Intraluminal oxygen can keep small bowel mucosa intact in a segmental ischemia model.

Intestinal preservation for transplantation is accompanied by hypoperfusion with long periods of ischemia with total blood cessation and absolute withdrawal of oxygen leading to structural damage. The application of intraluminal oxygen has been successfully tested in small-animal series during storage and transport of the organ but have been so far clinically unrelatable. In this study, we tested whether a simple and clinically approachable method of intraluminal oxygen application could prevent ischemic damage in a large animal model, during warm ischemia time. We utilised a local no-flow ischemia model of the small intestine in pigs. A low-flow and high-pressure intraluminal oxygen deliverance system was applied in 6 pigs and 6 pigs served as a control group. Mucosal histopathology, hypoxia and barrier markers were evaluated after two hours of no-flow conditions, in both treatment and sham groups, and in healthy tissue. Macro- and microscopically, the luminal oxygen delivered treatment group showed preserved small bowel's appearance, viability, and mucosal integrity. A gradual deterioration of histopathology and barrier markers and increase in hypoxia-inducible factor 1-α expression towards the sites most distant from the oxygen application was observed. Intraluminal low-flow, high oxygen delivery can preserve the intestinal mucosa during total ischemia of the small intestine. This finding can be incorporated in methods to overcome small bowel ischemia and improve intestinal preservation for transplantation.

Neutrophil to lymphocyte ratio predicts bowel ischemia in non-strangulated adhesive small bowel occlusions: a retrospective analysis from an acute care surgical service.

BACKGROUND: Adhesive small bowel obstruction (ASBO) is a leading cause of hospitalization in emergency surgery. The occurrence of bowel ischemia significantly increases the morbidity and mortality rates associated with this condition. Current clinical, biochemical and radiological parameters have poor predictive value for bowel ischemia. This study is designed to ascertain predictive elements for the progression to bowel ischemia in patients diagnosed with non-strangulated ASBO who are initially managed through conservative therapeutic approaches. METHODS: The study was based on the previously collected medical records of 128 patients admitted to the Department of Acute Care Surgery of Padua General Hospital, from August 2020 to April 2023, with a diagnosis of non-strangulated adhesive small bowel obstruction, who were then operated for failure of conservative treatment. The presence or absence of bowel ischemia was used to distinguish the two populations. Clinical, biochemical and radiological data were used to verify whether there is a correlation with the detection of bowel ischemia. RESULTS: We found that a Neutrophil-Lymphocyte ratio (NLR) > 6.8 (OR 2.9; 95% CI 1.41-6.21), the presence of mesenteric haziness (OR 2.56; 95% CI 1.11-5.88), decreased wall enhancement (OR 4.3; 95% CI 3.34-10.9) and free abdominal fluid (OR 2.64; 95% CI 1.08-6.16) were significantly associated with bowel ischemia at univariate analysis. At the multivariate logistic regression analysis, only NLR > 6.8 (OR 5.9; 95% CI 2.2-18.6) remained independent predictive factor for small bowel ischemia in non-strangulated adhesive small bowel obstruction, with 78% sensitivity and 65% specificity. CONCLUSIONS: NLR is a straightforward and reproducible parameter to predict bowel ischemia in cases of non-strangulated adhesive small bowel obstruction. Employing NLR during reevaluation of patients with this condition, who were initially treated conservatively, can help the acute care surgeons in the early prediction of bowel ischemia onset.

Mesenteric sparing approach for advanced nodal extent in small intestinal neuroendocrine tumors. Is there a limit to the vascular resection in order to avoid creating a short small bowel syndrome? An anatomic research study.

PURPOSE: By selectively perfusing the first three jejunal arteries (JA), we aim to assess the individual perfusion length of small bowel (SB) and its impact on nodal resection in stage III-up small-intestinal neuroendocrine tumors (SI-NET). METHODS: Our anatomical research protocol implies a midline laparotomy and three measures of the SB length. We then perform a classical anterior approach of the superior mesenteric vessels. We carry on with the complete dissection and checking of the superior mesenteric artery (SMA) in order to identify the first three JA. Then we selectively perfuse each artery with colored latex solutions and measure the length of small bowel perfused respectively. RESULTS: We conducted our protocol on six cadaveric subjects. Mean(SD) SB length was 413(5.7), 535(13.2), 485(15), 353(25.1), 730(17.3) and 525(16° cm respectively from subject one to six. Most JA originated from the left side of the SMA. The first JA originated from its posterior wall in two subjects. Mean(SD) distance of origin of the first three JA was 4.6(1.3)cm, 6(1.1)cm and 7.1(0.9)cm respectively. Mean(SD) diameter of SMA was 10.8(3.3)mm. Mean diameter of the three first JA was 4(1.4)mm, 4(1.5)mm and 5(1.2)mm respectively. Mean(SD) SB length perfused by first and second JA was 224(14.9)cm, 175(8.6)cm, 238.3(7.6)cm, 84.3(5.1)cm, 233.3(5.8)cm and 218.3(10.4)cm respectively from subject one to six. CONCLUSION: We observed a trend suggesting that the first and second JA may sustain a SB length beyond the viable 1.5 m limit, implying the feasibility of stage III-up SI-NET resection with just two JA.

