Background: Robotic-assisted colorectal surgery is gaining popularity, but limited data are available on the safety, efficacy, and cost of robotic-assisted restorative proctectomy with the construction of an ileal pouch and ileal pouch-anal anastomosis (IPAA) for ulcerative colitis (UC). Methods: A retrospective study was conducted comparing consecutively performed robotic-assisted and laparoscopic proctectomy with IPAA between 1 January 2016 and 31 September 2021. In total, 67 adult patients with medically refractory UC without proven dysplasia or carcinoma underwent surgery: 29 operated robotically and 38 laparoscopically. Results: There were no differences between both groups regarding postoperative complications within 30 days according to Clavien-Dindo classification’ grades 1–5 (51.7% vs. 42.1%, p = 0.468) and severe grades 3b–5 (17.2% vs. 10.5%, p = 0.485). Robotic-assisted surgery was associated with an increased urinary tract infection rate (n = 7, 24.1% vs. n = 1, 2.6%; p = 0.010) and longer operative time (346 ± 65 min vs. 281 ± 66 min; p < 0.0001). Surgery costs were higher when operated robotically (median EUR 10.377 [IQR EUR 4.727] vs. median EUR 6.689 [IQR EUR 3.170]; p < 0.0001), resulting in reduced total inpatient profits (median EUR 110 [IQR EUR 4.971] vs. median EUR 2.853 [IQR EUR 5.386]; p = 0.001). Conclusion: Robotic-assisted proctectomy with IPAA can be performed with comparable short-term clinical outcomes to laparoscopy but is associated with a longer duration of surgery and higher surgery costs. As experience increases, some advantages may become evident regarding operative time, postoperative recovery, and length of stay. The robotic procedure might then become cost-efficient.

Colitis-associated colorectal cancer (CAC) is a severe complication of inflammatory bowel disease (IBD). HIF-prolyl hydroxylases (PHD1, PHD2, and PHD3) control cellular adaptation to hypoxia and are considered promising therapeutic targets in IBD. However, their relevance in the pathogenesis of CAC remains elusive. We induced CAC in Phd1 ^–/– , Phd2 ^+/– , Phd3 ^–/– , and WT mice with azoxymethane (AOM) and dextran sodium sulfate (DSS). Phd1 ^–/– mice were protected against chronic colitis and displayed diminished CAC growth compared with WT mice. In Phd3 ^–/– mice, colitis activity and CAC growth remained unaltered. In Phd2 ^+/– mice, colitis activity was unaffected, but CAC growth was aggravated. Mechanistically, Phd2 deficiency (i) increased the number of tumor-associated macrophages in AOM/DSS-induced tumors, (ii) promoted the expression of EGFR ligand epiregulin in macrophages, and (iii) augmented the signal transducer and activator of transcription 3 and extracellular signal–regulated kinase 1/2 signaling, which at least in part contributed to aggravated tumor cell proliferation in colitis-associated tumors. Consistently, Phd2 deficiency in hematopoietic ( Vav:Cre-Phd2 ^fl/fl ) but not in intestinal epithelial cells ( Villin:Cre-Phd2 ^fl/fl ) increased CAC growth. In conclusion, the 3 different PHD isoenzymes have distinct and nonredundant effects, promoting (PHD1), diminishing (PHD2), or neutral (PHD3), on CAC growth.

Background: Pouchitis is the most common long-term complication after restorative proctocolectomy with ileal pouch–anal anastomosis (IPAA) for ulcerative colitis (UC) or familial adenomatous polyposis (FAP), which can eventually progress to pouch failure, necessitating permanent stoma construction. Hypoxia-inducible transcription factor prolyl hydroxylase–containing enzymes (PHD1, PHD2, and PHD3) are molecular oxygen sensors that control adaptive gene expression through hypoxia-inducible factor (HIF). Emerging evidence supports PHDs as being therapeutic targets in intestinal inflammation. However, pharmacological inhibition of PHDs has not been validated as a treatment strategy in pouchitis. Methods: PHD1-3 mRNA and protein expression were analyzed in mucosal pouch and prepouch ileal patient biopsies. After establishment of a preclinical IPAA model in rats, the impact of the pan-PHD small-molecule inhibitor dimethyloxalylglycine (DMOG) on dextran sulfate sodium (DSS)–induced pouchitis was studied. Clinical and molecular parameters were investigated. Results: PHD1, but not PHD2 or PHD3, was overexpressed in pouchitis in biopsies of patients with IPAA for UC but not FAP. In addition, PHD1 expression correlated with disease activity. DMOG treatment profoundly mitigated DSS-induced pouchitis in a rodent IPAA model. Mechanistically, DMOG restored intestinal epithelial barrier function by induction of tight junction proteins zona occludens-1 and claudin-1 and alleviation of intestinal epithelial cell apoptosis, thus attenuating pouch inflammation. Conclusions: Together, these results establish a strong therapeutic rationale for targeting PHD1 with small-molecule inhibitors in pouchitis after IPAA for UC.