Gastrointestinal Tract Injury Research Articles

Trefoil Factor 3 in human serum as a predictor of disease activity in Egyptian ulcerative colitis patients and its role in colorectal cancer

Ulcerative colitis (UC), a chronic idiopathic inflammatory disease, is caused by abnormal immune response to intestinal microflora. Colorectal cancer (CRC) is one of the leading causes of cancer-related mortality. The gold standard to establish diagnosis and assess disease activity remains endoscopy and histopathology. Non-invasive biomarkers are required for timely diagnosis of CRC and to assess disease activity as endoscopic assessment is not accepted by most patients. Enhanced trefoil factor 3 (TFF3) expression is seen following gastrointestinal tract injury. In the current study, the significance of serum TFF3 as a potential diagnostic biomarker of disease activity in naїve UC patients, and its diagnostic accuracy in CRC patients were investigated. We collected serum and fecal samples from 20 cases with active UC, 20 CRC patients, and 20 normal controls. TFF3 levels were higher in patients with active UC than in controls (p<0.001). TFF3 cut-off value of 7.9 ng/ml could predict disease activity with sensitivity and specificity of 90% and 100%, respectively. However, the combination of TFF3, C-reactive protein (CRP), and fecal calprotectin (FC) was able to predict disease activity better than each biomarker alone by raising the sensitivity and specificity to 100%. There was no correlation between TFF3, FC, and endoscopic activity in UC assessed by ulcerative colitis endoscopic index of severity (UCEIS). In the CRC patient group, the serum level of TFF3 was significantly higher when compared to controls (p=0.012). TFF3 and the degree of dysplasia were significantly correlated (r=0.496, p=0.026). At a cut-off value of 5.9 ng/ml, serum TFF3 had a diagnostic sensitivity and specificity for CRC of 82% and 90%, respectively. In conclusion, serum TFF3 may be used as a non-invasive biomarker to predict disease activity in UC both alone and in combination with CRP and FC and it could have a potential role in diagnosis of CRC.

Resveratrol attenuates non-steroidal anti-inflammatory drug-induced intestinal injury in rats in a high-altitude hypoxic environment by modulating the TLR4/NFκB/IκB pathway and gut microbiota composition.

Non-steroidal anti-inflammatory drugs (NSAIDs) are currently the most widely used anti-inflammatory medications, but their long-term use can cause damage to the gastrointestinal tract(GIT). One of the risk factors for GIT injury is exposure to a high-altitude hypoxic environment, which can lead to damage to the intestinal mucosal barrier. Taking NSAIDs in a high-altitude hypoxic environment can exacerbate GIT injury and impact gut microbiota. The aim of this study is to investigate the mechanisms by which resveratrol (RSV) intervention alleviates NSAID-induced intestinal injury in a high-altitude hypoxic environment, as well as its role in regulating gut microbiota. Aspirin was administered orally to rats to construct a rat model of intestinal injury induced by NSAIDs. Following the induction of intestinal injury, rats were administered RSV by gavage, and the expression levels of TLR4, NF-κB,IκB as well as Zonula Occludens-1 (ZO-1) and Occludin proteins in the different treatment groups were assessed via Western blot. Furthermore, the expression of the inflammatory factors IL-10, IL-1β, and TNF-α was evaluated using Elisa.16sRNA sequencing was employed to investigate alterations in the gut microbiota. The HCk group showed elevated expression of TLR4/NF-κB/IκB pathway proteins, increased expression of pro-inflammatory factors IL-1β and TNF-α, decreased expression of the anti-inflammatory factor IL-10, and expression of intestinal mucosal barrier proteins ZO-1 and Occludin. The administration of NSAIDs drugs in the plateau hypoxic environment exacerbates intestinal inflammation and damage to the intestinal mucosal barrier. After treatment with RSV intervention, the expression of TLR4/NF-κB/IκB signaling pathway proteins would be reduced, thereby lowering the expression of inflammatory factors in the HAsp group. The results of HE staining directly show the damage to the intestines and the repair of intestinal mucosa after RSV intervention. 16sRNA sequencing results show significant differences (P<0.05) in Ruminococcus, Facklamia, Parasutterella, Jeotgalicoccus, Coprococcus, and Psychrobacter between the HCk group and the Ck group. Compared to the HCk group, the HAsp group shows significant differences (P<0.05) in Facklamia, Jeotgalicoccus, Roseburia, Psychrobacter, and Alloprevotella. After RSV intervention, Clostridium_sensu_stricto bacteria significantly increase compared to the HAsp group. Resveratrol can attenuate intestinal damage caused by the administration of NSAIDs at high altitude in hypoxic environments by modulating the TLR4/NF-κB/IκB signaling pathway and gut microbiota composition.