Hyperspectral imaging combined with blood oxygen saturation for in vivo analysis of small intestinal necrosis tissue.

Acute mesenteric ischemia (AMI) is a clinically significant vascular and gastrointestinal condition, which is closely related to the blood supply of the small intestine. Unfortunately, it is still challenging to properly discriminate small intestinal tissues with different degrees of ischemia. In this study, hyperspectral imaging (HSI) was used to construct pseudo-color images of oxygen saturation about small intestinal tissues and to discriminate different degrees of ischemia. First, several small intestine tissue models of New Zealand white rabbits were prepared and collected their hyperspectral data. Then, a set of isosbestic points were used to linearly transform the measurement data twice to match the reference spectra of oxyhemoglobin and deoxyhemoglobin, respectively. The oxygen saturation was measured at the characteristic peak band of oxyhemoglobin (560 nm). Ultimately, using the oxygenated hemoglobin reflectance spectrum as the benchmark, we obtained the relative amount of median oxygen saturation in normal tissues was 70.0 %, the IQR was 10.1 %, the relative amount of median oxygen saturation in ischemic tissues was 49.6 %, and the IQR was 14.6 %. The results demonstrate that HSI combined with the oxygen saturation computation method can efficiently differentiate between normal and ischemic regions of the small intestinal tissues. This technique provides a powerful support for internist to discriminate small bowel tissues with different degrees of ischemia, and also provides a new way of thinking for the diagnosis of AMI.

Small Intestinal Arteriovenous Malformation Treated by Double-balloon Endoscopy.

A 42-year-old man was referred to our hospital because of anemia. The patient underwent gastroscopy and colonoscopy, but no bleeding site was detected. Abdominal contrast-enhanced computed tomography (CT) showed vascular dilatation along the wall of the small intestine. Small bowel capsule endoscopy and antegrade double-balloon endoscopy (DBE) were performed, and the patient was diagnosed with a small intestinal arteriovenous malformation (AVM). The AVM was clipped using DBE. After clipping, abdominal contrast-enhanced CT and small bowel angiography revealed the disappearance of the AVM. DBE may be a viable therapeutic option, helping avoid surgery and its associated risks.

Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia.

BACKGROUND: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels. RESULTS: Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels. CONCLUSIONS: In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).

Obscure Gastrointestinal Bleeding Caused by a Small Intestinal Lymphatic-venous Malformation: A Case Report with a Literature Review.

A 44-year-old woman presented with severe anemia. We strongly suspected gastrointestinal bleeding; however, esophagogastroduodenoscopy, colonoscopy, and computed tomography showed no bleeding sources. Video capsule endoscopy revealed an actively bleeding submucosal lesion within the jejunum. Double-balloon enteroscopy revealed a 20-mm continuously bleeding submucosal lesion in the distal jejunum. We suspected small intestinal vascular malformation and performed surgical resection. The resected specimen pathologically comprised dilated, thin-walled lymphatic channels and blood vessels involving the small intestinal submucosa. Therefore, the patient was diagnosed with small intestinal lymphatic-venous malformation. Postoperatively, the patient recovered well, and recurrence was not observed.

[Evaluation of resistance to transient occlusion of anterior mesenteric artery under the influence of the course of mineral water enriched with selenium (experimental research)]. / Otsenka ustoichivosti k tranzitornoi okklyuzii perednei bryzheechnoi arterii pod vliyaniem kursa mineral'noi vody, obogashchennoi selenom (eksperimental'noe issledovanie).

