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.

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.

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.

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.

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.

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.

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.

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.

Pouch Inflammation Is Associated With a Decrease in Specific Bacterial Taxa.

BACKGROUND & AIMS: Pouchitis is a common long-term complication in patients with ulcerative colitis (UC) undergoing proctocolectomy with ileal pouch-anal anastomosis. Because the inflammation occurs in a previously normal small bowel, studies of this process might provide information about the development of Crohn's disease. Little is known about the intestinal microbiome of patients with pouchitis. We investigated whether specific bacterial populations correlate with the pouch disease phenotype and inflammatory activity. METHODS: We performed a prospective study of patients with UC who underwent pouch surgery (N = 131) from 1981 through 2012 and were followed at Tel Aviv Medical Center. Patients were assigned to groups based on their degree and type of pouch inflammation. Patients with familial adenomatous polyposis after pouch surgery (n = 9), individuals with intact colons undergoing surveillance colonoscopy (n = 10), and patients with UC who did not undergo surgery (n = 9) served as controls. We collected demographic and disease activity data (based on the Pouchitis Disease Activity Index) and measured levels of C-reactive protein. Fecal samples were collected, levels of calprotectin were measured, and microbiota were analyzed by 16S ribosomal RNA gene amplicon pyrosequencing. RESULTS: Increased proportions of the Fusobacteriaceae family correlated with increased disease activity and levels of C-reactive protein in patients with UC who underwent pouch surgery. In contrast, proportions of Faecalibacterium were reduced in patients with pouchitis vs controls; there was a negative correlation between proportion of Faecalibacterium and level of C-reactive protein. There was an association between antibiotic treatment, but not biologic or immunomodulatory therapy, with reduced proportions of 11 genera and with increased proportions of Enterococcus and Enterobacteriaceae. CONCLUSIONS: Reductions in protective bacteria and increases in inflammatory bacteria are associated with pouch inflammation in patients with UC who underwent pouch surgery. The finding that antibiotics exacerbate dysbiosis indicates that these drugs might not provide long-term benefit for patients with pouchitis. Additional studies of this form of dysbiosis could provide information about the pathogenesis of Crohn's disease.

Gene expression alterations in ulcerative colitis patients after restorative proctocolectomy extend to the small bowel proximal to the pouch.

OBJECTIVES: To evaluate molecular profiles in the small bowel (SB) mucosa proximal to the pouch in ulcerative colitis (UC) patients after pouch surgery. DESIGN: Patients were prospectively recruited and stratified according to disease behaviour: normal pouch (NP), chronic pouchitis (CP), and Crohn's-like disease of the pouch (CLDP). Biopsies obtained from the pouch and the normal-appearing proximal SB (40 cm proximal to the anal verge) were compared to ileal biopsies from normal controls (NC). A histopathological score based on the degree of polymorphonuclear and mononuclear infiltrates was used to assess inflammation in the pouch and the proximal SB. Gene expression analysis was performed using microarrays, and validated by real-time PCR. Gene ontology and clustering were evaluated by bioinformatics. RESULTS: Thirty-six subjects were recruited (age 18-71 years, 16 males). Histopathology scores demonstrated minimal differences in the normal-appearing proximal SB of all groups. Nonetheless, significant (fold change ≥2, corrected p [FDR] ≤ 0.05) molecular alterations in the proximal SB were detected in all groups (NP n=9; CP n=80; and CLDP n=230) compared with NC. The magnitude of DUOX2 alteration in the proximal SB was highest. An increase of 6.0, 9.8 and 21.7 folds in DUOX2 expression in NP, CP, CLDP, respectively was observed. This was followed by alterations in MMP1, SLC6A14 and PGC. Gene alterations in the proximal SB overlapped with alterations within the pouch (76% and 97% overlap in CP and CLDP, respectively). Gene ontology analysis in the proximal SB and pouch were comparable. CONCLUSIONS: Significant gene expression alterations exist in an apparently unaffected proximal SB. Alterations in the pouch and the proximal SB were comparable, suggesting that inflammation may not be limited to the pouch, but that it extends to the proximal SB.

