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Background and Aims: Recent evidence suggests that the mesenteric adipose tissue (MAT) near the affected intestine may play a role in Crohn's disease (CD) pathophysiology. Modulation of several transcripts has already been identified in the MAT of CD in the literature. Therefore, our aim was to validate the microRNA (miRNA) transcript levels and their target genes in the MAT of active CD patients and correlate them with clinical and epidemiological data. Methods: Samples from the MAT of surgical specimens from 25 active CD patients were obtained. The control group comprised fifteen patients who underwent surgery for other diseases, except inflammatory bowel diseases. Transcriptional levels of miRNA and their target genes were assessed by quantitative real-time polymerase chain reaction. The correlation between transcripts and clinical characteristics was obtained using multiple linear regression. The mathematical models (M) underwent a statistical filter to ensure robustness and reliability (P value < .05; adjusted R-squared (Rˆ2)> .99; correct predictions of more than 60%). Results: miRNA-650 and miRNA-29c were upregulated in the MAT of CD compared to the control group (P < .0001 and P = .0032, respectively), besides presenting decreased levels of their target genes. Two were target genes of the miRNA-650: glutamine-fructose-6-phosphate transaminase 2 (P = .012) and aldehyde dehydrogenase 4 family (P = .0035); and 4 were targets of the miRNA-29c: cell death-inducing DFFA-like effector c (P = .001), E2F transcription factor-1 (P = .007), hypoxia-inducible factor 3 subunit alpha (P = .0029), and pyruvate dehydrogenase kinase 4 (P = .0054). We found 2 M with statistical strength and robustness. The performance test identified one model with 100% accuracy for predicting the month of recurrence and determining patients with less risk of early relapse after surgery. Conclusion: We demonstrate that miRNA-650 and miRNA-29c and some of their target genes, besides clinical and epidemiological variables, may be useful in a model to predict when disease relapse may occur in CD patients who underwent surgery. These findings constitute a potential tool to guide postoperative clinical management.

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BACKGROUND: To evaluate the relationship between the ratio of affected lymph nodes (LNR) and clinical and anatomopathological variables in patients with rectal adenocarcinoma submitted or not to neoadjuvant chemoradiotherapy. METHODS: The LNR was determined by dividing the number of compromised LNR by the total number of LNR dissected in the surgical specimen. Patients were divided into two groups: with QRT and without QRT. In each group, the relationship between LNR and the following variables was evaluated: degree of cell differentiation, depth of invasion in the rectal wall, angiolymphatic /perineural invasion, degree of tumor regression and occurrence of metastases. The LNR was evaluated in patients with more than 1, LNR (LNR >12) or less (LNR<12) in the surgical specimen with overall survival (OS) and disease-free survival (DFS). The results were expressed as the mean with the respective standard deviation. Qualitative variables were analyzed using Fisher's exact test, while quantitative variables were analyzed using the Kruskal -Wallis and Mann-Whitney tests. The significance level was 5%. RESULTS: We evaluated 282 patients with QRT and 114 without QRT, between 1995-2011. In the QRT Group, LNR showed a significant association with mucinous tumors (P=0.007) and degree of tumor regression (P=0.003). In both groups, LNR was associated with poorly differentiated tumors (P=0.001, P=0.02), presence of angiolymphatic invasion (P<0.0001 and P=0.01), perineural (P=0.0007, P=0.02), degree of rectal wall invasion (T3>T2; P<0.0001, P=0.02); Compromised LNR (P<0.0001, P<0.01), metastases (P<0.0001, P<0.01). In patients with QRT, LNR<12 was associated with DFS (5.889; 95%CI1.935-19.687; P=0.018) and LNR>12 with DFS and OS (17.984; 95%CI5.931-54.351; P<0.001 and 10.286; 95%CI 2.654-39.854; P=0.007, respectively). CONCLUSION: LNR was associated with histological aspects of poor prognosis, regardless of the use of QRT. In the occurrence of less than 12 evaluated LNR, the LNR was associated only with the DFS. BACKGROUND: • Assessment of the lymph nodes during pathological analysis of the surgical specimen is crucial to determine treatment and prognosis. BACKGROUND: • Neoadjuvance therapy reduces the number of lymph nodes, being lower than recommended, therefore the lymph node ratio can be an alternative analysis for a better prognosis.

