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Tumor hypoxia may compromise the results of chemotherapy for treating colorectal cancer because it stimulates angiogenesis and the release of tumor growth factors. Hyperbaric oxygen (HBO) supplementation may potentiate the effects of chemotherapy in such cases. This study aimed to assess the effect of HBO therapy combined with chemotherapy on the treatment of colorectal cancer in mice. C57BL6 mice were submitted to the intrarectal instillation of N-methyl-N-nitrosoguanidine (MNNG) and treated with 5-fluorouracil (5FU) and/or HBO therapy. The MNNG group presented the highest dysplastic crypt rate. The 5FU + HBO group presented the highest rate of apoptotic cells per dysplastic crypt. The 5FU group presented the highest expression of hypoxia-inducible factor-1 alpha and CD44. HBO therapy increased the effect of 5FU on the treatment of the experimental colorectal neoplasia in mice., (Copyright © 2024 Copyright: © 2024 Medical Gas Research.)

Although perianal Crohn's disease (PCD) is highly associated with the exacerbated inflammation, the molecular basis and immunological signature that distinguish patients who present a history of perianal lesions are still unclear. This paper aims to define immunological characteristics related to PCD. In this cross-sectional observational study, we enrolled 20 healthy controls and 39 CD patients. Blood samples were obtained for the detection of plasma cytokines and lipopolysaccharides (LPS). Peripheral blood mononuclear cells (PBMCs) were phenotyped by flow cytometry. Leukocytes were stimulated with LPS or anti-CD3/anti-CD28 antibodies. Our results show that CD patients had augmented plasma interleukin (IL)-6 and LPS. However, their PBMC was characterized by decreased IL-6 production, while patients with a history of PCD produced higher IL-6, IL-8, and interferon-γ, along with decreased tumor necrosis factor alpha (TNF). CD patients had augmented FoxP3 and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) regulatory markers, though the PCD subjects presented a significant reduction in CTLA-4 expression. CTLA-4 as well as IL-6 and TNF responses were able to distinguish the PCD patients from those who did not present perianal complications. In conclusion, IL-6, TNF, and CTLA-4 exhibit a distinct expression pattern in CD patients with a history of PCD, regardless of disease activity. These findings clarify some mechanisms involved in the development of the perianal manifestations and may have a great impact on the disease management., (© The Author(s) 2024. Published by Oxford University Press on behalf of the British Society for Immunology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

COVID-19 has a broad spectrum of clinical manifestations associated with the host immune response heterogeneity. Despite the advances in COVID-19 research, it is still crucial to seek a panel of molecular markers that enable accurate stratification of COVID-19 patients. Here, we performed a study that combined analysis of blood transcriptome, demographic data, clinical aspects and laboratory findings from 66 participants classified into different degrees of COVID-19 severity and healthy subjects. We identified a perturbation in blood-leukocyte transcriptional profile associated with COVID-19 aggravation, which was mainly related to processes that disfavoured lymphocyte activation and favoured neutrophil activation. This transcriptional profile stratified patients according to COVID-19 severity. Hence, it enabled identification of a turning point in transcriptional dynamics that distinguished disease outcomes and non-hospitalized from hospitalized moderate patients. Central genes of this unique neutrophil signature were S100A9, ANXA3, CEACAM6, VNN1, OLFM4, IL1R2, TCN1 and CD177. Our study indicates the molecular changes that are linked with the differing clinical aspects presented by humans when suffering from COVID-19, which involve neutrophil activation., (© 2023 John Wiley & Sons Ltd.)

