Anti-Integrins, Anti-Interleukin 12/23p40, and JAK Inhibitors for the Inflammatory Bowel Disease Treatment

Inflammatory bowel diseases (IBD) present a broad inflammatory cascade that is sometimes difficult to control. Patients with ulcerative colitis (UC) and Crohn’s disease (CD) are exposed to intense and harmful effects that compromise their quality of life. There is a constant need for new classes of drugs that act on different fronts of inflammation control. Initially, biologics revolutionized inflammatory bowel disease treatment. Anti-tumor necrosis factor (anti-TNF) agents and infliximab, followed by adalimumab and certolizumab pegol, have been proven to induce clinical and endoscopic remission. However, some patients are primary nonresponders, and a significant proportion of initial responders lose response throughout the treatment. The emergence of new therapies, such as anti-integrins, anti-interleukins, and inhibitors of Janus kinase (JAK), can become an alternative option for patients with previous therapeutic failures, besides offering greater safety than other biological therapies up to now. Among anti-integrins, vedolizumab is the drug with proven efficacy in both induction and maintenance of remission and has local and selective action in the intestine. Ustekinumab represents the group of anti-interleukins, acting to control interleukin-12 (IL12) and interleukin-23 (IL23). JAK inhibitors (tofacitinib) act on intracellular inflammatory mediators and have the advantage of being orally administered

The Role of Mesenteric Adipose Tissue in Crohn’s Disease

Inflammatory bowel disease (IBD) has become an increasingly frequent chronic health problem in the last few decades, particularly in developing countries. In young adults, one of the most common forms of IBD is Crohn’s disease (CD). CD is a multifactorial genetic disease characterized by a transmural granulomatous inflammation that especially affects the terminal ileum and the colon. As it involves defective inflammatory pathways, the immune adaptive complex, and environmental factors, this disease has periods of remission and recurrence followed by diarrhea, abdominal pain, and malnutrition, which often lead to lumen bowel stenosis associated to multiple fistulas. In addition, the growth of mesenteric adipose tissue (MAT) near the affected intestinal area is a hallmark of CD. Evidence linking the development of mesenteric and intestinal alterations in CD is increasing. The aim of this chapter is to address adipose tissue in general, the morphological and functional differences between its compartments, the main characteristics of MAT in CD, and its possible role in the etiopathology of this immune-mediated disease

Feasibility of endoscopic submucosal dissection for gastric and colorectal lesions: Initial experience from the Gastrocentro - Unicamp

OBJECTIVE: Endoscopic submucosal dissection is a technique developed in Japan for en bloc resection with a lower rate of recurrence. It is considered technically difficult and performed only in specialized centers. This study sought to report the initial experience from the Gastrocentro - Campinas State University for the treatment of gastric and colorectal lesions by endoscopic submucosal dissection. MATERIALS AND METHODS: The guidelines of the Japanese Association of Gastric Cancer were used as evaluative criteria. For colorectal lesions, the recommended standards proposed by Uraoka et al. and Saito et al. were employed. The practicability of the method, the development of complications and histological analysis of the specimens were evaluated. RESULTS: Sixteen patients underwent endoscopic submucosal dissection from June 2010 to April 2011; nine patients were treated for gastric lesions, and seven were treated for colorectal lesions. The average diameter of the gastric lesions was 28.6 mm, and the duration of resection was 103 min without complications. All lesions presented lesion-free margins. Of the seven colorectal tumors, four were located in the rectum and three were located in the colon. The average size was 26 mm, and the average procedure time was 163 min. Two complications occurred during the rectal resection procedures: perforation, which was treated with an endoscopic clip, and controlled bleeding. One of the lesions presented a compromised lateral margin without relapse after 90 days. Depth margins were all free of lesions. CONCLUSION: Endoscopic submucosal dissection at our institution achieved high success rates, with few complications in preliminary procedures. The procedure also made appropriate lesion staging possible

Desmoid Tumor In Patients With Familial Adenomatous Polyposis.

