Intestinal Tumors Research Articles

Lenvatinib-Loaded Poly(lactic-co-glycolic acid) Nanoparticles with Epidermal Growth Factor Receptor Antibody Conjugation as a Preclinical Approach to Therapeutically Improve Thyroid Cancer with Aggressive Behavior.

Lenvatinib, a tyrosine kinase inhibitor (TKI) approved for the treatment of progressive and radioactive iodine (RAI)-refractory differentiated thyroid cancer (DTC), is associated with significant adverse effects that can be partially mitigated through the development of novel drug formulations. The utilization of nanoparticles presents a viable option, as it allows for targeted drug delivery, reducing certain side effects and enhancing the overall quality of life for patients. This study aimed to produce and assess, both in vitro and in vivo, the cytotoxicity, biodistribution, and therapeutic efficacy of lenvatinib-loaded PLGA nanoparticles (NPs), both with and without decoration using antibody conjugation (cetuximab), as a novel therapeutic approach for managing aggressive thyroid tumors. Poly(lactic-co-glycolic acid) nanoparticles (NPs), decorated with or without anti-EGFR, were employed as a lenvatinib delivery system. These NPs were characterized for size distribution, surface morphology, surface charge, and drug encapsulation efficiency. Cytotoxicity was evaluated through MTT assays using two cellular models, one representing normal thyroid cells (Nthy-ori 3-1) and the other representing anaplastic thyroid cells (CAL-62). Additionally, an in vivo xenograft mouse model was established to investigate biodistribution and therapeutic efficacy following intragastric administration. The NPs demonstrated success in terms of particle size, polydispersity index (PDI), zeta potential, morphology, encapsulation efficiency, and cetuximab distribution across the surface. In vitro analysis revealed cytotoxicity in both cellular models with both formulations, but only the decorated NPs achieved an ID50 value in CAL-62 cells. Biodistribution analysis following intragastric administration in xenografted thyroid mice demonstrated good stability in terms of intestinal barrier function and tumor accumulation. Both formulations were generally well tolerated without inducing pathological effects in the examined organs. Importantly, both formulations increased tumor necrosis; however, decorated NPs exhibited enhanced parameters related to apoptotic/karyolytic forms, mitotic index, and vascularization compared with NPs without decoration. These proof-of-concept findings suggest a promising strategy for administering TKIs in a more targeted and effective manner.

Psoralea corylifolia formula extract-loaded silk fibroin/polycaprolactone fibrous membrane for the treatment of colorectal cancer

Intestinal obstructions caused by intestinal tumors pose life-threatening risks to patients. Adjuvant treatment using intestinal stents carrying drug loaded membranes has the advantages of timely relief of intestinal obstruction, as well as effective inhibition of tumor progression. The present work is to develop an intestinal stent loaded with a combination of traditional Chinese medicines capable of good biocompatibility, degradability, sustained drug release and anti-tumor properties. The drug combination extract was obtained from Psoralea corylifolia formula (PCF) and then was loaded into silk fibroin (SF)/polycaprolactone (PCL) fibrous membranes using emulsion electrospinning technology. Results showed that the membrane prepared by emulsion electrospinning technology has apparent core-shell structure, and the mechanical property and hydrophilicity of the membrane are gradually improved with the addition of PCF. Drug sustained release results demonstrated that there were no bursting phenomena, and showed a gradual sustained release up to 400 h. The antitumor efficacy was assessed in vitro using a human colorectal cancer cell line HCT-116 and an epithelial cell line NCM-460. Results showed that this drug-loaded membrane sustained antitumor cell growth performance, indicating its great potential for clinical treatment for intestinal cancer in the near future.

A Rare Histopathological Diagnosis: Endometrioid Adenocarcinoma Localized in the Rectum: a Case Report

Endometriosis-associated intestinal tumors represent malignant transformation of gastrointestinal endometriosis. Clinical features are similar to colon tumor with abdominal or pelvic pain, dyschezia, or bloody stools. Intestinal occlusion or perforation has also been described as a first presentation. The diagnosis is often postoperative, and it is based on specific immunohistochemical patterns (CK7+/CK20−). We present a rare case of a woman with a malignant transformation of an endometriotic lesion of the sigmoid colon, who underwent emergency surgery for intestinal occlusion. She underwent an exploratory laparotomy and Hartmann resection. The immunophenotypic analysis of the specimens revealed the following pattern: CK20−, CK7+, compatible with the diagnosis of endometrioid adenocarcinoma. Endometrioid carcinoma is a rare tumor, difficult to diagnose preoperatively because of similar symptoms of sigmoid carcinoma. A high index of suspicion in conjunction with careful histological and immunohistochemical examination (CK7, CK20, CDX2, CD10, ER, and PR) is important for establishing a correct diagnosis.