Patterns of Adenoma Recurrence in Familial Adenomatous Polyposis Patients after Ileal Pouch-Anal Anastomosis.

AIM: This study aims at identifying the risk factors for the development of pre-cancerous pouch and/or cuff adenomas post ileal pouch anal anastomosis (IPAA) in familial adenomatous polyposis patients. METHOD: We retrospectively studied 59 patients operated at a single medical center during a 26-year period. Data on the timing and location of adenoma recurrence were recorded and possible correlations with patients' gender, age, presence of desmoid tumor, duodenal adenomas, type of anastomosis and number of operation stages were analyzed. RESULTS: Thirty-five (59%) patients had at least one adenoma in either the cuff or the pouch, including 20 with isolated cuff adenomas, 4 with isolated pouch adenomas and 11 patients with adenomas in both the pouch and cuff. There was no significant correlation between gender, age at surgery, type of anastomosis, number of operative stages and the development of pouch or cuff adenomas. Desmoid tumor and pouch adenomas were significantly correlated with cuff adenomas formation. Duodenal adenomas were associated with pouch adenomas. There was some relationship between the development of cuff adenomas and the burden of colonic polyps, as well as the presence of duodenal adenomas. CONCLUSION: Adenomas in both the pouch and cuff commonly occur following IPAA, mandating lifelong annual endoscopic surveillance.

Should a loop ileostomy closure in rectal cancer patients be done during or after adjuvant chemotherapy?

BACKGROUND AND OBJECTIVE: The influence of ileostomy closure timing on surgical and oncologic outcome was investigated in patients with locally advanced rectal cancer receiving adjuvant chemotherapy after low anterior resection. METHODS: Consecutive patients diagnosed with T3-4/N+ rectal cancer, treated by neoadjuvant chemoradiation and low anterior resection during 2000-2012 were retrospectively evaluated. Patients undergoing closure during adjuvant chemotherapy (Group A) were compared to patients undergoing closure after completing chemotherapy (Group B). RESULTS: A total of the 165 patients met inclusion criteria, of whom 104 received adjuvant chemotherapy (25 in Group A and 79 in Group B). The pathologic stage was higher in Group B (P = 0.015). The rates of postoperative complications were similar (16% for Group A and 15% for Group B, P = 0.88), as was hospital stay (mean 5.78 days for Group A and 6.25 days for Group B, P = 0.7). There was no significant difference in recurrence rate and overall survival between the groups. CONCLUSIONS: Referral to ileostomy closure in relation to adjuvant chemotherapy is influenced by pathologic stage. Early referral appears to be reserved to a small number of patients with lower pathologic stage. Timing of ileostomy closure does not change short- or long-term results.

Long-term functional and quality-of-life outcomes after IPAA in children.

BACKGROUND: The impact of IPAA on long-term outcomes in adults is favorable. Studies on functional outcome and quality of life in children are sparse. OBJECTIVE: The aim of this study was to evaluate the functional and quality-of-life outcomes after IPAA in children and to investigate the possible correlations between the two. DESIGN: Standardized validated questionnaires of bowel/psychosocial functioning and quality of life were used to assess outcome. SETTING: This study was conducted at a tertiary medical center. PATIENTS: All children who had surgery at <18 years of age and were followed up at our institute were included. Global Assessment of Function Scale questionnaires were used to evaluate functional outcome. Quality of life in patients >18 years at the time of follow-up was scored by using the Short Form 36 questionnaire completed by the patients. Quality of life in the younger patients at the time of follow-up was scored using the Child Health Questionarie-28 filled by the parents. RESULTS: Data were obtained in 26 patients (25 with a preoperative diagnosis of ulcerative colitis) at a median follow-up of 6 years. The median age at surgery was 15 years. Quality of life was comparable to the general population for children >18 at the time of follow-up in 7 of 8 items, but was lower than in the general population in 7 of 12 items for those who were younger at the time of follow-up. The mean functional score was found to be negatively correlated to all 8 Short Form 36 parameters (r > 0.5; p < 0.005), but only to one of the Child Health Questionarie-28 parameters. LIMITATIONS: This study was limited by its small sample size. CONCLUSIONS: The functional outcomes among pediatric patients undergoing IPAA are good. Parents' perception of their child's quality of life is poorer in comparison with the perception by patients themselves when older and with no correlation to the functional results.