Background and Aims: Brazilian patients with inflammatory bowel diseases (IBD) requiring therapy with biological agents usually have access to medicines through the National Unified Health Care System (SUS). This study aimed to analyze Brazilian IBD patient perception regarding access (availability and provision quality) to high-cost drugs in the public health care system., Methods: A questionnaire-based survey was carried out in an IBD referral center in Brazil. All adult patients with an established diagnosis of ulcerative colitis (UC) or Crohn's disease (CD) that use biological therapy were invited to participate. Data were collected on the biological in use, lack of distribution (number of absences, average time to regularization, impairment in patient treatment), and difficulties reported by patients in obtaining the drugs., Results: Overall, 205 patients met the inclusion criteria and answered the questionnaire. Most of the patients had CD ( n = 161, 78.5%), nearly half of them ( n = 104, 50.7%) were female; 87 patients (42.4%) were unemployed, and of these, 40 patients (19.5%) had government assistance as the main source of income. Regarding the medications used, infliximab ( n = 128, 62.5%) was the most used medication, followed by adalimumab ( n = 39, 19.0%). Most patients ( n = 172, 83.9%) reported at least one failed delivery of biological medicine in the last year, with a single shortage in forty-two patients (24.4%), at least two shortages in forty-seven patients (27.3%), and three or more shortages in seventy-eight patients (45.3%). The average time to regularize the distribution was up to 1 month in 44 cases (25.6%), up to 2 months in 64 cases (37.2%), and more than 3 months in 56 patients (32.6%). Among patients who reported delays, 101 patients (58.7%) felt that it may have impaired their treatment., Conclusion: Brazilian IBD patients reported high rates of failure to dispense biological drugs by the national healthcare system within one year. Our data highlight the need for improvement in this system for the correct supply of medication to avoid treatment failure and relapse.

COVID-19 is associated with a dysregulated immune response. Currently, several medicines are licensed for the treatment of this disease. Due to their significant role in inhibiting pro-inflammatory cytokines and lipid mediators, glucocorticoids (GCs) have attracted a great deal of attention. Similarly, the endocannabinoid (eCB) system regulates various physiological processes including the immunological response. Additionally, during inflammatory and thrombotic processes, phospholipids from cell membranes are cleaved to produce platelet-activating factor (PAF), another lipid mediator. Nonetheless, the effect of GCs on this lipid pathway during COVID-19 therapy is still unknown. This is a cross-sectional study involving COVID-19 patients ( n = 200) and healthy controls ( n = 35). Target tandem mass spectrometry of plasma lipid mediators demonstrated that COVID-19 severity affected eCBs and PAF synthesis. This increased synthesis of eCB was adversely linked with systemic inflammatory markers IL-6 and sTREM-1 levels and neutrophil counts. The use of GCs altered these lipid pathways by reducing PAF and increasing 2-AG production. Corroborating this, transcriptome analysis of GC-treated patients blood leukocytes showed differential modulation of monoacylglycerol lipase and phospholipase A2 gene expression. Altogether, these findings offer a breakthrough in our understanding of COVID-19 pathophysiology, indicating that GCs may promote additional protective pharmacological effects by influencing the eCB and PAF pathways involved in the disease course.

Lipid and cholinergic mediators are inflammatory regulators, but their role in the immunopathology of COVID-19 is still unclear. Here, we used human blood and tracheal aspirate (TA) to investigate whether acetylcholine (Ach), fatty acids (FAs), and their derived lipid mediators (LMs) are associated with COVID-19 severity. First, we analyzed the perturbation profile induced by SARS-CoV-2 infection in the transcriptional profile of genes related to the ACh and FA/LM pathways. Blood and TA were used for metabolomic and lipidomic analyses and for quantification of leukocytes, cytokines, and ACh. Differential expression and coexpression gene network data revealed a unique transcriptional profile associated with ACh and FA/LM production, release, and cellular signaling. Transcriptomic data were corroborated by laboratory findings: SARS-CoV-2 infection increased plasma and TA levels of arachidonic acid, 5-hydroxy - 6 E, 8 Z, 11 Z, 14 Z -eicosatetraenoic acid, 11-hydroxy-5 Z, 8 Z, 12 E, 14 Z- eicosatetraenoic acid, and ACh. TA samples also exhibited high levels of PGE 2 , thromboxane B 2 , 12-oxo - 5 Z, 8 Z, 10 E, 14 Z- eicosatetraenoic acid, and 6- trans -leukotriene B 4 Bioinformatics and experimental approaches demonstrated robust correlation between transcriptional profile in Ach and FA/LM pathways and parameters of severe COVID-19. As expected, the increased neutrophil-to-lymphocyte ratio, neutrophil counts, and cytokine levels (IL-6, IL-10, IL-1β, and IL-8) correlated with worse clinical scores. Glucocorticoids protected severe and critical patients and correlated with reduced Ach levels in plasma and TA samples. We demonstrated that pulmonary and systemic hyperinflammation in severe COVID-19 are associated with high levels of Ach and FA/LM. Glucocorticoids favored the survival of patients with severe/critical disease, and this effect was associated with a reduction in ACh levels.

