Early Initiation of Adalimumab Significantly Diminishes Postoperative Crohn's Disease Endoscopic Recurrence and Is Superior to 6-Mercaptopurine Therapy: An Open-Label, Randomized Controlled Study.

Postoperative recurrence (POR) is the rule in patients with Crohn's disease (CD), mitigated with prophylactic therapy. The evidence for therapeutic choice and timing of intervention is lacking. We aimed to compare the rates of POR in patients treated early with prophylactic 6-mercaptopurine (6-MP) or adalimumab. We conducted a prospective single-center randomized open-label clinical study in which patients in surgical remission following their first ileocecectomy were randomized to receive early treatment with 6-MP or adalimumab. Patients were followed up clinically every 3 months and underwent endoscopy at weeks 32 and 58 postoperatively. The primary endpoint was endoscopic recurrence (ePOR) at 1 year (week 58), defined as a Rutgeerts score ≥ i2. We enrolled 35 patients (25 males, mean age 35 ± 1.4 years, median disease duration 5 ± 6.1 years) following ileocecectomy. Of these, seven (20%) were current smokers and nine (26%) biologics-experienced. Patients allocated to adalimumab had significantly less ePOR than patients treated with 6MP at week 32 (21% vs. 69%, p = 0.004) and 58 (47% vs. 75%), (p = 0.03, HR = 0.39, 95% CI = 0.16-0.93). POR was associated with an increased diameter of the resected small bowel surgical specimen, lower baseline body mass index (BMI), increased week 18 fecal calprotectin, increased week 18 serum alanine aminotransferase and decreased week 18 hemoglobin level. Adalimumab was more effective than 6-MP in preventing ePOR. Increased operative small bowel diameter and lower postoperative BMI were associated with ePOR. At eighteen weeks, serum hemoglobin, ALT and fecal calprotectin levels were predictive of endoscopic disease recurrence. (ClinicalTrials.gov ID NCT01629628).

Surveillance and Management of Pouch Neoplasia in Familial Adenomatous Polyposis: A Systematic Review.

BACKGROUND: Patients with familial adenomatous polyposis often require prophylactic colectomy with ileal pouch-anal anastomosis to treat and/or reduce to risk of colorectal neoplasia. However, after surgery, patients are still at some risk of developing pouch polyps and even cancer in both handsewn or stapled anastomoses. Management relies mainly on endoscopic or surgical interventions, while chemopreventive agents have a limited role in the management and prevention of pouch neoplasia. Novel endoscopic techniques are evolving and may gradually overtake surgical intervention in selected cases. Since familial adenomatous polyposis is relatively rare, there is scarcity of data regarding the natural history of pouch polyps and cancer in this population. OBJECTIVE: This systematic literature review aims to describe the evolution, characteristics, various treatment modalities and their outcomes as well as recommended surveillance strategies of pouch neoplasia. DATA SOURCES: PubMed and Cochrane databases, the international pouch consortium (for expert opinion). STUDY SELECTION: Studies between 1990 and 2023, in English were included. Studies reporting neoplastic outcomes of inflammatory bowel disease pouch patients only were excluded. MAIN OUTCOME MEASURES: Incidence of pouch neoplasia and its outcomes (successful resections, surgical complications, mortality). RESULTS: Thirty-five studies were included. LIMITATIONS: Most studies focus on inflammatory bowel diseases pouch patients, there is scarce data regarding polyposis patients only. Most cohorts are small and retrospective. Data on interventions is mainly descriptive and no randomized controlled trials are available. CONCLUSIONS: Pouch adenoma are common and well managed by endoscopic resections, as advanced-endoscopic techniques are becoming more available. Additional data are required for defining updated recommendations for either endoscopic or surgical intervention. Pouch cancer is a very rare event and may arise despite surveillance. Continued endoscopic surveillance is key in cancer prevention and early detection. Outcome of cancer cases is poor and management in a referral center should be advised with tumor board discussions.

Rectal Cancer following Local Excision of Rectal Adenomas with Low-Grade Dysplasia-A Multicenter Study.

