Anthony R. MacLean

Combined seton placement, infliximab infusion, and maintenance immunosuppressives improve healing rate in fistulizing anorectal Crohn's disease: a single center experience.

AbstractPURPOSE: Infliximab (anti-TNF α) has been used for the treatment of fistulizing Crohn’s disease with variable efficacy. The aim of this study was to evaluate the efficacy of infliximab combined with selective seton drainage in the healing of fistulizing anorectal Crohn’s disease. METHODS: This was a retrospective chart review of all patients with fistulizing Crohn’s disease treated with infliximab between March 2000 and February 2002. RESULTS: Twenty-nine patients (12 male; mean age, 31 years) received a mean of 3 (range, 1–5) doses of infliximab 5 mg/kg. Twenty-one patients had perianal fistulas; eight had rectovaginal fistulas, four with combined rectovaginal/perianal fistula. Fourteen of 21 patients (67 percent) with perianal fistula had a complete response (mean follow-up, 9 months), 4 of the 14 relapsed (mean, 6 months), but all had a complete response to retreatment (mean, 9 months). A partial response occurred in four patients (19 percent), defined by decreased drainage (2 patients) or infliximab dependence (2 patients) requiring repeated dosing every six to eight weeks. Three patients (14 percent) had no response. Seton drainage was used before infusion in 13 perianal patients for perianal infection and 17 were treated with maintenance azathioprine or methotrexate. Of eight patients with rectovaginal fistula, complete response occurred in one, partial response in five, and no response in two. Two partial responders became infliximab dependent. A complete response was observed in one patient with isolated rectovaginal fistula, a partial response in five. No patient with a combined rectovaginal/perianal fistula had a complete response. Five rectovaginal fistula patients were taking maintenance immunosuppressive agents and two had seton drainage before infusion. CONCLUSIONS: Selective seton placement combined with infliximab infusion and maintenance immunosuppressives resulted in complete healing in 67 percent of Crohn’s patients with perianal fistula and partial healing in 19 percent. Relapse was successfully treated with repeat infusion. Concomitant rectovaginal fistula was a poor prognostic indicator for successful infliximab therapy.

Postoperative complications following surgery for rectal cancer.

Objective:This systematic review was designed to determine postoperative complication rates of radical surgery for rectal cancer (abdominal perineal resection and anterior resection). Summary of Background Data:Lack of accepted complication rates for rectal cancer surgery may hinder quality improvement efforts and may impede the conception of future studies because of uncertainty regarding the expected event rates. Methods:All prospective studies of rectal cancer receiving radical surgery published between 1990 and August 2008 were obtained by searching Ovid MEDLINE, EMBASE, as well as ASCO GI, CAGS, and ASCRS meeting abstracts between 2004 and 2008. There was no language restriction. The outcomes extracted were anastomotic leak, pelvic sepsis, postoperative death, wound infection, and fecal incontinence. Summary complication rates were obtained using a random effects model; the Z-test was used to test for study heterogeneity. Results:Fifty-three prospective cohort studies and 45 randomized controlled studies with 36,315 patients (24,845 patients had an anastomosis) were eligible for inclusion. Most of the studies found were based in continental Europe (58%), followed by Asia (25%), United Kingdom (10%), North America (5%), and Australia/New Zealand. The anastomotic leak rate, reported in 84 studies, was 11% (95% CI: 10, 12); the pelvic sepsis rate, in 29 studies, was 12% (9, 16); the postoperative death rate, in 75 studies, was 2% (2, 3); and the wound infection rate, in 50 studies, was 7% (5, 8). Fecal incontinence rates were reported in too few studies and so heterogeneously that numerical summarization was inappropriate. Year of publication, use of preoperative radiation, use of laparoscopy, and use of protecting stoma were not significant variables, but average age, median tumor height, and method of detection (clinical vs. radiologic) showed significance to explain heterogeneity in anastomotic leak rates. Year of publication, study origin, average age, and use of laparoscopy were significant, but median tumor height and preoperative radiation use were not significant in explaining heterogeneity among observed postoperative death rates. With multivariable analysis, only average age for anastomotic leak and year of publication for postoperative death remained significant. Conclusions:Benchmark complication rates for radical rectal cancer surgery were obtained for use in sample size calculations in future studies and for quality control purposes. Postoperative death rates showed improvement in recent years.

Risk of small bowel obstruction after the ileal pouch-anal anastomosis.

