Aspects Towards the Anastomotic Healing in Crohn's Disease: Clinical Approach and Current Gaps in Research.

Anastomotic leakage is a major complication in gastrointestinal and colorectal surgery and its occurrence increases morbidity and mortality. Its incidence is even higher in Crohn's disease surgeries. Several authors have identified factors involved in the pathophysiology of anastomotic leak in the literature, aiming to reduce its occurrence and, therefore, improve its surgical treatment. Surgical technique is the most discussed topic in studies on guiding the performance of side-to-side stapled anastomosis. Preoperative nutritional therapy also has been shown to reduce the risk of anastomotic leakage. Other factors remain controversial - immunomodulator use and biologic therapy, antibiotics, and gut microbiota - with studies showing a reduction in the risk of complication while other studies show no correlation. Although mesenteric adipose tissue has been related to disease recurrence, there is no evidence in the literature that it is related to a higher risk of anastomotic leakage. Further exploration on this topic is necessary, including prospective research, to support the development of techniques to prevent anastomotic leakage, in this way benefiting the inflammatory bowel disease patients who have to undergo a surgical procedure.

Lipid excess affects chaperone-mediated autophagy in hypothalamus.

Obesity is a major health problem worldwide. Overweight and obesity directly affect health-related quality of life and also have an important economic impact on healthcare systems. In experimental models, obesity leads to hypothalamic inflammation and loss of metabolic homeostasis. It is known that macroautophagy is decreased in the hypothalamus of obese mice but the role of chaperone-mediated autophagy is still unknown. In this study, we aimed to investigate the role of hypothalamic chaperone-mediated autophagy in response to high-fat diet and also the direct effect of palmitate on hypothalamic neurons. Mice received chow or high-fat diet for 3 days or 1 week. At the end of the experimental protocol, chaperone-mediated autophagy in hypothalamus was investigated, as well as cytokines expression. In other set of experiments, neuronal cell lines were treated with palmitic acid, a saturated fatty acid. We show that chaperone-mediated autophagy is differently regulated in response to high-fat diet intake for 3 days or 1 week. Also, when hypothalamic neurons are directly exposed to palmitate there is activation of chaperone-mediated autophagy. High-fat diet causes hypothalamic inflammation concomitantly to changes in the content of chaperone-mediated autophagy machinery. It remains to be studied the direct role of inflammation and lipids itself on the activation of chaperone-mediated autophagy in the hypothalamus in vivo and also the neuronal implications of chaperone-mediated autophagy inhibition in response to obesity.

The role of the Gulf of Cadiz circulation in the redistribution of trace metals between the Atlantic Ocean and the Mediterranean Sea.

The GoC shelf waters present much higher concentrations of dissolved Cu, Cd, and Zn than other coastal areas, constituting an important source of these elements onto its neighbouring basins, i.e., the Atlantic Ocean and the Mediterranean Sea. In this study we assessed the role of the GoC surface currents in the trace metals transport. For this purpose, ten dissolved (<0.22 µm) trace metals were sampled (Ag, Cd, Co, Cu, Fe, Mo, Ni, Pb, Zn, V) along the GoC continental shelf, and their spatial and temporal distribution was interpreted according to the surface circulation. Results show that the complex surface circulation over the shelf confines the metals concentration mainly along the inner shelf and determines their transport patterns: under southeastward currents, Cd, Co, Cu, Ni, and Pb are transported toward the Mediterranean Sea; under northwestward countercurrents, Cd, Co, Cu, Fe, Ni, and Zn are transported toward the southern and, occasionally, the western Portuguese shelf; under variable currents, Ag, Cd, Co, Cu, Fe, Pb, and Zn tend to accumulate near their source. Considering that some of these metals have not been analysed before in this region (Ag, Mo, V), or that the spatial distribution of certain metals (Ag, Fe, Mo, Pb, V) has not been interpreted in terms of the ocean circulation, this work could be considered as a baseline study for future comparisons.

Serum levels and mesenteric fat tissue expression of adiponectin and leptin in patients with Crohn's disease.

Crohn's disease (CD) is characterized by inflammation and an aetiology that is still unknown. Hypertrophy of mesenteric fat is a reflection of disease activity, as this fat covers the entire length of the affected area. Adipocytes synthesize leptin and adiponectin, adipocytokines responsible for pro- and anti-inflammatory effects. Therefore, we evaluated serum levels of adiponectin and leptin, as well as mesenteral expression of adiponectin in active CD and those in remission. Sixteen patients with ileocaecal CD followed at the Outpatient Clinic, Coloproctology Unit of University of Campinas Clinical Hospital, participated in the study. Analysis of serum adiponectin and leptin by enzyme-linked immunosorbent assay was performed in patients with active CD (ACD group), remission CD (RCD group) and in six healthy controls. Ten patients with active ileocaecal CD (FCD group) and eight patients with non-inflammatory disease selected for surgery were also studied. The specimens were snap-frozen and the expression of adiponectin was determined by immunoblot of protein extracts. Serum C-reactive protein levels were higher in the ACD group when compared to the others and no difference of body mass index was observed between the groups. Serum adiponectin was lower in the ACD group when compared to control, but no differences were seen when comparing the ACD and RCD groups. Mesenteric adiponectin expression was lower in the FCD group when compared to the FC group. Serum leptin was similar in all groups. The lower levels of serum and mesenteric adiponectin in active CD suggest a defective regulation of anti-inflammatory pathways in CD pathogenesis.