Gastrointestinal Tract and Kidney Injury Pathogenesis in Post-COVID-19 Syndrome.

COVID-19 is a global health emergency that requires worldwide collaboration to control its spread. The scientific community is working to understand the different aspects of the post-COVID-19 syndrome and potential treatment strategies. Interestingly, there have been reports of gastrointestinal tract (GIT) involvement in the post-COVID-19 syndrome, suggesting the presence of both severe and mild GIT disorders. The development of the post-COVID-19- GIT syndrome involves various factors, such as impaired GIT mucosa cells, disruptions in the feeling of satiety, reduced blood supply due to the formation of small blood clots, and increased prostaglandin secretion caused by an excessive immune response. GIT symptoms have been observed in around 16% of COVID-19 patients. Other complications include kidney damage and prolonged impairment in the filtration and excretion functions of the glomeruli and tubules. The pathogenesis of post-COVID-19 renal syndrome involves factors, like an overactive immune response, reduced lung perfusion and oxygenation, viral infection in kidney tissues, endothelial dysfunction, and decreased blood volume. Roughly 20% of hospitalized patients experience renal manifestations after recovering from COVID-19.

Co-exposure of polystyrene nanoplastics and copper induces development toxicity and intestinal mitochondrial dysfunction in vivo and in vitro

Nanoplastics (NPs) have raised concerns about the combined toxicity to living organisms due to their ability to adsorb heavy metals. There is still uncertainty, however, whether NPs combined with heavy metals exert adverse effects on intestinal microenvironment, especially the intestinal cells and microbiota. Herein, the combined effects of 500 nm spherical-shaped polystyrene nanoplastics (PSNPs) and copper ions (Cu2+) on intestinal cells and gut microbiota were assessed using HCT-116 cells and zebrafish models. The combined exposure of PSNPs (10 mg/L) and Cu2+ (0.5 mg/L) induced more severer hatching interference of zebrafish embryos, deformation, and mortality. In larval stage, PSNPs (10 mg/L) accumulated and carried more Cu2+ in the gastrointestinal tract (GIT) of zebrafish after co-exposure for 5 days. Excessive neutrophil recruitment and oxidative stress in GIT of zebrafish larvae were observed. The mechanism of the combined toxicity was revealed by transmission electron microscopy (TEM) showing the injuries of GIT, transcriptome and 16S rDNA gene sequencing showing the toxicity pathways, including oxidative phosphorylation and respiratory electron transport chain, as well as microbial community analysis showing the induced microbiota dysbiosis. In vitro tests using HCT-116 cells showed that PSNPs (10 mg/L) and Cu2+ (0.5 mg/L) increased cell death while decreasing ATP concentration and mitochondrial membrane potential after 48 h exposure. These findings may provide new insights into the combined toxicity of nanoplastics and heavy metals in the intestinal microenvironment.

A Case Report of Corrosive Injury of Gastrointestinal Tract Managed with Pectoralis Major-Myocutaneous Patch Cover Over Pharyngo-Esophageal Anastomosis

Corrosive ingestion remains one of the most devastating problems in developing countries that cripples patient’s body, mind and soul depriving them from leading a normal social life and living with a scar on their emotions, psyche and charisma. Appropriate management in the acute phase of corrosive injury reduces tissue damage and further morbidity and mortality. The aim of this case discussion is to evoke a light of hope for those patients of corrosive injury and a guide to clinicians worldwide for further better management and sharing our experience of surgical management of a case of such corrosive injury of gastrointestinal tract.