Background: The effectiveness of ustekinumab (UST) in the treatment of Crohn's disease (CD) has been demonstrated in the pivotal Phase 3 UNITI 1 and 2 and IM-UNITI studies in both anti-TNF-naïve and anti-TNF-exposed patients. Given the selective nature of pivotal trial designs, real-world effectiveness and safety studies are warranted. We report our experience with UST treatment in a large, real-world multicenter cohort of Brazilian patients with CD., Methods: We performed a retrospective multicenter study including patients with CD, predominantly biologically refractory CD, who received UST. The primary endpoint was the proportion of patients in clinical remission at weeks 8, 24 and 56. Possible predictors of clinical and biological response/remission and safety outcomes were also assessed., Results: Overall, 245 CD (mean age 39.9 [15-87]) patients were enrolled. Most patients (86.5%) had been previously exposed to biologics. According to nonresponder imputation analysis, the proportions of patients in clinical remission at weeks 8, 24 and 56 were 41.0% (n = 98/239), 64.0% (n = 153/239) and 39.3% (n = 94/239), respectively. A biological response was achieved in 55.4% of patients at week 8, and 59.3% were in steroid-free remission at the end of follow-up. No significant differences in either clinical or biological remission were noted between bio-naïve and bio-experienced patients. Forty-eight patients (19.6%) presented 60 adverse events during the follow-up, of which 8 (13.3%) were considered serious adverse events (3.2% of 245 patients). Overall, a proximal disease location, younger age, perianal involvement, and smoking were associated with lower rates of clinical remission over time., Conclusions: UST therapy was effective and safe in the long term in this large real-life cohort of Brazilian patients with refractory CD, regardless of previous exposure to other biological agents., (© 2022. The Author(s).)

Uncontrolled inflammatory responses play a critical role in coronavirus disease (COVID-19). In this context, because the triggering-receptor expressed on myeloid cells-1 (TREM-1) is considered an intrinsic amplifier of inflammatory signals, this study investigated the role of soluble TREM-1 (sTREM-1) as a biomarker of the severity and mortality of COVID-19. Based on their clinical scores, we enrolled COVID-19 positive patients ( n = 237) classified into mild, moderate, severe, and critical groups. Clinical data and patient characteristics were obtained from medical records, and their plasma inflammatory mediator profiles were evaluated with immunoassays. Plasma levels of sTREM-1 were significantly higher among patients with severe disease compared to all other groups. Additionally, levels of sTREM-1 showed a significant positive correlation with other inflammatory parameters, such as IL-6, IL-10, IL-8, and neutrophil counts, and a significant negative correlation was observed with lymphocyte counts. Most interestingly, sTREM-1 was found to be a strong predictive biomarker of the severity of COVID-19 and was related to the worst outcome and death. Systemic levels of sTREM-1 were significantly correlated with the expression of matrix metalloproteinases (MMP)-8, which can release TREM-1 from the surface of peripheral blood cells. Our findings indicated that quantification of sTREM-1 could be used as a predictive tool for disease outcome, thus improving the timing of clinical and pharmacological interventions in patients with COVID-19.