Laparoscopic-assisted bowel resection with construction of a colonic reservoir for cavernous hemangioma of the rectum: report of two cases.

Diffuse cavernous hemangioma of the rectum is an unusual benign vascular lesion, marked by delayed diagnosis and often presenting recurrent rectal bleeding and anemia. Colorectal resection with coloanal anastomosis and construction of a colonic reservoir is the preferred surgical treatment. We report two cases of patients, a 23-year-old man and a 27-year-old woman, with cavernous hemangioma of the rectum, diagnosed by colonoscopy and confirmed by magnetic resonance imaging. Arteriography demonstrated vascular tumors in the rectal wall. Use of the embolization technique was not successful, since no large caliber vessel was available for this procedure. The patients underwent anterior abdominal excision of the rectum with a laparoscopic approach+ colonic reservoir and hand sewn coloanal anastomosis. Ileostomy closure was performed in both patients at 3 months after surgery, and they demonstrated good early and late postoperative outcomes. In summary, laparoscopic-assisted bowel resection may be a good option for surgical management of diffuse cavernous hemangioma of the rectum.

Activation of signal transducer and activator of transcription-1 (STAT-1) and differential expression of interferon-gamma and anti-inflammatory proteins in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis.

Pouchitis after total rectocolectomy is the most common complication of ulcerative colitis (UC). The immunological mechanisms involved in the genesis of pouchitis are unclear. Therefore, we evaluated the inflammatory activity in normal ileal pouch mucosa by determining signal transducers and activators of transcription (STAT-1) activation and cytokine expression in patients operated for UC and familial adenomatous polyposis (FAP). Eighteen asymptomatic patients, who underwent total rectocolectomy and J pouch, were evaluated: nine with UC and nine with FAP. The activation of STAT-1 and cytokine expression were determined by immunoblot of total protein extracts from pouch mucosal biopsies. The absence of pouchitis was assessed by clinical, histological and endoscopic parameters, according to the Pouchitis Disease Activity Index. The patients were not receiving any medication. Analysis of variance (anova) and Tukey-Kramer's test were applied. The local ethical committee approved the study and informed consent was signed by all participants. STAT-1 activation was increased in UC when compared to FAP and controls (P < 0.05). Higher levels of interferon (IFN)-gamma expression were observed in UC patients when compared to the control group (P < 0.05), but were similar to FAP. In contrast, cytokine signalling (SOCS-3) and interleukin (IL)-10 expression were similar in all groups (P > 0.05). These findings could explain the higher susceptibility to this inflammatory complication in UC when compared to FAP. A tendency towards increased levels of IFN-gamma and STAT-1 in patients with UC, even without clinical and endoscopic evidence of pouchitis, was observed; studying inflammatory activity in asymptomatic ileal pouches may help understanding of the pathogenesis of pouchitis.

Differential expression of pro-inflammatory cytokines and a pro-apoptotic protein in pelvic ileal pouches for ulcerative colitis and familial adenomatous polyposis.

BACKGROUND: Pouchitis after total rectocolectomy is among the most common complications of patients with ulcerative colitis (UC). However, its frequency is quite rare in patients with familial adenomatous polyposis (FAP). We evaluated the inflammatory and pro-apoptotic activity in endoscopically normal mucosa of the ileal pouch in patients with UC and FAP. METHODS: Twenty patients (10 with UC and 10 with FAP) with "J" pouch after total proctocolectomy were studied as were 10 normal controls. Biopsies were obtained from the mucosa of the pouch of UC and FAP patients and from the normal ileum of controls. The expression levels of TNF-alpha, IL-1beta, IL-6, IL-8 and phospho-BAD were determined by immunoblotting. Activated NFkappaB was evaluated by immuno-precipitation and immunoblotting for IkappaB kinase beta. RESULTS: Patients with UC had higher levels of IL-1beta, IL-6, IL-8 and TNF-alpha than patients with FAP. The level of TNF-alpha was higher in patients with UC than in patients with FAP; both patient groups had TNF-alpha levels higher than controls. Activation of NFkappaB was similar in all three groups. The expression of phospho-BAD was significantly lower in patients with FAP than in patients with UC. CONCLUSIONS: As compared with patients with FAP, patients with UC presented increased levels of some pro-inflammatory cytokines, even in the absence of clinical or endoscopic signs of pouchitis. Patients with FAP presented lower levels of pro-inflammatory proteins and of phospho-BAD. These findings may explain the higher rates of progression to pouchitis in UC patients, which could correlate with mucosal atrophy that occurs in inflamed tissue.

Mucinous adenocarcinoma derived from chronic perianal fistulas: report of a case and review of the literature.

Chronic perianal fistulas are a common clinical condition. However, their evolution into adenocarcinoma is rare. We report the case of a 68-year-old man with perineal and perianal chronic fistulas, who developed a perineal mass that extended proximally as a pararectal tumor. Diagnosis was confirmed by magnetic resonance imaging (MRI). Histopathological sections indicated extramucosal mucinous adenocarcinoma. No intestinal lesion was seen at endoscopic examination. The patient underwent abdominal perineal excision of the rectum without neoadjuvant or adjuvant therapy, and had a good postoperative outcome.