INFLUENCE OF NEOADJUVANT THERAPY ON THE RATIO OF LYMPH NODES.

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.

Influência da terapia neoadjuvante na razão de linfonodos / Influence of neoadjuvant therapy on the ratio of lymph nodes

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.

Ferric carboxymaltose for anemia in Crohn's disease patients at a tertiary center: A retrospective observational cohort study.

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.

VOLUMETRIC CAPNOGRAPHY FOR RESPIRATORY MONITORING OF PATIENTS DURING ROUTINE COLONOSCOPY WITH ROOM-AIR AND CARBON DIOXIDE INSUFFLATION.

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.

Capnografia volumétrica para monitoração respiratória de pacientes submetidos a colonoscopia diagnóstica com insuflação de ar comprimido e gás carbônico / Volumetric capnography for respiratory monitoring of patients during routine colonoscopy with room-air and carbon dioxide insufflation

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.

Pouchitis: insight into the pathogenesis and clinical aspects.

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.

Mucinous adenocarcinoma in perianal fistula in Crohn's disease: Case report and literature review.

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.

Endoplasmic Reticulum Stress in Colonic Mucosa of Ulcerative Colitis Patients Is Mediated by PERK and IRE1 Pathway Activation.

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.

EPIDEMIOLOGICAL PROFILE AND CLINICAL CHARACTERISTICS OF INFLAMMATORY BOWEL DISEASES IN A BRAZILIAN REFERRAL CENTER.

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.

Perfil epidemiológico e características clínicas das doenças inflamatórias intestinais em um centro de referência Brasileiro / Epidemiological profile and clinical characteristics of inflammatory bowel diseases in a brazilian referral center

ABSTRACT 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.

RESUMO CONTEXTO: O aumento na incidência e prevalência das doenças inflamatórias intestinais (DIIs) é evidente em muitos países recém-industrializados da Ásia, África, Europa Oriental e do continente Americano. No Brasil, os registros ainda são bastante escassos, sendo necessários mais estudos sobre este tema. OBJETIVO: Avaliar o perfil epidemiológico e as características clínicas dos doentes com DIIs, acompanhados em um serviço de referência no Estado de São Paulo. MÉTODOS: Análise retrospectiva, descritiva, dos prontuários médicos dos pacientes com DIIs acompanhados em um centro de referência no Brasil. RESULTADOS: Foram avaliados 625 doentes, sendo 416 com doença de Crohn (DC), 190 com retocolite ulcerativa (RCU) e 19 com colite indeterminada. A média de idade foi de 31,6 anos, sendo a distribuição homogênea entre os sexos. Na DC predominou a classificação de Montreal A2 L3 e B1, com 44,8% dos doentes apresentando doença perianal; na RCU, E2 e S0. A principal manifestação extraintestinal presente foi reumatológica, vindo a seguir as lesões cutâneas e as oftalmológicas. A maioria dos doentes (85,4%) fazia uso de alguma medicação, sendo as mais frequentes, aminossalicilatos na RCU e terapia biológica na DC. Em relação às cirurgias, na DC um significativo percentual de pacientes foi submetido a algum tipo de procedimento cirúrgico, ao contrário da RCU, incluindo fistulotomias e colocação de sedenhos, estomas de derivação, enterectomia, ileotiflectomia/colectomia direita, colectomia total ou parcial e plastias intestinais. Apenas 195 (31,2%) doentes eram da cidade de Campinas, mas 443 (70,9%) eram provenientes do 7º Departamento Regional de Saúde (DRS), que corresponde a Grande Campinas. CONCLUSÃO: No estudo, houve um predomínio de pacientes do DRS de Campinas; os doentes eram jovens, sem predominância de sexo; a frequência maior foi de doentes com DC (66,6%). A maioria (85,4%) estava em tratamento farmacológico, e um percentual significativo de doentes com DC, havia sido submetido à cirurgia.

The role of chemokines and adipokines as biomarkers of Crohn's disease activity: a systematic review of the literature.

