Table. Pathological Features and Molecular Profile of Early-Onset Colorectal Cancer Pathological features Molecular profile Poor differentiation Microsatellite stability Mucinous tumors More likely to exhibit LINE-1 hypomethylation and TP53 sequence variations Signet-ring morphology Less frequently harbor KRAS, BRAF V600E, and APC sequence variations Perineural/venous invasion Promoter methylation of CpG islands Abbreviations: APC, adenomatous polyposis coli; BRAF, B-Raf; KRAS, K-Ras; LINE-1, long interspersed nuclear elements; TP53, tumor protein 53.

Glomerular filtration rate, renal plasma flow, renal tubular sodium reabsorption (derived from lithium clearance) and renal excretion rates of kallikrein, prostaglandin E2 and systemic and renally-derived metabolites of prostacyclin and thromboxane A2 were measured in patients with Type 1 (insulin-dependent) diabetes mellitus and in normal subjects. Diabetic patients with glomerular hyperfiltration had greater active kallikrein and prostaglandin E2 excretion than patients with normal glomerular filtration rate or than normal control subjects. Both active kallikrein and prostaglandin E2 excretion correlated directly with glomerular filtration rate. Active kallikrein excretion correlated directly with the reabsorption of sodium in the distal tubule. The excretion rates of 6-keto prostaglandin F1 alpha, 2,3 dinor 6-keto prostaglandin F1 alpha, thromboxane B2, 2,3 dinor thromboxane B2 and 11-dehydro thromboxane B2 excretion were not different between the groups. This study confirms in man our previous finding of increased renal kallikrein production in the hyperfiltering streptozotocin-diabetic rat model. Given that kinins generated by kallikrein are extremely potent vasodilators and stimulate the renal production of eicosanoids that also regulate glomerular function, our findings suggest that increased kallikrein activity and prostaglandin E2 production may contribute to renal vasodilatation and hyperfiltration in human diabetes. The localization of kallikrein in the distal connecting tubule makes it plausible that altered sodium transport in the distal tubule may be a signal to increase generation of kallikrein.

Objective Crohn's disease (CD) is characterised by inflammation, predominantly associated with ilea. To investigate the basis for this inflammation in patients with CD, we examined dendritic cells (DC) which are pivotal for maintenance of immunological tolerance in the gut. Methods Ileal biopsies and blood DCs from CD patients and controls were examined by microscopy and flow cytometry for PD‐L1 and PD‐L2 expression, as PD‐L1 has been implicated in colitis but the contribution of PD‐L2 is less clear. In vitro studies, of blood samples from CD patients, were used to demonstrate a functional role for PD‐L2 in disease pathogenesis. Results Quantitative microscopy of CD11c+ DCs in inflamed and noninflamed ilea from CD patient showed > 75% loss of these cells from the villi, lamina propria and Peyer's patches compared with non‐CD controls. Given this loss of DCs from ilia of CD patients, we hypothesised DCs may have migrated to the blood as these patients can have extra‐intestinal symptoms. We thus examined blood DCs from CD patients by flow cytometry and found significant increases in PD‐L1 and PD‐L2 expression compared with control samples. Microscopy revealed an aggregated form of PD‐L2 expression, known to drive Th1 immunity, in CD patients but not in controls. In vitro functional studies with PD‐L2 blockade confirmed PD‐L2 contributes significantly to the secretion of pro‐inflammatory cytokines known to cause disease pathogenesis. Conclusion Taken together, this study shows that PD‐L2 can influence the progression of CD and blockade of PD‐L2 may have therapeutic potential.

We report outcomes and evaluate patient factors and the impact of surgical evolution on outcomes in consecutive ulcerative colitis patients who had restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) at an Australian institution over 26 years. Methods Data including clinical characteristics, medical therapy pre-surgery and surgical outcomes were collected. We divided eligible patients into three period arms (period 1: 1990-1999; period 2: 2000-2009; period 3: 2010-2016). Outcomes of interest were IPAA leak and pouch failure. Results Two hundred and twelve patients were included. Median follow up was 50 months (interquartile range [IQR]: 17-120). Rates of early and late complications were 35% and 52% respectively. Early complications included wound infection (9.4%), pelvic sepsis (8%) and small bowel obstruction (6.6%) while late complications included small bowel obstruction (19%), anal stenosis (17%) and pouch fistula (13%). Overall, IPAA leak rate was 6.1% and pouch failure rate was 4.8%. Eighty three patients (42%) had experienced pouchitis. Over time, we observed an increase in patient exposure to thiopurine (p=0.0025), cyclosporin (p=0.0002) and anti-tumour necrosis factor (p<0.00001) coupled with a shift to laparoscopic technique (p<0.00001), stapled IPAA (p<0.00001), J pouch configuration (p<0.00001), a modified two-stage procedure (p=0.00012) and a decline in defunctioning ileostomy rate at time of IPAA (p=0.00002). Apart from pouchitis, there was no significant difference in surgical and chronic inflammatory pouch outcomes with time. Conclusion Despite greater patient exposure to immunomodulatory and biologic therapy pre surgery coupled with a significant change in surgical techniques, surgical and chronic inflammatory pouch outcome rates have remained stable.

What does this paper add to the literature? This survey of Australian and New Zealand surgeons examines the use of diverting ileostomies in two common scenarios along with the use of both transanal tubes and pelvic drains.