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1.
Medicine (Baltimore) ; 103(28): e38984, 2024 Jul 12.
Article in English | MEDLINE | ID: mdl-38996097

ABSTRACT

RATIONALE: Aggressive fibromatosis (AF) is a fibroblastic/myofibroblastic tumor known for its locally aggressive properties. Intra-abdominal AF primarily occurs in the small intestine mesentery, ileocolic mesocolon, omentum, retroperitoneum, and pelvis, and rarely originates from the intestinal wall. Here, we report a rare case of small bowel obstruction caused by duodenum-derived AF with ß-catenin (CTNNB1) T41A mutation. PATIENT CONCERNS: A 35-year-old male had a 4-month history of abdominal pain, nausea, and vomiting, which gradually worsened over time. DIAGNOSES: Based on the results of CT examination, histopathology and Sanger sequencing, the patient was diagnosed with small bowel obstruction caused by duodenum-derived AF. INTERVENTIONS: Due to the extensive adhesion between the tumor and surrounding tissue, it is extremely challenging to completely remove the tumor through surgical resection with negative margins in this case. In order not to damage the function of surrounding vital organs, gastrojejunostomy was performed to relieve the symptoms of small bowel obstruction. OUTCOMES: The patient experienced a successful recovery. It is important to note that this patient is still at risk of local recurrence and requires regular follow-up. LESSONS: The best treatment should be taken based on the individual patient to relieve symptoms and improve quality of life. Moreover, histopathology plays a crucial role in diagnosing and differentiating duodenum-derived AF. The detection of mutations in exon 3 of the CTNNB1 has become strong evidence for diagnosing duodenum-derived AF.


Subject(s)
Fibromatosis, Aggressive , Intestinal Obstruction , Mutation , beta Catenin , Humans , Male , Adult , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Intestinal Obstruction/genetics , Intestinal Obstruction/diagnosis , beta Catenin/genetics , Fibromatosis, Aggressive/genetics , Fibromatosis, Aggressive/complications , Fibromatosis, Aggressive/diagnosis , Fibromatosis, Aggressive/surgery , Intestine, Small/pathology , Duodenal Neoplasms/genetics , Duodenal Neoplasms/surgery , Duodenal Neoplasms/complications , Duodenal Neoplasms/diagnosis
2.
Ann Afr Med ; 23(3): 313-316, 2024 Jul 01.
Article in French, English | MEDLINE | ID: mdl-39034552

ABSTRACT

BACKGROUND: Acute small intestinal obstruction is a common surgical emergency in the sub-Saharan region. Over the decades, complicated inguinal hernias have been identified as a leading cause. However, we observed from our clinical practice that complicated inguinal hernias were not the most common etiology. AIMS AND OBJECTIVES: This study aimed to evaluate the common etiology of acute small bowel obstruction in the study center and compare our findings with that from other centers and existing literature. MATERIALS AND METHODS: This was a retrospective, cross sectional study carried out over a period of five years (January 2017 to December 2021). This study looked at the patients presenting with acute, mechanical, small bowel obstruction that did not respond to conservative treatment in our hospital facility. Relevant information were extracted from patients' clinical details and entered into the proforma prepared for this study. RESULTS: A total of 147 patients were recruited into this study out of which 85(57.8%) were males and 62 (42.2%) were females (M:F=1.44:1). Majority (80.3%) of the patients that presented with post-operative bowel adhesion had previous appendectomy. Simple bowel obstruction was seen in 93 (63.3%) patients while strangulated obstruction and gangrenous bowel were seen in 26 (17.7%) patients and 22 (15.0%) patients respectively. Majority (47.6%) of the patients had adhesiolysis done while others had bowel resection. CONCLUSION: The common cause of acute small bowel obstruction as observed in this study is post-operative adhesions arising from previous appendectomy and laparotomies.


Résumé Contexte:Une faible obstruction intestinale a une urgence chirurgicale commune dans la région sub-saharienne. Au cours des décennies, des hernies inguiniques compliquées ont été identifiées comme une cause de premier plan. Cependant, nous avons observé de notre pratique clinique selon laquelle des hernies inguinales compliquées n'étaient pas l'étiologie la plus commune.Objectifs et objectifs:Cette étude visait à évaluer l'étiologie commune de l'obstruction aiguë aux petites interses dans le centre d'études et de comparer nos constatations avec celle d'autres centres et de la littérature existante.Matériaux et méthodes:C'était une étude rétrospective en coupe transversale réalisée sur une période de cinq ans (janvier 2017 à 2021). Cette étude a examiné les patients présentant une obstruction aiguë, mécanique et petite intestinale qui ne répondait pas au traitement conservateur dans notre installation hospitalière. Des informations pertinentes ont été extraites des détails cliniques des patients et ont conclu dans la proforma préparé pour cette étude.Résultats:Un total de 147 patients ont été recrutés dans cette étude dont 85 (57,8%) étaient des hommes et 62 (42,2%) étaient des femelles (M: F = 1.44: 1). La majorité (80,3%) des patients présentés par l'adhésion intestinale post-opératoire avaient une annexe antérieure. Un obstruction d'intestin simples a été observée dans des patients de 93 (63,3%) alors que l'obstruction étrangère et l'intestin gangreneux ont été observés dans des patients de 26 (17,7%) et respectivement respectivement les patients de 22 (15,0%). La majorité (47,6%) des patients avaient une adhésiose faite pendant que d'autres avaient une résection de l'intestin.Conclusion:La cause commune de l'obstruction aiguë aux petites interses comme observé dans cette étude est des adhérences post-opératoires découlant de l'appendecectomie et des laparotomies précédentes.


