Piergiorgio Danelli

Long-term results and multivariate analysis of prognostic factors in 138 consecutive patients operated on for Crohn’s disease using “bowel-sparing” techniques

BACKGROUND Conservative surgery has become accepted as a useful option for the surgical treatment of complicated Crohns disease (CD). METHODS One hundred thirty-eight consecutive patients treated with strictureplasty or miniresections for complicated CD have been observed prospectively. The possible influence of a number of variables on the risk of recurrence was investigated using the Cox proportional hazard model, and a time-to-event analysis was made using the Kaplan-Meier function. RESULTS There was no perioperative mortality; the morbidity rate was 5.7%. A close correlation was found between the risk of recurrence and the time between diagnosis and first surgery. The overall 5-year recurrence rate was 24%, being 36% in the patients requiring surgery within 1 year of diagnosis and 14% in those operated on more than 1 year after diagnosis. CONCLUSIONS Risk factor analysis highlighted a group of patients at high risk of surgical recurrence. Given that our results are similar to those reported in other series, we consider strictureplasty and miniresections safe and effective procedures for the treatment of complicated CD.

Visceral adipocytes: old actors in obesity and new protagonists in Crohn's disease?

Objective Crohns disease (CD) is a chronic inflammatory bowel disease characterised by a peculiar accumulation of mesenteric adipose tissue covering the inflamed intestinal wall. Methods The authors characterised different adipose tissue compartments of patients with CD using morphological and molecular techniques and compared them to those of subjects with obesity (OB) and healthy subjects with normal weight (N). Adipose tissue samples were taken from subcutaneous adipose tissue, omental visceral adipose tissue (VAT) and healthy mesenteric depot (hMES), as well as from fat wrapping the affected (unhealthy) intestinal tracts (uhMES). Microarray analyses, validated by real-time quantitative PCR technique, were performed in whole adipose tissue and in isolated adipocytes. Results The morphology of subcutaneous adipose tissue was similar in subjects with CD and those with N. In patients with CD, VAT adipocytes were smaller than those derived from uhMES and hMES and were smaller than VAT adipocytes of subjects with N. The molecular profiles of CD, VAT and uhMES were characterised by upregulation of genes related to inflammation and downregulation of those involved in lipid metabolism. Adipocytes isolated from VAT of subjects with CD and those with OB exhibited similar upregulation of genes involved in inflammation and immunity. VAT adipocytes of patients with CD compared to those of patients with OB also showed a greater upregulation of several anti-inflammatory genes. Conclusion In patients with CD, VAT distant from uhMES is affected by inflammation and displays features similar to those of VAT of patients with severe OB. The small diameter of VAT adipocytes of CD, together with their high expression of anti-inflammatory genes, suggests a potentially protective role for this tissue. VAT adipocytes may play an important role in the pathophysiology and/or activity of CD.

Preoperative Characteristics and Postoperative Behavior of Bowel Wall on Risk of Recurrence After Conservative Surgery in Crohn’s Disease: A Prospective Study

ObjectiveTo evaluate in patients with Crohn’s disease, using transabdominal ultrasound, the morphologic characteristics of the diseased bowel wall before and after conservative surgery and to assess whether these characteristics and their behavior in the postoperative follow-up are useful and reliable prognostic factors of clinical and surgical recurrence. Summary Background DataUltrasound is effective for evaluating the thickness of bowel wall, the most typical and constant finding of Crohn’s disease. No data are currently available concerning the behavior of the diseased intestinal wall after conservative surgery and whether the preoperative characteristics of bowel wall or its behavior after conservative surgery may predict recurrence. MethodsIn 85 consecutive patients treated with strictureplasty and miniresections for Crohn’s disease, clinical and ultrasonographic evaluations were performed before and 6 months after surgery. Assessed before surgery were the maximum bowel wall thickness, the length of bowel wall thickening, the bowel wall echo pattern (homogeneous, stratified, and mixed), and the postoperative bowel wall behavior, classified as normalized, improved, unchanged, or worsened. ResultsA significant correlation was found between a long preoperative bowel wall thickening and surgical recurrence. Bowel wall thickness after surgery was unchanged or worsened in 43.3% of patients; in these patients, there was a high frequency of previous surgery. Patients with unchanged or worsened bowel wall thickness had a higher risk of clinical and surgical recurrence compared with those with normalized or improved bowel wall thickness. ConclusionWith the use of abdominal ultrasound, the authors found that the thickening of diseased bowel wall may unexpectedly improve after conservative surgery, and this is associated with a favorable outcome in terms of clinical and surgical recurrence. In addition to its diagnostic usefulness, ultrasound also provides reliable prognostic information concerning clinical and surgical recurrence in patients with Crohn’s disease in the postoperative follow-up.

Early perioperative results and surgical recurrence after strictureplasty and miniresection for complicated Crohn's disease.

