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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).)

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.

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.