lesions into LI/LD tumour subsets. We contrasted transcriptional, methylation, morphological and clinical characteristics between groups.ResultsWnt disrupting mutations were mutually exclusive. Desmoplastic stromal upregulation of RSPO may compensate for absence of epithelial mutation in a subset of stromal-rich tumours. Key Wnt negative regulator genes were differentially expressed between LD/LI tumours, with targeted hypermethylation of some genes (AXIN2, NKD1) occurring even in CIMP-negative LD cancers. AXIN2 mRNA expression was used as a discriminatory molecular biomarker to distinguish LD/LI tumours (area under the curve >0.93).ConclusionsEpigenetic suppression of appropriate Wnt negative feedback loops is selectively advantageous in LD tumours and differential AXIN2 expression in LD/LI lesions can be exploited as a molecular biomarker. Distinguishing between LD/LI tumour types is important; patients with LD tumours retain sensitivity to Wnt ligand inhibition and may be stratified at diagnosis to clinical trials of Porcupine inhibitors.