Background/Aims: Strictureplasty (SP) or miniresective ‘bowel-sparing’ techniques (MR) can prevent the risk of intestinal stomia and short bowel syndrome in patients affected by Crohn’s disease (CD). The aim of this study was to analyze the perioperative morbidity and mortality in 104 of 138 consecutive patients treated for CD complications using bowel-sparing techniques. We also considered the factors that may be related to the risk of perioperative complications and the long-term outcome. Methods: One hundred and four patients were treated with SP and/or MR and then included in a prospectively maintained database. The factors claimed to influence perioperative complications were analyzed using Fisher’s exact test for categorical observations and the Mann-Whitney U test for continuous variables. A multivariate analysis, using logistic regression, and a long-term time-to-event analysis using the Kaplan-Meier function, were also performed. Results: Perioperative mortality was nil. In relation to the 6 postoperative complications (5.8%), 4 patients underwent minimal bowel resection (MR), 1 a MR with SP, and 1 SP alone. Three of these patients (2.9%) needed reoperation for septic complications, and 3 (2.9%) were treated as outpatients for enterocutaneous fistulas. A correlation (p < 0.05) was found between low serum hemoglobin levels and postoperative complications at univariate and multivariate analyses. The 5-year surgical recurrence-free rate was 75% overall, 73% for patients treated with SP, 78% with MR, and 77% with MR + SP. Conclusions: Postoperative complications are not related to conservative or miniresective surgery even when active disease is present at the resection margins or the site of SP. The higher risk reported for patients with low serum hemoglobin and hematocrit levels suggests that surgeons should consider using preoperative iron and vitamin support, parenteral nutrition and erythropoietin therapy, when necessary, in those cases. Our postoperative morbidity, mortality and long-term surgical recurrence rate results support the efficacy and safety of SP and MR surgery in the treatment of complicated CD.

Femoro-popliteal by-pass occlusion following mesh-plug for prevascular femoral hernia repair

SummaryMesh plug repair for both inguinal and femoral hernias had a minimal number of postoperative complications reported. Among femoral hernias, the prevascular type represents a variant, because of the peculiar position of the sac strictly adjacent to the vessels. The authors report a case of femoral occlusion following femoro-popliteal by-pass and concomitant homolateral femoral hernia repair by cylindrical polypropylene plug not secured by sutures, which laid directly on the vessels. This complication occurs three months following surgery, the plug being displaced over and tightly adherent to the femoral-graft anastomosis. The apposition of a polypropylene mesh plug directly over the PTFE vascular graft could have stimulated the massive local fibrous reaction found at histology, a reaction not explained by the insertion of the PTFE only. The authors suggest that polypropylene plugs for repair of prevascular type of femoral hernias should be avoided, when concomitant or future arterial grafting procedures are needed.

Differences in Visceral Fat and Fat Bacterial Colonization between Ulcerative Colitis and Crohn’s Disease. An In Vivo and In Vitro Study

Crohn’s disease (CD) is notably characterized by the expansion of visceral fat with small adipocytes expressing a high proportion of anti-inflammatory genes. Conversely, visceral fat depots in ulcerative colitis (UC) patients have never been characterized. Our study aims were a) to compare adipocyte morphology and gene expression profile and bacterial translocation in omental (OM) and mesenteric (MES) adipose tissue of patients with UC and CD, and b) to investigate the effect of bacterial infection on adipocyte proliferation in vitro. Specimens of OM and MES were collected from 11 UC and 11 CD patients, processed and examined by light microscopy. Gene expression profiles were evaluated in adipocytes isolated from visceral adipose tissue using microarray and RTqPCR validations. Bacteria within adipose tissue were immuno-detected by confocal scanning laser microscopy. Adipocytes were incubated with Enterococcus faecalis and cells counted after 24h. Morphology and molecular profile of OM and MES revealed that UC adipose tissue is less inflamed than CD adipose tissue. Genes linked to inflammation, bacterial response, chemotaxis and angiogenesis were down-regulated in adipocytes from UC compared to CD, whereas genes related to metallothioneins, apoptosis pathways and growth factor binding were up-regulated. A dense perinuclear positivity for Enterococcus faecalis was detected in visceral adipocytes from CD, whereas positivity was weak in UC. In vitro bacterial infection was associated with a five-fold increase in the proliferation rate of OM preadipocytes. Compared to UC, visceral adipose tissue from CD is more inflamed and more colonized by intestinal bacteria, which increase adipocyte proliferation. The influence of bacteria stored within adipocytes on the clinical course of IBD warrants further investigations.

In vitro and in vivo effects of metformin on human adipose tissue adiponectin.