ObjectiveTo determine the incidence of small bowel obstruction (SBO), to identify risk factors for its development, and to determine the most common sites of adhesions causing SBO in patients undergoing ileal pouch–anal anastomosis (IPAA). MethodsAll patients undergoing IPAA at Mount Sinai Hospital were included. Data were obtained from the institution’s database, patient charts, and a mailed questionnaire. SBO was based on clinical, radiologic, and surgical findings. Early SBO was defined as a hospital stay greater than 10 or 14 days because of delayed bowel function, or need for reoperation or readmission for SBO within 30 days. All patients readmitted after 30 days with a discharge diagnosis of SBO were considered to have late SBO. ResultsBetween 1981 and 1999, 1,178 patients underwent IPAA (664 men, 514 women; mean age 40.7 years). A total of 351 episodes of SBO were documented in 272 (23%) patients during a mean follow-up of 8.7 years (mean 1.29 episodes/patient). Fifty-four patients had more than one SBO. One hundred fifty-four (44%) of the SBOs occurred in the first 30 days; 197 (56%) were late SBOs. The cumulative risk of SBO was 8.7% at 30 days, 18.1% at 1 year, 26.7% at 5 years, and 31.4% at 10 years. The need for surgery for SBO was 0.8% at 30 days, 2.7% at 1 year, 6.7% at 5 years, and 7.5% at 10 years. In patients requiring laparotomy, the obstruction was most commonly due to pelvic adhesions (32%), followed by adhesions at the ileostomy closure site (21%). A multivariate analysis showed that when only late SBOs were considered, performance of a diverting ileostomy and pouch reconstruction both led to a significantly higher risk of SBO. ConclusionsThe risk of SBO after IPAA is high, although most do not require surgical intervention. Thus, strategies that reduce the risk of adhesions are warranted in this group of patients to improve patient outcome and decrease healthcare costs.

Postoperative Complications and Mortality Following Colectomy for Ulcerative Colitis

BACKGROUND & AIMS Complications after colectomy for ulcerative colitis (UC) have not been well characterized in large, population-based studies. We characterized postoperative in-hospital complications, stratified them by severity, and assessed independent clinical predictors, including use of immunosuppressants. METHODS We performed population-based surveillance using administrative databases to identify all adults (≥18 y) who had an International Classification of Diseases-9th/10th revisions code for UC and a colectomy from 1996 to 2009. All medical charts were reviewed. The primary outcome was severe postoperative complications, including in-hospital mortality. Logistic regression was used to assess predictors of complications after colectomy and then restricted to patients undergoing emergent or elective surgeries. RESULTS Of the 666 UC patients who underwent a colectomy, a postoperative complication occurred in 27.0% and the mortality rate was 1.5%. Independent predictors of postoperative complications were age (for patients >64 vs 18-34 y: odds ratio [OR], 1.95; 95% confidence interval [CI], 1.07-3.54), comorbidities (>2 vs none: OR, 1.89; 95% CI, 1.06-3.37), and admission status (emergent vs elective colectomy: OR, 1.62; 95% CI, 1.14-2.30). Significant risk factors for an emergent colectomy included time from admission to colectomy (>14 vs 3-14 d: OR, 3.32; 95% CI, 1.62-6.80) and a preoperative complication (≥1 vs 0: OR, 3.04; 95% CI, 1.33-6.91). A prescription of immunosuppressants before colectomies did not increase the risk for postoperative complications. CONCLUSIONS Postoperative complications frequently occur after colectomy for UC, predominantly among elderly patients with multiple comorbidities. Patients who were admitted to the hospital under emergency conditions and did not respond to medical treatment had worse outcomes when surgery was performed 14 or more days after admission.

Decreasing Colectomy Rates for Ulcerative Colitis: A Population-Based Time Trend Study

OBJECTIVES:Colectomy rates for ulcerative colitis (UC) have been inconsistently reported. We assessed temporal trends of colectomy rates for UC, stratified by emergent vs. elective colectomy indication.METHODS:From 1997 to 2009, we identified adults hospitalized for a flare of UC. Medical charts were reviewed. Temporal changes were evaluated using linear regression models to estimate the average annual percent change (AAPC) in surgical rates. Logistic regression analysis compared: (i) UC patients responding to medical management in hospital to those who underwent colectomy; (ii) UC patients who underwent an emergent vs. elective colectomy; and (iii) temporal trends of drug utilization.RESULTS:From 1997 to 2009, colectomy rates significantly dropped for elective colectomies with an AAPC of −7.4% (95% confidence interval (CI): −10.8%, −3.9%). The rate of emergent colectomies remained stable with an AAPC of −1.4% (95% CI: −4.8%, 2.0%). Azathioprine/6-mercaptopurine prescriptions increased from 1997 to 2009 (odds ratio (OR)=1.15; 95% CI: 1.09–1.22) and infliximab use increased after 2005 (OR=1.68; 95% CI: 1.25–2.26). A 13% per year risk adjusted reduction in the odds of colectomy (OR=0.87; 95% CI: 0.83–0.92) was observed in UC patients responding to medical management compared with those who required colectomy. Emergent colectomy patients had a shorter duration of flare (<2 weeks vs. 2–8 weeks, OR=5.31; 95% CI: 1.58–17.81) and underwent colectomy early after diagnosis (<1 year vs. 1–3 years, OR=5.48; 95% CI: 2.18–13.79).CONCLUSIONS:From 1997 to 2009, use of purine anti-metabolites increased and elective colectomy rates in UC patients decreased significantly. In contrast, emergent colectomy rates were stable, which may have been due to rapid progression of disease activity.