Intragastric infusion of a liquid diet with low-methoxyl pectin alleviates fecal inconsistency and local proinflammatory cytokine expression in lipopolysaccharide-septic rats

ObjectiveDiarrhea interrupts enteral nutrition management in hospitalized patients with severe illnesses, such as sepsis. Pectin, a water-soluble dietary fiber, has the potential to maintain intestinal function and may reduce inflammatory reactions. The aim of this study was to demonstrate that the addition of low-methoxyl (LM) pectin to a liquid diet suppresses softening of stool texture and reduces tissue inflammatory responses in enteral nutrition management during sepsis. MethodsA fat-enriched liquid diet with LM pectin (P-EN) or a liquid diet without dietary fiber (FF-EN) was given continuously to rats through a gastric catheter. Lipopolysaccharide (LPS; 10 mg/kg) was injected intraperitoneally 24 h (study 1) and 7 h (study 2) before sacrifice. ResultsLPS injection significantly worsened fecal property scores in rats infused with FF-EN compared with the rats given P-EN in study 1. Whereas many myeloperoxidase-positive cells infiltrated the liver, and the hepatic expressions of chemokine genes were markedly elevated 24 h after LPS administration, these findings were clearly alleviated in the LM pectin-containing liquid diet group. In study 2, protein expressions of proinflammatory cytokines, such as small intestinal tumor necrosis factor-α and hepatic interleukin-1β, and interleukin-6, were significantly downregulated in the P-EN LPS group compared with the FF-EN LPS group. ConclusionsA liquid diet containing LM pectin allows enteral nutrition management with a low risk for diarrhea and reduces local inflammation under septic conditions.

Derivation of oral cancer slope factors for hexavalent chromium informed by pharmacokinetic models and in vivo genotoxicity data

Hexavalent chromium [Cr(VI)] is present in drinking water from natural and anthropogenic sources at approximately 1 ppb. Several regulatory bodies have recently developed threshold-based safety criteria for Cr(VI) of 30–100 ppb based on evidence that small intestine tumors in mice following exposure to ≥20,000 ppb are the result of a non-mutagenic mode of action (MOA). In contrast, U.S. EPA has recently concluded that Cr(VI) acts through a mutagenic MOA based, in part, on scoring numerous in vivo genotoxicity studies as having low confidence; and therefore derived a cancer slope factor (CSF) of 0.5 (mg/kg-day)−1, equivalent to ∼0.07 ppb. Herein, we demonstrate how physiologically based pharmacokinetic (PBPK) models and intestinal segment-specific tumor incidence data can form a robust dataset supporting derivation of alternative CSF values that equate to Cr(VI) concentrations ranging from below background to concentrations similar to those derived using threshold approaches—depending on benchmark response level and risk tolerance. Additionally, we highlight weaknesses in the rationale EPA used to discount critical in vivo genotoxicity studies. While the data support a non-genotoxic MOA, these alternative toxicity criteria require only PBPK models, robust tumor data, and fair interpretation of published in vivo genotoxicity data for Cr(VI).

Wheat Alkylresorcinols Modulate Glucose Homeostasis through Improving GLP-1 Secretion in High-Fat-Diet-Induced Obese Mice.