Background: Since HLA-G is an immune checkpoint molecule and since Crohn's disease (CD) and ulcerative colitis (UC) exhibit deregulated immune-mediated mechanisms, we aimed to evaluate intestinal HLA-G expression and soluble HLA-G (sHLA-G) levels in CD/UC patients stratified according to the CD phenotype/localization and UC extension., Methods: HLA-G tissue expression was assessed by immunohistochemistry in biopsies collected from 151 patients (90 CD, 61 UC) and in surgical resection specimens (28 CD, 12 UC). Surgical material from 24 healthy controls was also assessed. Plasma sHLA-G levels (97 CD, 81 UC, and 120 controls) were evaluated using ELISA., Results: HLA-G expression was similarly observed in the intestinal epithelial cells of control and CD/UC specimens. However, in biopsies, the plasma cells/lymphocytes infiltrating the lamina propria in CD/UC presented (1) increased HLA-G expression compared to controls (P < 0.0001), (2) greater cell staining in UC cells than in CD cells irrespective of disease extent (P = 0.0011), and (3) an increased number of infiltrating cells in the inflammatory CD phenotype compared to that in the stenosing and fistulizing phenotypes (P = 0.0407). In surgical specimens, CD/UC patients exhibited higher infiltrating cell HLA-G expression in lesion areas than in margins. sHLA-G levels were higher in UC/CD patients (P < 0.0001) than in controls, but no difference was observed between diseases., Conclusions: Increased infiltrating cell HLA-G expression associated with increased sHLA-G levels in CD/UC patients may reflect ongoing host strategies to suppress chronic inflammation., (© 2020. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Crohn's disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBDs) with a remission-relapsing presentation and symptomatic exacerbations that have detrimental impacts on patient quality of life and are associated with a high cost burden, especially in patients with moderate-to-severe disease. The Real-world Data of Moderate-to-Severe Inflammatory Bowel Disease in Brazil (RISE BR) study was a noninterventional study designed to evaluate disease control, treatment patterns, disease burden and health-related quality of life in patients with moderate-to-severe active IBD. We report findings from the prospective follow-up phase of the RISE BR study in patients with active UC or CD., Aim: To describe the 12-mo disease evolution and treatment patterns among patients with active moderate-to-severe IBD in Brazil., Methods: This was a prospective, noninterventional study of adult patients with active Crohn's disease (CD: Harvey-Bradshaw Index ≥ 8, CD Activity Index ≥ 220), inadequate CD control ( i.e., calprotectin > 200 µg/g or colonoscopy previous results), or active ulcerative colitis (UC: Partial Mayo score ≥ 5). Enrollment occurred in 14 centers from October 2016 to February 2017. The proportion of active IBD patients after 9-12 mo of follow-up, Kaplan-Meier estimates of the time to mild or no activity and a summary of treatment initiation, discontinuation and dose changes were examined., Results: The study included 118 CD and 36 UC patients, with mean ± SD ages of 43.3 ± 12.6 and 44.9 ± 16.5 years, respectively. The most frequent drug classes at index were biologics for CD (62.7%) and 5-aminosalicylate derivates for UC patients (91.7%). During follow-up, 65.3% of CD and 86.1% of UC patients initiated a new treatment at least once. Discontinuations/dose changes occurred in 68.1% of CD patients [median 2.0 (IQR: 2-5)] and 94.3% of UC patients [median 4.0 (IQR: 3-7)]. On average, CD and UC patients had 4.4 ± 2.6 and 5.0 ± 3.3 outpatient visits, respectively. The median time to first mild or no activity was 319 (IQR: 239-358) d for CD and 320 (IQR: 288-358) d for UC patients. At 9-12 mo, 22.0% of CD and 20.0% of UC patients had active disease., Conclusion: Although a marked proportion of active IBD patients achieved disease control within one year, the considerable time to achieve this outcome represents an unmet medical need of the current standard of care in a Brazilian real-world setting., Competing Interests: Conflict-of-interest statement: Ligia Yukie Sassaki has received fees for serving as a speaker for AbbVie and Takeda. Sender Jankiel Miszputen has received fees for serving as a speaker and/or a consultant for Farmoquimica, Janssen and Marjan. He has received research funding from Ache, Roche and Takeda. Wilson Roberto Catapani has received fees for serving as a speaker and/or an advisory board member for Janssen and Takeda. Mauro Bafutto has received fees for serving as a speaker for Takeda, AbbVie, Janssen, UCB and Farmoquimica. He has received fees for serving as an advisory board member for AbbVie and Janssen. Antonio Scafuto Scotton has received fees for serving as a speaker for Janssen, Novartis, AbbVie, MSD, EMS. He has received research funding from Janssen, Novartis, AbbVie, Roche, Pfizer, Bristol, Lilly, Novo Nordisk, Anthera, AstraZeneca, GSK, UCB, Sanofi, Takeda, Parexel, IQVIA, PPD, PRA, ICON, INP Research, Covance, In Trials. Cyrla Zaltman has received fees for serving as a speaker for UCB, Janssen, Takeda, AbbVie. She has received research funding from AbbVie, Takeda, Janssen. Julio Pinheiro Baima has received fees for serving as a speaker for Janssen and Takeda. Cristina Flores has received fees for serving as a speaker for Janssen, Takeda, AbbVie. She has received fees for serving as an advisory board member for Janssen. Rodrigo Bremer Nones has received fees for serving as a speaker for AbbVie, Ferring Pharmaceuticals, Janssen, Nestle, Novartis, Pfizer, UCB