Neoadjuvant chemoradiation increases the risk of pelvic sepsis after radical excision of rectal cancer.

PURPOSEThis study was designed to examine the effect of neoadjuvant chemoradiation on pelvic sepsis after mesorectal excision for rectal cancer.METHODSA retrospective chart review was conducted for all patients who underwent curative mesorectal excision for rectal cancer during an eight-year period. Demographic, preoperative, perioperative data were collected. Pelvic sepsis was defined as clinical or radiographically demonstrable leak or a pelvic abscess. Neoadjuvant chemoradiation included 5,040 Gy in conjunction with three cycles of 5-fluorouracil-based chemotherapy, followed by a one-month waiting period.RESULTSFrom January 1994 to December 2002, 246 patients (151 males; mean age 68 (range, 36–97) years) underwent curative resection for rectal cancer. Procedures included 186 anterior resections, 52 abdominoperineal resections, and 8 Hartmann’s. Of 60 patients (24.4 percent) who had neoadjuvant chemoradiation, 9 (15 percent) developed pelvic sepsis (3 leaks, 6 abscesses) compared with 9 of 186 (4.8 percent) after primary surgery (6 leaks, 3 abscesses; P < 0.01). Ninety-three patients had an anastomosis ≤6 cm from the anal verge. Of these, 9 patients (9.7 percent) developed pelvic sepsis (5 leaks, 4 abscesses): 5 of 28 (17.9 percent) after neoadjuvant chemoradiation vs. 4 of 65 (6.2 percent) after primary surgery (P = 0.22). Only 6 of 93 patients (6.5 percent) with an anastomosis ≥7 cm developed pelvic sepsis (5 leaks and 1 abscess), of whom 1 had preoperative radiation. Pelvic abscess developed in 3 of 24 patients after neoadjuvant chemotherapy and abdominoperineal resection. After primary abdominoperineal resection, none of the remaining 28 patients developed pelvic sepsis. A multivariable logistic regression model was constructed to determine predictors of sepsis. Neoadjuvant chemotherapy was the only variable that was predictive (odds ratio, 3.4; 95 percent confidence interval, 1.3–9).CONCLUSIONSThe addition of neoadjuvant chemoradiation to mesorectal excision significantly increased the rate of pelvic sepsis. This was particularly true for anastomoses in the lower third of the rectum. Fecal diversion should be considered in these patients.

Effect of ambient air pollution on the incidence of appendicitis

Background: The pathogenesis of appendicitis is unclear. We evaluated whether exposure to air pollution was associated with an increased incidence of appendicitis. Methods: We identified 5191 adults who had been admitted to hospital with appendicitis between Apr. 1, 1999, and Dec. 31, 2006. The air pollutants studied were ozone, nitrogen dioxide, sulfur dioxide, carbon monoxide, and suspended particulate matter of less than 10 μ and less than 2.5 μ in diameter. We estimated the odds of appendicitis relative to short-term increases in concentrations of selected pollutants, alone and in combination, after controlling for temperature and relative humidity as well as the effects of age, sex and season. Results: An increase in the interquartile range of the 5-day average of ozone was associated with appendicitis (odds ratio [OR] 1.14, 95% confidence interval [CI] 1.03–1.25). In summer (July–August), the effects were most pronounced for ozone (OR 1.32, 95% CI 1.10–1.57), sulfur dioxide (OR 1.30, 95% CI 1.03–1.63), nitrogen dioxide (OR 1.76, 95% CI 1.20–2.58), carbon monoxide (OR 1.35, 95% CI 1.01–1.80) and particulate matter less than 10 μ in diameter (OR 1.20, 95% CI 1.05–1.38). We observed a significant effect of the air pollutants in the summer months among men but not among women (e.g., OR for increase in the 5-day average of nitrogen dioxide 2.05, 95% CI 1.21–3.47, among men and 1.48, 95% CI 0.85–2.59, among women). The double-pollutant model of exposure to ozone and nitrogen dioxide in the summer months was associated with attenuation of the effects of ozone (OR 1.22, 95% CI 1.01–1.48) and nitrogen dioxide (OR 1.48, 95% CI 0.97–2.24). Interpretation: Our findings suggest that some cases of appendicitis may be triggered by short-term exposure to air pollution. If these findings are confirmed, measures to improve air quality may help to decrease rates of appendicitis.