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ABSTRACT Background: To evaluate the relationship between the ratio of affected lymph nodes (LNR) and clinical and anatomopathological variables in patients with rectal adenocarcinoma submitted or not to neoadjuvant chemoradiotherapy. Methods: The LNR was determined by dividing the number of compromised LNR by the total number of LNR dissected in the surgical specimen. Patients were divided into two groups: with QRT and without QRT. In each group, the relationship between LNR and the following variables was evaluated: degree of cell differentiation, depth of invasion in the rectal wall, angiolymphatic /perineural invasion, degree of tumor regression and occurrence of metastases. The LNR was evaluated in patients with more than 1, LNR (LNR >12) or less (LNR<12) in the surgical specimen with overall survival (OS) and disease-free survival (DFS). The results were expressed as the mean with the respective standard deviation. Qualitative variables were analyzed using Fisher's exact test, while quantitative variables were analyzed using the Kruskal -Wallis and Mann-Whitney tests. The significance level was 5%. Results: We evaluated 282 patients with QRT and 114 without QRT, between 1995-2011. In the QRT Group, LNR showed a significant association with mucinous tumors (P=0.007) and degree of tumor regression (P=0.003). In both groups, LNR was associated with poorly differentiated tumors (P=0.001, P=0.02), presence of angiolymphatic invasion (P<0.0001 and P=0.01), perineural (P=0.0007, P=0.02), degree of rectal wall invasion (T3>T2; P<0.0001, P=0.02); Compromised LNR (P<0.0001, P<0.01), metastases (P<0.0001, P<0.01). In patients with QRT, LNR<12 was associated with DFS (5.889; 95%CI1.935-19.687; P=0.018) and LNR>12 with DFS and OS (17.984; 95%CI5.931-54.351; P<0.001 and 10.286; 95%CI 2.654-39.854; P=0.007, respectively). Conclusion: LNR was associated with histological aspects of poor prognosis, regardless of the use of QRT. In the occurrence of less than 12 evaluated LNR, the LNR was associated only with the DFS.

RESUMO Contexto: Avaliar a relação entre a razão de linfonodos (RLA) acometidos e variáveis clínicas e anatomopatológicas em portadores de adenocarcinoma de reto submetidos ou não à quimiorradioterapia neoadjuvante. Métodos: A RLA foi determinada dividindo-se o número total de linfonodos (LFNs) dissecados no espécime cirúrgico pelo número de comprometidos. Os doentes foram divididos em dois grupos: com QRT e sem QRT. Em cada grupo foi avaliada a relação entre a RLA e as seguintes variáveis: grau de diferenciação celular, profundidade de invasão na parede retal, invasão angiolinfática/perineural, grau de regressão tumoral e ocorrência de metástases. Avaliou-se a RLA em pacientes com mais do que 12 LFNs (RLA>12) ou menos (RLA<12) na peça cirúrgica com a sobrevida global (SG) e sobrevida livre de doença (SLD). Os resultados foram expressos pela média com o respectivo desvio padrão. As variáveis qualitativas foram analisadas utilizando-se o teste exato de Fisher, enquanto as quantitativas pelos testes de Kruskal-Wallis e Mann-Whitney. O nível de significância foi de 5%. Resultados: Foram avaliados 282 pacientes com QRT e 114 sem QRT, entre 1995-2011. No Grupo QRT, RLA mostrou associação significativa com os tumores mucinosos (P=0,007) e grau de regressão tumoral (P=0,003). Nos dois grupos, a RLA associou-se com tumores pouco diferenciados (P=0,001 e P=0,02), presença de invasão angiolinfática (P<0,0001 e P=0,01), perineural (P=0,0007 e P=0,02), grau de invasão da parede retal (T3>T2; P<0,0001 e P=0,02); LFNs comprometidos (P<0,0001 e P<0,01), metástases (P<0,0001 e P<0,01). Nos pacientes com QRT, a RLA <12 associou-se com a SLD (5,889; IC95%1,935-19,687; P=0,018) e a RLA >12 com SLD e SG (17,984; IC95%5,931-54,351; P<0,001 e 10,286; IC95%2,654-39,854; P=0,007, respectivamente). Conclusão: A RLA associou-se a aspectos histológicos de mau prognóstico, independentemente do emprego de QRT. Na ocorrência de menos de 12 LFNs avaliados, a RLA associou-se apenas com a SLD.