Subject(s)
Intestinal Obstruction , Intestine, Small , Humans , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Male , Female , Nigeria/epidemiology , Retrospective Studies , Cross-Sectional Studies , Adult , Intestine, Small/surgery , Intestine, Small/pathology , Middle Aged , Aged , Acute Disease , Appendectomy , Adolescent , Young Adult , Tissue Adhesions/surgery , Tissue Adhesions/complications , Hernia, Inguinal/surgery , Hernia, Inguinal/complications , Postoperative Complications/epidemiology
3.
Am J Case Rep ; 25: e944218, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38949995

ABSTRACT

BACKGROUND Cryptogenic multifocal ulcerating stenosing enteropathy (CMUSE) is a rare noninfectious chronic inflammatory disease of the digestive tract confined to the small bowel. Chronic inflammatory wasting leads to protein loss and weight reduction, and some patients eventually develop small bowel stenosis. The etiopathogenesis of CMUSE remains unknown. CASE REPORT A thin 62-year-old man was admitted to the hospital with abdominal pain and distension accompanied by bilateral lower-extremity edema for 2 months. After a series of medical tests, rheumatic or immune-related diseases, hyperthyroidism, and tuberculosis were excluded, and common digestive system diseases were also excluded. Abdominal CT showed incomplete obstruction of the small bowel. Enteroscopy showed small-bowel luminal narrowing. The patient subsequently underwent partial resection of the small bowel with end-to-side anastomosis. The small-bowel stricture was about 120 cm from the ileocecal junction, and about 12 cm of small bowel was resected. Postoperative pathology of the resected material revealed multifocal ulceration of the mucosa with massive inflammatory cell infiltration and extensive hyperplastic fibrous tissue, consistent with the characteristics of CMUSE disease. At follow-up 6 months after surgery, he had no abdominal pain or distension, and his anemia and lower-extremity edema were improved. CONCLUSIONS CMUSE diagnosis requires a combination of patient history, imaging, endoscopy, pathology, and exclusion of other digestive disorders, such as Crohn's disease. It is a chronic wasting disease, often accompanied by weight loss, abdominal pain, melena, and hypoproteinemia. Surgery is an important treatment for intestinal strictures caused by CMUSE.


Subject(s)
Intestinal Obstruction , Intestine, Small , Humans , Male , Middle Aged , Intestinal Obstruction/etiology , Intestinal Obstruction/surgery , Intestine, Small/pathology , Ulcer , Constriction, Pathologic
4.
BMC Pediatr ; 24(1): 396, 2024 Jun 18.
Article in English | MEDLINE | ID: mdl-38890589

ABSTRACT

BACKGROUND:  Chronic enteropathy associated with SLCO2A1 gene (CEAS) is a unique type of inflammatory bowel disease. CEAS is monogenic disease and is thought to develop from childhood, but studies on pediatric CEAS are scarce. We analyzed characteristics of pediatric CEAS. METHODS: Eleven patients diagnosed with CEAS at Seoul National University Children's Hospital were identified and analyzed. Clinical data of patients were collected. Sanger sequencing of SLCO2A1 was performed on all patients. RESULTS: Patients were diagnosed at a median age of 16.0 years (IQR 11.0 ~ 20.0), and the median age at symptoms onset was only 4.0 years (IQR 2.5 ~ 6.0). Growth delay was observed at the time of diagnosis. Patients showed multiple ulcers or strictures in the small intestine, while the esophagus and colon were unaffected in any patients. Almost half of the patients underwent small intestine resection. The major laboratory features of pediatric CEAS include iron deficiency anemia (IDA), hypoalbuminemia, and near-normal levels of C-reactive protein (CRP). Two novel mutations of SLCO2A1 were identified. The most prevalent symptoms were abdominal pain and pale face. None of the immunomodulatory drugs showed a significant effect on CEAS. CONCLUSIONS: Pediatric CEAS typically develop from very young age, suggesting it as one type of monogenic very early onset inflammatory bowel disease. CEAS can cause growth delay in children but there is no effective treatment currently. We recommend screening for SLCO2A1 mutations to pediatric patients with chronic IDA from a young age and small intestine ulcers without elevation of CRP levels.