OBJECTIVE: To evaluate the effect of the preventive course of drinking mineral water enriched with selenium on the processes of resistance to the damaging action of reversible occlusion of the anterior mesenteric artery based on the comparison of intestinal morphological changes in the experiment. MATERIAL AND METHODS: There has been modeled ischemic reperfusion injury of the intestinal wall according to H. Ikeda and co-authors using reversible occlusion of the anterior mesenteric artery with 33 outbred male rats. The rats were divided into four groups by block randomization: the 1st group - intact animals (n=7) - without an exposure; the control group - sham operated animals (n=6); the group of comparison (n=7) - with a model-operation; the experimental group (n=11) - animals with a model operation that had courses of intragastric watering of bottled sulfate-chloride-hydrocarbonate-sodium low-mineralized (2.2 g/l) drinking mineral water «Psyzh¼ enriched with selenium. Biopsies of the small intestine were taken for histological examination. RESULTS: Histological examination of the small intestine of experimental animals determines various degrees of severity of damage: on average, the animals of the experimental group on the scale of C.J. Chiu (1970) had the lowest degree of severity of pathological changes, the animals of the group of comparison - 1.4 times higher (p=0.02). That is, the effect of a preventive course of mineral water «Psyzh¼ enriched with selenium was manifested in the formation of resistance to the damaging effect of reversible occlusion of the anterior mesenteric artery; in the presence of ischemic reperfusion damage to the intestinal wall, comparable in severity to changes with the animals without prevention, the most significant positive effect was realized in the containment of reactive changes. CONCLUSION: The effect of the preventive course of drinking mineral water «Psyzh¼ enriched with selenium manifested itself in the formation of resistance to the damaging effect of reversible occlusion of the anterior mesenteric artery, which is the basis for introducing this technique into clinical practice in order to prevent the development of reperfusion injuries of the intestine.

CD16+CD163+ monocytes traffic to sites of inflammation during necrotizing enterocolitis in premature infants.

Necrotizing enterocolitis (NEC) is a severe gastrointestinal complication of prematurity. Using suspension and imaging mass cytometry coupled with single-cell RNA sequencing, we demonstrate severe inflammation in patients with NEC. NEC mucosa could be subtyped by an influx of three distinct neutrophil phenotypes (immature, newly emigrated, and aged). Furthermore, CD16+CD163+ monocytes/Mϕ, correlated with newly emigrated neutrophils, were specifically enriched in NEC mucosa, found adjacent to the blood vessels, and increased in circulation of infants with surgical NEC, suggesting trafficking from the periphery to areas of inflammation. NEC-specific monocytes/Mϕ transcribed inflammatory genes, including TREM1, IL1A, IL1B, and calprotectin, and neutrophil recruitment genes IL8, CXCL1, CXCL2, CXCL5 and had enrichment of gene sets in pathways involved in chemotaxis, migration, phagocytosis, and reactive oxygen species generation. In summary, we identify a novel subtype of inflammatory monocytes/Mϕ associated with NEC that should be further evaluated as a potential biomarker of surgical NEC and a target for the development of NEC-specific therapeutics.

Evaluating the Risk of Irreversible Intestinal Necrosis Among Critically Ill Patients With Nonocclusive Mesenteric Ischemia.

INTRODUCTION: To identify factors associated with irreversible transmural necrosis (ITN) among critically ill patients experiencing nonocclusive mesenteric ischemia (NOMI) and to compare the predictive value regarding ITN risk stratification with that of the previously described Clichy score. METHODS: All consecutive patients admitted to the intensive care unit between 2009 and 2019 who underwent exploratory laparotomy for NOMI and who had an available contrast-enhanced computed tomography with at least 1 portal venous phase were evaluated for inclusion. Clinical, laboratory, and radiological variables were collected. ITN was assessed on pathological reports of surgical specimens and/or on laparotomy findings in cases of open-close surgery. Factors associated with ITN were identified by univariate and multivariate analysis to derive a NOMI-ITN score. This score was further compared with the Clichy score. RESULTS: We identified 4 factors associated with ITN in the context of NOMI: absence of bowel enhancement, bowel thinning, plasma bicarbonate concentration ≤15 mmol/L, and prothrombin rate <40%. These factors were included in a new NOMI-ITN score, with 1 point attributed for each variable. ITN was observed in 6%, 38%, 65%, 88%, and 100% of patients with NOMI-ITN score ranging from 0 to 4, respectively. The NOMI-ITN score outperformed the Clichy score for the prediction of ITN (area under the receiver operating characteristics curve 0.882 [95% confidence interval 0.826-0.938] vs 0.674 [95% confidence interval 0.582-0.766], respectively, P < 0.001). DISCUSSION: We propose a new 4-point score aimed at stratifying risk of ITN in patients with NOMI. The Clichy score should be applied to patients with occlusive acute mesenteric ischemia only.

