Abstract Background Up to one-third of ileal pouch–anal anastomosis (IPAA) patients develop pouch dysfunction, and rarely, twisted pouch syndrome. Current diagnostics lack three-dimensionality. We aimed to develop and validate staple line tortuosity from routine computed tomography (CT) scans to objectively characterise pouch geometry, distinguish twisted from normal anatomy, and evaluate association with patient-reported outcomes (PROs) after surgical correction with redo pouch procedures. Methods A sample of patients from 2015-2025 with either normal or surgically confirmed twisted pouches (outlet or inlet) with CT imaging were analyzed. Semi-automated segmentation of staple lines was performed using 3D Slicer, followed by Python-based 3D reconstruction to compute 5 tortuosity metrics: anterior (Ta), posterior (Tp), mean, pouch tortuosity index (PTI), and delta (absolute Ta-Tp). Statistical analysis included non-parametric tests with false-discovery-rate correction, ROC analysis (sensitivity and specificity), voxel-level analysis, and principal component analysis. Our primary predictor was PTI. Clinical outcomes included PROs: quality of life (QoL), health (QoH), energy (QoE), pain, cramping, and bloating. QoL measures ranged from 1 (worst) to 10 (best). Results We analysed 63 CT scans from 38 patients (Table 1). Baseline scans in outlet twist patients showed higher PTI than normal controls (median PTI 1.95 (IQR 1.79–2.19) vs. 1.31 (1.19–1.33); p 0.001). PTI discriminated twisted from normal pouches with an AUC of 0.98 (95% CI 0.93-1.00) and an optimal threshold of ≤ 1.48 (sensitivity 95%, specificity 92%). Among the 19 outlet pre-to-post redo pairs (Figure 1), median tortuosity Δ was –0.44 (95% CI –0.82 to –0.36; p 0.001), and 13 (68%) achieved a PTI of ≤ 1.48. Skeleton voxel density positively (ρ = 0.52, p = 0.006) and z-span inversely (ρ= –0.57, p = 0.003) correlated with the PTI. PCA identified 2 orthogonal axes explaining 98.7% of variation: global tortuosity (80%) and anterior-posterior asymmetry (19%). After redo IPAA, compared with before, twisted pouch patients (n = 23) reported improved QoL (4 vs. 8; p = 0.005), QoH (4 vs. 7; p = 0.002), and QoE (4 vs. 8; p = 0.002) and decreased stool frequency (–3 per day; p = 0.01). After redo IPAA, reduction in PTI was moderately correlated with less cramping (ρ = 0.48, p = 0.04). Conclusion 3D pouchography (CT-based 3D staple-line reconstruction) and the pouch tortuosity index is a reproducible and interpretable imaging biomarker that distinguishes twisted and normal ileal pouches, quantifies geometric correction after redo surgery, and parallels improvements in patient-reported outcomes. This novel digital biomarker enables objective postoperative monitoring and supports integration of the PTI into clinical workflows. Conflict of interest: Dr. Feroz, Shah: SHF: received research funding: Cleveland Clinic Catalyst Grant, Cleveland Clinic Digestive Disease Institute Chief’s Innovation and Research Award Chen, Kevin: No conflict of interest Rieder, Florian: consulting fees: Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena, Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, Celltrion, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Landos, Jannsen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Palisade, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, UCB, Ysios, 89Bio Holubar, Stefan: SDH received research funding: Crohn’s & Colitis Foundation, American Society of Colon and Rectal Surgeons. Cleveland Clinic Catalyst Grant, Cleveland Clinic Digestive Disease Institute Chief’s Innovation and Research Award
Feroz et al. (Thu,) studied this question.