Expression of ACE2, TMPRSS2, and SARS-CoV-2 nucleocapsid protein in gastrointestinal tissues from COVID-19 patients and association with gastrointestinal symptoms

BackgroundAlthough severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can infect the gastrointestinal (GI) tract in coronavirus disease 2019 (COVID-19) patients, the mechanism of GI tract injury is largely unknown. We aimed to study the potential factors that cause COVID-19 GI symptoms. MethodsWe investigated the expression and co-localization of angiotensin converting enzyme 2 (ACE2), transmembrane serine protease 2 (TMPRSS2), SARS-CoV-2 nucleocapsid protein (NP), and the severity of inflammation in GI tissues from COVID-19 patients (n = 19) by immunofluorescence and histopathologic staining, and then studied their associations with GI symptoms. ResultsInfected stomach tissues showed significantly higher ACE2 expression than uninfected ones, while infected duodenum tissues showed significantly higher TMPRSS2 expression than uninfected ones. The expression of TMPRSS2 exhibited a moderate correlation with viral NP across different GI tissues, while no significant association was observed between ACE2 and viral NP. Some GI symptoms such as diarrhea and nausea, were related to the expression level of ACE2, TMPRSS2 or the severity of inflammation. Furthermore, age and elevated aspartate transaminase were major risk factors for disease progression. ConclusionsACE2 and TMPRSS2 were essential proteins in the SARS-CoV-2 infection of GI tract, while TMPRSS2 rather than ACE2 may play a more important role. GI symptoms may derive from the host receptor expression level and pro-inflammatory response in COVID-19 patients after viral infection of GI tissues, and further exacerbate the disease. So targeting TMPRSS2 and inflammation may represent an effective strategy for treating COVID-19 patients with GI symptoms.

The Role of Activating Transcription Factor 3 in Metformin’s Alleviation of Gastrointestinal Injury Induced by Restraint Stress in Mice

Metformin is one of the most commonly used drugs for type 2 diabetes mellitus. In addition to its anti-diabetic property, evidence suggests more potential applications for metformin, such as antiaging, cellular protection, and anti-inflammation. Studies have reported that metformin activates pathways with anti-inflammatory effects, enhances the integrity of gut epithelial tight junctions, and promotes a healthy gut microbiome. These actions contribute to the protective effect of metformin against gastrointestinal (GI) tract injury. However, whether metformin plays a protective role in psychological-stress-associated GI tract injury remains elusive. We aim to elucidate the potential protective effect of metformin on the GI system and develop an effective intervention strategy to counteract GI injury induced by acute psychological stress. By monitoring the levels of GI-nonabsorbable Evans blue dye in the bloodstream, we assessed the progression of GI injury in live mice. Our findings demonstrate that the administration of metformin effectively mitigated GI leakage caused by psychological stress. The GI protective effect of metformin is more potent when used on wild-type mice than on activating-transcription-factor 3 (ATF3)-deficient (ATF3−/−) mice. As such, metformin-mediated rescue was conducted in an ATF3-dependent manner. In addition, metformin-mediated protection is associated with the induction of stress-induced GI mRNA expressions of the stress-induced genes ATF3 and AMP-activated protein kinase. Furthermore, metformin treatment-mediated protection of CD326+ GI epithelial cells against stress-induced apoptotic cell death was observed in wild-type but not in ATF3−/− mice. These results suggest that metformin plays a protective role in stress-induced GI injury and that ATF3 is an essential regulator for metformin-mediated rescue of stress-induced GI tract injury.