Purpose: Rectal polyps with low-grade dysplasia (LGD) can be removed by local excision surgery (LE). It is unclear whether these lesions pose a higher risk for recurrence and cancer development and might warrant an early repeat rectal endoscopy. This study aims to assess the rectal cancer rate following local excision of LGD rectal lesions. Methods: A retrospective multicenter study including all patients that underwent LE for rectal polyps over a period of 11 years was conducted. Demographic, clinical, and surgical data of patients with LGD werecollected and analyzed. Results: Out of 274 patients that underwent LE of rectal lesions, 81 (30%) had a pathology of LGD. The mean patient age was 65 ± 11 years, and 52 (64%) were male. The mean distance from the anal verge was 7.2 ± 4.3 cm, and the average lesion was 3.2 ± 1.8 cm. Full thickness resection was achieved in 68 patients (84%), and four (5%) had involved margins for LGD. Nine patients (11%) had local recurrence and developed rectal cancer in an average time interval of 19.3 ± 14.5 months, with seven of them (78%) diagnosed less than two years after the initial LE. Seven of the nine patients were treated with another local excision, whilst one had a low anterior resection, and one was treated with radiation. The mean follow-up time was 25.3 ± 22.4 months. Conclusions: Locally resected rectal polyps with LGD may carry a significant risk of recurring and developing cancer within two years. This data suggests patients should have a closer surveillance protocol in place.

Reduction in surgical site infections by localized administration with D-PLEX100 in patients with multiple risk factors undergoing colorectal surgery.

BACKGROUND: D-PLEX100 is a novel drug-eluting lipid polymer matrix that supplies a high, local concentration of doxycycline for approximately 30 days. The objective of this post-hoc analysis was to assess the efficacy of D-PLEX100 in preventing superficial and deep SSIs in patients with ≥2 risk factors. PATIENTS AND METHODS: A post-hoc analysis of a previously reported prospective randomized trial assessing D-PLEX100 plus Standard of Care (SOC) versus SOC alone in colorectal surgery was performed to assess SSI rate in patients with ≥2 risk factors. RESULTS: The overall incidence of SSI was significantly lower for the D-PLEX100 arm (9.9%) versus SOC (21%), p = 0.033. Patients with ≥2 risk factors, SSI incidence was 37.5% for SOC and 15.8% in D-PLEX100 treated patients. CONCLUSIONS: D-PLEX100 reduces the incidence of SSIs beyond benefits associated with SOC treatment alone and including patients with ≥2 risk factors. D-PLEX100 may be a promising addition to established SSI prophylaxis bundles.

Revised risk factors and patient characteristics for failure to close a defunctioning ileostomy following low anterior resection for locally advanced rectal cancer.

BACKGROUND: Our clinical experience led us to raise questions about the validity of the reported risk factors and patient characteristics associated with permanent stomas after sphincter-preserving resection for rectal cancer. OBJECTIVE: The present retrospective study aimed to identify and compare our center's incidence and risk factors for a permanent ostomy after low anterior resection (LAR) with a diverting stoma for locally advanced mid and low rectal cancer with those in published reports. PATIENTS: A total of 239 patients underwent a sphincter-preserving procedure (LAR) for rectal cancer between 2000 and 2018, and 236 of them (age range 33-83 years, 100 males (42%)) were included in the analysis. The study cohort was divided into 2 groups comprised of patients with and without permanent stomas after rectal cancer surgery. RESULTS: Only 25 of the 236 operated patients (10.6%) remained with permanent stomas after rectal cancer surgery. Factors associated with stoma non-closure in the multivariate analysis were pathological stage 3 (13 (52%) vs 51 (24.2%) for patients with closed stomas, p = 0.032), disease recurrence (14 (56%) vs 40 (18.9%), respectively, p = 0.048), length of stay > 10 days, p = 0.032), and anastomotic leaks with a Clavien-Dindo score > 2 or reoperations (6 (24%) vs 13 (6.1%), p = 0.019). CONCLUSIONS: Sphincter-preserving surgery for rectal cancer was associated with a lower incidence of stoma non-closure than published values. The major risk factors for non-closure were aggressive disease and severe complications of surgery.

Long-term Antibiotic Treatment in Pouchitis-Patterns of Use and Safety.