INTRODUCTION: Crohn's disease (CD) is an inflammatory bowel disease (IBD) that affects the gastrointestinal tract and can have a major impact on the patient's quality of life and social/professional activities. Asymptomatic patients, or those with mild symptoms, experience the active disease with subclinical manifestation. Systematic review (SR) was performed to look for evidence for the role of chemokines and adipokines as markers for CD activity. METHODS: This SR was conducted by searching published studies in international and regional databases up till July, 2020. CD patients were adults with the disease in activity or remission. All adipokines and chemokines were considered for the analysis and the Rayyan QCRI system was used. RESULTS: In total, 20 studies were included. Six addressed chemokines and eight adipokines as potential biomarkers of CD activity. CXCL8 was the most studied chemokine (8 studies) and the results were controversial, with 62.5% showing a significant association with CD activity. CXCL10 was investigated by 4 studies and 50% identified it as a potential biomarker. CCL2, CCL11, CCL26 and CXCL1 were examined by 2 articles each. CXCL8 (P=0.002/P=0.001) and CXCL1 (P<0.001) presented the lowest? P value, which qualifies them as potential markers of disease activity. All the adipokines were tested in peripheral blood but 44.4% were also tested in intestinal mucosa, while the percentage in the chemokines' studies was 76.9% in peripheral blood, 46.1% in intestinal mucosa and 7.6% in urine sample respectively. CONCLUSION: The development of disease activity biomarkers for CD is becoming relevant for clinical practice. Chemokines and adipokines have the potential to signalize CD activity, but validation in larger cohorts of patients, preferable multicenter studies are still needed.

Microbiota-derived short-chain fatty acids do not interfere with SARS-CoV-2 infection of human colonic samples.

Microbiota-derived molecules called short-chain fatty acids (SCFAs) play a key role in the maintenance of the intestinal barrier and regulation of immune response during infectious conditions. Recent reports indicate that SARS-CoV-2 infection changes microbiota and SCFAs production. However, the relevance of this effect is unknown. In this study, we used human intestinal biopsies and intestinal epithelial cells to investigate the impact of SCFAs in the infection by SARS-CoV-2. SCFAs did not change the entry or replication of SARS-CoV-2 in intestinal cells. These metabolites had no effect on intestinal cells' permeability and presented only minor effects on the production of anti-viral and inflammatory mediators. Together our findings indicate that the changes in microbiota composition of patients with COVID-19 and, particularly, of SCFAs do not interfere with the SARS-CoV-2 infection in the intestine.

Role of diet and nutrition in inflammatory bowel disease.

Inflammatory bowel diseases (IBDs) are closely linked to nutrition. The latest research indicates that diet and nutrition are significantly involved in the etiopathogenesis of the disease, although their specific role throughout its clinical course still remains unclear. This study reviewed how diet and nutrition are associated with IBD development and management. Even though specific diets have been shown to bring about positive outcomes, there is currently no scientific consensus regarding an appropriate diet that would benefit all IBD patients. We suggest that individualized dietary recommendations are of the greatest importance and that diets should be planned to provide individual IBD patients with specific nutrient requirements while keeping all the clinical aspects of the patients in mind. Further research is clearly necessary to investigate nutritional factors involved in IBD development and, especially, to evaluate the applications of the diets during the course of the disease.

Anti-TNF therapy and immunogenicity in inflammatory bowel diseases: a translational approach.

Inflammatory bowel diseases are chronic illnesses that involve intestinal inflammation and are usually diagnosed as Crohn's disease or ulcerative colitis. As these diseases do not have a cure, the goal of treatment is to induce and maintain remission. Monoclonal antibodies have been recognized as the most advanced therapy to avoid complications and reduce the need for surgical approaches. However, although their effectiveness has been proven by several studies, they can trigger the immune system, induce the occurrence of immunogenicity, which may lead to the loss of response and treatment failure. The purpose of this review is to determine what are the main mechanisms involved in IBD; to assess the recommended treatments; to explore the mechanisms of immunogenicity. We also try to explain the detection and describe the existing advances that make possible the clinical application of these approaches.

Assessment of disease activity in inflammatory bowel diseases: Non-invasive biomarkers and endoscopic scores.

Inflammatory bowel diseases (IBD) comprise two major forms: Crohn's disease and ulcerative colitis. The diagnosis of IBD is based on clinical symptoms combined with results found in endoscopic and radiological examinations. In addition, the discovery of biomarkers has significantly improved the diagnosis and management of IBD. Several potential genetic, serological, fecal, microbial, histological and immunological biomarkers have been proposed for IBD, and they have been evaluated for clinical routine and clinical trials. Ileocolonoscopy, especially with biopsy collection, has been considered the standard method to diagnose IBD and to assess clinical activity of the disease, but it is limited to the colon and terminal ileum and is considered invasive. For this reason, non-invasive biomarkers are necessary for this type of chronic inflammatory disease, which affects mostly young individuals, as they are expected to have a long follow-up.