An alternative electrode implantation and tethering approach for neuromodulation of non-cranial areas in freely moving rats

Electrical stimulation and recording from non-cranial areas in freely moving rodents often require tethered devices for monitoring from a distant location. Inspired by our experience in electrode implantation for deep brain stimulation (DBS), we developed an implantation approach, which allows for performing electrical modulation of the urinary bladder. In order to prevent the wires from being damaged by rats in freely moving conditions and compromising animal welfare, we guided the wires subcutaneously toward the nape to reach a plug, which was mounted on the skull. No complications such as infection, gastrointestinal tract injury, or inflammation occurred during or after surgery. The device allowed easy plugging and unplugging throughout the bladder stimulation and behavioral testing sessions undertaken in freely moving animals. This method enables modulation of peripheral organs in combination with DBS in freely moving rodents and can encompass many procedures such as electrical stimulation and recording, drug delivery, or electromyography.

TRAUMATIC GASTROINTESTINAL INJURIES: AN OVERVIEW OF CLINICAL PROFILE, MODE AND SITE OF INJURIES

Introduction:Trauma has become the major health care challenge, with abdomen being the third most commonly involved region of the body. Gastrointestinal tract injuries require prompt attention owing to potential for sepsis, caused either by blunt or penetrating injuries. Blunt trauma usually affects solid organs while as penetrating trauma mostly affects Gastrointestinal tract, commonly ileum, jejunum, colon, etc Material and methods: The patients with traumatic gastrointestinal perforation resulting from both blunt as well as penetrating trauma, were identified based on clinical presentation like pain abdomen, vomiting, fever, distension of abdomen, tenderness and supportive radiological evidences. The patients were examined and resuscitated and data was collected and organized according to the following categories: age, gender, clinical presentation, mode of trauma, duration of injury prior to admission/ presentation, radiological assessment, diagnosis, anatomical location. Results: Maximum patients were found to be in the age group of 21-40 years, with male preponderance. RTA (50%) was the most common mode of trauma, with Ileum (61.36%) being the most commonly involved site of GI tract. Conclusion:Traumatic GIT injuries is on the rise, mainly among young males with RTA being the most common mode of trauma.

Epidemiological Characteristics, Spectrum of Upper Gastrointestinal Tract Injuries and Burden of Corrosive Intake Patients in A Tertiary Care Hospital in Islamabad

Objective: To investigate the epidemiology and spectrum of upper gastrointestinal (UGI) tract injuries, as well as to assess the burden of Corrosive intake patients who presented to an Islamabad tertiary care hospital.Study Design: Descriptive cross-sectional.Place and Duration of Study: The study was carried out at the Department of Gastroenterology of Pakistan Institute of Medical Sciences, Islamabad, Pakistan from January 2021 to December 2021.Materials and Methods: A retrospective descriptive study was carried out at the department of Gastroenterology using patient records. After taking a thorough history, patients were admitted in the hospital, which was followed by a physical examination, necessary investigations, and an initial emergency management. The study did not include any follow-up cases. Corrosive ingestion induced tissue damage was assessed via endoscopy using Zargar’s classification. The data was analyzed using SPSS version 26.Results: The total number of patients who were brought to emergency department with corrosive ingestion during one year were 74. There were 45 females (60.81%) and 29 male patients (39.19%). Age ranged from 13 to 60 years (mean 27.01 ± 18.91) with highest incidence in the age group of 21-30 years which was 44.59 % followed by 11-20 age Group (28.28 %). 41 patients were unmarried (55.41%), whereas 33 were married (44.59 %). Corrosive ingestion was most common in illiterate patients (44.59 %). 46 patients (62.16%) confessed that they ingested corrosive substance intentionally while 28 (37.84 %) claimed it happened due to accidental ingestion. Washroom cleaner was found to be the most commonly used corrosive Agent (90.54%). The most common sites that sustained corrosive injuries were the oropharynx and oesophagus, while the duodenum was found to be the least affected with normal endoscopic examination in the majority of the patients (51.35 %).Conclusion: In developing countries, corrosive ingestion is a major public health concern, with a high proportion of suicidal ingestions. It is particularly common in suicidal young people with easy access to washroom cleaners. The seriousness of this problem emphasises the importance of pursuing multidisciplinary solutions. In addition, strict action and stringent legislation by governing bodies are required in developing countries to limit adults' unrestricted access to hazardous corrosive elements.