Targeting the Rat's Small Bowel: Long-Term Infusion into the Superior Mesenteric Artery.

The superior mesenteric artery can be cannulated in humans through minimally invasive radiological catheterization of the femoral or axillary artery. SMA cannulation is more difficult in rats due to small anatomical dimensions. The aim of the study is to describe a surgical technique for cannulation of the SMA in rats to perform long-term infusion of drugs into the SMA vascular bed in unrestricted animals, which will result in a high rate of catheter patency after the post surgical recovery for 24 hours. To avoid the risk of SMA thrombosis or bleeding from direct access, a proximal branch of the SMA is isolated, ligated distally and cannulated with a 0.25 mm polyurethane capillary tube whose tip is advanced close to the origin of the SMA from the aorta. The cannula is then tunnelled subcutaneously to the back of the animal's neck and through the skin via an artificial valve. The external portion of the cannula is inserted in a semi-rigid support system and connected to the continuous infusion pump outside the cage where the rat is free to move. Correct positioning of the cannula was demonstrated by post-surgical angiography and autopsy findings. Catheter patency after 24 hours of saline infusion into the SMA region was assured in most rats by the total discharge of the pump and recognition of a functional cannula for blood sampling or saline infusion.

Ex vivo normothermic perfusion of isolated segmental porcine bowel: a novel functional model of the small intestine.

BACKGROUND: There is an unmet need for suitable ex vivo large animal models in experimental gastroenterology and intestinal transplantation. This study details a reliable and effective technique for ex vivo normothermic perfusion (EVNP) of segmental porcine small intestine. METHODS: Segments of small intestine, 1.5-3.0 m in length, were retrieved from terminally anaesthetized pigs. After a period of cold ischaemia, EVNP was performed for 2 h at 37°C with a mean pressure of 80 mmHg using oxygenated autologous blood diluted with Ringer's solution. The duration of EVNP was extended to 4 h for a second set of experiments in which two segments of proximal to mid-ileum (1.5-3.0 m) were retrieved from each animal and reperfused with whole blood (control) or leucocyte-depleted blood to examine the impact of leucocyte depletion on reperfusion injury. RESULTS: After a mean cold ischaemia time of 5 h and 20 min, EVNP was performed in an initial group of four pigs. In the second set of experiments, five pigs were used in each group. In all experiments bowel segments were well perfused and exhibited peristalsis during EVNP. Venous glucose levels significantly increased following luminal glucose stimulation (mean(s.e.m.) basal level 1.8(0.6) mmol/l versus peak 15.5(5.8) mmol/l; P < 0.001) and glucagon-like peptide 1 (GLP-1) levels increased in all experiments, demonstrating intact absorptive and secretory intestinal functions. There were no significant differences between control and leucocyte-depleted animals regarding blood flow, venous glucose, GLP-1 levels or histopathology at the end of 4 h of EVNP. CONCLUSIONS: This novel model is suitable for the investigation of gastrointestinal physiology, pathology and ischaemia reperfusion injury, along with evaluation of potential therapeutic interventions.

[Timing of surgery, intestinal ischemia and other real factors of mortality in acute adhesive small bowel obstruction: a multiple-center study]. / Faktory riska letal'nogo iskhoda pri ostroi spaechnoi tonkokishechnoi neprokhodimosti. Rezul'taty mnogotsentrovogo issledovaniya.

OBJECTIVE: To analyze the factors of mortality in patients with acute adhesive small bowel obstruction (ASBO). MATERIAL AND METHODS: A retrospective multiple-center study included 143 (85.6%) patients with ASBO out of 167 consecutive patients with small bowel obstruction for the period 2017-2019. All patients were divided into 3 groups: early surgery group (within 12 hours after admission), late surgery (after 12 hours), non-surgical management group. The outcomes and Kaplan-Meier survival were compared in all groups. RESULTS: ASBO was resolved without surgery in 77 (53.8%) patients 19.6±17.4 (M=14) hours. In the Early Surgery Group (n=36), 24 patients had strangulation, 12 ones had non-strangulated bowel obstruction. In the Late Surgery Group (n=30), 15 patients had strangulation and 15 ones had no strangulation. Mortality was similar in early and late surgery (p=0.287), early and late surgery in patients with strangulation (p=0.940), early and late surgery in patients without strangulation (p=0.76). Patients died (n=10) after surgery only. Thus, postoperative mortality was 15.2%, overall mortality - 7.0%. All patients who underwent surgery after 24 hours (n=14) survived. Surgery increased the mortality risk compared to non-surgical management (95% CI 0 - 15.9, p=0.001). There was no effect of surgery time (more or less than 12 hours) on mortality for strangulation (95% CI 13.0-16.7, p 0.788) and non-strangulated obstruction (95% CI 29.4-5.4, p=0.061), bowel resection (95% CI 33.3-14.0, p=0.187), presence of bowel ischemia (95% CI 14.3-17.9, p 0.613). CONCLUSION: Delayed surgery may be advisable in patients with ASBO and no obvious signs of strangulation due to less mortality.