Desmoid tumors constitute one of the most important extraintestinal manifestations of familial adenomatous polyposis. The development of desmoids is responsible for increasing morbidity and mortality rates in cases of familial adenomatous polyposis. To evaluate the occurrence of desmoid tumors in familial adenomatous polyposis cases following prophylactic colectomy and to present patient outcome. Between 1984 and 2008, 68 patients underwent colectomy for familial adenomatous polyposis at the School of Medical Sciences Teaching Hospital, University of Campinas, SP, Brazil. Desmoid tumors were found in nine (13.2%) of these patients, who were studied retrospectively by consulting their medical charts with respect to clinical and surgical data. Of nine patients, seven (77.8%) were submitted to laparotomy for tumor resection. Median age at the time of surgery was 33.9 years (range 22-51 years). Desmoid tumors were found in the abdominal wall in 3/9 cases (33.3%) and in an intra-abdominal site in the remaining six cases (66.7%). Median time elapsed between ileal pouch-anal anastomosis and diagnosis of desmoid tumor was 37.5 months (range 14-60 months), while the median time between colectomy with ileorectal anastomosis and diagnosis was 63.7 months (range 25-116 months). In 6/9 (66.7%) patients with desmoid tumors, the disease was either under control or there was no evidence of tumor recurrence at a follow-up visit made a mean of 63.1 months later (range 12-240 months). Desmoid tumors were found in 13.2% of cases of familial adenomatous polyposis following colectomy; therefore, familial adenomatous polyposis patients should be followed-up and surveillance should include abdominal examination to detect signs and symptoms. Treatment options include surgery and clinical management with antiestrogens, antiinflammatory drugs or chemotherapy.47373-

Oxigenoterapia hiperbárica e resistência mecânica das anastomoses cólicas em ratos com peritonite

PURPOSE: To analyze the effects of hyperbaric oxygen therapy (HBO) on the mechanical resistance of anastomosis performed in rats' distal colon presenting peritonitis induced by ligature and cecal punction using the Total Energy Rupture biomechanical test (ETR). METHODS: It was used 45 rats divided into three groups of 15 animals each. In Control Group (CG), it was performed anastomosis in distal colon without peritonitis. In Peritonitis Group (PG), it was performed anastomosis six hours after the induction of peritonitis by ligature and cecal punction. In Hyperbaric Chamber Group (HCG), it was performed six hours after the induction of peritonitis by ligature and cecal punction. The animals on CG and PG were kept at place air while the animals on HCG were placed on an experimental hyperbaric chamber in order to inhale oxygen at 100%, two absolute atmospheres, for 120 minutes, for four consecutive days. Euthanasia took place on the fifth day of the experiment. All the animals underwent to Total Energy Rupture Biomechanical Resistance test (ETR). Total Energy Rupture was defined as the necessary internal energy stored up to promote the colon rupture after an external traction force imposition. RESULTS: The Peritonitis Group presents smaller average ETR than Control Group. There was no statistical difference between Peritonitis Group and Hyberbaric Chamber Group. CONCLUSION: Hyperbaric oxygen therapy did not alter the mechanical resistance of anastomosis performed in distal colon of rats under the presence of peritonitis induced by ligature and cecal puncture.OBJETIVO: Analisar o efeito da oxigenoterapia hiperbárica (HBO) sobre a resistência mecânica de anastomoses realizadas em cólon distal de ratos na presença de peritonite induzida por ligadura e punção cecal utilizando o teste biomecânico de Energia Total de Ruptura (ETR). MÉTODOS: Foram utilizados 45 ratos distribuídos em três grupos de 15 animais. No Grupo Controle (GC), realizou-se anastomose no cólon distal sem peritonite. No Grupo Peritonite (GP), realizou-se anastomose seis horas após a indução da peritonite por ligadura e punção cecal. No Grupo Câmara Hiperbárica (GCH), realizou-se anastomose seis horas após a indução da peritonite por ligadura e punção cecal. Os animais dos GC e GP foram mantidos em ar ambiente. Os animais do GCH foram colocados em uma câmara hiperbárica experimental para inalarem oxigênio a 100%, a duas atmosferas absolutas, durante 120 minutos, por quatro dias consecutivos. A eutanásia ocorreu no quinto dia do experimento. Todos os animais foram submetidos ao Teste de Resistência Biomecânico Energia Total de Ruptura (ETR). A Energia Total de Ruptura foi definida como a energia interna acumulada necessária para promover o rompimento do cólon após a imposição de uma força externa de tração. RESULTADOS: O Grupo Peritonite apresentou menor média de ETR que o Grupo Controle. Não houve diferença estatística entre o Grupo Peritonite e o Grupo Câmara Hiperbárica. CONCLUSÃO: A oxigenoterapia hiperbárica não alterou a resistência mecânica de anastomoses realizadas no cólon distal de ratos na presença de peritonite induzida por ligadura e punção cecal.36837