The Spectrum of Digestive Tract Histopathologic Findings in the Setting of Severe Acute Respiratory Syndrome Coronavirus-2 Infection: What Pathologists Need to Know.

Although the novel severe acute respiratory syndrome coronavirus-2 is known primarily to affect the respiratory system, current evidence supports its capability to infect and induce gastrointestinal tract injury. Data describing the histopathologic alterations of the digestive system in patients infected with severe acute respiratory syndrome coronavirus-2 are becoming more detailed, as the number of studies is increasing and the quality of our insight into the infection and the histopathologic findings is improving. This review highlights the range of pathologic findings that could be observed in gastrointestinal specimens from patients infected with coronavirus disease 2019 and the potential underlying pathogenetic mechanisms of this disease.

Evaluation of gastrointestinal tract injury within 1year of surgery for pelvic organ prolapse.

To identify the incidence and risk factors of gastrointestinal injury (GITI) related to pelvic organ prolapse (POP) surgery. Women who underwent POP surgery between 2000 and 2020 were identified in the Premier Healthcare Database. The primary outcome was GITI, defined as small or large bowel injury or repair, and fistula or fistula repair. Differences between patients with and without GITI were evaluated, and a multivariable regression was performed to determine independent predictors of GITI. We identified 563,661 index POP surgeries in female patients aged 18years and older. Of these, 4582 (0.8%) had a bowel injury code within 1year of index POP surgery. Patients who experienced GITI were more likely to be younger (49.9 ± 12.8 vs 50.9 ± 13.7), and receive surgery with a surgeon who performed less than 12 surgeries per year (48% vs 42%). Most GITI was diagnosed in the same month (73.4%) and same hospital encounter (54%) as index POP surgery. After adjusting for confounders, lysis of adhesions (aOR = 2.03, 95% CI: 1.48-2.72) and perioperative hematoma/hemorrhage (aOR = 2.87, 95%C I: 1.70-4.59) were strongly associated with GITI, while having surgery with a surgeon performing > 50 POP surgeries per year (aOR = 0.66, 95%C I: 0.59-0.75 and concomitant obliterative procedures (aOR = 0.48, 95% CI: 0.34-0.65) were associated with a lower probability of GITI. The rate of GITI after POP surgery is less than 1%, and injuries are commonly diagnosed and treated in the same month as index surgery. High-volume surgeons and obliterative procedures may be protective against GITI.

Value of multi-detector computed tomography in the diagnosis of blunt bowel and mesenteric injuries

Purpose: The purpose of this study was to evaluate the role of MDCT in detecting and predicting blunt bowel and mesenteric injuries. Materials and methods: This is a retrospective observational study of 66 patients (54 males, 12 females, average age of 45.5 years) who underwent laparotomy at Nghe An Friendship General Hospital between April 2020 and August 2021 with a diagnosis of bowel and/or mesenteric injuries in blunt abdominal trauma. All of these patients had a contrast-enhanced MDCT prior to surgery. All CT findings were documented and calculated for their diagnostic performance compared to surgical outcomes. Results: The most common finding was mesenteric infiltration (75.8%), followed by bowel wall thickening (63.6%). Bowel wall discontinuity had the highest specificity and positive predictive value of 100%. The most sensitive signs were free air 81.6%, mesenteric infiltration 79.7%. The specificity of bowel hypoenhancement and mesenteric vessel abnormalities were highest at 92.3% and 98.1%, respectively. Bowel wall thickening, bowel wall hypoenhancement, mesenteric vessel abnormalities, and free air had strongest association with blunt bowel and/or mesenteric injury requiring surgery (OR = 5.7, 51, 68 and 14.4, respectively). Conclusion: The multi-detector computed tomography provides high-specificity important findings indicating bowel and mesenteric injuries necessitating surgery. Key words: bowel and mesenteric injury, gastrointestinal tract injury, blunt abdominal trauma, computed tomography.

