Francesco Selvaggi

Non-colorectal intestinal tract carcinomas in inflammatory bowel disease: results of the 3rd ECCO Pathogenesis Scientific Workshop (II)

Patients with inflammatory bowel diseases (IBD) have an excess risk of certain gastrointestinal cancers. Much work has focused on colon cancer in IBD patients, but comparatively less is known about other more rare cancers. The European Crohns and Colitis Organization established a pathogenesis workshop to review what is known about these cancers and formulate proposals for future studies to address the most important knowledge gaps. This article reviews the current state of knowledge about small bowel adenocarcinoma, ileo-anal pouch and rectal cuff cancer, and anal/perianal fistula cancers in IBD patients.

Complications and functional outcomes of restorative proctocolectomy for ulcerative colitis in the elderly

BackgroundRestorative proctocolectomy with ileopouch-anal anastomosis (IPAA) is the treatment of choice for intractable or complicated ulcerative colitis (UC). Debate exists concerning outcomes of IPAA in the elderly and literature data are scarce. We report our experience of IPAA in older population.MethodsWe gathered data on a prospective database of patients undergoing IPAA for UC over 70 years of age in our Unit from January 1990 through January 2010. Patients were compared with randomly selected younger controls on a 1:3 ratio. Patients underwent IPAA in 2 or 3 stages. Demographical data, disease characteristics, comorbidities, concomitant medications, peri-operative management, intra- and post-operative complications were analyzed. Function and quality of life were assessed by clinical visit and Inflammatory Bowel Disease Questionnaire 1 and 3 years after ileostomy takedown.ResultsTwenty-seven elderly patients underwent IPAA for UC in the study period; these were compared with 81 younger controls. The former had more comorbidities and higher ASA score. All patients underwent loop-ileostomy closure. There were no differences between groups concerning the rate of major complications, but elderly patients more frequently had nuisances due to stoma output. Younger patients experienced significantly more episodes of small bowel obstruction. No significant differences in bowel control and health-related quality of life was observed, except for an higher rate of elderly patients taking antidiarrhoeals at 1-year follow-up; this observation was not confirmed at 3-year follow-up. A minimal decrease in continence was observed, but this did not affect overall satisfaction.ConclusionsIPAA can be safely offered to selected elderly UC patients who are strongly motivated and with no clinical disturbances of continence. In experienced hands no differences are likely to be expected concerning complications, quality of life and function. Results are stable with time and comparable to those of younger patients.

Systematic review of cuff and pouch cancer in patients with ileal pelvic pouch for ulcerative colitis.

Background:Ileal pouch–anal anastomosis (IPAA) is the procedure of choice for refractory or complicated ulcerative colitis (UC). Since 1990, pouch-related adenocarcinomas have been described. The aim of this study was to review the literature to evaluate the burden of this complication, seeking for risk factors, prevention, and ideal management. Methods:We performed a systematic review of the literature to identify all described pouch-related adenocarcinoma in patients operated on with IPAA for UC. Studies were thoroughly evaluated to select authentic de novo pouch carcinomas. Some authors were contacted for additional information. Data of patients were pooled. Meta-analyses of suitable studies were attempted to identify risk factors. Results:Thirty-four articles reported on 49 patients (2:1, male:female) who developed unequivocal pouch-related adenocarcinoma, 14 (28.6%) and 33 (67.3%) arising from the pouch and anorectal mucosa, respectively. Origin was not reported in 2 (4%). Pooled cumulative incidence of pouch-related adenocarcinoma was 0.33% (95% confidence interval [CI], 0.31–0.34) 50 years after the diagnosis and 0.35% (95% CI, 0.34–0.36) 20 years after IPAA. Primary pouch cancer incidence was below 0.02% 20 years after IPAA. Neoplasia on colectomy specimen was the strongest risk factor (odds ratio, 8.8; 95% CI, 4.61–16.80). Mucosectomy did not abolish the risk of subsequent cancer but avoiding it increased 8 times the risk of cancer arising from the residual anorectal mucosa (odds ratio, 8; 95% CI, 1.3–48.7; P = 0.02). Surveillance is currently performed yearly starting 10 years since diagnosis, but cancers escaping this pathway are reported. In patients receiving mucosectomy, a 5-year delay for surveillance could be proposed. Conclusions:Pouch-related adenocarcinomas are rare. Diagnosis of Crohns disease in the long term may further decrease the rates in UC. Presumed evolution from dysplasia might offer a time window for cancer prevention. Abdominoperineal excision should be recommended for pouch-related adenocarcinomas.

Rectal diverticulum: a new complication of STARR procedure for obstructed defecation

We report a case of rectal diverticulum developed after stapled transanal rectal resection (STARR) procedure for obstructed defecation. A 21-year-old woman with chronic constipation was diagnosed with a rectocele at defecography. The patient underwent STARR procedure. Six months later, she presented with severe constipation requiring enemas and a worse condition than that preoperatively. Defecography and rectoscopy revealed a rectal wall diverticulum cavity with incomplete elimination of barium enema. The patient underwent transanal diverticulectomy and direct rectal wall repair. STARR procedure can produce new and difficult-to-treat complications and should be reserved for expert colorectal surgeons with proved familiarity in transanal surgery.

