Saloomeh Sahami

The prognostic value of micrometastases and isolated tumour cells in histologically negative lymph nodes of patients with colorectal cancer: A systematic review and meta-analysis

INTRODUCTION Detection of occult tumour cells in lymph nodes of patients with stage I/II colorectal cancer is associated with decreased survival. However, according to recent guidelines, occult tumour cells should be categorised in micrometastases (MMs) and isolated tumour cells (ITCs). This meta-analysis evaluates the prognostic value of MMs and of ITCs, separately. METHODS PubMed, Embase, Biosis and the World Health Organization International Trials Registry Platform were searched for papers published until April 2013. Studies on the prognostic value of MMs and ITCs in lymph nodes of stage I/II colorectal cancer patients were included. Odds ratios (ORs) for the development of disease recurrence were calculated to analyse the predictive value of MMs and ITCs. RESULTS From five papers, ORs for disease recurrence could be calculated for MMs and ITCs separately. In patients with colorectal cancer, disease recurrence was significantly increased in the presence of MMs in comparison with absent occult tumour cells (OR 5.63; 95%CI 2.4-13.13). This was even more pronounced in patients with colon cancer (OR 7.25 95% CI 1.82-28.97). In contrast, disease recurrence was not increased in the presence of ITCs (OR 1.00 95% CI 0.53-1.88). CONCLUSION Patients with stage I/II colorectal cancer and MMs have a worse prognosis than patients without occult tumour cells. However, ITCs do not have a predictive value. The distinction between ITCs and MMs should be made if the detection of occult tumour cells is incorporated in the clinical decision for adjuvant treatment.

Defunctioning Ileostomy is not Associated with Reduced Leakage in Proctocolectomy and Ileal Pouch Anastomosis Surgeries for IBD

BACKGROUND Anastomotic leakage is a serious complication after restorative proctocolectomy with ileal pouch-anal anastomosis. Previous studies have shown significantly decreased leak rates in diverted patients with less severe clinical consequences. The aim of this study was to evaluate short- and long-term outcome of selective ileostomy formation in a multicentre cohort of patients undergoing pouch surgery. METHODS In a retrospective study, 621 patients undergoing pouch surgery for inflammatory bowel disease [IBD] were identified from three large centres. Anastomotic leakage was defined as any leak confirmed by either contrast extravasation on imaging or during surgical re-intervention. RESULTS In 305 patients [49.1%], primary defunctioning ileostomy was created during pouch surgery and 41 [6.6%] patients received a secondary ileostomy because of a leaking non-diverted pouch. Primary ileostomy formation was associated with male sex, weight loss, American Society of Anesthesiologists score [ASA] > 2, steroid use, one-stage surgery, hand-sewn anastomosis, and blood transfusion. Leak rates were comparable between diverted and non-diverted patients [16.7% vs 17.1%, p = 0.92], which remained unchanged in subgroups with immunosuppressive medication. Having had an ileostomy was demonstrated to be an independent predictor of small bowel obstruction (odds ratio [OR] 2.58, 95% confidence interval [CI] 1.45 - 4.67) and pouch fistulas [OR 3.05, 95%CI 1.06 - 8.73]. The 10-year pouch survival was comparable for patients with and without ileostomy [89% versus 88%, p = 0.718]. CONCLUSIONS Leakage rates of diverted and non-diverted pouches in IBD patients were similar and relatively high. Defunctioning was independently associated with long-term complications. A staged approach without defunctioning might be the best strategy.

The Link between the Appendix and Ulcerative Colitis: Clinical Relevance and Potential Immunological Mechanisms

The human appendix has long been considered as a vestigial organ, an organ that has lost its function during evolution. In recent years, however, reports have emerged that link the appendix to numerous immunological functions in humans. Evidence has been presented for an important role of the appendix in maintaining intestinal health. This theory suggests that the appendix may be a reservoir or ‘safe house’ from which the commensal gut flora can rapidly be reestablished if it is eradicated from the colon. However, the appendix may also have a role in the development of inflammatory bowel disease (IBD). Several large epidemiological cohort studies have demonstrated the preventive effect of appendectomy on the development of ulcerative colitis, a finding that has been confirmed in murine colitis models. In addition, current studies are examining the possible therapeutic effect of an appendectomy to modulate disease course in patients with ulcerative colitis. This literature review assesses the current knowledge about the clinical and immunological aspects of the vermiform appendix in IBD and suggests that the idea of the appendix as a vestigial remnant should be discarded.