Subject(s)
Inflammatory Bowel Diseases , Organic Anion Transporters , Humans , Male , Female , Adolescent , Child , Organic Anion Transporters/genetics , Inflammatory Bowel Diseases/genetics , Young Adult , Mutation , Chronic Disease , Child, Preschool , Intestine, Small/pathology , Age of Onset , Intestinal Diseases/genetics , Intestinal Diseases/diagnosis
5.
Ugeskr Laeger ; 186(25)2024 Jun 17.
Article in Danish | MEDLINE | ID: mdl-38904283

ABSTRACT

This is a case report of a 70-year-old woman with possible cholestyramine-induced bowel perforation. She had a prior history of pancreaticoduodenectomy for pancreatic cancer with a daily intake of cholestyramine. She underwent emergency laparotomy for small bowel perforation twice. Subsequent pathology reports showed crystal depositions in the small bowel wall. Leasions spread out on the small bowel and the omentum during the second surgery were thought to be carcinomatosis. However, the pathology report showed no malignant cells but plenty of crystal depositions as seen with cholestyramine intake.


Subject(s)
Cholestyramine Resin , Intestinal Perforation , Humans , Aged , Female , Intestinal Perforation/surgery , Intestinal Perforation/chemically induced , Intestinal Perforation/etiology , Cholestyramine Resin/adverse effects , Intestine, Small/pathology , Intestine, Small/surgery , Pancreaticoduodenectomy/adverse effects , Anticholesteremic Agents/adverse effects , Pancreatic Neoplasms/surgery , Pancreatic Neoplasms/pathology
7.
Vet Q ; 44(1): 1-11, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38832661

ABSTRACT

Hemorrhagic bowel syndrome (HBS) is characterized by a dissecting intramucosal hematoma at the small bowel, causing obstruction and severe hemorrhage in dairy cattle. Recent investigation revealed the presence of early-stage lesions in cows affected by HBS. These are presumed to be the initial stage of the hematoma, as both share unique dissection of the lamina muscularis mucosae (LMM) as histological hallmark. Early-stage lesions of HBS have not been characterized in greater detail, and neither has the hypothesis of mucosal abrasion as etiology been explored. Therefore, the first objective of the present study was to characterize the morphology of early-stage lesions, by gross examination, histochemistry, immunohistochemistry and transmission electron microscopy. The second objective was to determine the effect of mucosal abrasion to the small intestine in an ex vivo model. A total of 86 early-stage lesions from 10 cows with HBS were characterized. No underlying alterations at the LMM were evident which could explain their occurrence. However, degeneration at the ultrastructural level of the LMM smooth muscle cells was present in 3 of 4 lesions, it is however unclear whether this is primary or secondary. Bacteriological examination did not reveal any association with a specific bacterium. Experimental-induced and early-stage lesions were gross and histologically evaluated and scored in three cows with HBS and seven controls. Experimentally induced lesions in both affected cows and controls, were histologically very similar to the naturally occurring early-stage lesions. Altogether, the results are suggestive for mucosal trauma to play a role in the pathogenesis of HBS.


Subject(s)
Cattle Diseases , Gastrointestinal Hemorrhage , Intestinal Mucosa , Animals , Cattle , Cattle Diseases/pathology , Intestinal Mucosa/pathology , Intestinal Mucosa/ultrastructure , Female , Gastrointestinal Hemorrhage/veterinary , Gastrointestinal Hemorrhage/pathology , Microscopy, Electron, Transmission/veterinary , Intestine, Small/pathology , Immunohistochemistry/veterinary , Intestinal Diseases/veterinary , Intestinal Diseases/pathology
8.
Sci Rep ; 14(1): 13732, 2024 06 14.
Article in English | MEDLINE | ID: mdl-38877069

ABSTRACT

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.


Subject(s)
Intestinal Mucosa , Intestine, Small , Ischemia , Oxygen , Animals , Intestinal Mucosa/metabolism , Intestinal Mucosa/pathology , Intestinal Mucosa/blood supply , Intestine, Small/metabolism , Intestine, Small/blood supply , Intestine, Small/pathology , Oxygen/metabolism , Swine , Ischemia/metabolism , Ischemia/pathology , Ischemia/therapy , Disease Models, Animal , Organ Preservation/methods , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism
9.
Surg Endosc ; 38(7): 3905-3916, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38831215

ABSTRACT

BACKGROUND: Small intestinal stromal tumors (SISTs) are a rare type of mesenchymal tumor. Gender is known to influence the incidence and prognosis of various tumors, but its role on the survival of SISTs at the population level remains unclear. Therefore, we aim to explore the relationship between gender and the prognosis of SISTs using the Surveillance, Epidemiology, and End Results (SEER) database. METHODS: Data on SISTs patients from 2000 to 2019 were derived from the SEER database. Multiple imputation was used to address missing data. Kaplan-Meier analyses and Cox proportional hazard models were applied to evaluate the impact of demographic and clinical characteristics on overall survival (OS) and cancer-specific survival (CSS). RESULTS: A total of 3513 patients with SISTs were analyzed, including 1921 males and 1592 females. Kaplan-Meier analysis coupled with log-rank testing demonstrated a significantly higher mortality rate among male patients compared to females (P < 0.001). Notably, female patients exhibited superior OS (hazard ratio [HR] 0.808, 95% confidence interval [CI] 0.724-0.902, P < 0.001) and CSS (HR 0.801, 95% CI 0.692-0.927, P = 0.003) compared to male patients. While the mean 1-year CSS rates were comparable between genders (95.3% for males vs. 96.0% for females, P = 0.332), male patients consistently showed lower mean survival rates at 3-, 5-, and 10-year intervals. Surgical intervention significantly boosted 5-year OS and CSS rates in both male and female patients (P < 0.001). Multivariate Cox regression analysis identified age, sex, grade, TNM stage, surgery, and mitotic rate as independent risk factors for OS and CSS in patients with SISTs. CONCLUSIONS: Our findings suggest that male patients with SISTs have a higher risk of mortality compared to female patients, indicating that gender may serve as a predictive indicator for survival in this patient population.


