Parenteral nutrition (PN) has revolutionized the care of patients with intestinal failure by providing nutrition intravenously. Worldwide, PN remains a standard tool of nutrition delivery in neonatal, pediatric, and adult patients. Though the benefits are evident, patients receiving PN can suffer serious cholestasis due to lack of enteral feeding and sometimes have fatal complications from liver injury and gut atrophy, including PN-associated liver disease or intestinal failure-associated liver disease. Recent studies into gut-systemic cross talk via the bile acid-regulated farnesoid X receptor (FXR)-fibroblast growth factor 19 (FGF19) axis, gut microbial control of the TGR5-glucagon-like peptide (GLP) axis, sepsis, and role of prematurity of hepatobiliary receptors are greatly broadening our understanding of PN-associated injury. It has also been shown that the composition of ω-6/ω-3 polyunsaturated fatty acids given parenterally as lipid emulsions can variably drive damage to hepatocytes and cell integrity. This manuscript reviews the mechanisms for the multifactorial pathogenesis of liver disease and gut injury with PN and discusses novel ameliorative strategies. (Nutr Clin Pract. 2020;35:63-71)

Extensive bowel resection results in short bowel syndrome. Absence of the ileocecal valve and length of remaining bowel are important prognostic factors. Such patients require total parenteral nutrition for survival, which has significant side effects, thus understanding mechanisms driving total parenteral nutrition-associated complications in short bowel syndrome is a major research focus. We hypothesized that we could develop an ambulatory total parenteral nutrition-short bowel syndrome piglet model recapitulating human short bowel syndrome for advanced research. Fourteen neonatal pigs received duodenal, jugular catheters, and a jacket with a miniaturized pump. Animals were randomly allocated to enteral nutrition ( n = 5), total parenteral nutrition only ( n = 5) or total parenteral nutrition with 75% small bowel, ileocecal valve resection, and ileo-colonic anastomosis ( n = 4). Blood, liver, and gut were analyzed. Animals underwent successful bowel resection and anastomosis. Increased bilirubin was noted in short bowel syndrome and total parenteral nutrition. Mean conjugated bilirubin (mg/dL)±SE was 0.036 ± 0.004 for enteral nutrition ( P = 0.03), 1.29 ± 0.613 for total parenteral nutrition ( P = 0.01), and 3.89 ± 0.51 for short bowel syndrome ( P = 0.000064). Linear gut density was reduced in short bowel syndrome and total parenteral nutrition vs. enteral nutrition. The mean linear gut density (g/cm)±SE for distal gut was 0.30 ± 0.02 for enteral nutrition ( P = 0.0005); 0.16 ± 0.01 for total parenteral nutrition ( P = 0.01), and 0.11 ± 0.008 for short bowel syndrome ( P = 0.0001). We noted gut adaptation in short bowel syndrome ( P = 0.015) with significant reduction in gut FXR, gut FGF19, and enhanced hepatic CyP7A1 expression in short bowel syndrome and total parenteral nutrition ( P < 0.05). We successfully created an ambulatory total parenteral nutrition-short bowel syndrome model with distal small bowel and ileocecal valve resection recapitulating human short bowel syndrome. Our model validated total parenteral nutrition-related hyperbilirubinemia and gut changes, as noted in human short bowel syndrome. This model holds great potential for future innovative research and clinical applications. Impact statement Short bowel syndrome is associated with significant comorbidities and mortality. This study is important as unlike current systems, it provides a validated piglet model which mirrors anatomical, histological, and serological characteristics observed in human SBS. This model can be used to advance knowledge into mechanistic pathways and therapeutic modalities to improve outcomes for SBS patients. This study is novel in that in addition to significant reduction in the remnant bowel and noted liver disease, we also developed a method to emulate ileocecal valve resection and described gut adaptive responses which has important clinical implications in humans.

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Objective Combining 18F-FDG PET with whole-body MR for paediatric cancer staging is practically feasible if imaging protocols can be streamlined. We compared 18F-FDG PET/STIR with accelerated 18F-FDG PET/FSPGR for whole-body tumour imaging in children and young adults. Methods Thirty-three children and young adults (17.5±5.5 years, range 10–30 years) with malignant lymphoma or sarcoma underwent a 18F-FDG PET staging exam, followed by ferumoxytol-enhanced STIR and FSPGR whole-body MR. 18F-FDG PET scans were fused with MR data and the number and location of tumours on each integrated exam was determined. Histopathology and follow-up imaging served as standard of reference. The agreement of each MR sequence with the reference and the whole-body imaging times were compared using Cohen’s kappa coefficient and student t-test, respectively. Results Comparing 18F-FDG PET/FSPGR to 18F-FDG PET/STIR, sensitivities were 99.3% for both, specificities were statistically equivalent, 99.8% versus 99.9% and the agreement with the reference based on Cohen’s kappa coefficient was also statistically equivalent, 0.989 versus 0.992. However, the total scan-time for accelerated FSPGR of 19.8±5.3 minutes was significantly shorter compared to 29.0±7.6 minutes for STIR (p=0.001). Conclusion 18F-FDG PET/FSPGR demonstrated equivalent sensitivities and specificities for cancer staging compared to 18F-FDG PET/STIR, but could be acquired with shorter acquisition time.

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