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BACKGROUND: Although the gastrointestinal tract is the most affected by Crohn's disease (CD), the condition triggers other consequent manifestations, and iron deficiency anemia (IDA) is one of the most common. Intravenous (IV) iron replacement is currently available through several drugs, such as ferric hydroxide sucrose and ferric carboxymaltose (FCM). However, the clinical management of these conditions can be challenging. AIM: To elucidate the drug's effectiveness, the present study analyzed, through medical records, the clinical and epidemiological data of a cohort of patients with active CD who received IV FCM for the IDA treatment. METHODS: This retrospective observational study included 25 patients with active CD, severe anemia, and refractory to previous conventional treatments. Patients were evaluated two times: During the last treatment with ferric hydroxide sucrose and treatment with FCM. RESULTS: After treatment with FCM, parameters of IDA assessment significantly improved, serum hemoglobin (Hb) levels increased in 93% of patients (P < 0.0001), and in 44%, there was an increase of ≥ 2 g/dL in a single application. In addition, 86% of the patients showed an increase in serum iron (P < 0.0001) and ferritin (P = 0.0008) and 50% in transferrin saturation (P = 0.01). The serum iron levels at baseline showed a negative association with the ileal and colonic CD and use of biologics and a positive association with patients who developed CD later in life after the age of 40 (A3) and with a stenosing (B2) and fistulizing (B3) phenotype. The values of Hb and hematocrit after ferric hydroxide sucrose treatment remained similar to those found before treatment. CONCLUSION: This study demonstrated that FCM is an important therapeutic strategy for treating IDA in CD patients, achieving satisfactory results in refractory cases.

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BACKGROUND: Capnography and carbon dioxide (CO2) insufflation during gastrointestinal endoscopy under sedation are associated with safety and comfort improvements, respectively. Capnography can provide early detection of apnea and hypoxemia, whereas CO2 insufflation causes lower periprocedural discomfort. This is the first study to report the application of volumetric capnography in colonoscopy. OBJECTIVE: This study aimed to evaluate the use of volumetric capnography with room air (RA) and CO2 insufflation during routine colonoscopy. METHODS: In this prospective cohort study, 101 patients who underwent routine colonoscopy under sedation with volumetric capnography monitoring were included. Insufflation with RA was used to distend the intestinal lumen in group 1 (n=51), while group 2 (n=50) used CO2 insufflation. The primary endpoints were episodes of hypoxia, alveolar hypoventilation, and end-tidal CO2 (EtCO2). The secondary endpoints were tidal volume per minute, consumption of sedation medications, and post-procedure pain using the Gloucester modified pain scale. RESULTS: The number of episodes of hypoxia (SpO2<90%) was similar between the groups: four episodes in Group 1 and two episodes in Group 2. The duration of hypoxia was significantly longer in group 2 (P=0.02). Hypoalveolar ventilation (EtCO2) occurred more frequently in Group 2 than in Group 1 (27 vs 18 episodes, P=0.05). Regarding EtCO2, Group 2 showed higher values in cecal evaluation (28.94±4.68 mmHg vs 26.65±6.12 mmHg, P=0.04). Regarding tidal volume per minute, Group 2 had significantly lower values at the cecal interval compared to Group 1 (2027.53±2818.89 vs 970.88±1840.25 L/min, P=0.009). No episodes of hypercapnia (EtCO2 > 60 mmHg) occurred during the study. There was no difference in the consumption of sedation medications between the groups. Immediately after colonoscopy, Group 2 reported significantly less pain than Group 1 (P=0.05). CONCLUSION: In our study, volumetric capnography during colonoscopy was feasible and effective for monitoring ventilatory parameters and detecting respiratory complications. CO2 insufflation was safe and associated with less pain immediately after colonoscopy.

