Strictureplasty for Crohn's disease of the small bowel in the biologic era: long-term outcomes and risk factors for recurrence.

BACKGROUND: The number of indications for strictureplasty for Crohn's disease has been greatly reduced since the widespread use of biologics, although the risk of intestinal failure remains. The aim of the study was to analyze the outcomes of strictureplasty and to identify risk factors for site-specific recurrence in the era of biologics. METHODS: Consecutive patients treated with strictureplasty for Crohn's disease between 2002 and 2018 were retrospectively included. Univariate analysis was carried out. Risk factors for recurrence were identified through a multilevel logistic regression analysis. RESULTS: Two hundred sixty-six patients were included in the study ( 171 males, median age 39.5 years, range 18-76 years). The majority of the 718 strictures requiring surgery in these patients were located in the ileum (61%), treated with conventional strictureplasty (89.6%) and required an additional resection (73.7%). Median follow-up time and time to recurrence were 96 months and 62.5 months respectively. The site-specific recurrence rate was 12.2% at 5 years and 25.7% at 10 years. Smoking was associated with a higher risk of recurrence in patients with milder disease. The 10-year recurrence rate was significantly higher for strictureplasties performed in the terminal ileum (30.9%, p = 0.0019) as compared to the ileum (21.8%) and the jejunum (8.4%). Multilevel logistic regression analysis showed that postoperative exposure to biologics (OR 4.74, p 0.001), nonconventional strictureplasty (OR 3.57, p 0.008) and a strictureplasty performed on a previous anastomosis (OR 13.58, p 0.002) were associated with site-specific recurrence. CONCLUSIONS: Strictureplasty is associated with optimal long-term outcomes in the biologic era and should be performed when feasible, to reduce the risk of intestinal failure in Crohn's disease patients.

Inflammatory bowel disease position statement of the Italian Society of Colorectal Surgery (SICCR): Crohn's disease.

The Italian Society of Colorectal Surgery (SICCR) promoted the project reported here, which consists of a position statement of Italian colorectal surgeons to address the surgical aspects of Crohn's disease management. Members of the society were invited to express their opinions on several items proposed by the writing committee, based on evidence available in the literature. The results are presented, focusing on relevant points. The present paper is not an alternative to available guidelines; rather, it offers a snapshot of the attitudes of SICCR surgeons about the surgical treatment of Crohn's disease. The committee was able to identify some points of major disagreement and suggested strategies to improve quality of available data and acceptance of guidelines.

Correction to: Inflammatory bowel disease position statement of the Italian Society of Colorectal Surgery (SICCR): Crohn's disease.

The affiliation of the author Silvio Danese has been incorrectly published in the original publication.

Endoluminal vacuum-assisted therapy as treatment for anastomotic leak after ileal pouch-anal anastomosis: a pilot study.

BACKGROUND: Anastomotic leak after ileal pouch-anal anastomosis (IPAA) could lead to poor functional results and failure of the pouch. The aim of the present study was to analyze the outcomes of the vacuum-assisted closure therapy as the unique treatment for anastomotic leaks following IPAA without any additional surgical operations. METHODS: Consecutive patients with anastomotic leak after IPAA treated at our institution between March 2016 and March 2017 were prospectively enrolled. After diagnosis, the Endosponge® device was positioned in the gap and replaced until the cavity was reduced in size and covered by granulating tissue. A pouchoscopy was performed every week for the first month and monthly subsequently. No additional procedures were performed. RESULTS: Eight patients were included in the study. The leak was diagnosed at a median of 14 (6-35) days after surgery. At the time of diagnosis, seven patients had a defunctioning ileostomy performed as routine at the time of pouch formation, while one patient was diagnosed after ileostomy closure and underwent emergency diversion ileostomy. The Endosponge® treatment started after a median of 6.5 (1-158) days after the diagnosis of the leakage and was carried on for a median of 12 (3-42) days. The device was replaced a median of 3 (1-10) times. The median length of hospital stay after the first application of the treatment was 15.5 (6-48) days. The complete healing of the leak was documented in all patients, after a median of 60 (24-90) days from the first treatment. All patients but one had their ileostomy reversed at a median of 2.5 (1-6) months from the confirmation of the complete closure. CONCLUSIONS: Endosponge® is effective as the only treatment after IPAA leak. Based on the results of our prospective pilot study, application of Endosponge® should be the treatment of choice in selected pouch anastomotic leaks not requiring immediate surgery. These results will have to be confirmed by future prospective studies including a larger number of patients.