Subject(s)
Gastrointestinal Stromal Tumors , SEER Program , Humans , Male , Female , Middle Aged , Gastrointestinal Stromal Tumors/mortality , Gastrointestinal Stromal Tumors/surgery , Gastrointestinal Stromal Tumors/pathology , Sex Factors , Aged , Survival Rate , Prognosis , Intestinal Neoplasms/mortality , Intestinal Neoplasms/pathology , Adult , Kaplan-Meier Estimate , Intestine, Small/pathology , United States/epidemiology , Proportional Hazards Models , Retrospective Studies
10.
Zhonghua Yi Xue Za Zhi ; 104(21): 2003-2006, 2024 Jun 04.
Article in Chinese | MEDLINE | ID: mdl-38825945

ABSTRACT

To investigate the clinical characteristics of metastatic tumors in small intestine. The clinical manifestations, imaging and endoscopic findings, treatment methods and follow-up of patients with small bowel metastatic tumors admitted to the First Affiliated Hospital of Zhengzhou University from January 1, 2018 to December 31, 2022 were retrospectively analyzed. A total of 10 patients were included, including 7 males and 3 females, aged 33-77 (56.4±12.6) years. The main clinical manifestations were intestinal obstruction (8 cases), such as abdominal pain, abdominal distension, nausea, vomiting, and reduced defecation. Some patients had intussusception (abdominal pain, vomiting, black stool and other symptoms, 1 case) or gastrointestinal bleeding (1 case) with early symptoms imperceptible. The primary tumors include gastric cancer (3 cases), malignant melanoma (2 cases), ovarian cancer (2 cases), colon cancer (1 case), rectal cancer (1 case), and lung cancer (1 case). Most of the primary tumors were poorly differentiated (6 cases) or moderately to poorly differentiated (2 cases). The median time from primary tumor surgery to detection of small bowel metastasis [M (Q1, Q3)] was 22 (18, 28) months.The metastatic lesions were single (6 cases) or multiple (4 cases), in both jejunum and ileum. Positron emission tomography-computed tomography (PET-CT, 3 cases) and endoscopy (2 cases) were helpful for detection of small intestinal metastases. The main treatment methods were surgical resection (9 cases), supplemented by radiotherapy, targeted drugs, immunotherapy, etc. Postoperative recurrence and metastasis occurred in some patients (5 cases). Most patients died within 4 to 29 months after diagnosis. Metastatic tumors in small intestine are rare in clinical practice with atypical early symptoms. The patients often present with complications such as intestinal obstruction, which is prone to delayed diagnosis and poor prognosis.


Subject(s)
Intestinal Neoplasms , Intestine, Small , Humans , Female , Middle Aged , Male , Aged , Intestine, Small/pathology , Adult , Retrospective Studies , Intestinal Neoplasms/pathology , Intestinal Obstruction/etiology , Melanoma/pathology , Stomach Neoplasms/pathology
11.
J Vet Intern Med ; 38(4): 2316-2323, 2024.
Article in English | MEDLINE | ID: mdl-38858174

ABSTRACT

BACKGROUND: Regional lymph nodes are frequently sampled in cats with suspected intestinal lymphoma; however, their diagnostic value has not been explored. OBJECTIVES: To investigate whether histologic and immunohistochemical analysis of mesenteric lymph nodes correlates with the diagnosis of intestinal lymphoma in cats. ANIMALS: One hundred 2 client-owned cats diagnosed with intestinal lymphoma. METHODS: Retrospective study. The inclusion criteria required a full-thickness biopsy of the small intestine and concurrent excision of mesenteric lymph nodes. Histologic and immunophenotypic analyses were performed on intestinal biopsies and corresponding lymph nodes. Selected nodal samples diagnosed with reactive lymph nodes underwent clonality testing. RESULTS: Transmural T-cell lymphomas, encompassing small and large cell types, were predominant (64 cases, 62.7%), with large B-cell lymphomas being more frequently transmural (68.8%) than mucosal (31.2%). Among all lymph nodes examined, 44 (43.1%; 95% CI: 33.9%-52.8%) exhibited neoplastic infiltration. Among cases of small cell lymphoma, 51 out of 72 (70.8%; 95% CI: 59.4%-80.1%) showed no nodal involvement. Clonality results correctly identified 19/30 (63.3%; 95% CI: 45.5%-78.2%) reactive lymph nodes. Concerns were raised regarding clonal identification in the remaining cases and potential misdiagnoses based on phenotypic characteristics. CONCLUSION AND CLINICAL IMPORTANCE: The study underscores the potential drawbacks of relying solely on mesenteric lymph nodes for diagnosing intestinal lymphomas in cats, particularly small cell subtypes. It emphasizes the importance of full-thickness biopsies for assessing transmural infiltration and recommends caution when utilizing mesenteric lymph nodes for histologic, immunohistochemical and clonality evaluations in mucosal lymphomas. Despite limitations, this research highlights the need for comprehensive diagnostic strategies in cats with intestinal lymphoma.