INTRODUCTION: Pouchitis, often developing after colectomy and ileal pouch-anal anastomosis for ulcerative colitis, is highly responsive to antibiotics. Ciprofloxacin and/or metronidazole are commonly used, often for prolonged periods. We report patterns of antibiotic use, adverse events, and resistant infections in patients with pouchitis with long-term antibiotic treatment. METHODS: In a cohort of patients following pouch surgery, a retrospective nested case-control analysis was performed between 2010 and 2017. Ultra-long-term use, defined as the top 10% of users, was compared with the remaining users. Patterns of antibiotic use, adverse events, and resistant infections were analyzed. RESULTS: The cohort included 205 patients with UC, of whom 167 (81.5%) used antibiotics for pouchitis, predominantly ciprofloxacin. The long-term antibiotic use rate was 18% and 42% at 5 and 20 years postsurgery, respectively. Mean antibiotic use of at least 1, 3, and 6 months/year was noted in 54 (26.3%), 31 (15.1%), and 14 (6.8%) patients, respectively. Twenty-two (13.2%) and 4 (2.4%) patients reported mild and severe (transient) adverse events, respectively, without mortalities, tendinopathies or arrhythmias. Adverse event rates for ciprofloxacin and metronidazole were 1per 10,000 and 6 per 10,000 use-days, respectively. Longer, but not ultra-long antibiotic use, was associated with mild adverse events. There was no association between antibiotic use and resistant infections. Thirteen (6.3%) patients required ileostomy procedures-more commonly in the ultra-long-term antibiotic users. CONCLUSIONS: Patients with pouchitis may require prolonged antibiotic treatment, reflecting clinical benefit and favorable safety profile. Few adverse events and resistant infections were observed with long-term antibiotics use. However, resistant microbial strains selection, which are potentially transmittable, warrants consideration of different therapeutic alternatives.

Fecal Calprotectin Is Increased in Pouchitis and Progressively Increases With More Severe Endoscopic and Histologic Disease.

BACKGROUND & AIMS: Data regarding fecal calprotectin (FC), commonly used for noninvasive monitoring in inflammatory bowel diseases, are scarce in patients with ileal pouch-anal anastomosis (IPAA). We aimed to assess the association between FC levels and pouch inflammation in patients with ulcerative colitis who underwent IPAA. METHODS: A cross-sectional study of adults with ulcerative colitis who underwent IPAA with J-pouch formation prospectively followed in a dedicated pouch clinic. Patients had clinical, endoscopic, and histologic assessments within 90 days of FC sampling. Each patient encounter was evaluated separately. Pouchitis was defined as a Pouchitis Disease Activity Score of ≥7 (maximum score: 18). RESULTS: Overall, 156 patients had 296 encounters that met inclusion criteria. A total of 52% of patients were male, median age at evaluation was 43 (IQR, 35-58) years, and median pouch age was 10 (interquartile range [IQR], 2.5-15) years. Median FC values were significantly lower in patients without compared with those with pouchitis (208 [IQR, 96-478] µg/g vs 550 [IQR, 250-1051] µg/g; P < .0001). Mean FC values increased among patients with higher endoscopic and histologic scores. FC performed better than C-reactive protein as a predictor of pouchitis. FC of >460 µg/g had >80% specificity for predicting significant endoscopic disease (Pouchitis Disease Activity Score endoscopic subscore ≥5), while an FC of <125 µg/g had over 80% specificity in predicting endoscopic remission. CONCLUSIONS: FC levels are increased in patients with endoscopic and histologic inflammation of the pouch. FC may be a useful tool in the management of patients following IPAA.

Patients' perceptions of surgery for inflammatory bowel disease.

AIM: Surgery is indicated in selected patients with inflammatory bowel disease (IBD). However, due to a negative perception, surgery may be delayed, leading to possible unfavourable outcomes. The aim of this work was to investigate patients' perceptions of surgery and the impact on reported outcomes. METHOD: An international multilingual online survey was used to query IBD patients' experiences of surgery, information sources, expectations and concerns, quality of life (QoL) and feelings. RESULTS: The survey was completed by 425 of 510 participants. Crohn's disease was more frequent (61%) than ulcerative colitis (36%). Most patients primarily learned about surgery from their gastroenterologist and were informed of the risks and benefits by the surgeon. In almost one-third of patients indication for surgery was not a shared decision between gastroenterologist and surgeon. Seventy per cent of patients naïve to surgery were not aware of any surgical options. The majority of patients (80%) perceived surgery as the last option after many medical treatments rather than an alternative therapeutic option (20%). Sixteen per cent of patients obtained their primary information from the Internet, while 82.4% used the Internet to obtain additional information. Fear of surgical complications was cited by 73% of patients, while relief from symptoms was indicated by 31%. Most patients coped with their stoma better than expected or as they expected. Negative feelings decreased after surgery, while a lasting improvement in positive feelings and QoL was reported. CONCLUSION: Despite the negative perception of surgery and the delayed involvement of surgeons as a source of information and in the decision-making process, the majority of respondents experienced positive outcomes from surgery, including improvement QoL and acceptance of the stoma.