ER stress activation in the intestinal mucosa but not in mesenteric adipose tissue is associated with inflammation in Crohn's disease patients.

Chronic/abnormal activation of endoplasmic reticulum (ER) stress is linked to the exacerbation of the inflammatory process and has been recently linked to Crohn's disease (CD) pathophysiology. We investigated the intestinal mucosa and the mesenteric adipose tissue (MAT) collected from CD patients with active disease (CD group) and from non-IBD patients (CTR group) to study ER stress activation and to address tissue-specific modulation in CD. The intestinal mucosa of CD patients showed an upregulation in the expression of ER stress related genes, including ATF3, DNAJC3, STC2, DDIT3, CALR, HSPA5 and HSP90B1. Results showed that EIF2AK3 gene was upregulated, along with increased protein expression of p-eIF2α and p-eIF2α/eIF2α ratio. Additionally, ERN1 gene expression was upregulated, along with an increased spliced/activated form sXBP1 protein. Despite the upregulation of ATF6 gene expression in the intestinal mucosa of CD patients, no differences were found in ATF6 protein expression. Lastly, the analysis of MAT revealed unchanged levels of ER stress markers along with no differences in the activation of UPR. However, chaperone gene expression was modulated in the MAT of CD patients. To conclude, our results address tissue-specific differences in UPR activation in CD and point the ER stress as an important pro-inflammatory mechanism in CD, specifically in the intestinal mucosa.

Internal hernia through mesocolon defect after left laparoscopic colectomy / Hérnia interna pelo defeito mesocólico após colectomia esquerda laparoscópica

ABSTRACT Introduction: The development of internal hernias due to the mesocolon defect after laparoscopic colectomy is a rare complication with only 39 cases described. There are controversies whether the closure of the defect of the mesocolon after resection of the colon could prevent the development of this complication. Objective: To describe a case of intestinal obstruction due to internal hernia through the mesocolon defect after laparoscopic rectosigmoidectomy and to perform a literature review. Case report: A 59-year-old woman was hospitalized for laparoscopic rectosigmoidectomy due to an adenocarcinoma located in the rectosigmoid junction. She underwent a rectosigmoidectomy by laparoscopy, with an extracorporeal mechanical anastomosis, without closure of the mesocolon defect. In the fifth postoperative day the patient presented an intestinal obstruction due to an internal hernia through the mesocolon defect confirmed by computerized tomography. During the exploratory laparotomy approximately 120 cm jejunum was identified through the mesocolon defect. The reduction of herniated small bowel was done without the need of intestinal resection. The mesocolon defect was corrected by continuous suture. After the reoperation, the patient presented a favorable recovery being discharged on the fifth day. Conclusion: Intestinal obstruction due to internal hernia after laparoscopic rectosigmoidectomy is a rare postoperative complication that can be avoided by the adequate closure of the mesocolon defect.

RESUMO Introdução: O desenvolvimento de hérnias internas pelo defeito mesocólico após a realização de colectomia laparoscópica é uma complicação rara com apenas 39 casos descritos. Existem controvérsias se fechamento do defeito após a ressecção do cólon preveniria o desenvolvimento desta complicação. Objetivo: Descrever um caso de obstrução intestinal por hérnia interna pelo defeito mesocólico, após retossigmoidectomia laparoscópica e revisar a literatura relacionada ao tema. Relato do caso: Mulher, 59 anos foi internada para realizar ressecção cirúrgica de adenocarcinoma localizado na junção retossigmoideana. Foi submetida à retossigmoidectomia laparoscópica, com confecção de anastomose mecânica extracorpórea. O defeito mesocólico não foi corrigido no final do procedimento. No quinto dia de pós-operatório, a doente apresentou quadro de obstrução intestinal cuja tomografia computadorizada identificou presença de hérnia interna pelo defeito do mesocólon. Na laparotomia exploradora identificou-se que aproximadamente 120 cm de alças jejunais estavam herniadas através do defeito mesocólico. Realizou-se a redução do intestino delgado herniado sem necessidade de ressecção intestinal. O defeito foi corrigido por sutura contínua. Após a reoperação a doente apresentou evolução favorável recebendo alta no quinto dia. Conclusão: Obstrução intestinal após retossigmoidectomia laparoscópica consequente à formação de hérnia interna é complicação pós-operatória rara, com alta mortalidade, que pode ser evitada pelo fechamento criterioso do defeito do mesocólico.