Subject(s)
Cat Diseases , Intestinal Neoplasms , Lymph Nodes , Lymphoma , Animals , Cats , Cat Diseases/pathology , Cat Diseases/diagnosis , Retrospective Studies , Intestinal Neoplasms/veterinary , Intestinal Neoplasms/pathology , Intestinal Neoplasms/diagnosis , Lymph Nodes/pathology , Male , Female , Lymphoma/veterinary , Lymphoma/pathology , Lymphoma/diagnosis , Biopsy/veterinary , Intestine, Small/pathology , Mesentery/pathology , Lymphoma, T-Cell/veterinary , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell/diagnosis
12.
Ecotoxicol Environ Saf ; 281: 116628, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38905936

ABSTRACT

Microplastics (MPs) and okadaic acid (OA) are known to coexist in marine organisms, potentially impacting humans through food chain. However, the combined toxicity of OA and MPs remains unknown. In this study, mice were orally administered OA at 200 µg/kg bw and MPs at 2 mg/kg bw. The co-exposure group showed a significant increase in malondialdehyde (MDA) content and significant decreases in superoxide dismutase (SOD) activity and glutathione (GSH) level compared to the control, MPs and OA groups (p < 0.05). Additionally, the co-exposure group exhibited significantly higher levels of IL-1ß and IL-18 compared to other groups (p < 0.05). These results demonstrated that co-exposure to MPs and OA induces oxidative stress and exacerbates inflammation. Histological and cellular ultrastructure analyses suggested that this combined exposure may enhance gut damage and compromise barrier integrity. Consequently, the concentration of OA in the small intestine of the co-exposure group was significantly higher than that in the OA group. Furthermore, MPs were observed in the lamina propria of the gut in the co-exposure group. Transcriptomic analysis revealed that the co-exposure led to increased expression of certain genes related to the NF-κB/NLRP3 pathway compared to the OA and MPs groups. Overall, this combined exposure may disrupt the intestinal barrier, and promote inflammation through the NF-κB/NLRP3 pathway. These findings provide precious information for the understanding of health risks associated with MPs and phycotoxins.


Subject(s)
Intestine, Small , Microplastics , Okadaic Acid , Oxidative Stress , Polystyrenes , Animals , Microplastics/toxicity , Mice , Okadaic Acid/toxicity , Intestine, Small/drug effects , Intestine, Small/pathology , Intestine, Small/ultrastructure , Polystyrenes/toxicity , Oxidative Stress/drug effects , Malondialdehyde/metabolism , Male , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , Glutathione/metabolism , Superoxide Dismutase/metabolism , Water Pollutants, Chemical/toxicity
13.
J Pharmacol Exp Ther ; 390(1): 108-115, 2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38834354

ABSTRACT

Nonsteroidal anti-inflammatory drugs (NSAIDs) possess anti-inflammatory, antipyretic, and analgesic properties and are among the most commonly used drugs. Although the cause of NSAID-induced gastric ulcers is well understood, the mechanism behind small intestinal ulcers remains elusive. In this study, we examined the mechanism through which indomethacin (IM), a prominent NSAID, induces small intestinal ulcers, both in vitro and in vivo. In IEC6 cells, a small intestinal epithelial cell line, IM treatment elevated levels of LC3-II and p62. These expression levels remained unaltered after treatment with chloroquine or bafilomycin, which are vacuolar ATPase (V-ATPase) inhibitors. IM treatment reduced the activity of cathepsin B, a lysosomal protein hydrolytic enzyme, and increased the lysosomal pH. There was a notable increase in subcellular colocalization of LC3 with Lamp2, a lysosome marker, post IM treatment. The increased lysosomal pH and decreased cathepsin B activity were reversed by pretreatment with rapamycin (Rapa) or glucose starvation, both of which stabilize V-ATPase assembly. To validate the in vitro findings in vivo, we established an IM-induced small intestine ulcer mouse model. In this model, we observed multiple ulcerations and heightened inflammation following IM administration. However, pretreatment with Rapa or fasting, which stabilize V-ATPase assembly, mitigated the IM-induced small intestinal ulcers in mice. Coimmunoprecipitation studies demonstrated that IM binds to V-ATPase in vitro and in vivo. These findings suggest that IM induces small intestinal injury through lysosomal dysfunction, likely due to the disassembly of lysosomal V-ATPase caused by direct binding. Moreover, Rapa or starvation can prevent this injury by stabilizing the assembly. SIGNIFICANCE STATEMENT: This study elucidates the largely unknown mechanisms behind small intestinal ulceration induced by indomethacin and reveals the involvement of lysosomal dysfunction via vacuolar ATPase disassembly. The significance lies in identifying potential preventative interventions, such as rapamycin treatment or glucose starvation, offering pivotal insights that extend beyond nonsteroidal anti-inflammatory drugs-induced ulcers to broader gastrointestinal pathologies and treatments, thereby providing a foundation for novel therapeutic strategies aimed at a wide array of gastrointestinal disorders.