Does microscopic involvement of the surgical margins after ileocecectomy in Crohn's patients predict early recurrence?

OBJECTIVE: The primary aim of this study was to determine whether the microscopic presence of Crohn's disease (CD) in the resected specimen margins in patients undergoing ileocecectomy predicts disease recurrence. The secondary aim was to identify other risk factors which can predict recurrence. METHODS: All CD patients who underwent ileocecectomy in a single colorectal unit between 2000 and 2015 were retrospectively evaluated. The diagnosis of CD and margin involvement status were retrieved from pathology reports. Recurrence was determined according to medical records or via a telephone questionnaire. Demographic, clinical, and surgical parameters were compared between patients with and without histopathologic evidence of CD in the resected margins. RESULTS: A total of 202 CD patients were included, 49 with and 153 without evidence of microscopic involvement in the resected margins. The main demographic characteristics, surgical approach and procedure, and postoperative course, including medical treatment, clinical or endoscopic recurrence, and reoperation rates, were similar for both groups. Patients who were operated laparoscopically (n=58, p 0.016), conversion from laparoscopic to open (n=25, p 0.016), stapled anastomosis (n=150, p 0.004), when stricturoplasty was required (n=12, p 0.046), and those with perianal disease (n=32, p 0.045) had shorter time to recurrence. Male gender had increased hazard ratio (n=106, HR 1.38) for reoperation, but not significantly (p=0.058). CONCLUSIONS: The presence of microscopic CD at the resected specimen margins was not associated with the risk of disease recurrence. Other demographic, clinical, and technical features that did correlate with early recurrence were identified. These results support a conservative approach to the extent of resection in CD patients undergoing ileocecectomy. TRIAL REGISTRATION: Not relevant.

Quality of Care Standards in Inflammatory Bowel Diseases: a European Crohn's and Colitis Organisation [ECCO] Position Paper.

The management of inflammatory bowel disease [IBD] is complex, and requires tight control of disease activity, close monitoring to avoid treatment side effects, health care professionals with expertise in IBD, and an interdisciplinary, holistic approach. Despite various efforts to standardise structures, processes, and outcomes,1-8 and due to the high variability at the local, national, and international levels, there are still no clear definitions or outcome measures available to establish quality of care standards for IBD patients which are applicable in all contexts and all countries. For this reason, the European Crohn's and Colitis Organisation [ECCO] supported the construction of a list of criteria summarising current standards of care in IBD. The list comprises 111 quality standard points grouped into three main domains [structure n = 31, process n = 42, outcomes n = 38] and is based on scientific evidence, interdisciplinary expert consensus, and patient-oriented perspectives. The list of proposed criteria is intended to represent the position of ECCO regarding the optimum quality of care that should be available to patients. Since health care systems and regulations vary considerably between countries, this list may require adaptation at local and national levels. It is recognised that not all these criteria that have been identified as optimal will be available in every unit. However, ECCO will continue its efforts to develop and coordinate projects and initiatives that will help to guarantee optimal quality of care for all IBD patients.

Predominantly Antibiotic-resistant Intestinal Microbiome Persists in Patients With Pouchitis Who Respond to Antibiotic Therapy.