Pharma and Takeda. Jose Miguel Luz Parente has received fees for serving as a speaker for Takeda. Julio Maria Fonseca Chebli has received fees for serving as a speaker for AbbVie, Janssen, UCB Pharma and Takeda. Maria de Lourdes de Abreu Ferrari has received fees for serving as a speaker and/or advisory board member for AbbVie, Ferring Pharmaceuticals, Janssen, UCB Pharma, and Takeda. Rogerio Serafim Parra has received fees for serving as a speaker and/or an advisory board member for AbbVie, Ferring Pharmaceuticals, Janssen, UCB Pharma and Takeda. Jose Joaquim Ribeiro da Rocha has received fees for serving as a speaker for Nestle. Marley Ribeiro Feitosa has received fees for serving as a speaker for AbbVie and Janssen. Rosana Fusaro Caratin was an employee of Takeda Pharmaceuticals Brazil at the time the manuscript was developed. Juliana Tosta Senra is an employee of Takeda Pharmaceuticals Brazil. Genoile Oliveira Santana has received fees for serving as a speaker for Takeda, AbbVie, Janssen, UCB Pharma. She has received research funding from Celgene and Roche. She has received fees for serving as an advisory board member for Janssen. No conflict of interest: Roberto Luiz Kaiser Junior, Mikaell Alexandre Gouvea Faria, Carolina Dias Goncalves, Isabella de Miranda Guimaraes, Heda Maria Barska dos Santos Amarante, Murilo Moura Lima, Odery Ramos, Omar Feres, Hagata Souza Ramos, Julia Faria Campos, and Maria das Gracas Pimenta Sanna., (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background and Purpose: Despite the advances achieved in surgical techniques in recent years, an intestinal stoma is still needed in many patients undergoing colorectal surgery. However, the intestinal stoma may be associated with serious complications and the need for a second surgical procedure. In extreme cases, when it is not possible to access the abdominal cavity, the management of a complicated stoma is challenging. The purpose of this study was to describe the use of a Dacron vascular prosthesis (DVP) in patients with intestinal stoma complications., Methods: In patients with a shallow, superficial stoma or mucocutaneous separation (MCS), we sutured the prosthesis in the intestinal loop (at the edge of an intestinal fistula) to create a device to direct the fecal content to the collection bag., Results: We included 9 patients in this series (colorectal cancer, n = 5; Crohn's disease, n = 2; giant abdominal hernia and morbid obesity, n = 2). The results obtained were promising since they showed good evolution in patients with severe intestinal complications and an impossibility of surgical correction of the stoma. Five patients presented complete healing, and two patients presented partial healing. There were two deaths caused by sepsis, which were not related to the surgical procedure. With this technique, there was a reduction in the leakage of intestinal contents into the peritoneal cavity and an increase in the healing of the peristomal dermatitis in most of the patients. The DVP could possibly represent a surgical alternative in selected patients with complicated stomas when surgical correction may not be a suitable option., Conclusions: The authors recommend this technique for selected complex cases of stoma complications after unsuccessful attempts to adapt collecting equipment. The placement of the DVP allowed the peristomal skin to heal and improved the contamination of the peritoneal cavity.

Background: Colorectal cancer (CRC) is one of the most common cancers worldwide; it is the fourth leading cause of death in the world and the third in Brazil. Mutations in the APC, DCC, KRAS and TP53 genes have been associated with the progression of sporadic CRC, occurring at defined pathological stages of the tumor progression and consequently modulating several genes in the corresponding signaling pathways. Therefore, the identification of gene signatures that occur at each stage during the CRC progression is critical and can present an impact on the diagnosis and prognosis of the patient. In this study, our main goal was to determine these signatures, by evaluating the gene expression of paired colorectal adenoma and adenocarcinoma samples to identify novel genetic markers in association to the adenoma-adenocarcinoma stage transition., Methods: Ten paired adenoma and adenocarcinoma colorectal samples were subjected to microarray gene expression analysis. In addition, mutations in APC, KRAS and TP53 genes were investigated by DNA sequencing in paired samples of adenoma, adenocarcinoma, normal tissue, and peripheral blood from ten patients., Results: Gene expression analysis revealed a signature of 689 differentially expressed genes (DEG) (fold-change> 2, p< 0.05), between the adenoma and adenocarcinoma paired samples analyzed. Gene pathway analysis using the 689 DEG identified important cancer pathways such as remodeling of the extracellular matrix and epithelial-mesenchymal transition. Among these DEG, the ETV4 stood out as one of the most expressed in the adenocarcinoma samples, further confirmed in the adenocarcinoma set of samples from the TCGA database. Subsequent in vitro siRNA assays against ETV4 resulted in the decrease of cell proliferation, colony formation and cell migration in the HT29 and SW480 colorectal cell lines. DNA sequencing analysis revealed KRAS and TP53 gene pathogenic mutations, exclusively in the adenocarcinomas samples., Conclusion: Our study identified a set of genes with high potential to be used as biomarkers in CRC, with a special emphasis on the ETV4 gene, which demonstrated involvement in proliferation and migration.