Subject(s)
Indomethacin , Lysosomes , Sirolimus , Vacuolar Proton-Translocating ATPases , Animals , Indomethacin/toxicity , Lysosomes/drug effects , Lysosomes/metabolism , Vacuolar Proton-Translocating ATPases/metabolism , Vacuolar Proton-Translocating ATPases/antagonists & inhibitors , Sirolimus/pharmacology , Mice , Male , Rats , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Cathepsin B/metabolism , Mice, Inbred C57BL , Cell Line , Intestine, Small/drug effects , Intestine, Small/pathology , Intestine, Small/metabolism , Ulcer/chemically induced , Ulcer/pathology , Ulcer/metabolism
14.
BMC Surg ; 24(1): 179, 2024 Jun 12.
Article in English | MEDLINE | ID: mdl-38867261

ABSTRACT

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.


Subject(s)
Intestinal Obstruction , Intestine, Small , Lymphocytes , Neutrophils , Humans , Retrospective Studies , Intestinal Obstruction/etiology , Intestinal Obstruction/diagnosis , Intestinal Obstruction/surgery , Male , Female , Aged , Intestine, Small/blood supply , Intestine, Small/pathology , Middle Aged , Lymphocytes/pathology , Tissue Adhesions/diagnosis , Ischemia/diagnosis , Ischemia/etiology , Predictive Value of Tests , Aged, 80 and over , Adult
15.
Viruses ; 16(6)2024 May 24.
Article in English | MEDLINE | ID: mdl-38932125

ABSTRACT

The COVID-19 pandemic, which emerged in early 2020, has had a profound and lasting impact on global health, resulting in over 7.0 million deaths and persistent challenges. In addition to acute concerns, there is growing attention being given to the long COVID health consequences for survivors of COVID-19 with documented cases of cardiovascular abnormalities, liver disturbances, lung complications, kidney issues, and noticeable cognitive deficits. Recent studies have investigated the physiological changes in various organs following prolonged exposure to murine hepatitis virus-1 (MHV-1), a coronavirus, in mouse models. One significant finding relates to the effects on the gastrointestinal tract, an area previously understudied regarding the long-lasting effects of COVID-19. This research sheds light on important observations in the intestines during both the acute and the prolonged phases following MHV-1 infection, which parallel specific changes seen in humans after exposure to SARS-CoV-2. Our study investigates the histopathological alterations in the small intestine following MHV-1 infection in murine models, revealing significant changes reminiscent of inflammatory bowel disease (IBD), celiac disease. Notable findings include mucosal inflammation, lymphoid hyperplasia, goblet cell hyperplasia, and immune cell infiltration, mirroring pathological features observed in IBD. Additionally, MHV-1 infection induces villous atrophy, altered epithelial integrity, and inflammatory responses akin to celiac disease and IBD. SPIKENET (SPK) treatment effectively mitigates intestinal damage caused by MHV-1 infection, restoring tissue architecture and ameliorating inflammatory responses. Furthermore, investigation into long COVID reveals intricate inflammatory profiles, highlighting the potential of SPK to modulate intestinal responses and restore tissue homeostasis. Understanding these histopathological alterations provides valuable insights into the pathogenesis of COVID-induced gastrointestinal complications and informs the development of targeted therapeutic strategies.


Subject(s)
COVID-19 , Disease Models, Animal , Murine hepatitis virus , SARS-CoV-2 , Animals , Mice , COVID-19/pathology , COVID-19/virology , COVID-19/immunology , Murine hepatitis virus/pathogenicity , SARS-CoV-2/pathogenicity , Intestinal Mucosa/pathology , Intestinal Mucosa/virology , Intestines/pathology , Intestines/virology , Intestine, Small/virology , Intestine, Small/pathology , Female
17.
World J Surg Oncol ; 22(1): 151, 2024 Jun 07.
Article in English | MEDLINE | ID: mdl-38849854

ABSTRACT

BACKGROUND: Small bowel adenocarcinoma (SBA) is a rare gastrointestinal malignancy forwhich survival is hampered by late diagnosis, complex responses to treatment, and poor prognosis. Accurate prognostic tools are crucial for optimizing treatment strategies and improving patient outcomes. This study aimed to develop and validate a nomogram based on the Surveillance, Epidemiology, and End Results (SEER) database to predict cancer-specific survival (CSS) in patients with SBA and compare it to traditional American Joint Committee on Cancer (AJCC) staging. METHODS: We analyzed data from 2,064 patients diagnosed with SBA between 2010 and 2020 from the SEER database. Patients were randomly assigned to training and validation cohorts (7:3 ratio). Kaplan‒Meier survival analysis, Cox multivariate regression, and nomograms were constructed for analysis of 3-year and 5-year CSS. The performance of the nomograms was evaluated using Harrell's concordance index (C-index), the area under the receiver operating characteristic (ROC) curve, calibration curves, decision curve analysis (DCA), net reclassification improvement (NRI), and integrated discrimination improvement (IDI). RESULTS: Multivariate Cox regression identified sex, age at diagnosis, marital status, tumor site, pathological grade, T stage, N stage, M stage, surgery, retrieval of regional lymph nodes (RORLN), and chemotherapy as independent covariates associated with CSS. In both the training and validation cohorts, the developed nomograms demonstrated superior performance to that of the AJCC staging system, with C-indices of 0.764 and 0.759, respectively. The area under the curve (AUC) values obtained by ROC analysis for 3-year and 5-year CSS prediction significantly surpassed those of the AJCC model. The nomograms were validated using calibration and decision curves, confirming their clinical utility and superior predictive accuracy. The NRI and IDI indicated the enhanced predictive capability of the nomogram model. CONCLUSION: The SEER-based nomogram offers a significantly superior ability to predict CSS in SBA patients, supporting its potential application in clinical decision-making and personalized approaches to managing SBA to improve survival outcomes.