BACKGROUND & AIMS: Pouchitis that develops in patients with ulcerative colitis after total proctocolectomy and ileal pouch anal anastomosis is usually treated with antibiotics. Some patients have recurrence of flares, or become antibiotic-dependent, and require repeated courses or prolonged periods of antibiotic therapy. We investigated microbial factors associated with response to antibiotic treatment and development of antibiotic dependence in patients with pouchitis. METHODS: We performed a prospective study of 49 patients who had undergone pouch surgery at a tertiary center. Disease activity was determined based on clinical, endoscopic, and histologic criteria. Pouch phenotype was defined as recurrent-acute pouchitis (n = 6), chronic pouchitis and Crohn's-like disease of the pouch (n = 27), normal pouch from patient with ulcerative colitis (n = 10), and normal pouch from patient with familial adenomatous polyposis (n = 6). Fecal samples (n = 234) were collected over time during or in the absence of antibiotic treatment (ciprofloxacin and/or metronidazole). Thirty-three patients were treated with antibiotics, for a median of 425 days of cumulative antibiotic therapy, during follow-up. Calprotectin was measured and fecal DNA was sequenced using shotgun metagenomics and analyzed with specifically designed bioinformatic pipelines. Bacterial strains were isolated from fecal samples. We assessed their ciprofloxacin resistance and ability to induce secretion of inflammatory cytokines by HT-29 intestinal epithelial cells. RESULTS: Most antibiotic-treated patients (79%) had a clinical response to each course of antibiotics; however, 89% of those who completed a 4-week course relapsed within 3 months. Median calprotectin levels decreased by 40% in response to antibiotics. Antibiotic treatment reduced disease-associated bacteria such as Clostridium perfringens, Ruminococcus gnavus, and Klebsiella pneumoniae, but also beneficial species, such as Faecalibacterium prausnitzii. The microbiomes of antibiotic-responsive patients were dominated by facultative anaerobic genera (Escherichia, Enterococcus, and Streptococcus), with multiple ciprofloxacin-resistance mutations in drug target genes and confirmed drug resistance. However, these strains had lower potential for virulence and did not induce secretion of inflammatory cytokines by epithelial cells. After antibiotic cessation, patients had an abrupt shift in microbiome composition, with blooms of oral and disease-associated bacteria. In addition, antibiotic treatment enriched for strains that acquired multidrug resistance loci, encoding enzymes that confer resistance to nonrelated antibiotics, including extended-spectrum beta-lactamases. CONCLUSIONS: The efficacy of antibiotic treatment of pouchitis might be attributed to the establishment of an antibiotic-resistant microbiome with low inflammatory potential. This microbiome might provide resistance against colonization by bacteria that promote inflammation. To avoid progression to antibiotic-dependent disease and its consequences, strategies such as short-term alternating antibiotics and nutrition- and microbiome-based interventions should be considered.

Faecal Proteases from Pouchitis Patients Activate Protease Activating Receptor-2 to Disrupt the Epithelial Barrier.

BACKGROUND AND AIMS: The pathogenesis of pouch inflammation may involve epithelial barrier disruption. We investigated whether faecal proteolytic activity is increased during pouchitis and results in epithelial barrier dysfunction through protease activating receptor [PAR] activation, and assessed whether the intestinal microbiome may be the source of the proteases. METHODS: Faecal samples were measured for protease activity using a fluorescein isothiocyanate [FITC]-casein florescence assay. Caco-2 cell monolayers were exposed to faecal supernatants to assess permeability to FITC-dextran. Tight junction protein integrity and PAR activation were assessed by immunoblot and immunofluorescence. A truncated PAR2 protein in Caco-2 cells was achieved by stable transfection using CRISPR/Cas9 plasmid. PAR2 activation in pouch biopsies was examined using antibodies directed to the N-terminus of the protein. Microbial composition was analysed based on 16S rRNA gene sequence analysis. RESULTS: Ten pouchitis patients, six normal pouch [NP] patients and nine healthy controls [HC] were recruited. The pouchitis patients exhibited a 5.19- and 5.35-fold higher faecal protease [FP] activity [p ≤ 0.05] compared to the NP and HC participants, respectively. The genus Haemophilus was positively associated with FP activity [R = 0.718, false discovery rate < 0.1]. Faecal supernatants from pouchitis patients activated PAR2 on Caco-2 monolayers, disrupted tight junction proteins and increased epithelial permeability. PAR2 truncation in Caco-2 abrogated faecal protease-mediated permeability. Pouch biopsies obtained from pouchitis patients, but not from NP patients, displayed PAR2 activation. CONCLUSIONS: Protease-producing bacteria may increase faecal proteolytic activity that results in pouch inflammation through disruption of tight junction proteins and increased epithelial permeability in a PAR2-dependent manner. This mechanism may initiate or propagate pouch inflammation.

Genotype-Phenotype Associations of APC Mutations With Pouch Adenoma in Patients With Familial Adenomatous Polyposis.