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ABSTRACT Background: Capnography and carbon dioxide (CO2) insufflation during gastrointestinal endoscopy under sedation are associated with safety and comfort improvements, respectively. Capnography can provide early detection of apnea and hypoxemia, whereas CO2 insufflation causes lower periprocedural discomfort. This is the first study to report the application of volumetric capnography in colonoscopy. Objective: This study aimed to evaluate the use of volumetric capnography with room air (RA) and CO2 insufflation during routine colonoscopy. Methods: In this prospective cohort study, 101 patients who underwent routine colonoscopy under sedation with volumetric capnography monitoring were included. Insufflation with RA was used to distend the intestinal lumen in group 1 (n=51), while group 2 (n=50) used CO2 insufflation. The primary endpoints were episodes of hypoxia, alveolar hypoventilation, and end-tidal CO2 (EtCO2). The secondary endpoints were tidal volume per minute, consumption of sedation medications, and post-procedure pain using the Gloucester modified pain scale. Results: The number of episodes of hypoxia (SpO2<90%) was similar between the groups: four episodes in Group 1 and two episodes in Group 2. The duration of hypoxia was significantly longer in group 2 (P=0.02). Hypoalveolar ventilation (EtCO2) occurred more frequently in Group 2 than in Group 1 (27 vs 18 episodes, P=0.05). Regarding EtCO2, Group 2 showed higher values in cecal evaluation (28.94±4.68 mmHg vs 26.65±6.12 mmHg, P=0.04). Regarding tidal volume per minute, Group 2 had significantly lower values at the cecal interval compared to Group 1 (2027.53±2818.89 vs 970.88±1840.25 L/min, P=0.009). No episodes of hypercapnia (EtCO2 > 60 mmHg) occurred during the study. There was no difference in the consumption of sedation medications between the groups. Immediately after colonoscopy, Group 2 reported significantly less pain than Group 1 (P=0.05). Conclusion: In our study, volumetric capnography during colonoscopy was feasible and effective for monitoring ventilatory parameters and detecting respiratory complications. CO2 insufflation was safe and associated with less pain immediately after colonoscopy.