Wheat alkylresorcinols (ARs) consumption has been evidenced to improve obesity and its associated insulin resistance. However, the effect of ARs on glucagon-like peptide 1 (GLP-1) secretion and the underlying mechanism of action are still unclear. In this study, C57BL/6J mice were fed low-fat diet (LFD), high-fat diet (HFD), and HFD supplemented with 0.4% (w/w) ARs separately for 9 weeks. The results showed that ARs intervention significantly improved glucose homeostasis and restored the serum level of GLP-1 compared with the HFD control group. Moreover, ARs treatment alleviated HFD-induced ileal epithelium damage according to TUNEL staining, immunofluorescence, and transmission electron microscopy observation. The alleviative effect was further verified by apoptosis analysis and mitochondrial function evaluation. Furthermore, palmitic acid (PA) was administered to the intestinal secretin tumor cell line (STC-1) to clarify the protective effect of ARs on GLP-1 secretion in vitro. In consistence with the results of animal studies, ARs treatment could significantly improve GLP-1 secretion in STC-1 cells compared with PA treatment alone in a dose-dependent manner, accompanied by a reduction in apoptosis and mitochondrial dysfunction. In addition, ARs treatment notably enhanced the abundance of SCFA (short-chain fatty acid)-producing bacteria, such as Bacteroides, Bifidobacterium, and Akkermansia. The increased levels of intestinal SCFAs, such as acetic acid, propionic acid, and butyric acid, improved the expression of short-chain fatty acid receptors (FFAR3) and glucagon-like peptide-1 receptor (GLP-1R), enhancing the secretion of the intestinal hormones GLP-1. Thus, this study provides potential clinical implications of whole wheat as a dietary strategy to improve glucose homeostasis for obese populations.

Management Strategies and Outcomes for Small Intestinal Neuroendocrine Tumours with Involvement of the Superior Mesenteric Vessels: A Systematic Review.

Small intestinal neuroendocrine tumours (SI-NETs) are the most common small intestinal tumours. A particularly challenging subset of these tumours is those that involve the superior mesenteric artery or vein for which the role and feasibility of surgery are often questioned. This systematic review aimed to identify and evaluate the management strategies used for these complex SI-NETs. The identified studies showed positive outcomes with surgery and multimodality therapy.

Gain-of-Function p53 Mutation Acts as a Genetic Switch for TGFβ Signaling-Induced Epithelial-to-Mesenchymal Transition in Intestinal Tumors.

KRAS and TP53 mutations shift activin-mediated signaling to overcome growth inhibition and promote partial EMT, identifying a subset of patients with colorectal cancer that could benefit from inhibition of TGFβ signaling.

Performance of capsule endoscopy for the detection of small intestinal neuroendocrine tumors in familial carcinoid: a prospective single-site study

Background and AimsSmall bowel neuroendocrine tumors are slow growing, clinically silent tumors whose prognosis depends on disease stage. Members of kindreds with a familial form of small intestine neuroendocrine tumors (SI-NET) represent a high-risk population for whom early detection improves disease outcome. The aim was to determine the utility of small bowel capsule endoscopy (SB-CE) for screening high-risk asymptomatic relatives from kindreds with familial carcinoid. Methods174 asymptomatic subjects with a family history (≥ 2 family members) of SI-NET were screened under Protocol NCT00646022, Natural History of Familial Carcinoid Tumor at the National Institutes of Health. All patients were imaged with SB-CE and 18F-DOPA PET/CT and results were independently analyzed. Patients with a positive imaging study underwent surgical exploration. ResultsThirty-five of 174 asymptomatic subjects screened for SI-NET were positive on either SB-CE or 18F-DOPA PET. Thirty-two of 35 patients with a positive study were confirmed at surgery. SB-CE was positive in 28 of 32 patients with confirmed tumors for a per patient sensitivity of 87.5%. SB-CE had a specificity of 97.3% and a negative predictive value (NPV) of 96.5%. The average tumor number and size was 7.7 and 5.0 mm, respectively, and 81.2% of patients had multiple tumors. 18F-DOPA PET/CT imaging had a similar sensitivity of 84% versus surgery. ConclusionsSB-CE is a sensitive and specific method comparable to 18F-DOPA PET/CT for screening high-risk patients with familial SI-NET.

GPR4 Knockout Attenuates Intestinal Inflammation and Forestalls the Development of Colitis-Associated Colorectal Cancer in Murine Models.

GPR4 is a proton-sensing G protein-coupled receptor highly expressed in vascular endothelial cells and has been shown to potentiate intestinal inflammation in murine colitis models. Herein, we evaluated the proinflammatory role of GPR4 in the development of colitis-associated colorectal cancer (CAC) using the dextran sulfate sodium (DSS) and azoxymethane (AOM) mouse models in wild-type and GPR4 knockout mice. We found that GPR4 contributed to chronic intestinal inflammation and heightened DSS/AOM-induced intestinal tumor burden. Tumor blood vessel density was markedly reduced in mice deficient in GPR4, which correlated with increased tumor necrosis and reduced tumor cell proliferation. These data demonstrate that GPR4 ablation alleviates intestinal inflammation and reduces tumor angiogenesis, development, and progression in the AOM/DSS mouse model.