Serum metabolomic profile as a means to distinguish stage of colorectal cancer

BackgroundPresently, colorectal cancer (CRC) is staged preoperatively by radiographic tests, and postoperatively by pathological evaluation of available surgical specimens. However, present staging methods do not accurately identify occult metastases. This has a direct effect on clinical management. Early identification of metastases isolated to the liver may enable surgical resection, whereas more disseminated disease may be best treated with palliative chemotherapy.MethodsSera from 103 patients with colorectal adenocarcinoma treated at the same tertiary cancer center were analyzed by proton nuclear magnetic resonance (1H NMR) spectroscopy and gas chromatography-mass spectroscopy (GC-MS). Metabolic profiling was done using both supervised pattern recognition and orthogonal partial least squares-discriminant analysis (O-PLS-DA) of the most significant metabolites, which enables comparison of the whole sample spectrum between groups. The metabolomic profiles generated from each platform were compared between the following groups: locoregional CRC (N = 42); liver-only metastases (N = 45); and extrahepatic metastases (N = 25).ResultsThe serum metabolomic profile associated with locoregional CRC was distinct from that associated with liver-only metastases, based on 1H NMR spectroscopy (P = 5.10 × 10-7) and GC-MS (P = 1.79 × 10-7). Similarly, the serum metabolomic profile differed significantly between patients with liver-only metastases and with extrahepatic metastases. The change in metabolomic profile was most markedly demonstrated on GC-MS (P = 4.75 × 10-5).ConclusionsIn CRC, the serum metabolomic profile changes markedly with metastasis, and site of disease also appears to affect the pattern of circulating metabolites. This novel observation may have clinical utility in enhancing staging accuracy and selecting patients for surgical or medical management. Additional studies are required to determine the sensitivity of this approach to detect subtle or occult metastatic disease.

Bowel obstruction following appendectomy: what is the true incidence?

Introduction:Appendicitis is a common problem that is typically treated with an appendectomy. Following abdominal surgery, adhesions may form and may cause a subsequent small bowel obstruction (SBO). The purpose of our study was to determine the rate of post-appendectomy SBO in an adult population, and to observe any difference in SBO rates between open versus laparoscopic appendectomies. Methods:All patients who underwent an appendectomy at an adult hospital in the Calgary Health Region between 1999 and 2002 were identified by using the administrative discharge database. Pathology and operative technique (laparoscopic, McBurney incision, midline laparotomy) were reviewed. Using those regional health numbers, any further admissions with a diagnostic code for bowel obstruction were identified. Medical charts (n = 1777) were reviewed to confirm the rate of post-appendectomy SBO. A logistic regression was performed to identify risk factors of post-appendectomy SBO and expressed as odds ratios (95% confidence interval). Results:The overall SBO rate was 2.8% over an average 4.1-year follow-up period. The risk factors for developing SBO following appendectomy for appendicitis included, perforated appendicitis (odds ratio [OR] = 3.1, 95% confidence interval [CI]: 1.5–6.6), and midline incisions (OR = 5.4, 95% CI: 2.8–10.4). Those with pathology of cancer or chronic appendicitis conferred the greatest overall risk of SBO (OR = 7.4, 95% CI: 2.7–20.3). Conclusions:The rate of SBO following appendectomy in adults was 2.8%, or 0.0069 cases per person-year. The greatest risk factors for developing SBO were midline incision and nonappendicitis pathology. There is no statistically significant difference in SBO rates following laparoscopic appendectomy compared with open approaches.

Comparison of Stapled versus Handsewn Loop Ileostomy Closure: A Meta-analysis

The purpose of this study was to compare the rates of small bowel obstruction, anastomotic complications, and wound infections between stapled and handsewn closures of loop ileostomies. A literature search in Embase, PubMed, and Cochrane Database for Clinical Trials using search terms “closure,” “loop ileostomy,” and “stapled” was performed. All abstracts were reviewed to identify relevant articles, and their references were hand searched for additional studies. Six articles were identified for inclusion. Three independent reviewers extracted the following data: rates of small bowel obstruction, anastomotic complications, wound infection; length of hospital stay; and operative time. Data analysis was performed using Stata statistical software. Comparing stapled versus hand-sewn closures, there were no statistically significant differences in bowel obstruction (relative risk [RR] 0.69, 95% confidence interval [CI] 0.44 to 1.09), wound infection (RR 0.91, 95% CI 0.53 to 1.97), or anastomotic complication rates (RR 1.01, 95% CI 0.99 to 1.03). Two studies showed shorter operative times favoring stapled anastomoses. No difference was seen in length of stay. Current literature suggests no statistically significant differences between stapled and hand-sewn loop ileostomy closures, but there may be a trend favoring stapled closures with regard to lower small bowel obstruction rates and shorter operative time.