Risk of permanent stoma in extensive Crohn's colitis: the impact of biological drugs.

AIM: The overall risk of permanent stoma was determined in patients with extensive Crohn's colitis. An attempt was made to analyse whether biological drugs have modified the surgical approach in patients with anorectal involvement. METHOD: In all, 233 patients with Crohn's disease colitis operated on between 1995 and 2010 were reviewed retrospectively. Fifty-one were treated before 2002 (prebiological era) and 182 after 2002 (biological era). The relationship was determined between the use of immunosuppressors, biological drugs, the presence of perianal disease and anorectal stenosis and the rate of permanent stoma formation. RESULTS: In the prebiological era 23 (45.1%) patients without anorectal involvement underwent colectomy and ileorectal anastomosis, 17 (33.3%) with severe anorectal disease had proctocolectomy and 11 (21.6%) with anorectal involvement had abdominal colectomy with permanent ileostomy. In the biological era 73 (40.1%) patients without anorectal involvement underwent colectomy and ileorectal anastomosis, nine (5%) with severe anorectal involvement had proctocolectomy and 100 (54.9%) with anorectal involvement had colectomy with terminal ileostomy. Of these 100, 75 have subsequently been treated with biological drugs with full regression of anorectal lesions in 81.3%. Rates of permanent stoma in the prebiological and biological era were 60.8% and 19.2% (P < 0.001). Univariate and multivariate analysis showed that only the use of biological drugs was significantly associated with an increased rate of rectal preservation (P < 0.05). CONCLUSION: The risk of a permanent stoma in patients with Crohn's colitis and anorectal involvement is significantly reduced with combined surgical and biological treatment.

Oral budesonide in the treatment of chronic refractory pouchitis.

BACKGROUND: Pouchitis is the major long-term complication after ileal-pouch nal anastomosis for ulcerative colitis. Ten to 15% of patients develop a chronic pouchitis, either treatment responsive or treatment refractory. AIM: To evaluate the efficacy of oral budesonide in inducing remission and improving quality of life in patients with chronic refractory pouchitis. METHODS: Twenty consecutive patients with active pouchitis, not responding after 1 month of antibiotic treatment were treated with budesonide controlled ileal release 9 mg/day for 8 weeks. Symptomatic, endoscopic and histological evaluations were undertaken before and after treatment according to Pouchitis Disease Activity Index. Remission was defined as a combination of Pouchitis Disease Activity Index clinical score of < or = 2, endoscopic score of < or = 1 and total Pouchitis Disease Activity Index score of < or = 4. The quality of life was assessed with the Inflammatory Bowel Disease Questionnaire. RESULTS: Fifteen of 20 patients (75%) achieved remission. The median total Pouchitis Disease Activity Index scores before and after therapy were, respectively, 14 (range 9-16) and 3 (range 2-10) (P < 0.001). The median Inflammatory Bowel Disease Questionnaire score also significantly improved from 105 (range 77-175) to 180 (range 85-220) (P < 0.001). CONCLUSION: Eight-week treatment with oral budesonide appears effective in inducing remission in patients with active pouchitis refractory to antibiotic treatment in this open-label study.

Controlled study using wireless capsule endoscopy for the evaluation of the small intestine in chronic refractory pouchitis.

BACKGROUND: Pouchitis is a common long-term complication after ileal pouch anal anastomosis for ulcerative colitis. Chronic refractory pouchitis is a treatment-resistant condition that affects 5-15% of patients. AIM: To test the hypothesis of a small bowel involvement using wireless capsule endoscopy. MATERIAL AND METHODS: This is a single-blind, prospective, cohort study. Twenty-four patients: 16 were patients with chronic refractory pouchitis and eight, with a macroscopically and histologically normal ileal pouch, were considered as control subjects. Diagnosis of pouchitis was confirmed using the pouchitis disease activity index. All subjects were submitted to wireless capsule endoscopy procedure. Within 2 weeks before wireless capsule endoscopy, patients underwent a pouch endoscopy and a small bowel follow-through. Re-examination of the colonic surgical and histological specimens was also performed. RESULTS: One patient with chronic pouchitis was excluded because of incomplete bowel cleaning. At small bowel follow-through of 16 patients, two subjects (13%) showed only a focal ectasia of the middle ileum and a substenosis of the pouch. At wireless capsule endoscopy all the 15 evaluable patients with chronic pouchitis (100%) showed diffuse lesions from duodenum to ileum consisting of aphthae, erosions, erythema, atrophy, cobblestone, deep/fissural ulcers. CONCLUSIONS: This enteropathy needs further research, and wireless capsule endoscopy could be useful to show involvement of small bowel in patients with chronic pouchitis.