Newly discovered genomic mutation patterns in radiation-induced small intestinal tumors of ApcMin/+ mice.

Among the small intestinal tumors that occur in irradiated mice of the established mouse model B6/B6-Chr18MSM-F1 ApcMin/+, loss of heterozygosity analysis can be utilized to estimate whether a deletion in the wild-type allele containing the Adenomatous polyposis coli (Apc) region (hereafter referred to as Deletion), a duplication in the mutant allele with a nonsense mutation at codon 850 of Apc (Duplication), or no aberration (Unidentified) has occurred. Previous research has revealed that the number of Unidentified tumors tends to increase with the radiation dose. In the present study, we investigated the molecular mechanisms underlying the development of an Unidentified tumor type in response to radiation exposure. The mRNA expression levels of Apc were significantly lower in Unidentified tumors than in normal tissues. We focused on epigenetic suppression as the mechanism underlying this decreased expression; however, hypermethylation of the Apc promoter region was not observed. To investigate whether deletions occur that cannot be captured by loss of heterozygosity analysis, we analyzed chromosome 18 using a customized array comparative genomic hybridization approach designed to detect copy-number changes in chromosome 18. However, the copy number of the Apc region was not altered in Unidentified tumors. Finally, gene mutation analysis of the Apc region using next-generation sequencing suggested the existence of a small deletion (approximately 3.5 kbp) in an Unidentified tumor from a mouse in the irradiated group. Furthermore, nonsense and frameshift mutations in Apc were found in approximately 30% of the Unidentified tumors analyzed. These results suggest that radiation-induced Unidentified tumors arise mainly due to decreased Apc expression of an unknown regulatory mechanism that does not depend on promoter hypermethylation, and that some tumors may result from nonsense mutations which are as-yet undefined point mutations.

THU081 Differences In Circulating Microrna Levels In Genetically Confirmed Multiple Endocrine Neoplasia Type 1 And Multiple Endocrine Neoplasia Type 1 Phenocopies As Assessed By Next Generation Sequencing

Abstract Disclosure: D.A. Trukhina: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). E.O. Mamedova: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). P.A. Koshkin: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). A.G. Nikitin: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). G.A. Melnichenko: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). Z.E. Belaya: Grant Recipient; Self; Russian Science Foundation (project N 19-15-00398-П). Multiple endocrine neoplasia type 1 (MEN1) is a rare disease caused by mutations in the MEN1 gene encoding the menin protein (gMEN1). This syndrome is characterized by the occurrence of parathyroid tumors, gastroenteropancreatic neuroendocrine tumors (GEP-NETs), pituitary adenomas, as well as other endocrine and non-endocrine tumors. Patients with MEN1 phenotype without MEN1 mutations are considered MEN1 phenocopies (phMEN1). It has not been studied whether the development of MEN1 phenocopies is determined by epigenetic changes, particularly by altered microRNA expression, which can affect menin. Materials & methods Single-center, case-control study: assessment of plasma microRNA expression in patients with gMEN1, phMEN1 and healthy controls. Morning plasma samples were collected from fasting patients and gender-matched controls and stored at –80C. Total RNA isolation was performed using miRNeasy Mini Kit with QIAcube. The libraries were prepared by the QIAseq miRNA Library Kit. Circulating miRNA sequencing was performed on Illumina NextSeq 500. Subsequent data processing was performed using DESeq2 bioinformatics algorithm. Results We enrolled 24 patients with gMEN1 and 12 patients with phMEN1, along with 12 gender-matched controls. The median age of gMEN1 patients was 39 [35; 46]; in phMEN1 — 59 [51;60]; control — 59 [51.5; 62.5]. The gMEN1 group differed in age (p<0,01) compared to phMEN1 and control groups. We divided all assessed microRNAs into 3 groups based on the significance of the results: the first group consisted of samples with the highest level of detected microRNAs (>50 counts), the second group — moderate (10–50), the third group — the lowest (<10).98 microRNAs were differently expressed in groups gMEN1 and phMEN1 (84 upregulated microRNAs, 14 — downregulated). We found increased expression of microRNAs in gMEN1 which interact with menin: hsa-miR-421 (p adj = 0.0004362), hsa-miR-664a-5p (p adj = 0.0037814). We found several microRNAs associated with intestinal and pituitary tumors in gMEN1 and phMEN1 groups: up-regulated hsa-miR-7-5p (p adj = 0.0000084); downregulated hsa-miR-423-5p (p adj < 0.000001) and hsa-miR-432-5p (p adj = 0.0087227). 84 microRNA were differently expressed in groups gMEN1 and control (67 up-regulated microRNAs, 17 — downregulated). When comparing gMEN1 with phMEN1 and control a decrease in hsa-let-7a-5p miRNA was found, which, according to the literature, is downregulated in Men1 gene knockout cell lines. The phMEN1 vs control group showed downregulation of hsa-miR-122-5p (p adj = 0.0080138) and upregulation of hsa-miR-191-5p (p adj = 0.0002144), hsa-miR-486-5p (p adj = 0.0491822) that has been detected in GEP-NETs. Conclusion We found microRNAs which could potentially become biomarkers in the differential diagnosis of gMEN1 and phMEN1. The results need to be validated using a different measurement method with a larger sample size. Presentation: Thursday, June 15, 2023