Subject(s)
Adenocarcinoma , Intestinal Neoplasms , Nomograms , SEER Program , Humans , Male , Female , SEER Program/statistics & numerical data , Adenocarcinoma/mortality , Adenocarcinoma/pathology , Adenocarcinoma/therapy , Middle Aged , Survival Rate , Aged , Intestinal Neoplasms/mortality , Intestinal Neoplasms/pathology , Intestinal Neoplasms/therapy , Intestinal Neoplasms/diagnosis , Prognosis , Follow-Up Studies , Neoplasm Staging , Intestine, Small/pathology , ROC Curve , Adult , Retrospective Studies
18.
J Nanobiotechnology ; 22(1): 303, 2024 May 31.
Article in English | MEDLINE | ID: mdl-38822376

ABSTRACT

Radiation-induced intestinal injury is the most common side effect during radiotherapy of abdominal or pelvic solid tumors, significantly impacting patients' quality of life and even resulting in poor prognosis. Until now, oral application of conventional formulations for intestinal radioprotection remains challenging with no preferred method available to mitigate radiation toxicity in small intestine. Our previous study revealed that nanomaterials derived from spore coat of probiotics exhibit superior anti-inflammatory effect and even prevent the progression of cancer. The aim of this work is to determine the radioprotective effect of spore coat (denoted as spore ghosts, SGs) from three clinically approved probiotics (B.coagulans, B.subtilis and B.licheniformis). All the three SGs exhibit outstanding reactive oxygen species (ROS) scavenging ability and excellent anti-inflammatory effect. Moreover, these SGs can reverse the balance of intestinal flora by inhibiting harmful bacteria and increasing the abundance of Lactobacillus. Consequently, administration of SGs significantly reduce radiation-induced intestinal injury by alleviating diarrhea, preventing X-ray induced apoptosis of small intestinal epithelial cells and promoting restoration of barrier integrity in a prophylactic study. Notably, SGs markedly improve weight gain and survival of mice received total abdominal X-ray radiation. This work may provide promising radioprotectants for efficiently attenuating radiation-induced gastrointestinal syndrome and promote the development of new intestinal predilection.


Subject(s)
Probiotics , Radiation-Protective Agents , Spores, Bacterial , Animals , Probiotics/pharmacology , Mice , Administration, Oral , Radiation-Protective Agents/pharmacology , Radiation-Protective Agents/therapeutic use , Radiation-Protective Agents/chemistry , Spores, Bacterial/radiation effects , Radiation Injuries/drug therapy , Reactive Oxygen Species/metabolism , Intestine, Small/microbiology , Intestine, Small/radiation effects , Intestine, Small/pathology , Humans , Apoptosis/drug effects , Male , Gastrointestinal Microbiome/drug effects , Intestines/radiation effects , Intestines/microbiology , Intestines/pathology , Radiation Injuries, Experimental/pathology
19.
Eur J Gastroenterol Hepatol ; 36(7): 845-849, 2024 Jul 01.
Article in English | MEDLINE | ID: mdl-38829942

ABSTRACT

BACKGROUND: Meckel diverticulum (MD) is an important cause of gastrointestinal bleeding in children. Small bowel capsule endoscopy (SBCE) is a first-line examination method applied to patients with obscure gastrointestinal bleeding, but there are few studies on its application in children with MD. This article aims to provide evidence in favor of the auxiliary diagnosis of MD in children by analyzing its characteristics using SBCE. METHODS: We retrospectively collected the clinical data of patients with suspected MD. RESULTS: A total of 58 children were included in this study. All 58 children presented overt gastrointestinal bleeding (bloody stool or melena). Capsule endoscopy identified protruding lesions in 2 cases, double-lumen changes in 30 cases (all considered as MD), vascular lesions in 7 cases, intestinal mucosal inflammatory lesions in 3 cases, ulcers or erosion in 3 cases, and no obvious abnormalities in SBCE in 12 cases. Both SBCE and technetium-99 scans were performed for 24 cases, 22 of which were diagnosed MD by their combined results, giving a diagnostic coincidence rate of 91.7%. Eight cases were highly suspected as MD but were negative for the technetium-99 scan and positive for SBCE. CONCLUSION: SBCE has high accuracy in the diagnosis of MD in children, especially when performed in combination with a technetium-99 scan, which can greatly improve the diagnostic rate of MD in children.