Background: Understanding the treatment landscape of inflammatory bowel diseases (IBD) is essential for improving disease management and patient outcomes. Brazil is the largest Latin American country, and it presents socioeconomic and health care differences across its geographical regions. This country has the highest increase in IBD incidence and prevalence in Latin America, but information about the clinical and treatment characteristics of IBD is scarce., Aim: To describe the sociodemographic, clinical, and treatment characteristics of IBD outpatients in Brazil overall and in the Southeast, South and Northeast/Midwest regions., Methods: Multicenter, cross-sectional study with a 3-year retrospective chart review component. Patients with moderate-to-severe Crohn's disease (CD) or ulcerative colitis (UC) were consecutively enrolled between October 2016 and February 2017. Active CD at enrollment was defined as a Harvey Bradshaw Index ≥ 8 or a CD Activity Index ≥ 220 or a calprotectin level > 200 μg/g or an active result based on colonoscopy suggestive of inadequate control during the previous year; active UC was defined as a partial Mayo score ≥ 5. Descriptive statistics were used to analyze all variables., Results: In a total of 407 included patients, CD was more frequent than UC, both overall (264 CD/143 UC patients) and by region (CD:UC ratios of 2.1 in the Southeast, 1.6 in the South and 1.2 in the Northeast/Midwest). The majority of patients were female (54.2% of CD; 56.6% of UC), and the mean ages were 45.9 ± 13.8 years (CD) and 42.9 ± 13.0 years (UC). The median disease duration was 10.0 (range: 0.5-45) years for both IBD types. At enrollment, 44.7% [95% confidence interval (CI): 38.7-50.7] of CD patients and 25.2% (95%CI: 18.1-32.3) of UC patients presented with active disease. More than 95% of IBD patients were receiving treatment at enrollment; CD patients were commonly treated with biologics (71.6%) and immunosuppressors (67.4%), and UC patients were commonly treated with mesalazine [5-Aminosalicylic acid (5-ASA)] derivates (69.9%) and immunosuppressors (44.1%). More than 50% of the CD patients had ileocolonic disease, and 41.7% presented with stricturing disease. One-quarter of CD patients had undergone CD-related surgery in the past 3 years, and this proportion was lower in the Northeast/Midwest region (2.9%)., Conclusion: In Brazil, there are regional variations in IBD management. CD outweighs UC in both frequency and disease activity. However, one-quarter of UC patients have active disease, and most are receiving 5-ASA treatment., Competing Interests: Conflict-of-interest statement: Cyrla Zaltman has received speaker fees from AbbVie, Janssen, Pfizer, UCB Pharma and Takeda, and received research funding from AbbVie, Takeda, and Janssen; Rogerio Serafim Parra has received fees for serving as speaker or as an advisory board member for AbbVie, Ferring Pharmaceuticals, Janssen, UCB Pharma and Takeda; Ligia Yukie Sassaki has received speaker fees from AbbVie and Takeda; Genoile Oliveira Santana has received speaker fees from AbbVie, Janssen, Takeda and UCB Pharma; and received research funding from Celgene, Roche and Takeda; Maria de Lourdes Abreu Ferrari has received fees for serving as a speaker or as an advisory board member for AbbVie, Ferring Pharmaceuticals, Janssen, UCB Pharma, and Takeda; Sender Jankiel Miszputen has received fees for serving as speaker or as a consultant for Farmoquimica, Janssen and Marjan, and received research funding from Ache, Roche and Takeda; Cristina Flores has received speaker fees from Janssen, Takeda, and AbbVie; and received fees for serving as an advisory board member for Janssen; Wilson Roberto Catapani has received fees for serving as a speaker or as an advisory board member for Janssen and Takeda; Jose