Discrete cutaneous lesions in a critically ill patient treated only for AIDS and miliary tuberculosis: a case report of disseminated histoplasmosis

Histoplasmosis is a systemic mycosis caused by the dimorphic fungus Histoplasma capsulatum, with disseminated histoplasmosis (HD) being one of its clinical forms. As a consequence of the HIV-AIDS pandemic, HD has become prevalent not only in regions that are recognized as endemic but also in areas not considered endemic, such as Europe and Asia. Its clinical manifestations are varied and mimic several infectious diseases, mainly tuberculosis. In endemic areas, it is the first manifestation of AIDS in 50 to 70% of patients. The diagnosis of histoplasmosis is difficult and HD can lead to death if not diagnosed early and if proper treatment is not instituted. The present report presents a patient with a recent diagnosis of HIV-AIDS, in treatment for miliary tuberculosis, who was diagnosed with disseminated histoplasmosis because of his dermatological manifestations

Adenocarcinoma of the right colon in a patient with bloom syndrome

Bloom syndrome (BS) is an inherited disorder due to mutation in BLM gene. The diagnosis of BS should be considered in patients with growth retardation of prenatal onset, a photosensitive rash in a butterfly distribution over the cheeks, and an increased risk of cancer at an early age. Clinical manifestations also include short stature, dolichocephaly, prominent ears, micrognathia, malar hypoplasia and a high-pitched voice, immunodeficiency, type II diabetes, and hypogonadism associated with male infertility and female subfertility. The aim of this report is to describe case of patient with BS who developed adenocarcinoma of the cecum, successfully treated by right colectomy. Case Report. A 40-year-old man underwent colonoscopy to investigate the cause of his diarrhea, weight loss, and anemia. The patient knew that he was a carrier of BS diagnosed at young age. The colonoscopy showed an expansive and vegetating mass with 5.5 cm in diameter, located within the ascending colon. Histopathological analysis of tissue fragments collected during colonoscopy confirmed the presence of tubular adenocarcinoma, and he was referred for an oncological right colectomy. The procedure was performed without complications, and the patient was discharged on the fifth postoperative day. Histopathological examination of the surgical specimen confirmed the presence of a grade II tubular adenocarcinoma (stage IIA). The patient is currently well five years after surgery, without clinical or endoscopic signs of relapse in a multidisciplinary approach for the monitoring of comorbidities related to BS. Conclusion. Despite the development of colorectal cancer to be, a possibility rarely described the present case shows the need for early screening for colorectal cancer in all patients affected by B

Defective Apoptosis In Intestinal And Mesenteric Adipose Tissue Of Crohn's Disease Patients.

Crohn's disease (CD) is associated with complex pathogenic pathways involving defects in apoptosis mechanisms. Recently, mesenteric adipose tissue (MAT) has been associated with CD ethiopathology, since adipose thickening is detected close to the affected intestinal area. However, the potential role of altered apoptosis in MAT of CD has not been addressed. To evaluate apoptosis in the intestinal mucosa and MAT of patients with CD. Samples of intestinal mucosa and MAT from patients with ileocecal CD and from non-inflammatory bowel diseases patients (controls) were studied. Apoptosis was assessed by TUNEL assay and correlated with the adipocytes histological morphometric analysis. The transcriptional and protein analysis of selected genes and proteins related to apoptosis were determined. TUNEL assay showed fewer apoptotic cells in CD, when compared to the control groups, both in the intestinal mucosa and in MAT. In addition, the number of apoptotic cells (TUNEL) correlated significantly with the area and perimeter of the adipose cells in MAT. Transcriptomic and proteomic analysis reveal a significantly lower transcript and protein levels of Bax in the intestinal mucosa of CD, compared to the controls; low protein levels of Bax were found localized in the lamina propria and not in the epithelium of this tissue. Furthermore, higher level of Bcl-2 and low level of Caspase 3 were seen in the MAT of CD patients. The defective apoptosis in MAT may explain the singular morphological characteristics of this tissue in CD, which may be implicated in the pathophysiology of the disease.9e9854