Lésions iatrogènes du tube digestif vues par le pathologiste

The number of drugs available to clinicians, especially targeted therapies, grows continuously. Some drugs are known to cause frequent digestive adverse effects, which may affect the gastro-intestinal tract in a diffuse or localized manner. Some treatments may leave relatively pathognomonic deposits, but histological lesions of iatrogenic origin are mostly non-specific. The diagnostic and etiological approach is often complex because of these non-specific aspects and also because (1) a single type of drug may cause different histological lesions, (2) different drugs may cause identical histological lesions, (3) the patient may receive different drugs, and (4) drug-induced lesions may mimic other pathological entities such as inflammatory bowel disease, celiac disease, or graft versus host disease. The diagnosis of iatrogenic gastrointestinal tract injury therefore requires close anatomic-clinical correlation. The iatrogenic origin can only be formally established if the symptomatology improves when the incriminating drug is stopped. This review aims to present the different histological patterns of gastrointestinal tract iatrogenic lesions, the potentially incriminate drugs, as well as the histological signs to look for in order to help the pathologist to distinguish an iatrogenic injury from another pathology of the gastrointestinal tract.

Evaluation of gastrointestinal tract injury during surgery for pelvic organ prolapse within one year after surgery

Evaluation of gastrointestinal tract injury during surgery for pelvic organ prolapse within one year after surgery

Endoscopic Aspects of Caustic Injuries of the Upper Gastrointestinal Tract in Parakou, Benin Republic: A Multicenter Study

Endoscopic Aspects of Caustic Injuries of the Upper Gastrointestinal Tract in Parakou, Benin Republic: A Multicenter Study

Protective Effect of Irsogladine against Aspirin-Induced Mucosal Injury in Human Induced Pluripotent Stem Cell-Derived Small Intestine

Background and Objectives: Acetylsalicylic acid (ASA) is widely used for preventing cerebrovascular and cardiovascular diseases. Gastrointestinal (GI) tract injury is one of the major complications of aspirin use, potentially leading to severe GI bleeding. However, no drugs for preventing aspirin-induced small intestinal injury have been developed. The aim of this study was to establish a human experimental model for investigating aspirin-induced small intestinal mucosal injury. In addition, we evaluated the protective effect of Irsogladine against aspirin-induced small intestinal mucosal injury using human induced pluripotent stem cell-derived 2D monolayer crypt-villus structural small intestine (2D-hiPSC-SI). Materials and Methods: Human iPS cell-derived intestinal organoids were seeded and cultured in Air-liquid interface. The permeability of 2D-hiPSC-SI was evaluated using Lucifer yellow. Changes in structure and mucosal permeability of 2D-hiPSC-SI after addition of aspirin were confirmed over time, and changes in intestinal epithelium-related markers were evaluated by real-time qPCR and Immunofluorescence staining. The effect of Irsogladine on prevention of aspirin mucosal injury was examined by adding Irsogladine to the culture medium. Results: Cultured 2D-hiPSC-SI showed multi-lineage differentiation into small intestinal epithelium comprised of absorptive cells, goblet cells, enteroendocrine cells, and Paneth cells, which express CD10, MUC2, chromogranin A, and lysozyme, respectively. RNA in situ hybridization revealed intestinal stem cells that express Lgr5. ASA administration induced an increase in the mucosal permeability of 2D-hiPSC-SI. ASA-injured 2D-hiPSC-SI showed decreased mRNA expression of multi-lineage small intestinal cell markers as well as intestinal stem cell marker Lgr5. Administration of Irsogladine on the basal side of the 2D-hiPSC-SI resulted in significant increases in Mki67 and Muc2 mRNA expression by 2D-hiPSCs at 48 h compared with the control group. Administration of 400 µg/mL Irsogladine to the ASA-induced small intestinal injury model resulting in significantly decreased mucosal permeability of 2D-hiPSC-SI. In immunofluorescence staining, Irsogladine significantly increased the fluorescence intensity of MUC2 under normal conditions and administration of 400 µg/mL ASA. Conclusions: we established a novel ASA-induced small intestinal injury model using human iPSC-derived small intestine. Irsogladine maintains mucosal permeability and goblet cell differentiation against ASA-induced small intestinal injury.