Miguel Luz Parente has received speaker fees from Takeda; Mauro Bafutto has received speaker fees from Takeda, AbbVie, Janssen, UCB and Farmoquimica; and received fees for serving as an advisory board member for AbbVie and Janssen; Jose Joaquim Ribeiro da Rocha has received speaker fees from Nestle; Marley Ribeiro Feitosa has received speaker fees from Janssen and Nestle, and fees for scientific congresses’ support by Janssen, AbbVie, Takeda, Ferring and Nestle and was a subinvestigator in scientific studies sponsored by Janssen, AbbVie and Takeda; Rogerio Saad Hossne has received speaker fees from AbbVie, Janssen, Pfizer and Takeda; Francisco Guilherme Cancela e Penna has received speaker fees from Janssen, Takeda, AbbVie and UCB; Tarcia Nogueira Ferreira Gomes has received research funding from Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior and Takeda; and has received speaker fees from Janssen; Rodrigo Bremer Nones has received speaker fees from AbbVie, Ferring Pharmaceuticals, Janssen, Nestle, Novartis, Pfizer, UCB Pharma and Takeda; Antonio Scafuto Scotton has received speaker fees from Janssen, Novartis, AbbVie, MSD, and EMS, and has received research funding from Janssen, Novartis, AbbVie, Roche, Pfizer, Bristol, Lilly, Novo Nordisk, Anthera, AstraZeneca, GSK, UCB, Sanofi, Takeda, Parexel, IQVIA, PPD, PRA, ICON, INP Research, Covance, and In Trials; Rosana Fusaro Caratin was an employee at Takeda Pharmaceuticals Brazil at the time of the study and when this manuscript was written; Juliana Tosta Senra is an employee at Takeda Pharmaceuticals Brazil; Julio Maria Fonseca Chebli has received speaker fees from AbbVie, Janssen, UCB Pharma and Takeda; Heda Maria Barska dos Santos Amarante, Roberto Kaiser Junior, Odery Ramos, Carolina Dias Gonçalves, Isabella de Miranda Guimaraes, Omar Feres, Mikaell Alexandre Gouvea Faria, Pedro Ferrari Sales da Cunha, Mírian Perpétua Palha Dias Parente declare that they have no conflict of interest, (©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.)

Background: COVID-19 has affected the entire world. We aimed to determine the impact of COVID-19 containment measures on the daily life and follow up of patients with inflammatory bowel disease (IBD)., Methods: During May 2020, we evaluated 179 (79.6%) patients with Crohn's disease (CD) and 46 (20.4%) with ulcerative colitis (UC) by telephone, using a structured questionnaire to gather information on social impact and IBD follow up., Results: Some kind of social distancing measure was reported by 95.6% of our patients, self-quarantine (64.9%) being the most frequent. Depressive mood was the most prevalent social impact (80.2%), followed by anxiety/fear of death (58.2%), insomnia (51.4%), daily activity impairment (48%), sexual dysfunction (46.2%), and productivity impairment (44%). The results were similar when we compared patients with active disease to those in remission and patients with UC to those with CD. Analysis of IBD follow up showed that 83.1% of all patients missed an IBD medical appointment, 45.5% of the patients missed laboratory tests, 41.3% missed the national flu vaccination program, 31.3% missed any radiologic exam, 17.3% missed colonoscopy, and 16.9% failed to obtain biologic therapy prescriptions. Biologics were discontinued by 28.4% of the patients. UC patients had higher rates of missed vaccination than CD patients (56.5% vs. 37.4%, P=0.02) and more failures to obtain a biologic prescription (28.3% vs. 14.0%, P=0.02)., Conclusions: Our study reveals alarming social impacts and declining follow-up care for IBD patients during the COVID-19 outbreak. These findings may have implications for disease control in the near future., Competing Interests: Conflict of Interest: None, (Copyright: © 2021 Hellenic Society of Gastroenterology.)