RESUMO Contexto: A capnografia e a insuflação de gás carbônico (CO2) durante endoscopia digestiva sob sedação são associados à maior segurança e conforto do paciente, respectivamente. A capnografia pode detectar precocemente a apneia e hipoxemia, enquanto a insuflação de CO2 causa menor desconforto periprocedimento. Relatos da aplicação da capnografia volumétrica em colonoscopias são escassos. Objetivo: Avaliar o uso de capnograifa volumétrica durante colonoscopia diagnóstica com insuflação de ar comprimido e CO2. Métodos: Em estudo prospectivo de coorte, foram incluídos um total de 101 pacientes submetidos a colonoscopia diagnóstica sob sedação com monitoração respiratória por meio de capnografia volumétrica. Insuflação com ar comprimido foi usado para distender o lúmen intestinal no Grupo 1 (n=51), enquanto o Grupo 2 (n=50) utilizou CO2 para insuflação. Objetivos primários foram avaliar episódios de hipóxia, hipoventilação alveolar e CO2 expirado (EtCO2). Objetivos secundários foram avaliar o volume alveolar por minuto, consumo de sedativos e a dor pós-colonoscopia por meio da Escala de Dor Modificada de Gloucester. Resultados: O número de episódios de hipóxia (SpO2 <90%) foi semelhante entre os grupos: quatro episódios no Grupo 1 e dois episódios no Grupo 2. A duração da hipóxia foi significativamente maior no Grupo 2 (P=0,02). A hipoventilação alveolar (EtCO2 ≥25% do valor basal) ocorreu mais frequentemente no Grupo 2 quando comparado ao Grupo 1 (27 vs 18 episódios, P=0,05). Em relação ao EtCO2, o Grupo 2 apresentou valores maiores no momento de aferição cecal (28.94±4.68 vs 26.65±6.12 mmHg, P=0,04). Quanto ao volume alveolar por minuto, o Grupo 2 apresentou valores significativamente menores no momento de aferição cecal quando comparado ao Grupo 1 (2027.53±2818.89 vs 970.88±1840.25 L/min, P=0,009). Não houve ocorrência de hipercapnia durante o estudo (EtCO2 >60 mmHg). Não houve diferença em relação ao consumo de sedativos entre os dois grupos. Imediatamente após a colonoscopia, o Grupo 2 apresentou significativamente menos dor que o Grupo 1 (P=0,05). Conclusão: Em nosso estudo, a capnografia volumétrica durante colonoscopia foi factível e eficaz para monitorar parâmetros ventilatórios e detectar complicações respiratórias, e a insuflação com CO2 foi segura e associada a menor dor imediatamente pós-colonoscopia.

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Ulcerative colitis (UC) is a chronic intestinal inflammatory disease and familial adenomatous polyposis (FAP) is an autosomal dominant inherited disease. Both diseases, despite being different, may require the same surgical procedure: proctocolectomy with ileal pouch-anal anastomosis (IPAA). The main complication after this procedure is pouch inflammation (pouchitis). This inflammatory complication can affect up to 60 percent of patients who receive IPAA for UC, and a very small percentage of the FAP patients. The purpose of this review was to determine the current molecular mechanisms in its pathogenesis and detail the risk factors involved in pouchitis, its diagnosis, and treatment.

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INTRODUCTION AND IMPORTANCE: Crohn's disease (CD) is a chronic bowel disease that, due to exacerbated inflammation, can lead to complications such as the development of perianal fistulas. The development of mucinous adenocarcinoma in perianal fistulas in patients with CD is rare and, consequently, few reports exist in the literature. CASE PRESENTATION: We report the case of a 71-year-old man diagnosed 22 years ago with CD with perineal involvement, who came with complaints of intense perianal pain, a gluteal mass, and local bleeding. Tomography of his abdomen showed an expansive, heterogeneous, and solid perianal mass on the right, with interspersed necrotic/liquefied areas and possible mucinous content. The patient was referred to the surgery department for an incisional biopsy, which confirmed mucinous adenocarcinoma. The patient underwent extra levator abdominoperineal rectal resection (APR) with partial prostatectomy. CLINICAL DISCUSSION: Perineal mucinous adenocarcinoma arising in a fistula associated with CD is very rare. Since the symptoms overlap, early diagnosis of malignancy is difficult. Histological analysis is the gold standard for its diagnosis. Surgical resection through APR is well-established and, despite being a complex procedure with potential complications, tends to have good results. However, the locoregional and inguinal lymph node involvement was related to a worse progression in this case. CONCLUSION: The diagnostic hypothesis of mucinous adenocarcinoma should be suspected in CD patients who present long-term perineal involvement with fistulas. Biopsies and imaging exams should be performed to aid the diagnosis of the condition and thus contribute to the surgical plan.