BACKGROUND: Patients with familial adenomatous polyposis (FAP) may carry various adenomatous polyposis coli (APC) mutations. However, genotype-phenotype correlation for APC mutations is still debated and is yet to be evaluated with regard to pouch polyp formation. OBJECTIVE: To evaluate the association between APC mutation type and exon location and the outcome of pouch adenoma. DESIGN SETTING AND PATIENTS: Forty-five FAP patients with defined pathogenic APC mutations, who underwent total proctocolectomy and ileal pouch anal anastomosis were classified by mutation type and location. Analysis was conducted for clinical and endoscopic parameters. RESULTS: Twenty patients had either indel/deletion mutations and 25 had nonsense/missense mutations. The indel/deletion group was associated with higher prevalence of preoperative hundreds of colonic adenomas (66.7% vs. 30%; P=0.030), lower rates of stapled versus sewn anastomosis (46.7% vs. 76%; P=0.060), of single stage surgery (13.3% vs. 44%; P=0.045) and with higher pouch adenoma formation rate (50% vs. 8%; P=0.002). Twenty-seven were carriers of exons 1 to 14 mutations and 18 were carriers of exon 15 mutations. Carriers of exon 15 mutations had higher prevalence of preoperative hundreds of colonic adenomas (55.6% vs. 22.2%; P=0.003) and a higher tendency for pouch and cuff adenoma formation rate. Adjusted odds ratio for pouch adenoma formation was 8.32 (1.42-48.80; P=0.019) for the indel/deletion group versus nonsense/missense, but no significant independent association was noted with mutation location. The mean number of pouch and cuff adenoma formation (per endoscopy) was higher among carriers of exon 15 mutations, but no significant independent association was noted the with mutation type. CONCLUSIONS: Type and location of APC mutation are associated with colonic polyp burden, surgical outcome and likelihood of developing pouch adenomas. These findings may contribute to surgical and endoscopic surveillance decisions for FAP patients.

Starch Consumption May Modify Antiglycan Antibodies and Fecal Fungal Composition in Patients With Ileo-Anal Pouch.

BACKGROUND: Inflammatory bowel diseases (IBDs) are characterized by serologic responses to glycans. Patients with ulcerative colitis (UC) after proctocolectomy with ileo-anal anastomosis (pouch surgery) may develop inflammation (pouchitis) that resembles Crohn's disease (CD). We hypothesized that patients' serologic responses were affected by their consumption of dietary sugars. This study analyzed the correlations between antiglycan antibody expression and dietary sugar consumption in patients with UC pouch and the evolution in antibody levels over time. METHODS: Patients were followed prospectively for 2 consecutive visits. The following antiglycan carbohydrate antibodies were detected by enzyme-linked immunosorbent assay: antichitobioside (ACCA), antilaminaribioside (ALCA), antimannobioside (AMCA), and anti-Saccharomyces cerevisiae (ASCA) antibodies. Patients completed a food frequency questionnaire. The fungal community in patients' fecal samples was analyzed by sequencing the internal transcribed spacer 2 (ITS2) region of nuclear ribosomal DNA. RESULTS: We included 75 UC pouch patients aged 45.2 ± 14 years who underwent pouch surgery 9.8 ± 6.7 years previously. Of these patients, 34.7% (n = 26) showed seropositivity for antiglycan antibodies. Starch consumption was significantly higher in patients with positive serologic responses (P = 0.05). Higher starch consumption was associated with higher AMCA and ACCA titers, which increased by 4.08% (0.8%-7.4%; P = 0.014) and 4.8% (0.7%-9.1%; P = 0.007), respectively, for each 10-g increase of dietary starch. The per-patient change in the relative abundance of Candida albicans in fecal samples correlated positively with changes in starch consumption (Spearman's r = 0.72; P = 0.012). CONCLUSIONS: Starch consumption correlated with positive antiglycan serology (ACCA and AMCA), suggesting that increased dietary starch intake may promote a specific immune response in patients with IBD.

Comparison between laparoscopic and open Hartmann's reversal: results of a decade-long multicenter retrospective study.