The immunology of the vermiform appendix: a review of the literature

This literature review assesses the current knowledge about the immunological aspects of the vermiform appendix in health and disease. An essential part of its immunological function is the interaction with the intestinal bacteria, a trait shown to be preserved during its evolution. The existence of the appendiceal biofilm in particular has proved to have a beneficial effect for the entire gut. In assessing the influence of acute appendicitis and the importance of a normally functioning gut flora, however, multiple immunological aspects point towards the appendix as a priming site for ulcerative colitis. Describing the immunological and microbiotical changes in the appendix during acute and chronic inflammation of the appendix, this review suggests that this association becomes increasingly plausible. Sustained by the distinct composition of cells, molecules and microbiota, as well as by the ever more likely negative correlation between the appendix and ulcerative colitis, the idea of the appendix being a vestigial organ should therefore be discarded.

A multicentre evaluation of risk factors for anastomotic leakage after restorative proctocolectomy with ileal pouch-anal anastomosis for inflammatory bowel disease

BACKGROUND Anastomotic leakage is a major complication after restorative proctocolectomy with ileal pouch-anal anastomosis [IPAA]. Identification of patients at high risk of leakage may influence surgical decision making. The aim of this study was to identify risk factors associated with anastomotic leakage after restorative proctocolectomy with IPAA. METHODS Between September 1990 and January 2015, patients who underwent IPAA for inflammatory bowel disease [IBD] were identified from prospectively maintained databases of three tertiary referral centres. Retrospective chart review identified additional data on demographic and surgical variables. Multivariable regression models were developed to identify risk factors for anastomotic leakage. Separate analyses were performed for type of procedure. RESULTS A total of 640 patients [56.9% male] were included, with a median age of 38 years [interquartile range 29-48]; 96 [15.0%] patients developed anastomotic leakage. Multivariable regression analysis demonstrated that being overweight (body mass index [BMI] > 25], (odds ratio [OR] 1.92; 95% confidence interval [CI] 1.15 - 3.18), and American Society of Anesthesiologists classification [ASA score > 2] [OR 1.91; 95% CI 1.03 - 3.54] were independent risk factors for anastomotic leakage in patients who underwent a completion proctectomy. A disease course of > 5 years [OR 2.34; 95% CI 1.42 - 3.87] and concurrent combination of anti-tumour necrosis factor [TNF] and steroids [OR 6.40; 95% CI 1.76 - 23.20] were independent risk factors for anastomotic leakage in patients who underwent a proctocolectomy and IPAA. CONCLUSIONS Independent risk factors for anastomotic leakage in IBD patients undergoing IPAA are BMI >25, ASA score >2, disease course > 5 years, and concurrent steroid and anti-TNF treatment, with a different risk profile for one-stage proctocolectomy and completion proctectomy procedures.

Comparison of health-related quality of life and disability in ulcerative colitis patients following restorative proctocolectomy with ileal pouch-anal anastomosis versus anti-tumor necrosis factor therapy.

Background and aims Health-related quality of life (HRQL) and disability were compared in ulcerative colitis (UC) patients who underwent restorative proctocolectomy versus patients who received treatment with anti-tumor necrosis factor (anti-TNF) agents. Patients and methods UC patients who underwent restorative proctocolectomy or started anti-TNF treatment between January 2010 and January 2015 were included at two tertiary referral centers. A matched cohort was created using propensity score matching for the covariates disease duration, Montreal classification, age, and sex. HRQL and disability were assessed using the Colorectal Functional Outcome (COREFO), Inflammatory Bowel Disease Disability Index (IBD-DI), EuroQol-5D-3L, and Short Form 36 (SF-36) questionnaires. Results In total, 297 patients were included, of whom 205 (69%) patients responded. Fifty-nine pouch patients were matched to 59 anti-TNF-treated patients. Pouch patients reported better general health scores (P=0.042) compared with the anti-TNF group (SF-36). No differences were found for the EuroQol-5D-3L and IBD-DI between the two groups. Pouch patients had significantly higher COREFO scores compared with anti-TNF-treated patients for ‘stool frequency’ (P<0.001), ‘antidiarrheal medication use’ (P<0.001), and ‘stool-related aspects’ (P=0.004), of which the latter was because of a higher perianal skin irritation frequency (P<0.001). Conclusion UC patients who underwent restorative proctocolectomy reported a higher bowel movement frequency and more perianal skin irritation compared with anti-TNF-treated patients, but this did not affect overall disease-specific disability outcomes. Patients in the surgery group reported better outcomes for generic health compared with those in the anti-TNF group.