RELATIONSHIP AMONG PSYCHOLOGICAL WELL-BEING, RESILIENCE AND COPING WITH SOCIAL AND CLINICAL FEATURES IN CROHN'S DISEASE PATIENTS.

BACKGROUND: Crohn's disease is chronic, requires prolonged treatment, affects the physical and psychosocial health of patients and may alter their routine, quality of life and well-being. Recent studies recommend monitoring the health of these patients considering physical, psychological and psychosocial aspects, because they are directly related to the disease activity. These studies highlight the relevance of patients' emotional and behavioral conditions and suggest that the identification of the factors that influence the psychological well-being, resilience and Coping in these patients can favor the proper treatment. OBJECTIVE: To relate psychological well-being, resilience and Coping with social and clinical features of Crohn's disease patients. METHODS: Prospective study including 104 patients with Crohn's disease, both genders and mean age of 39 years. Standardized scales were used to assess and to relate psychological well-being, resilience and Coping with social and clinical variables. A questionnaire to characterize the sample and standardized scales in data collection (psychological well-being, resilience pillars and Coping strategies inventory - Folkman & Lazarus) were used. Descriptive analysis of data and statistics for comparison of results were performed. RESULTS: There were significant differences (P<0.05) showing better psychological well-being for male patients, those who without children, were not religious, were employed and were doing complementary activities in addition to clinical treatment. More resilience for the male gender, those who without children, were not religious, divorced, separated or widowed, that received some monthly income; who did not undergo surgery, had the first symptoms after 30 years old and who had complementary activity. There were also significant differences in the use of Coping: usually, women used more developed escape and avoidance strategies; single, married or in stable-union patients used more self-control; not religious used positive revaluation strategy; the ones who were employed showed more self-control and positive reassessment; the ones who had lower family income indicated that they used less the self-control; the ones who had higher family income used more positive re-evaluation; patients who were diagnosed with Crohn's disease between the second decade of life showed to use mores more the positive reassessment strategy than those who were 20 years old or younger. CONCLUSION: Social aspects influenced psychological well-being, resilience and Coping in patients with Crohn's disease more strongly than clinical aspects. It was possible to identify the profiles with better and worse psychological well-being, resilience and Coping of those who need more support, as well as to know the most used Coping strategies in the studied group.

Relação entre bem-estar psicológico, resiliência e coping com fatores sociais e clínicos em pacientes com doença de Crohn / Relationship among psychological well-being, resilience and coping with social and clinical features in crohn's disease patients

ABSTRACT BACKGROUND: Crohn's disease is chronic, requires prolonged treatment, affects the physical and psychosocial health of patients and may alter their routine, quality of life and well-being. Recent studies recommend monitoring the health of these patients considering physical, psychological and psychosocial aspects, because they are directly related to the disease activity. These studies highlight the relevance of patients' emotional and behavioral conditions and suggest that the identification of the factors that influence the psychological well-being, resilience and Coping in these patients can favor the proper treatment. OBJECTIVE: To relate psychological well-being, resilience and Coping with social and clinical features of Crohn's disease patients. METHODS: Prospective study including 104 patients with Crohn's disease, both genders and mean age of 39 years. Standardized scales were used to assess and to relate psychological well-being, resilience and Coping with social and clinical variables. A questionnaire to characterize the sample and standardized scales in data collection (psychological well-being, resilience pillars and Coping strategies inventory - Folkman & Lazarus) were used. Descriptive analysis of data and statistics for comparison of results were performed. RESULTS: There were significant differences (P<0.05) showing better psychological well-being for male patients, those who without children, were not religious, were employed and were doing complementary activities in addition to clinical treatment. More resilience for the male gender, those who without children, were not religious, divorced, separated or widowed, that received some monthly income; who did not undergo surgery, had the first symptoms after 30 years old and who had complementary activity. There were also significant differences in the use of Coping: usually, women used more developed escape and avoidance strategies; single, married or in stable-union patients used more self-control; not religious used positive revaluation strategy; the ones who were employed showed more self-control and positive reassessment; the ones who had lower family income indicated that they used less the self-control; the ones who had higher family income used more positive re-evaluation; patients who were diagnosed with Crohn's disease between the second decade of life showed to use mores more the positive reassessment strategy than those who were 20 years old or younger. CONCLUSION: Social aspects influenced psychological well-being, resilience and Coping in patients with Crohn's disease more strongly than clinical aspects. It was possible to identify the profiles with better and worse psychological well-being, resilience and Coping of those who need more support, as well as to know the most used Coping strategies in the studied group.