Surgical outcome and long-term follow up after laparoscopic rectosigmoid resection in women with deep infiltrating endometriosis.

The aim of this study was to assess the long-term outcome of treating severely symptomatic women with deep infiltrating intestinal endometriosis by laparoscopic segmental rectosigmoid resection. Detailed intraoperative and postoperative records and questionnaires (preoperatively, 1 month postoperatively and every 6 months for 3 years) were collected from 22 women. The estimated blood loss during surgery was 290 +/- 162 ml (range 180-600), and average hospital stay was 8 days (range 6-19). One woman required blood transfusion after surgery. Two cases were converted to laparotomy. One woman had early dehiscence of the anastomosis. Six months after surgery, there was a significant reduction of symptom scores (greater than 50% for most types of pain) related to intestinal localisation of endometriosis (P < 0.05). Score improvements were maintained during the whole period of follow up. Noncyclic pelvic pain scores showed significant reductions (P < 0.05) after 6 and 12 months, but there was a high recurrence rate later. Dysmenorrhoea and dyspareunia improved in 18/21 and 14/18 women with preoperative symptoms, respectively. Constipation, diarrhoea and rectal bleeding improved in all affected women for the whole period of follow up. Laparoscopic segmental rectosigmoid resection seems safe and effective in women with deep infiltrating colorectal endometriosis resulting in significant reductions in painful and dysfunctional symptoms associated with deep bowel involvement.

Reoviruses and the host cell.

Reovirus infection of target cells can perturb cell cycle regulation and induce apoptosis. Differences in the capacity of reovirus strains to induce cell cycle arrest at G1 and G2/M have been mapped to the viral S1 genome segment, which also determines differences in the ability of reovirus strains to induce apoptosis and to activate specific mitogen-activated protein kinase (MAPK) cascades selectively. Reovirus-induced apoptosis involves members of the tumor necrosis factor (TNF) superfamily of death receptors and is associated with activation of both death receptor- and mitochondrial-associated caspases. Reovirus infection is also associated with the activation of a variety of transcription factors, including nuclear factor (NF)-kappaB. Junctional adhesion molecule (JAM) has recently been identified as a novel reovirus receptor. Reovirus binding to JAM appears to be required for induction of apoptosis and activation of NF-kappaB, although the precise cellular pathways involved have not yet been identified.

Combined carriership of TLR9-1237C and CD14-260T alleles enhances the risk of developing chronic relapsing pouchitis.

AIM: To investigate the single nucleotide polymorphisms (SNPs) in genes involved in bacterial recognition and the susceptibility to pouchitis or pouchitis severity. METHODS: Analyses of CD14 -260C>T, CARD15/NOD2 3020insC, Toll-like receptor (TLR)4 +896A>G, TLR9 -1237T>C, TLR9+2848G>A, and IRAKM + 22148G>A SNPs were performed in 157 ileal-pouch anal anastomosis (IPAA) patients (79 patients who did not develop pouchitis, 43 infrequent pouchitis patients, 35 chronic relapsing pouchitis patients) and 224 Italian Caucasian healthy controls. RESULTS: No significant differences were found in SNP frequencies between controls and IPAA patients. However, a significant difference in carriership frequency of the TLR9-1237C allele was found between the infrequent pouchitis and chronic relapsing pouchitis groups [P = 0.028, oddos ratio (OR) = 3.2, 95%CI = 1.2-8.6]. This allele uniquely represented a 4-locus TLR9 haplotype comprising both studied TLR9 SNPs in Caucasians. Carrier trait analysis revealed an enhanced combined carriership of the alleles TLR9 -1237C and CD14 -260T in the chronic relapsing pouchitis and infrequent pouchitis group (P = 0.018, OR = 4.1, 95%CI = 1.4 -12.3). CONCLUSION: There is no evidence that the SNPs predispose to the need for IPAA surgery. The significant increase of the combined carriership of the CD14 -260T and TLR9 -1237C alleles in the chronic relapsing pouchitis group suggests that these markers identify a subgroup of IPAA patients with a risk of developing chronic or refractory pouchitis.