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 Fishers 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.

Incidence and Severity of Prepouch Ileitis: A Distinct Disease Entity or a Manifestation of Refractory Pouchitis?

Background:Restorative proctocolectomy with ileal pouch–anal anastomosis is the operation of choice for patients with treatment-refractory ulcerative colitis. However, after this intervention, up to 50% of patients develop pouchitis. Moreover, a subgroup will also develop inflammation in the afferent ileum proximal to the pouch, a condition named prepouch ileitis (PI). Methods:Data on 546 patients who underwent ileal pouch–anal anastomosis for ulcerative colitis were retrospectively collected from 3 tertiary inflammatory bowel disease referral centers in the Netherlands, Belgium, and England. PI was considered present if there was endoscopic and histological inflammation in the afferent limb proximal to the pouch. Crohns disease was excluded by reviewing the histology of colectomy resection specimens. Results:PI was present in 33/546 (6%) patients and all of these had concurrent pouchitis. One hundred forty-four (26%) patients had pouchitis without PI and 369 (68%) patients did not have inflammatory pouch disease. Of the 33 patients with PI, 6 (18%) received no specific treatment, 9 (27%) responded to antibiotics, and 18 (54%) required escalation in therapy to steroids/immunomodulators or anti–tumor necrosis factor agents. Potent immunosuppressive treatment was required more frequently in patients with PI than those with pouchitis alone. Conclusions:PI is less common and more treatment refractory than pouchitis alone. Once PI is diagnosed, clinicians should be aware that response to antibiotic therapy is less likely than in pouchitis alone. Immunomodulatory therapy and escalation to anti–tumor necrosis factor agents should be considered early in cases of nonresponse. The suggestion that PI represents misdiagnosed Crohns disease could not be substantiated in our cohort.

Risk factors for proximal disease extension and colectomy in left-sided ulcerative colitis

Objective The primary objective of this study was to assess proximal disease extension of ulcerative colitis (UC) over time, with disease behaviour pattern and risk factors for proximal disease extension and colectomy as secondary aims. Methods All cumulative incident cases diagnosed with UC at the Academic Medical Center between January 1990 and December 2009 were studied. The cumulative risk of colectomy was calculated by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify risk factors associated with proximal disease extension and colectomy. Results In total, 506 UC patients were included with a median age of 33 years (IQR 23–41) at diagnosis. Ninety-five (18.8%) patients underwent colectomy during follow-up. Median follow-up was 10 years (IQR 5–15). Initial disease extent was evaluable in 416 patients, of whom 142 (34.1%) had proctitis, 155 (37.3%) left-sided colitis and 119 (28.6%) pancolitis. Proximal disease extension was observed in 120 (28.8%) patients during follow-up (51 proctitis to left-sided colitis, 39 proctitis to extensive colitis and 30 left-sided to extensive colitis). Disease behaviour was evaluable in 378 patients, of whom 244 (64.6%) had less than one relapse per year. Younger age at diagnosis (HR 0.98, 95% CI 0.96–0.99) and continuous active disease (HR 2.18, 95% CI 1.27–3.73) were independent risk factors for proximal disease extension. The cumulative risk of colectomy did not change over time between patients diagnosed before and after the year 2000 (p = 0.341). Continuous active disease (HR 7.05, 95% CI 4.23–11.77), systemic steroids (HR 3.25, 95% CI 1.37–7.71) and cyclosporine treatment (HR 2.80, 95% CI 1.66–4.72) were independent risk factors for colectomy, whereas proctitis at diagnosis (HR 0.43, 95% CI 0.22–0.86) carried a lower risk. Conclusion In one-third of UC patients, left-sided disease at diagnosis will extend proximally during 10 years of follow-up. Proximal disease extension was not a risk factor for colectomy, but the risk of colectomy is rather determined by continuous disease activity, and use of systemic steroids and cyclosporine.

External validation of a prognostic model of preoperative risk factors of failure of restorative proctocolectomy

The Cleveland Clinic has proposed a prognostic model of preoperative risk factors for failure of restorative proctocolectomy (RPC) with ileal pouch–anal anastomosis. The model incorporates four predictive variables: completion proctectomy, handsewn anastomosis, diabetes mellitus and Crohns disease. The aim of the present study was to perform an external validation of this model in a new cohort of patients who had RPC.