RESUMO CONTEXTO: A doença de Crohn é crônica, exige tratamento prolongado e afeta a saúde física e psicossocial dos pacientes podendo alterar sua rotina, qualidade de vida e bem-estar. Estudo recentes recomendam a monitoração da saúde destes pacientes considerando aspectos físicos, psicológicos e psicossociais, por estarem diretamente relacionados com a atividade da doença. Destacam a relevância das condições emocionais e comportais dos pacientes e sugerem que a identificação dos fatores que influenciam o bem-estar psicológico, resiliência e Coping nestes pacientes pode favorecer as ações de cuidado/tratamento apropriado. OBJETIVO: Relacionar bem-estar psicológico, resiliência e Coping com aspectos sociais e clínicos de pacientes com doença de Crohn. MÉTODOS: Estudo prospectivo incluindo 104 pacientes portadores de doença de Crohn, ambos os sexos e idade média de 39 anos. Foi utilizado um questionário para caracterização da amostra e escalas padronizadas na coleta de dados (bem-estar psicológico, pilares de resiliência e inventário de estratégias de Coping de Folkman & Lazrus). Realizada análise descritiva dos dados e estatística para comparação de resultados (P-valor). RESULTADOS: Foram identificadas diferenças significativas (P<0,05) evidenciando melhor bem estar-psicológico para os pacientes do gênero masculino, aqueles que não possuíam filhos, não religiosos, com atividade profissional remunerada e que realizavam alguma atividade complementar ao tratamento clínico. Maior resiliência para o gênero masculino, aqueles que não possuíam filhos, não religiosos, divorciados, separados ou viúvos, que recebiam alguma renda mensal; que não passaram por cirurgia, tiveram os primeiros sintomas após 30 anos de idade e que faziam alguma atividade complementar ao tratamento clínico. Também foram observadas diferenças significativas no uso do Coping: as mulheres demonstraram usar mais a estratégia de fuga e esquiva; pacientes solteiros, casados ou em união estável utilizavam mais o autocontrole; não religiosos utilizavam mais a estratégia de reavaliação positiva; os que trabalhavam faziam mais uso do autocontrole e reavaliação positiva; os de menor renda familiar indicou usar menos o autocontrole e os de maior renda empregavam mais a reavaliação positiva; os que tiveram diagnóstico da doença de Crohn durante a segunda décadas de vida demonstraram utilizar mais a estratégia de reavaliação positiva que aqueles que tiveram diagnóstico em idade inferior a 20 anos. CONCLUSÃO: Aspectos sociais influenciaram mais fortemente o bem-estar psicológico, resiliência e Coping em pacientes com doença de Crohn que os aspectos clínicos. Possibilitou identificar os perfis com melhor e pior bem-estar psicológico, resiliência e Coping; aqueles que necessitam de maior apoio, bem como conhecer as estratégias de Coping mais utilizadas no grupo estudado.

Ileal pouch of ulcerative colitis and familial adenomatous polyposis patients exhibit modulation of autophagy markers.

Total retocolectomy with ileal pouch-anal anastomosis (IPAA) is the surgery of choice for patients with ulcerative colitis (UC) that are refractory to clinical treatment. Pouchitis is one of the most common complications after this procedure. Defects in autophagy have been reported in inflammatory bowel diseases. However, there are no studies on the IP. Therefore, we studied markers for autophagy in the IP mucosa of UC and FAP patients comparing them to controls with a normal distal ileum. Sixteen patients with IP in "J" shape, asymptomatic and with endoscopically normal IP were evaluated. The control group consisted of eight patients with normal colonoscopy. There was a significant decrease in the transcriptional levels of ATG5, MAP1LC3A and BAX in the FAP group. There was also a decrease in the protein level of Beclin-1 in the UC and FAP compared to the control group. Although the LC3II levels by immunoblot were higher in the UC group, LC3/p62 co-localization were lower in the immunofluorescence analysis in the UC and FAP compared to the control group. Corroborating these results, there was an increase of p62 by immunoblot in the UC group. These findings indicated a modulation of macroautophagy markers in the IP, which may explain the mucosa inflammation predisposition.