Review article: indication and type of surgery in Crohn's disease.

The large majority of patients affected by Crohn's disease require surgery during their clinical history. Radical resection originally advocated for Crohn's disease does not decrease the recurrence rate, and repeated resections predispose patients to the development of short-bowel syndrome. Over the last few years, conservative surgery has become accepted by many authors as a safe means of treating obstructive Crohn's disease. In this review article we analyse the efficacy and safety of conservative techniques, in comparison with resective surgery. Indications, advantages and technical aspects of resective and conservative surgery are reported. The experience with 489 patients treated for complicated or treatment refractory Crohn's disease in our Institution suggests that strictureplasty is a safe and effective procedure in many cases, as reported by other authors. The risk of cancer in areas of active disease as in stenosis treated with strictureplasty seems to be negligible. Resective surgery still represents the 'gold standard' in patients with perforating Crohn's disease; however, conservative surgery, usually contraindicated in perforating Crohn's disease, can be advocated in patients with localized perforating disease presenting an actual risk of short bowel syndrome.

Four-week open-label trial of metronidazole and ciprofloxacin for the treatment of recurrent or refractory pouchitis.

BACKGROUND: Preliminary data suggest that short-term antibiotic therapy with a single drug is effective for the treatment of patients with pouchitis. However, some patients are resistant to treatment. AIM: To evaluate the therapeutic efficacy of a prolonged course of a combination of two antibiotics in patients with refractory or recurrent pouchitis, as well as its impact on their quality of life. METHODS: Patients with active refractory or recurrent pouchitis were recruited. This was defined as both: (i) a history of pouchitis at least twice in the last 12 months or persistent pouchitis requiring continual intake of antibiotics; and (ii) a Pouchitis Disease Activity Index score 3 7 (best to worst pouchitis=0-18) at the beginning of therapy. Treatment consisted of a combination of metronidazole, 400 or 500 mg twice daily, and ciprofloxacin, 500 mg twice daily, for 28 days. Symptomatic, endoscopic and histological evaluations were undertaken before and after antibiotic therapy using the Pouchitis Disease Activity Index score. Remission was defined as a combination of a Pouchitis Disease Activity Index clinical score of

Long-term efficacy of bismuth carbomer enemas in patients with treatment-resistant chronic pouchitis.

BACKGROUND: Mucosal inflammation of the ileal pouch (pouchitis) is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. Broad-spectrum antibiotics are the mainstay of treatment, however, 15% of patients with pouchitis have a chronic, treatment-resistant disease. AIM: To determine the safety and efficacy of bismuth carbomer enemas in achieving and maintaining remission in treatment-resistant chronic pouchitis. METHODS: Twelve patients with treatment-resistant chronic pouchitis were treated nightly for 45 days with enemas containing elemental bismuth complexed with carbomer. Diagnosis of pouchitis and response to treatment were evaluated with the Pouchitis Disease Activity Index (PDAI), which includes clinical, sigmoidoscopic and histological criteria. Serum bismuth concentrations were determined by atomic absorption. RESULTS: Ten of 12 patients (83%) went into remission, with a significant decrease of mean total PDAI score from 12 (range 9-15) to 6 (4-15) (P < 0.002), and were continued on bismuth carbomer enemas administered every third night for 12 months. Patients were monitored clinically, sigmoidoscopically and histologically every 2 months for evidence of recurrence (increase > or = 2 in the clinical symptom portion of the PDAI). Six of 10 patients (60%) were able to maintain remission throughout the 12-month trial; 4/10 had an exacerbation, two of which occurred soon after discontinuing daily treatment. Serum bismuth levels were negligible in all patients and no side-effects were registered. CONCLUSIONS: Our findings suggest that bismuth carbomer enemas are safe and effective in achieving and maintaining remission in patients with treatment-resistant chronic pouchitis.