Objective: The effects of metformin on adiponectin production are controversial and have never been investigated in human adipose tissue. We analysed whether metformin modulates, in vitro and in vivo, gene expression, protein content, and secretion of adiponectin. Methods: For the in vitro study, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) samples from 5 non-diabetic obese patients were collected. For the in vivo investigation, 22 obese patients were randomly assigned to metformin+lifestyle (ML) or placebo+lifestyle (PL) intervention. SAT specimens and blood samples were collected before and after the intervention in both groups. Results: In in vitro experiments, treatment with metformin increased the expression and secretion of adiponectin in SAT, but not in VAT explants. In the in vivo study, a significant increase in adiponectin and a decreased expression of a macrophage activation marker (CD68) were observed only in SAT of the ML group. Conclusion: These results demonstrate that metformin is able to up-regulate adiponectin gene expression, both in vivo and in vitro, and to stimulate adiponectin protein secretion from human SAT in vitro. It could be hypothesised that metformin-induced adiponectin increase within adipose tissue may have an unexpected role in the reduction of local inflammation.

Intermittent small-bowel obstruction caused by gastric adenocarcinoma in a Meckel's diverticulum

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Ultrasonographic detection of toxic megacolon in inflammatory bowel diseases.

Toxic megacolon (TMC) is the most severe lifethreatening complication of ulcerative colitis (UC). In patients with inflammatory bowel diseases (IBD), the diagnosis of TMC relies on clinical suspicion and requires plain films of the abdomen, laboratory tests, and sigmoidoscopy. The latter should be performed without colonic preparation, since intestinal preparation or total examination may result in a dramatic deterioration in the clinical condition (1). Any safe, noninvasive, readily available diagnostic technique that adds information to clinical suspicion in the attempt to diagnose TMC correctly is welcome. Abdominal ultrasound (US) is considered a useful and accurate tool in the assessment of Crohn’s disease (CD) and UC (2–5). Abdominal US, thanks to its ready availability, repeatability, and low cost is frequently used as the primary investigation in patients with abdominal pain or acute abdomen, even before performing, or instead of, conventional x-ray studies. US is also used in the follow-up of IBD patients, since it can accurately demonstrate the classic features of IBD as well as the frequent intraabdominal complications. In this regard, US detection of stenoses, fistulae, abscesses, and free perforations has been reported and described (6–8). Unlike these complications, the potential of abdominal US in the detection of TMC has not been reported so far. Therefore, with the increasing use of US as a primary diagnostic tool in acute conditions and/or in the followup of IBD patients, it is possible to encounter TMC, and suspicion, or even recognition, of the condition may be useful in clinical practice.

Role of the advanced glycation end products receptor in Crohn's disease inflammation.

AIM To investigate the level of mucosal expression and the involvement of the receptor for the advanced glycation end products (RAGE) in delayed apoptosis and tumor necrosis factor (TNF)-α production in Crohns disease (CD). METHODS Surgical and endoscopic specimens from both inflamed and non-inflamed areas of the ileum and/or colon were collected from 20 and 14 adult CD patients, respectively, and used for the assessment of RAGE expression by means of immunohistochemistry and western blotting analysis. Normal tissues from 21 control subjects were used for comparison. The same polyclonal anti-human RAGE antibody (R and D System) was used in all experimental conditions. RAGE staining was quantized by a score including both the amount of positive cells and intensity of immunoreactivity; cellular pattern was also described. The effects of RAGE blocking on apoptotic rate and TNF-α production were investigated on immune cells freshly isolated from CD mucosa and incubated both with and without the muramyl dipeptide used as antigenic stimulus. Statistical analysis was performed via the test for trend, with regression models to account for intra-patient correlations. A 2-sided P < 0.05 was considered significant. RESULTS In inflamed areas, RAGE expression in both the epithelial and lamina propria compartments was higher than control tissues (P = 0.001 and 0.021, respectively), and a cluster of positive cells were usually found in proximity of ulcerative lesions. Similar results were obtained in the lamina propria compartment of non-inflamed areas (P = 0.025). The pattern of staining was membranous and granular cytosolic at the epithelial level, while in the lamina propria it was diffuse cytosolic. When evaluating the amount of protein expression by immunoblotting, a significant increase of both surface area and band intensity (P < 0.0001 for both) was observed in CD inflamed areas compared to control tissue, while in non-inflamed areas a significant increase was found only for band intensity (P < 0.005). Moreover, a significantly lower expression in non-inflamed areas in comparison with inflamed areas was found for both surface area and band intensity (P < 0.0006 for both). Finally, RAGE blocking largely affects both the apoptotic rate of mucosal cells (towards an increase in both non-inflamed and inflamed areas of P < 0.001 and < 0.0001, respectively) and TNF-α secretion (towards a decrease in both non-inflamed and inflamed areas of P < 0.05 and < 0.01, respectively), mainly in the presence of antigenic stimulation. CONCLUSION RAGE is up-regulated in CD, especially in inflamed areas, and it appears to play a role in the mechanisms involved in chronic inflammation.