Evaluation of Quantitative PET/MR Enterography Biomarkers for Discrimination of Inflammatory Strictures from Fibrotic Strictures in Crohn Disease

PURPOSE To retrospectively evaluate positron emission tomography (PET)/magnetic resonance (MR) enterography for the differentiation of fibrotic strictures from inflammatory strictures in patients with Crohn disease. MATERIALS AND METHODS This HIPAA-compliant retrospective study was approved by the institutional review board. Patients gave their written informed consent for study enrollment. PET/MR enterography images were evaluated in 19 patients with Crohn disease who had strictures that underwent surgical resection with pathologic confirmation. Two radiologists and a nuclear medicine physician in consensus evaluated the following bowel wall PET/MR enterography biomarkers: signal intensity (SI) on T2-weighted images, apparent diffusion coefficient (ADC), PET maximum standardized uptake value (SUVmax), SI on T2-weighted images × SUVmax, and ADC × SUVmax values at levels that corresponded to pathologic specimens. MR, PET, and hybrid PET/MR biomarkers were compared, and the performance for differentiation of inflammatory strictures from fibrotic strictures was assessed. Mixed-model regression analysis was used to compare the mean imaging parameters between groups; the P values were corrected for the five comparisons by using the Bonferroni method. RESULTS Three of the PET/MR enterography biomarkers, SUVmax, SI on T2-weighted images × SUVmax, and ADC × SUVmax, showed significant differences in the fibrosis group compared with the fibrosis with active inflammation group and the active inflammation only group. The best discriminator between fibrosis and active inflammation was the combined PET/MR enterography biomarker ADC × SUVmax cutoff of less than 3000, which was associated with accuracy, sensitivity, and specificity values of 0.71, 0.67, and 0.73, respectively. CONCLUSION PET/MR enterography offers a potential noninvasive technique for the differentiation of purely fibrotic strictures from mixed or inflammatory strictures. A hybrid biomarker that incorporates both MR and PET information performed better for stricture evaluation than either modality alone.

Randomized, controlled trial to compare the J-pouch and W-pouch configurations for ulcerative colitis in the maturation period.

PURPOSE: Proctocolectomy with ileal pouch-anal anastomosis has become the procedure of choice for the treatment of ulcerative colitis. Functional results may differ with different pouch designs. This randomized study aimed to evaluate the relative effectiveness of two-limb J and four-limb W reservoir designs in the so-called maturation period after ileostomy closure. METHODS: Twenty-four patients underwent ileal pouch-anal anastomosis for ulcerative colitis. Eleven were randomly assigned to the J-pouch group and 13 to the W-pouch group. Frequency of defecation and other functional data were collected at 4, 8, and 12 months after ileostomy closure. Maximum tolerated volume was assessed in the same period by a latex balloon inflated with water. Maximum resting anal pressure, maximum voluntary contraction, and the rectoanal inhibitory reflex were assessed in the preoperative period and at 4, 8, and 12 months after ileostomy closure. RESULTS: Frequency of defecation decreased from 4 to 12 months after ileostomy closure in both groups (P=0.04), but patients with a W-pouch had significantly lower values than patients with J-pouches (P<0.01). Night-time defecation (P=0.04) and use of antidiarrheals (P=0.04) were significantly lower for patients with a W-pouch. Maximum tolerated volume was greater in the W-pouch group throughout the whole period (P=0.01). Maximum resting anal pressure, maximum voluntary contraction, and rectoanal inhibitory reflex did not differ between the study arms CONCLUSION: Patients with W-pouch have better functional results than those with J-pouches in the “maturation period” after ileostomy closure.

FGD‐PET in the follow‐up of recurrent colorectal cancer

Objective  The current methods of detection of recurrent colorectal cancer after surgical treatment are inaccurate using conventional imaging. This study set out to detect early recurrence by means of PET in patients treated surgically for colorectal cancer by curative resection.

Effects of a new pocket device for negative pressure wound therapy on surgical wounds of patients affected with Crohn's disease: a pilot trial.