Antibiotic combination therapy in patients with chronic, treatment-resistant pouchitis.

BACKGROUND: Pouchitis is the major long-term complication after ileal pouch-anal anastomosis for ulcerative colitis. About 15% of patients have a chronic, treatment-resistant disease. AIMS: To evaluate the efficacy of an antibiotic combination for chronic active, treatment-resistant pouchitis. PATIENTS AND METHODS: Eighteen patients were treated orally with rifaximin 1 g b.d. + ciprofloxacin 500 mg b.d. for 15 days. Symptoms assessment, endoscopic and histological evaluations were performed at screening and after 15 days using the Pouchitis Disease Activity Index (PDAI). Improvement was defined as a decrease of at least 3 points in PDAI score, and remission as a PDAI score of 0. Systemic absorption of rifaximin was determined by high performance liquid chromatography. Faecal samples were collected before and after antibiotic treatment for stool culture. RESULTS: Sixteen out of 18 patients (88.8%) either improved (n=10) or went into remission (n=6); the median PDAI scores before and after therapy were 11 (range 9-17) and 4 (range 0-16), respectively (P < 0.002). No side-effects were reported. Rifaximin plasma levels and urinary excretion were negligible, confirming its mainly topical activity. A significant decrease in total anaerobes and aerobes, enterococci, lactobacilli, bifidobacteria and bacteroides in faecal samples was observed, while the reduction in number of coliforms and Clostridium perfringens did not reach a statistical significance. CONCLUSIONS: A combination of rifaximin and ciprofloxacin was effective in patients with active chronic, treatment-resistant pouchitis, suggesting the need, in these patients, for treatment using antibiotic agents with wide antibacterial spectrum of activity.

Nutritional status of patients undergoing ileal pouch-anal anastomosis.

The nutritional consequences of total colectomy and ileal pouch-anal anastomosis (IPAA) were assessed by evaluating 36 patients at the end of the defunctionalised stage (DS group) and 18 patients with recanalised IPAA (IPAA group). The changes in protein-calorie and zinc status occurring after the closure of the diverting ileostomy were evaluated also in 11 patients assessed both during the DS and the IPAA stage. The results were compared with those observed in 14 patients who underwent a Brooke-type permanent ileostomy (PI group). In the DS group there were protein-calorie malnutrition in 50% of cases characterised by body weight, TSF and AMC values lower than normal associated with normal serum protein levels; severe salt and water depletion with secondary aldosteronism in 90%; normal calcium-phosphorus balance in all but few cases, low values of parameters related to vitamin D and K, Fe, Zn and Cu status in 6-25% of cases and normal folate status. In the IPAA group all the anthropmetric parameters improved significantly after the closure of the protective ileostomy, but muscle mass (AMC) remained lower than normal in 40% of cases; mild salt depletion (urinary Na K ratio between 1 and 2) was observed in 1 3 of cases and of severe degree (urinary Na K < 1 ) in 20%; lower serum Zn occurred in 60% of patients probably due to greater requirements of the metal, secondary to increased muscle protein synthesis; parameters of calcium-phosphorus balance, vitamin D and K, folate, Fe and Cu status, were normal in almost all the cases. In the PI group, protein-calorie and salt and mineral nutritional status were similar to those of the IPAA group, whereas Zn status was normal in all the patients and erythrocytes folate levels and prothrombin time were significantly lower than in the IPAA group. These last two results might be explained by the different characteristics of the small bowel flora occurring in the two types of ileostomy.

Functional outcome in handsewn versus stapled ileal pouch-anal anastomosis.

Eighty-eight of 119 patients who underwent ileal pouch-anal anastomosis for ulcerative colitis were evaluated. Forty patients had a handsewn anastomosis (Hs) with mucosectomy, and 48 had a stapled anastomosis (St). In each patient, we evaluated operative, morphologic, functional, and manometric features. The results in the Hs and St groups were similar when the anastomosis was within 1 cm of the dentate line. In particular, there was no correlation between the type of anastomosis and the number of bowel movements in a 24-hour period, the presence of the urge to defecate, and the use of antidiarrheal drugs. Leakage was significantly higher in the Hs group, even when the anastomosis was less than 1 cm from the dentate line. Pouchitis was more frequent in the Hs group, and, within this group, among those with a short distance between the anastomosis and the dentate line. No correlations were found between the presence of columnar epithelium or active colitis in the mucosa below the anastomosis, the functional outcomes, and the incidence of pouchitis.