BACKGROUND: Hartmann's reversal is a challenging surgical procedure with significant postoperative morbidity rates. Various surgical methods have been suggested to lower the risk of postoperative complications. In this study, we aimed to compare the postoperative results between open and laparoscopic techniques for Hartmann's reversal. METHODS: A retrospective study of all patients who underwent Hartmann's reversal in five centers in central Israel between January 2004 and June 2015 was conducted. Medical charts were reviewed, analyzing preoperative and operative parameters and short-term postoperative outcomes. RESULTS: 260 patients were included in the study. 76 patients were operated laparoscopically with a conversion rate of 26.3% (20 patients). No differences were found between patients operated laparoscopically and those operated in an open technique regarding gender (p = 0.785), age (61.34 vs. 62.64, p = 0.521), body mass index (26.6 vs. 26.2, p = 0.948), Charlson index score (1.79 vs. 1.95, p = 0.667), and cause for Hartmann's procedure (neoplastic vs. non-neoplastic, p = 0.644). No differences were seen in average time from the Hartmann's procedure to reversal (204.89 vs. 213.60 days, p = 0.688) and in overall complication rate (46.4 vs. 46.5%, p = 1). The Clavien-Dindo score for distinguishing between minor (0-2 score, p = 1) and major complications (3-5 score, p = 0.675) failed to demonstrate an advantage to laparoscopy, as well as to average length of stay (10.91 days in the laparoscopic group vs. 11.72 days in the open group, p = 0.529). An analysis based on the intention-to-treat with laparoscopy, including converted cases in the laparoscopic group, showed similar results, including overall complication rate (48.6 vs. 45.6%, p = 0.68) and Clavien-Dindo score in both minor (p = 0.24) and major complications (p = 0.44). Length of stay (10.92 vs. 11.81 days, p = 0.45) was also similar between the two groups. CONCLUSION: In this series, a laparoscopic approach to Hartmann's reversal did not offer any short-term advantage when compared to an open surgical approach.

Considerations for Hartmann's reversal and Hartmann's reversal outcomes-a multicenter study.

PURPOSE: Hartmann's procedure is commonly practiced in emergent cases with the restoration of bowel continuity planned at a second stage. This study assessed the rate of restorations following Hartmann's procedure and evaluated factors affecting decision-making. METHODS: Data on patient demographics, comorbidities, causes for Hartmann's procedure, reversal rate, and complications were collected in a multicenter retrospective cohort study of patients who underwent Hartmann's procedure in five medical centers. RESULTS: Six hundred forty patients underwent Hartmann's procedure for diverticular disease (36.1%), obstructing malignancy (31.8%), benign obstruction (5%), and other reasons (23.1%). Overall, 260 (40.6%) patients underwent subsequent restoration of bowel continuity. One hundred twenty-one (46.5%) patients had post-reversal complications, with an average Clavien-Dindo score of 1.4 and a mortality rate of 0.77%. Decision to avoid reversal was mostly related to comorbidities (49.7%) and metastatic disease (21.6%). Factors associated with the decision to restore bowel continuity included male gender (P = 0.02), patient age (62.3 years in Hartmann's reversal patients vs 73.5 years in non-reversal patients; P < 0.0001), number of comorbidities (1.1 vs 1.58; P < 0.001), average Charlson score (1.93 vs 3.44; P < 0.001), and a neoplastic etiology (P < 0.0001). A sub-analysis excluding all patients who died in the 30 days following Hartmann's procedure showed similar factors associated with ostomy closure. CONCLUSION: Many patients do not have restoration of bowel continuity after undergoing Hartmann's procedure. Hartmann's reversal is associated with a significant postoperative morbidity. Surgeons and patients should be aware of the possibility that the colostomy might become permanent.

Restorative Proctocolectomy in Elderly IBD Patients: A Multicentre Comparative Study on Safety and Efficacy.

BACKGROUND AND AIMS: Restorative proctocolectomy in elderly inflammatory bowel disease [ IBD] patients is controversial and limited data are available on the outcomes of surgery. The aim of this study was to evaluate the safety, efficacy, and long-term results of ileal-pouch-anal anastomosis in elderly patients, in a multicentre survey from European referral centres. METHODS: The International Pouch Database [IPD] combined 101 variables. Patients aged ≥ 65 years were matched on the basis of open versus laparoscopic surgery with a control group of consecutive younger unselected patients with a ratio of 1:2. Statistical analysis was performed using two-tailed t test, chi square and Fisher's exact tests, Kaplan-Meier function, and log-rank tests where appropriate. RESULTS: In the IPD, 77 patients aged ≥ 65 years [Group A] and 154 control patients [Group B] were identified. Elderly patients had more comorbidities [p = 0.0001], longer disease duration [p = 0.001], less extensive disease [p = 0.006], more previous abdominal operations [p = 0.0006], surgery for cancer or dysplasia more frequently [p = 0.0001], fewer single-stage procedures [p = 0.03], more diversions after ileal pouch-anal anastomosis [IPAA] [p = 0.05], and a higher laparoscopic conversion rate [p = 0.04]. Postoperative complications and pouch failure were similar between the groups, but Group A had more Clavien-Dindo IV-V complications [p = 0.04], and longer length of stay [p = 0.007]. Laparoscopy was associated with a shorter duration of surgery [p = 0.0001], and length of stay [p = 0.0001], and the same complication rate as open surgery. CONCLUSIONS: Restorative proctocolectomy can be performed in selected elderly patients, but there is a higher risk of postoperative complications and longer length of stay in this group. Laparoscopy is associated with shorter operating time and length of stay.

