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Tolerance is the Holy Grail of solid organ transplantation (SOT) and remains its primary challenge since its inception. In this topic, the seminal contributions of Thomas Starzl at Pittsburgh University outlined foundational principles of graft acceptance and tolerance, with chimerism emerging as a pivotal factor. Immunologically, intestinal transplantation (ITx) poses a unique hurdle due to the inherent characteristics and functions of the small bowel, resulting in increased immunogenicity. This necessitates heavy immunosuppression (IS) while IS drugs side effects cause significant morbidity. In addition, current IS therapies fall short of inducing clinical tolerance and their discontinuation has been proven unattainable in most cases. This underscores the unfulfilled need for immunological modulation to safely reduce IS-related burdens. To address this challenge, the Leuven Immunomodulatory Protocol (LIP), introduced in 2000, incorporates various pro-tolerogenic interventions in both the donor to the recipient, with the aim of facilitating graft acceptance and improving outcome. This review seeks to provide an overview of the current understanding of tolerance in ITx and outline recent advances in this domain. [ABSTRACT FROM AUTHOR]

Short bowel syndrome (SBS) features nutrients malabsorption and impaired intestinal barrier. Patients with SBS are prone to sepsis, intestinal flora dysbiosis and intestinal failure associated liver disease. Protecting intestinal barrier and preventing complications are potential strategies for SBS treatment. This study aims to investigate the effects of farnesoid X receptor (FXR) agonist, obeticholic acid (OCA), have on intestinal barrier and ecological environment in SBS. Through testing the small intestine and serum samples of patients with SBS, impaired intestinal barrier was verified, as evidenced by reduced expressions of intestinal tight junction proteins (TJPs), increased levels of apoptosis and epithelial cell damage. The intestinal expressions of FXR and related downstream molecules were decreased in SBS patients. Then, global FXR activator OCA was used to further dissect the potential role of the FXR in a rat model of SBS. Low expressions of FXR-related molecules were observed on the small intestine of SBS rats, along with increased proinflammatory factors and damaged barrier function. Furthermore, SBS rats possessed significantly decreased body weight and elevated death rate. Supplementation with OCA mitigated the damaged intestinal barrier and increased proinflammatory factors in SBS rats, accompanied by activated FXR-related molecules. Using 16S rDNA sequencing, the regulatory role of OCA on gut microbiota in SBS rats was witnessed. LPS stimulation to Caco-2 cells induced apoptosis and overexpression of proinflammatory factors in vitro. OCA incubation of LPS-pretreated Caco-2 cells activated FXR-related molecules, increased the expressions of TJPs, ameliorated apoptosis and inhibited overexpression of proinflammatory factors. OCA supplementation could effectively ameliorate the intestinal barrier disruption and inhibit overexpression of proinflammatory factors in a rat model of SBS and LPS-pretreated Caco-2 cells. As a selective activator of FXR, OCA might realize its protective function through FXR activation. The FXR agonist, OCA, attenuates the intestinal barrier disruption in a rat model of short bowel syndrome. [Display omitted] • OCA upregulates the repressed FXR expression in SBS rats and Caco-2 cells. • OCA ameliorates the intestinal barrier disruption in SBS rats and LPS-pretreated Caco-2 cells. • OCA, as a selective activator of FXR, might realize its protective function through FXR activation. • Targeting FXR might offer new promises in SBS-induced intestinal barrier disruption. [ABSTRACT FROM AUTHOR]

Purpose: Creation of an optimal bowel anastomosis with low postoperative leakage rate is an immanent part of colorectal surgery contributing to recovery, length of hospital stay and overall hospital costs. We aimed to investigate costs of small and large bowel resection, length of hospital stay, anastomotic leakage rate and its risk factors depending on the anastomotic technique.Methods: Retrospective analysis of 198 patients (67 stapled and 131 hand-sewn anastomoses) undergoing elective bowel resection with a single anastomosis without protective ileostomy either stapled or in double-rowed running suture technique between 1st October 2012 and 30th September 2018 at Charité University Hospital Berlin, Campus Benjamin Franklin. We analyzed costs of treatment, total length of hospital stay, rate of anastomotic leakage and possible risk factors for anastomotic leak.Results: No significant difference between both anastomotic techniques could be detected for hospital stay (p = 0.754), 30-day-readmission rate (p = 0.827), or anastomotic leakage (p = 606). Neither comorbidities (p = 0.449), underlying disease (p = 0.132), experience of the surgical team (p = 0.828) nor scheduling of the operation (p = 0.531) were associated with anastomotic leakage. Stapled anastomoses took 22 min less operation time than sutured anastomoses (130 vs. 152 min. Median) (p = 0.001). Operations with stapled anastomoses saved 183 € in operation costs and 496 € in overall hospital costs.Conclusion: Stapled and hand-sewn bowel anastomoses can be performed equally safe without differences in postoperative outcome. No patient, procedure or surgeon related risk factors for anastomotic leakage could be detected. Bowel resections with stapled anastomoses take less time and save operation and overall hospital costs. [ABSTRACT FROM AUTHOR]

In infants undergoing bowel resection, side-to-side stapled anastomosis (SSA) may restore intestinal continuity. We describe cases of abnormal symptomatic intestinal dilation secondary to SSA in patients with short bowel syndrome (SBS). Case 1 is an infant who underwent SSA for meconium ileus. He developed progressive malabsorption and was found to have a dilated segment of 9 by 8 cm at the prior SSA. This was narrowed into two lumens. He continues to gain weight appropriately. Case 2 is an infant with compartment syndrome resulting in partial colectomy and small bowel resection. Continuity was restored with SSA. On abdominal exploration years later for persistent abdominal pain, the area of prior SSA measured 14 by 9 cm and was narrowed into two lumens. He has excelled postoperatively. Case 3 and Case 4 are older patients referred after initial resection and SSAs as infants. Both had adequate intestinal length excluding their dilated areas and underwent resection with redo SSA as young adults. Both continue to do well. Case 5 is an ex-premature boy with neonatal necrotizing enterocolitis and two prior SSAs. He developed chronic pain and underwent resection of dilated intestine with redo SSA. This dilation recurred at the new SSA two years later. He then underwent division back into two lumens. He is now doing well. In patients undergoing bowel resection, SSA can cause abnormal dilatation requiring narrowing. Based on these outcomes, we caution against SSA in patients with anticipated SBS. [ABSTRACT FROM AUTHOR]

During recent years, distraction enterogenesis has been extensively studied as a treatment for short bowel syndrome, which is the most common cause of intestinal failure. Although different strategies such as parenteral nutrition and surgical lengthening have been used to manage the difficulties that patients with SBS deal with, these treatments are associated with high complication rates. Distraction enterogenesis uses mechanical force to increase the length and stimulate growth of the small intestine. In this study we combine in vivo experiments with computational modeling to explore the biomechanics of spring dependent distraction enterogenesis. We hypothesize that the self-expanding spring provides mechanical force for elastic tissue lengthening and triggers cellular proliferation. The additional growth of the intestine suggests signaling between mechanical stress and tissue response. We developed a computational modeling platform to test the correlation of applied mechanical force and tissue growth. We further validated our computational models with experimental measurements using spring-mediated distraction enterogenesis in a porcine model. This modeling platform can incorporate patient biometrics to estimate an individual's tissue response to spring mediated distraction enterogenesis. [ABSTRACT FROM AUTHOR]