Deoxycholic acid enhancement of lymphocyte migration through direct interaction with the intestinal vascular endothelium.

BACKGROUND AND AIM: The small intestine plays a central role in gut immunity, and enhanced lymphocyte migration is involved in the pathophysiology of various enteropathy. Bile acid (BA) is closely related to lipid metabolism and gut microbiota and essential for gut homeostasis. However, the effects of BA on gut immunity have not been studied in detail, especially on the small intestine and lymphocyte migration. Therefore, we aimed to investigate the effect of BA on small intestinal lymphocyte microcirculation. METHODS: The effect of deoxycholic acid (DCA), taurocholic acid (tCA), or cholic acid (CA) on the indomethacin (IND)-induced small intestinal enteropathy in mice was investigated. Lymphocyte movements were evaluated after exposure to BA using intravital microscopy. The effects of BA on surface expression of adhesion molecules on the vascular endothelium and lymphocytes through BA receptors were examined in vitro. RESULTS: IND-induced small intestinal enteropathy was histologically aggravated by DCA treatment alone. The expression of adhesion molecules ICAM-1 and VCAM-1 was significantly enhanced by DCA. Exposure to DCA increased lymphocyte adhesion in the microvessels of the ileum, which was partially blocked by anti-α4ß1 integrin antibody in vivo. The expression of ICAM-1 and VCAM-1 was significantly enhanced by DCA in vitro, which was partially suppressed by the sphingosine-1-phosphate receptor 2 (S1PR2) antagonist. The S1PR2 antagonist significantly ameliorated IND-induced and DCA-exaggerated small intestinal injury. CONCLUSION: DCA exacerbated IND-induced small intestinal enteropathy. DCA directly acts on the vascular endothelium and enhances the expression levels of adhesion molecules partially via S1PR2, leading to enhanced small intestinal lymphocyte migration.

Small Intestine Varices in Cirrhosis at a High-Volume Liver Transplant Center: A Retrospective Database Study and Literature Review.

INTRODUCTION: Esophageal varices are a well-characterized sequela of portal hypertension; however, less is known about varices arising in ectopic locations. We aimed to describe bleeding small intestine varices (SIV) in patients with cirrhosis and compare characteristics and outcomes to published case reports. METHODS: We performed an institutional chart review using billing codes and natural language processing between 2008 and 2019. Inclusion criteria were adult patients with cirrhosis and SIV verified by endoscopy, video capsule, or imaging. Patients with noncirrhotic portal hypertension and stomal varices were excluded. We examined demographic and clinical factors, characteristics of SIV, bleeding, intervention, and outcomes in our series and collated data from published cases identified during a literature review. RESULTS: We identified 71 patients with cirrhosis and SIV (18 bled). The literature search yielded 76 cases with bleeding SIV. Our series and published cases were matched for age, sex, liver disease etiology, and SIV location. Length of stay and transfusion requirements were similar. Aggregate initial treatments (number, hemostasis rate) included medical (n = 7, 57%), endoscopic (n = 48, 56%), interventional radiology (n = 31, 77%), and surgery (n = 8, 87%). Hospital and overall mortality rates were higher in our series (22% and 38%) compared with the published cases (5.3% and 18.4%), respectively (P = 0.02 and P = 0.07). DISCUSSION: A quarter of patients with cirrhosis and SIV experience bleeding, with high transfusion requirements, frequent need for secondary interventions, and high mortality. These findings highlight the need for a multidisciplinary approach and second-line therapeutic modalities in the timely management of bleeding SIV in cirrhosis.

[A man with abdominal pain after esophageal surgery]. / Een man met buikpijn na een slokdarmoperatie.

A 66-year-old man is evaluated in the Emergency Department for abdominal pain and vomiting since 2 days. Medical history showed esophageal resection because of an esophageal carcinoma. On physical examination there was tenderness of the right hemi-abdomen. A CT-angiography-chest/abdomen proved intrathoracically located small intestines with signs of ischemia.