Introduction. Surgical site infections (SSIs) affect costs of care and prolong length of stay. Crohn’s disease (CD) represents an independent risk factor for SSI. The risk can be further increased by concomitant administration of immunosuppressive drugs and poor performance status at the time of surgery. Patients suffering from CD often need more than one surgical intervention during life, sometimes requiring fashioning of a stoma. The aim of this pilot study was to compare a portable device for negative pressure wound therapy (PICO, Smith & Nephew, London, UK) to conventional gauze dressings in patients undergoing surgery for stricturing CD. Methods. Between January 2010 and November 2011, this controlled trial enrolled 30 patients, who were assigned to treatment with either PICO (n = 13) or conventional dressings (n = 17). Each patient completed a 3-month follow-up. Results. Patients receiving PICO experienced significantly less postoperative wound complications (P = .001) and SSI (P = .017) compared with those who received conventional dressings. This resulted in shorter hospital stay (P = .0007). No significant differences in cosmetic results were found. Conclusion. These data suggest that PICO allows faster and safe discharge by reducing the incidence of SSI and wound-related complications in selected patients undergoing surgical intervention for stricturing CD. This could be particularly useful in patients receiving steroids.

Effect of preoperative biologic drugs on complications and function after restorative proctocolectomy with primary ileal pouch formation: systematic review and meta-analysis.

Background:Debate exists concerning the presumed risk of postoperative complications in patients with ulcerative colitis (UC) receiving preoperative infliximab (IFX). Meta-analyses are contrasting because of many confounders included into analysis. Our aim was to determine the impact of IFX on pouch-related postoperative complications in patients with UC undergoing surgery with primary ileal pouch–anal anastomosis. Methods:We performed a systematic review to identify studies comparing the outcomes of patients undergoing surgery for UC with or without previous IFX exposure. The primary end points were (1) early ileal pouch–anal anastomosis–related complications after surgery with primary pouch formation and (2) those occurring after ileostomy closure. Secondary end points were the effects of IFX on total, infectious, and noninfectious complications in patients with UC undergoing any type of surgery. Results are reported as pooled odds ratio (OR) with 95% confidence intervals (CIs). Results:Seven papers, including 162 patients receiving biologics and 468 controls all undergoing primary pouch formation, were included for the primary aim. Patients receiving IFX were more likely developing early (OR = 4.12; 95% CI, 2.37–7.15; P < 0.001) and post-ileostomy closure (OR = 2.27; 95% CI, 1.27–4.05; P = 0.005) ileal pouch–anal anastomosis–related complications. Number needed to harm was calculated to be 5 and 4, respectively. Having received at least 3 IFX effusions increased the risk of early complications (OR = 9.59; 95% CI, 2.92–31.44; P = 0.0002), whereas an interval of <12 weeks since last effusion did not (OR = 2.35; 95% CI, 0.98–5.64; P = 0.06). Meta-analyses of 14 studies reporting on any type of surgery found that IFX showed a trend toward higher total and infectious complications, but no significant differences were observed. Biologics were associated with lower surgical site infection (OR = 0.67; 95% CI, 0.45–0.99; P = 0.04). Conclusions:IFX exposure increases early pouch-specific complications and complications after ileostomy closure in UC. Avoiding primary pouch formation could be a prudent approach.

Vascular endothelial growth factor and cyclooxygenase-2 are overexpressed in ileal pouch-anal anastomosis

PurposePathophysiology of pouchitis after ileal pouch-anal anastomosis is controversial because of the potential for development of carcinoma. Cyclooxygenase-2-derived prostaglandins may be involved in the inflammatory process and play a role in the pathogenesis of colon cancer. Vascular endothelial growth factor plays a major role in neoangiogenesis and is overexpressed in a number of gastrointestinal malignancies. The goal of this study was to evaluate the expression of cyclooxygenase-2 and vascular endothelial growth factor and to assess neoangiogenesis and epithelial cell proliferation in patients with ileal pouch-anal anastomosis.MethodsEndoscopic biopsies were obtained from 15 patients with ileal pouch-anal anastomosis without pouchitis (10 biopsies from the ileal pouch and 10 from ileal nonpouch mucosa) and from 15 subjects with irritable bowel syndrome (10 biopsies from normal-appearing ileum and rectum). Cyclooxygenase-1, cyclooxygenase-2, and vascular endothelial growth factor messenger ribonucleic acid expression was determined by reverse transcriptase polymerase chain reaction. Cyclooxygenase-2 and vascular endothelial growth factor protein expression was evaluated by Western blot. Cyclooxygenase-2, vascular endothelial growth factor, CD34 (neoangiogenesis marker), and Ki67 (proliferation marker) mucosal localizations were evaluated by immunohistochemistry.ResultsExpression of cyclooxygenase-2 and vascular endothelial growth factor was increased in ileal pouch mucosa compared with ileal nonpouch mucosa, normal ileum, and rectum. Cyclooxygenase-2 and vascular endothelial growth factor immunostaining in ileal pouch mucosa was more intense in the crypt area than in the surface epithelium compared with ileal nonpouch mucosa. CD34 (neoangiogenesis marker) and Ki67 (proliferation marker) expression was increased in ileal pouch mucosa.ConclusionsCyclooxygenase-2 and vascular endothelial growth factor are overexpressed in the ileal pouch mucosa. This is associated with increased proliferative activity and neoangiogenesis. Cyclooxygenase-2 and vascular endothelial growth factor overexpression might play a role in the pathogenesis of pouchitis.