Intestinal-specific Hdac3 deletion increases susceptibility to colitis and small intestinal tumour development in mice fed a high fat diet.

High fat diets, and inflammation are risk factors for colon cancer, however the underlying mechanisms remain to be fully elucidated. The transcriptional co-repressor HDAC3 has recently emerged as a key regulator of intestinal epithelial responses to diet and inflammation with intestinal-specific Hdac3 deletion (Hdac3IKO) in mice increasing lipid oxidation genes and the rate of lipid oxidation in enterocytes. Hdac3IKO mice are also predisposed to experimentally induced colitis, however whether this is driven by the intestinal metabolic reprogramming, and whether this predisposes these mice to intestinal tumourigenesis is unknown. Herein, we examined the effects of intestinal-specific Hdac3 deletion on colitis-associated intestinal tumourigenesis in mice fed a standard (STD) or HF diet (HFD). Hdac3IKO mice were highly prone to experimentally induced colitis, which was further enhanced by a HFD. Hdac3deletion also accelerated intestinal tumour development, specifically when fed a HFD and most notably in the small intestine where lipid absorption is maximal. Expression of proteins involved in fatty acid metabolism and oxidation (SCD1, EHHADH) were elevated in the small intestine of Hdac3IKO mice fed a HFD, and these mice displayed increased levels of lipid peroxidation, DNA damage, and apoptosis in their villi, as well as extensive expansion of the stem cell and progenitor cell compartment. These findings reveal a novel role for Hdac3 in suppressing colitis and intestinal tumorigenesis, particularly in the context of consumption of a HFD, and reveal a potential mechanism by which HFDs may increase intestinal tumorigenesis by increasing lipid oxidation, DNA damage and intestinal epithelial cell turnover.

The roles of the native cell differentiation program aberrantly recapitulated in Drosophila intestinal tumors

Many tumors recapitulate the developmental and differentiation program of their tissue of origin, a basis for tumor cell heterogeneity. Although stem-cell-like tumor cells are well studied, the roles of tumor cells undergoing differentiation remain to be elucidated. We employ Drosophila genetics to demonstrate that the differentiation program of intestinal stem cells is crucial for enabling intestinal tumors to invade and induce non-tumor-autonomous phenotypes. The differentiation program that generates absorptive cells is aberrantly recapitulated in the intestinal tumors generated by activation of the Yap1 ortholog Yorkie. Inhibiting it allows stem-cell-like tumor cells to grow but suppresses invasiveness and reshapes various phenotypes associated with cachexia-like wasting by altering the expression of tumor-derived factors. Our study provides insight into how a native differentiation program determines a tumor's capacity to induce advanced cancer phenotypes and suggests that manipulating the differentiation programs co-opted in tumors might alleviate complications of cancer, including cachexia.

1245P A lymph nodal staging assessment model for various histologic types of small intestinal tumors

1245P A lymph nodal staging assessment model for various histologic types of small intestinal tumors

A case of rectal endometriosis misdiagnosed as rectal malignancy on three colonoscopies and biopsies sharing a combined literature review

Endometriosis involves the intestine, and its clinical manifestations are nonspecific and lack of etiological manifestations. The diagnosis is difficult, which often leads to misdiagnosis. We report a case of endometriosis which was misdiagnosed as intestinal malignant tumor after colonoscopy and three biopsies.