Six cases of acute toilet cleaners

The oral toilet cleaners poisoning can result in devastating gastrointestinal tract injuries with the risk of perforation and/or hemorrhage, and sometimes potentially fatal systemic complications and sequelas. It should be given positive treatment. In this paper, six cases of acute toilet cleaners poisoning were analyzed, and the clinical characteristics and treatment effect were summarized, so as to improve the understanding, diagnosis and treatment level of the disease.

Abstract B026: Implicating SATB2 loss in a metaplasia-dysplasia sequence in human inflammatory bowel disease

Abstract Epithelial metaplasia, or the histologically evident replacement of one differentiated somatic cell type with another, offers insights into mucosal homeostasis as an adaptation to diverse inflammatory pathogenic stimuli. The cellular framework for metaplasia can be created by coordination of tissue-specific transcription factors (TFs) with epigenetic regulators of chromatin remodeling, allowing altered TF binding of inflammation-associated exposed genomic loci. For example, intestinal metaplasia (aberrant goblet cell differentiation and CDX2 expression, a pan-intestinal TF) is a common metaplastic response to chronic injury in the upper gastrointestinal tract, associated with increased risk of epithelial dysplasia and cancer. Inflammatory bowel disease (IBD) is an etiologically complex chronic inflammatory disease characterized by relapsing cycles of intestinal injury and healing. IBD patients carry increased risk of colitis-associated dysplasia and colorectal cancer (CAC) proportional to disease duration, extent, and severity. SATB2, or special AT-rich binding protein 2, is a chromatin organizing protein with homeostatic roles in osteoblastic, neural, and colonic differentiation. Intriguingly, others have recently shown that SATB2 is uniquely lost in human IBD dysplasia and CAC, in contrast to sporadic CRC where its expression is typically retained. (By contrast, CDX2 shows retained expression in both CAC and CRC.) Other recent work has shown that colon-specific Satb2 knockout in mice results in conversion of colon to small intestine, including emergence of villi and Paneth cells. Colonic mucosal biopsies from chronic IBD patients show histologic features reminiscent of small intestine with so-called Paneth cell metaplasia (PCM) and villiform, distorted growth. The molecular mediators of this epithelial remodeling in IBD are unknown. We hypothesized that SATB2 loss could result in a form of “small intestinal metaplasia” in human IBD colon. To investigate this, we selected a cohort of 20 IBD distal colon mucosal biopsies with marked crypt architectural changes and PCM and performed SATB2 immunostaining (n=7 Crohn’s disease, n=13 ulcerative colitis). Indeed, 19 of 20 such samples showed striking evidence of SATB2 loss. The pattern of SATB2 loss was heterogeneous; some tissue fragments showed complete epithelial loss as expected in small intestine, whereas others showed patchy loss in alternating crypts, even some showing heterogeneous expression within the same crypt. As positive and negative controls, we included normal distal colon and terminal ileum samples, observing expected intact and negative SATB2 expression, respectively. Of note, CDX2 was strongly expressed across the entire cohort, even in IBD tissue with loss of SATB2 expression. We propose that SATB2 loss is a pre-neoplastic metaplastic response to chronic injury in human colon. Future work will investigate how SATB2 loss enables a plasticity state permissive for emergence of TP53 mutations, dysplasia, and CAC. Citation Format: Maged Zeineldin, Reem Abu-Shamma, Tatianna Larman. Implicating SATB2 loss in a metaplasia-dysplasia sequence in human inflammatory bowel disease [abstract]. In: Proceedings of the AACR Special Conference on Colorectal Cancer; 2022 Oct 1-4; Portland, OR. Philadelphia (PA): AACR; Cancer Res 2022;82(23 Suppl_1):Abstract nr B026.

Pharmacotherapy of Gastrointestinal Tract Injuries Caused by Radioactive Particles in Animals

Pharmacotherapy of Gastrointestinal Tract Injuries Caused by Radioactive Particles in Animals