Alterations of Enteric Microbiota in Patients with a Normal Ileal Pouch Are Predictive of Pouchitis.

Objective: To examine whether patients with a mature normal pouch [> 1 year post ileostomy closure] have microbial stool characteristics that can predict pouch inflammation. Design: Patients undergoing pouch surgery were recruited prospectively. Microbiota analysis of faecal samples was by 16S rRNA gene pyrosequencing. All patients had a normal pouch at baseline [T1]. Those without pouchitis during the first year of follow-up [T2] comprised the 'Normal Pouch-sustained' group and those who had experienced an episode of pouchitis comprised the 'Pre-Pouchitis' group. Results: Twenty patients were recruited (age 53.6±13.1 years, pouch age [time from ileostomy closure] 8.1±5.1 years). Seven patients developed pouchitis during follow-up [within 265±93.6 days] and they were assigned to the Pre-Pouchitis group at T1: they had a decreased microbial diversity at T1 compared with the Normal Pouch-sustained patients [n = 13]. The Shannon diversity index for the Pre-Pouchitis patients was 3.4 vs 4.23 for the Normal Pouch-sustained patients [p = 0.011]. There were no substantial group differences in high taxonomic levels [order or above]. The genus Ruminococcus was significantly decreased in the Pre-Pouchitis patients' samples compared with those of the Normal Pouch-sustained patients (0.19% vs 0.78%, respectively, false discovery rate [FDR] = 0.05). The linear discriminant analysis with effect size estimation algorithm revealed that Lachnospira and Coprococcus genera were also decreased among Pre-Pouchitis patients compared with Normal Pouch-sustained patients [0.6% vs 1.95% and 2.1% vs 4%, respectively]. Conclusions: Patients with a normal mature pouch may be predisposed to acute pouchitis when faecal microbial diversity and certain microbial groups are decreased. These findings may aid in risk stratification of those patients.

Correction: MicroRNAs Expression in the Ileal Pouch of Patients with Ulcerative Colitis Is Robustly Up-Regulated and Correlates with Disease Phenotypes.

[This corrects the article DOI: 10.1371/journal.pone.0159956.].

MicroRNAs Expression in the Ileal Pouch of Patients with Ulcerative Colitis Is Robustly Up-Regulated and Correlates with Disease Phenotypes.

BACKGROUND: Gene expression alterations are associated with disease behavior in inflammatory bowel disease (IBD). microRNAs (miRNAs) are dominant in the regulation of gene expression, and may affect IBD phenotype. Our aim was to assess mucosal miRNA expression in IBD and the correlation with intestinal inflammation. METHODS: We performed a large-scale analysis of ileal mucosal miRNA. Biopsies were retrieved from patients with ileal Crohn's disease (CD), unoperated ulcerative colitis (UC) patients, UC patients after pouch surgery, and normal controls (NC). Pouch UC patients were classified as having a normal pouch (NP), chronic pouchitis (CP), and Crohn's-like disease of the pouch (CLDP). miRNA expression was analyzed by parallel massive (next-generation) sequencing (NGS). Bioinformatics tools were applied for clustering and the detection of potential targets. RESULTS: Sixty-one subjects were recruited. The ileum of unoperated UC patients was comparable with NC. There were significant miRNA expression alterations (fold change ≥2, corrected P ≤.05) in NP (n = 6), CP (n = 40) and CLDP (n = 139), but only two expression alterations were noted in CD. More than 90% of the altered miRNAs were up-regulated, and many were predicted to be associated with significantly decreased transcripts. miRNAs alterations were generally clustered with disease phenotypes. CONCLUSIONS: Ileal inflammation causes increased miRNA expression. miRNA alterations correlate with IBD phenotype, apparently by controlling the down-regulation of specific mRNAs.