Elevated CA 19-9 is associated with worse survival in patients with resected ampullary adenocarcinoma

BackgroundThe prognostic utility of Carbohydrate Antigen 19-9 (CA 19-9) and Carcinoembryonic Antigen (CEA) in ampullary adenocarcinoma is unclear. We sought to evaluate the association between initial tumor marker levels and survival in patients with resected ampullary adenocarcinoma. MethodsThis was a single-institution, retrospective cohort study of consecutive patients who underwent pancreatoduodenectomy for ampullary adenocarcinoma from 1999 to 2021. CA 19-9 was assessed after biliary decompression. Contal and O'Quigley method determined optimal biomarker cutoff levels which were correlated with overall survival (OS) using the Kaplan-Meier method and Cox Proportional Hazards Regression. ResultsA total of 180 patients underwent pancreatoduodenectomy. Patients with CA 19-9 >100 U/mL had a shorter median OS (28 vs. 132 months, p < 0.001) compared to patients with CA 19-9 ≤ 100 U/mL at diagnosis. Survival was similar between pancreaticobiliary and intestinal tumor subtypes when CA 19-9 was >100 U/mL (OS:25 vs. 33 months, p = 0.415). By Cox regression analysis, CA 19-9 >100 U/mL was independently associated with worse OS (HR 2.8, p = 0.001). ConclusionsPreoperative CA 19-9 >100 U/mL was associated with shorter OS in patients with resected ampullary adenocarcinoma. CA 19–9 may be useful when counseling patients about prognosis or when considering the role of perioperative systemic therapy.

Clinical and genealogical criteria for intestinal tumors

Difficulties in timely diagnosis, the high cost and complexity of treatment, as well as the high mortality rate of malignant neoplasms determine the relevance of combating them. The highest cumulative incidence of colon cancer is observed in the industrial centers of the region. Primary multiple tumors and breast cancer in men are found with a high frequency. The role of the Amsterdam Criteria in the diagnosis of hereditary non-polyposis colon cancer in the region is limited. The risk of developing colon cancer of hereditary genesis is present in 0,49% of the region's population. The proposed criteria for the formation of risk groups are adequate and convenient for oncogenetic counseling.

Organoids and metastatic orthotopic mouse model for mismatch repair-deficient colorectal cancer.

Genome integrity is essential for the survival of an organism. DNA mismatch repair (MMR) genes (e.g., MLH1, MSH2, MSH6, and PMS2) play a critical role in the DNA damage response pathway for genome integrity maintenance. Germline mutations of MMR genes can lead to Lynch syndrome or constitutional mismatch repair deficiency syndrome, resulting in an increased lifetime risk of developing cancer characterized by high microsatellite instability (MSI-H) and high mutation burden. Although immunotherapy has been approved for MMR-deficient (MMRd) cancer patients, the overall response rate needs to be improved and other management options are needed. To better understand the biology of MMRd cancers, elucidate the resistance mechanisms to immune modulation, and develop vaccines and therapeutic testing platforms for this high-risk population, we generated organoids and an orthotopic mouse model from intestine tumors developed in a Msh2-deficient mouse model, and followed with a detailed characterization. The organoids were shown to be of epithelial origin with stem cell features, to have a high frameshift mutation frequency with MSI-H and chromosome instability, and intra- and inter-tumor heterogeneity. An orthotopic model using intra-cecal implantation of tumor fragments derived from organoids showed progressive tumor growth, resulting in the development of adenocarcinomas mixed with mucinous features and distant metastasis in liver and lymph node. The established organoids with characteristics of MSI-H cancers can be used to study MMRd cancer biology. The orthotopic model, with its distant metastasis and expressing frameshift peptides, is suitable for evaluating the efficacy of neoantigen-based vaccines or anticancer drugs in combination with other therapies.

Intestinal cavernous hemangioma as a cause of anemic syndrome and gastrointestinal bleeding

There are multiple causes of non-variceal gastrointestinal bleeding, some more commonly diagnosed than others. Therefore, the finding of a cavernous hemangioma in the jejunum should make us consider patients who present with anemic syndrome due to occult gastrointestinal bleeding, once the more common pathologies have been ruled out, this after extensive studies, including upper endoscopy, colonoscopy, imaging studies and some cases endoscopic capsule. It is described that cavernous hemangiomas account for 0.05% of gastrointestinal neoplasms and up to 7-10% of benign tumors of the small intestine. They can also be found in up to 7.7% of patients with gastrointestinal bleeding.