Colorectal cancer and high grade dysplasia complicating ulcerative colitis in Italy. A retrospective co-operative IG-IBD study.

BACKGROUND: Ulcerative colitis is a well-known risk factor for colorectal cancer. AIM: To take a census of the cases of colorectal cancer in ulcerative colitis patients observed in Italy and to evaluate the clinical presentation of neoplastic complication. PATIENTS AND METHODS: Experts from 28 Italian centres specialised in the management of inflammatory bowel disease or malignancies participated to the study. They were invited to send clinical data of patients with ulcerative colitis complicated by colorectal cancer or high-grade dysplasia consecutively observed between 1985 and 2000. One hundred and twelve patients (92 with cancer and 20 with high-grade dysplasia) were collected. Fourteen of them had undergone colectomy and ileo-rectal anastomosis for ulcerative colitis. Data of surgical patients were analysed separately. RESULTS: The mean age at diagnosis of ulcerative colitis and colorectal cancer patients was 39.3 and 53.2 years, respectively, and the mean duration between diagnosis of ulcerative colitis and cancer was 13.9 years (range 0-53). Inflammation was proximal to the splenic flexure in 71 cases (76.3%). One hundred and three colorectal cancers were registered (93 patients with single lesion and five patients with two synchronous cancers), with 76.7% of cancers being located in the left colon. As to the surgical patients, the mean age at diagnosis of ulcerative colitis and cancer was 28.9 and 47.0 years, respectively, and the mean diagnostic interval for ulcerative colitis and cancer was 18.1 years. Only 51 out of 112 patients were in follow-up. An early diagnosis of neoplasia (high grade dysplasia, stage A or B sec. Dukes) occurred in 72.5% of patients who were subjected to endoscopic surveillance and in 48.0% of patients who did not undergo endoscopic surveillance (p=0.02). CONCLUSIONS: These data show an earlier diagnosis of cancer in patients who had undergone endoscopic surveillance. The poor compliance to the follow-up program, however, reduces its effectiveness. Moreover, total colectomy allows an easier follow-up, with only the rectum being controlled. Colectomy with ileo-rectal anastomosis or proctocolectomy with ileo-anal anastomosis, could represent a valid alternative in patients at high risk of cancer who refuse endoscopic surveillance.

Review--antibiotic treatment in inflammatory bowel disease: rifaximin, a new possible approach.

The etiology of inflammatory disease is still unknown, but a body of evidence from clinical and experimental observation indicates a role for intestinal microflora in the pathogenesis of this disease. Reduction of microflora using antibiotics, bowel rest and fecal diversion decreases activity in Crohn's disease and in ulcerative colitis. Several trials have been carried out on the use of antibiotic treatment in patients with active ulcerative colitis with contrasting results. A number of trials have been carried out using Rifaximin, a non-absorbable broad-spectrum antibiotic, confirming the absence of systemic bioavalaibility of the drug even when administered at very high doses and for prolonged periods. It may therefore be useful in treatment of ulcerative colitis and pouchitis, since its absorption through inflamed mucosa is negligible, it maintains a topical action without systemic effects and the lack of resistant bacterial strains may allow prolonged and repeated treatments.

Aorto-enteric fistulae: spontaneous and after aorto-iliac operations.

Ten case of arterio-enteric fistula are presented, 3 spontaneous and 7 following surgery on the aorta. In the majority of cases "herald bleeding" allows enough time to study the patient. Spontaneous fistulae are very rare and their diagnosis can be very difficult if the aneurysm is not palpable. In any case of gastrointestinal haemorrhage in a patient who has undergone an aortic operation an A-E fistula will be suspect. The only useful diagnostic procedure is gastroduodenoscopy which usually does not show any organic cause for the bleeding. Arteriography seems only a dangerous waste of time: emergency explorative laparotomy, if a fistula is suspected, is surely harmless and preferable. The only sure surgical technique consists in removal of the prosthesis followed by an extra-anatomic by-pass.