Subject(s)
Capsule Endoscopy , Gastrointestinal Hemorrhage , Meckel Diverticulum , Humans , Meckel Diverticulum/complications , Meckel Diverticulum/diagnostic imaging , Meckel Diverticulum/diagnosis , Capsule Endoscopy/methods , Male , Female , Retrospective Studies , Child , Child, Preschool , Gastrointestinal Hemorrhage/etiology , Adolescent , Infant , Intestine, Small/diagnostic imaging , Intestine, Small/pathology , Predictive Value of Tests , Radionuclide Imaging , Radiopharmaceuticals
20.
Gastroenterol. hepatol. (Ed. impr.) ; 47(5): 491-499, may. 2024.
Article in English | IBECS | ID: ibc-CR-359

ABSTRACT

Background Small bowel tumors (SBT) are infrequent and represent a small proportion of digestive neoplasms. There is scarce information about SBT in Latin America.AimTo describe the epidemiology, clinical characteristics, diagnostic methods, and survival of malignant SBTs.MethodsRetrospective observational study of adult patients with histopathological diagnosis of SBT between 2007 and 2021 in a university hospital in Chile.ResultsA total of 104 patients [51.9% men; mean age 57 years] with SBT. Histological type: neuroendocrine tumor (NET) (43.7%, n=38), gastrointestinal stromal tumors (GIST) (21.8%, n=19), lymphoma (17.2%, n=15) and adenocarcinoma (AC) (11.5%, n=10). GIST was more frequent in duodenum (50%; n=12) and NET in the ileum (65.8%; n=25). Metastasis was observed in 17 cases, most commonly from colon and melanoma. Nausea and vomiting were significantly more often observed in AC (p=0.035), as well as gastrointestinal bleeding in GIST (p=0.007). The most common diagnostic tools were CT and CT enteroclysis with an elevated diagnostic yield (86% and 94% respectively). The 5-year survival of GIST, NET, lymphoma and AC were 94.7% (95%CI: 68.1–99.2), 82.2% (95%CI: 57.6–93.3), 40.0% (95%CI: 16.5–82.8) and 25.9% (95%CI: 4.5–55.7%), respectively. NET (HR 6.1; 95%CI: 2.1–17.2) and GIST (HR 24.4; 95%CI: 3.0–19.8) were independently associated with higher survival compared to AC, adjusted for age and sex.ConclusionsMalignant SBT are rare conditions and NETs are the most common histological subtype. Clinical presentation at diagnosis, location or complications may suggest a more probable diagnosis. GIST and NET are associated with better survival compared to other malignant subtypes. (AU)


Introducción Los tumores del intestino delgado (TID) son infrecuentes y la información sobre ellos es escasa en Latinoamérica.ObjetivoDescribir la epidemiología, características clínicas, métodos diagnósticos y supervivencia de los TID malignos.MétodosEstudio observacional retrospectivo de pacientes adultos con diagnóstico histopatológico de TID entre 2007-2021 en un hospital universitario de Chile.ResultadosSe observaron 104 pacientes (51,9% hombres; edad media 57 años) con TID. El tipo histológico fue tumor neuroendocrino (TNE) (43,7%, n=38), tumor estromal gastrointestinal (GIST) (21,8%, n=19), linfoma (17,2%, n=15) y adenocarcinoma (AC) (11,5%, n=10). Los GIST fueron más frecuentes en el duodeno (50%; n=12) y los TNE en el íleon (65,8%; n=25). Hubo 17 casos de metástasis, más comúnmente de colon y melanoma. Las náuseas y los vómitos se observaron con mayor frecuencia en AC (p=0,035), así como el sangrado gastrointestinal en GIST (p=0,007). Las herramientas de valoración más comunes fueron TC y enteroclisis por TC con un rendimiento diagnóstico alto (86% y 94%, respectivamente). La supervivencia a cinco años de los GIST, TNE, linfoma y AC fue 94,7% (intervalo de confianza [IC] 95%: 68,1-99,2), 82,2% (IC 95%: 57,6-93,3), 40,0% (IC 95%: 16,5-82,8) y 25,9% (IC 95%: 4,5-55,7), respectivamente. Los TNE (hazard ratio [HR] 6,1; IC 95%: 2,1-17,2) y GIST (HR 24,4; IC 95%: 3,0-19,8) se asociaron de forma independiente con una mayor supervivencia en comparación con AC, ajustado por edad y sexo.ConclusionesLos TID malignos son enfermedades poco frecuentes y los TNE son el subtipo histológico más común. La presentación clínica en el momento del diagnóstico, localización o complicaciones pueden sugerir un dictamen más probable. Los GIST y TNE se asocian a una mejor supervivencia en comparación con otros subtipos malignos. (AU)


Subject(s)
Humans , Intestine, Small/pathology , Intestinal Neoplasms/diagnosis , Intestinal Neoplasms/epidemiology , Neuroendocrine Tumors/diagnosis , Neuroendocrine Tumors/epidemiology , Gastrointestinal Stromal Tumors/diagnosis , Gastrointestinal Stromal Tumors/epidemiology
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