Introduction: Endometriosis of the appendix is very uncommon, accounting for only about 1% of all cases of endometriosis. However, endometriosis is found in the appendix in approximately 8-13% of patients with deep infiltrating endometriosis and is particularly common in patients with severe forms of deep infiltrating endometriosis. Neuroendocrine tumors are the most common neoplasms of the appendix and may be misdiagnosed when there are multiple endometriosis lesions in the pelvis., Case Presentation: We describe a case of a Caucasian patient with deep infiltrating endometriosis with rectal involvement, retrocervical lesions, and a right ovarian endometrioma with no suspected lesions in the appendix. She underwent laparoscopy and, after a systematic intraoperative evaluation, suspected involvement of the appendix was observed. The patient underwent ovarian cystectomy, excision of the pelvic endometriosis lesions, appendectomy, and anterior stapler discoid resection. Histopathological analysis of the appendix revealed endometriosis and a well-differentiated neuroendocrine carcinoma at the appendix tip., Discussion: Our patient's case emphasizes the need to approach these lesions carefully and strengthens the indication for appendectomy when the appendix is affected in the setting of endometriosis. Despite the more likely diagnosis of appendiceal endometriosis, neuroendocrine tumors cannot be ruled out by imaging examinations, and both conditions can occur in the same patient.

Background and purpose: The discovery of chemical substances with carcinogenic properties has allowed the development of several experimental models of colorectal cancer (CRC). Classically, experimental models of CRC in mice have been evaluated through clinical or serial euthanasia. The present study aims to investigate the role of low endoscopy in the analysis of carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG). Methods: Thirty C57BL6 mice were divided into two groups: a control group with fifteen animals that underwent rectal instillation of saline solution on day 0 and a carcinogen group with fifteen animals that underwent a 100 mg/kg MNNG rectal instillation on day 0. In both groups, low endoscopies were performed on weeks 4 and 8. We used a validated endoscopic scoring system to evaluate the severity of colitis and colorectal tumor. Euthanasia was carried out at week 12. Results: We observed higher inflammation scores (p <0.001) and a higher number of tumors (p <0.05) in the MNNG group than the control group, both at weeks 4 and 8. A worsening of inflammation scores from the first to the second endoscopy was also noticeable in the MNNG group. There were no bowel perforations related to the procedure, and there was one death in the control group. Conclusion: Low endoscopy in experimental animals allows safe macroscopic evaluation of colorectal carcinogenesis without the need for euthanasia., Competing Interests: COMPETING INTERESTS: The authors have declared that no competing interest exists., (© The author(s).)

Background: KRAS gene mutations play an important role in the carcinogenesis of colorectal tumors. However, studies that have assessed the association between KRAS gene mutation status and disease characteristics report conflicting results. To assess KRAS gene status (mutated or wild-type) and its association with the clinical, epidemiological, and histopathological features of metastatic colorectal adenocarcinoma as well its association with clinical outcomes., Methods: Cross-sectional descriptive study in which clinical and histopathological data were collected from the medical records of 65 patients diagnosed with metastatic colorectal adenocarcinoma at the Clinical Oncology Service of the Teaching Hospital of the School of Medicine of Ribeirao Preto, University of Sao Paulo (Hospital das Clinicas da Faculdade de Medicina de Ribeirao Preto, Universidade de Sao Paulo -HCFMRP-USP) between 2005 and 2012 and analyzed based on their KRAS gene status., Results: KRAS gene mutations were found in 49.2% of the tumors, and G/A (25.5%) and Gly12Asp (34.37%) were the most frequent mutations. Among the investigated clinical features (gender, ECOG (Eastern Cooperative Oncology Group), histology, degree of cell differentiation, lymph node ratio, primary tumor site, staging, presence of synchronous metastasis, lung metastasis, and liver metastasis), the association between age less than 65 years with KRAS mutation was statistically significant (P = 0.046). KRAS mutation status did not exhibit a significant correlation with the overall survival of the patients (P = 0.078); however, the cases with KRAS mutation exhibited shorter survival. In the multivariate analysis, synchronous metastasis (P = 0.03) and liver metastasis (P = 0.008) behaved as independent factors of poor prognosis relative to the overall survival of the patients., Conclusion: The KRAS mutation status did not exhibit prognostic value in the investigated sample. Among the older patients (> 65 years old), wild-type KRAS was more frequently observed compared to mutated KRAS., Competing Interests: None.