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Ulcerative colitis (UC) is characterized by a chronic overproduction of proinflammatory cytokines. During an acute phase, the endoplasmic reticulum (ER) is overloaded and the protein folding process is impaired, a condition named ER stress. This state induces a response (unfolded protein response (UPR)), initiated by the activation of IRE1/Xbp-1, PERK/eIF2α, and ATF6 pathways, which has previously been linked to intestinal inflammation in experimental models. ER stress and UPR activation trigger the activation of proinflammatory, autophagy, and apoptosis genes, in addition to promoting protein degradation. Therefore, the goal of this study was to evaluate the activation of ER stress and UPR in colonic mucosa of UC patients. Patient and Methods. Transcriptional analysis of ER stress- and UPR-related genes was performed by qPCR from intestinal mucosa of patients with UC. We also performed in situ hybridization (ISH) and immunohistochemistry (IHQ) of PERK/eIF2α and IRE1/Xbp-1 pathways and UPR-related chaperones. Results. We first evaluated inflammatory genes via qPCR, and we observed that all analyzed proinflammatory transcripts were upregulated in UC patients. ISH and IHQ images showed that ER stress is activated via PERK/eIF2α and IRE1/Xbp-1 pathways not only in intestinal epithelial cells but also in cells of the lamina propria of UC colonic mucosa. Transcriptional analysis confirmed that EIF2AK3 was upregulated in UC patients. UPR-related genes, such as ATF3, STC2, and DDIT3, along with the chaperones and cochaperones DNAJC3, CALR, HSP90B1, and HSPA5, were also upregulated in UC patients. In addition, we observed that proapoptotic and autophagy genes (Bax and ATG6L1, respectively) were also upregulated. Conclusion. Our results suggest that ER stress and UPR are indeed activated in UC patients and this may contribute to the chronic inflammatory process seen in UC. The increased apoptosis and autophagy markers further support the activation of these findings once they are activated to counterbalance tissue damage. These findings provide new insights into the molecular mechanisms that maintain UC activity and open new possibilities to attenuate intestinal inflammation.

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BACKGROUND: The increase in the incidence and prevalence rates of inflammatory bowel disease (IBD) is evident in many newly industrialized countries in Asia, Africa, Eastern Europe, and the American continent. In Brazil, records are still scarce, and further studies on this topic are needed. OBJECTIVE: To evaluate the epidemiological profile and clinical characteristics of patients with IBD who were followed up at a reference service in the state of São Paulo. METHODS: We retrospectively analyzed the medical records of patients with IBD who were followed up in a Brazilian Referral Center. RESULTS: A total of 625 patients was evaluated, 416 with Crohn's disease (CD), 190 with ulcerative colitis (UC), and 19 with indeterminate colitis. The average age of the patients was 31.6 years, with a homogeneous distribution between males and females patients. In patients with CD, the most predominant Montreal classification was A2, L3, and B1, with 44.8% of patients presenting with perianal disease; in UC, it was E2, and S0. The main extraintestinal manifestation was rheumatologic, followed by cutaneous and ophthalmic lesions. The majority of patients (85.4%) used some type of medication, the most frequent being aminosalicylates in patients with UC and biological therapy in patients with CD. Regarding surgeries, in CD, a significant percentage of patients underwent some type of surgical procedure, unlike the UC patients, including fistulotomies and placement of seton, derivative ostomies, enterectomy, ileocecectomy/right colectomy, total or partial colectomy, and strictureplasty. Only 195 (31.2%) patients lived in the city of Campinas, while 443 (70.9%) were from the 7th Regional Health Department (RHD), which corresponds to the macro-region of Campinas. CONCLUSION: In this study, most patients came from the 7th RHD of Campinas; the patients were young, with no predominance of either sex; there was a higher frequency of patients with CD (66.6%). Most of them (85.4%) were undergoing pharmacological treatment, and a significant percentage of CD patients had undergone surgery.

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