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.

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.

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).

Positive histological inflammatory margins are associated with increased risk for intra-abdominal septic complications in patients undergoing ileocolic resection for Crohn's disease.

BACKGROUND: Rates of postoperative complications are particularly high among patients with Crohn's disease. OBJECTIVE: The aim of this study was to assess whether positive inflammatory histological margins, among other factors, pose a risk for intra-abdominal septic complications in patients with Crohn's disease undergoing ileocolic resection. DESIGN: A retrospective study of patient records, during 2000-2010, was conducted. SETTINGS: This investigation was performed at a single medical center. PATIENTS: Included were 166 individuals with Crohn's disease (85 males, mean age 35.6). INTERVENTION: Ileocolic resection with primary anastomosis was performed. MAIN OUTCOME MEASURE: The primary outcomes measured were postoperative intra-abdominal septic complications. RESULTS: Twenty-five patients (15%) developed intra-abdominal septic complications, including anastomotic leak, intra-abdominal abscesses and collections, and enterocutaneous fistulas. There were no postoperative deaths. Univariate analysis revealed that a long course of disease before surgery, an emergency surgery, steroid treatment of more than 3 months before surgery, additional sigmoidectomy, and positive surgical margins detected on histopathological examination were associated with intra-abdominal septic complications. In a multivariate analysis, only disease duration longer than 10 years (OR 4.575 (CI 1.592-13.142), p = 0.005), additional sigmoidectomy (OR 5.768 (CI 1.088-30.568), p = 0.04), and positive histological resection margins (OR 2.996 (CI 1.085-8.277), p = 0.03) were found to be independent risk factors. LIMITATIONS: This study was limited by the incomplete data regarding preoperative albumin levels. CONCLUSIONS: Positive histological margins, disease duration of more than 10 years, and added sigmoidectomy are independent risk factors that are associated with postoperative intra-abdominal septic complications in patients undergoing ileocolic resection for Crohn's disease. These risk factors should be considered when the need for a diverting stoma is questionable. A frozen section of the margins may assist in the decision as to a temporary ileostomy construction.

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.

Long-term results of fibrin glue treatment for cryptogenic perianal fistulas: a multicenter study.

BACKGROUND: Instillation of fibrin glue, a simple and safe procedure, has been shown to have a moderate short-term success rate in the treatment of cryptogenic perianal fistulas. OBJECTIVE: This study aimed to assess the long-term outcome of this procedure. DESIGN: This study included a retrospective chart review and telephone interviews. SETTINGS: This study was conducted at 4 university-affiliated medical centers. PATIENTS: Patients were included who underwent fibrin glue instillation for complex cryptogenic fistula between 2002 and 2003 within a prospective trial and had successful healing. INTERVENTIONS: Fibrin glue was instilled for complex cryptogenic fistula. MAIN OUTCOME MEASURES: The main outcome measure was long-term fistula healing. RESULTS: Sixty patients participated in the initial trial; the fistulas in 32 of these patients were healed at 6 months. We have located and interviewed 23 (72%) of those patients. Seventeen (74%) patients remained disease free at a mean follow-up of 6.5 years. Six (26%) patients had variable degrees of recurrence; 4 needed further surgical intervention and 2 were treated with antibiotics only. Recurrent disease occurred at an average of 4.1 years (range, 11 mo to 6 y) from surgery, and on several occasions was at a different location in the perianal region. None of the patients experienced incontinence following the procedure. LIMITATIONS: The retrospective nature of this long-term follow-up was a limitation. Twenty-eight percent of the potentially eligible patients were lost to long-term follow-up. CONCLUSIONS: Short-term success of fibrin glue in the treatment of cryptogenic perianal fistula is predictive of long-term healing, but a quarter of those healed in the short term may develop recurrent symptoms in the long run. Injection of fibrin glue remains a safe and simple procedure and may preclude extensive surgery.