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).

The effect of prophylaxis with ertapenem versus cefuroxime/metronidazole on intestinal carriage of carbapenem-resistant or third-generation-cephalosporin-resistant Enterobacterales after colorectal surgery.

OBJECTIVES: Compared to cephalosporin-based prophylaxis, ertapenem prophylaxis lowers the risk of surgical site infection among carriers of extended-spectrum ß-lactamase-producing Enterobacterales (ESBL-PEs) undergoing colorectal surgery. We aimed to determine whether ertapenem prophylaxis leads to increased postoperative colonization with carbapenem-resistant Enterobacterales (CREs) and third-generation-cephalosporin-resistant Enterobacterales (3GCR-Es). METHODS: This study was nested within a quality improvement study of prophylaxis for ESBL-PE carriers undergoing colorectal surgery. Patients were screened 4-6 days after surgery for carriage of ESBL-PEs or other 3GCR-Es and CREs. When CREs were detected, pre- and postsurgical clones were compared using Fourier-transform infrared (FT-IR) spectroscopy. RESULTS: The sample consisted of 56 patients who carried ESBL-PEs before surgery and received cefuroxime/metronidazole prophylaxis (Group 1), 66 who carried ESBL-PEs before surgery and received ertapenem (Group 2), and 103 ESBL-PE non-carriers who received cefuroxime/metronidazole prophylaxis (Group 3). CRE carriage was detected postoperatively in one patient (1.5%) in Group 2 versus eight patients (14.3%) in Group 1 (RD -12.8%; 95%CI -22.4% to -3.1%). For seven out of nine patients, preoperative ESBL-PE and postoperative CRE isolates were compared; in five of them, the pre- and postoperative clones were identical. Postoperative 3GCR-E carriage was detected in 37 patients (56.1%) in Group 2 versus 46 patients in Group 1 (82.1%) (aRD -20.7%, 95%CI -37.3% to -4.1%). CONCLUSIONS: Among ESBL-PE carriers undergoing colorectal surgery, detection of short-term postsurgical colonization by CREs and 3GCR-Es was significantly lower among patients who received ertapenem prophylaxis than those who received cephalosporin-metronidazole prophylaxis. Resistance development in a colonizing bacterial clone, rather than carbapenemase acquisition, was the major mechanism of carbapenem resistance.

Personalized Ertapenem Prophylaxis for Carriers of Extended-spectrum ß-Lactamase-producing Enterobacteriaceae Undergoing Colorectal Surgery.

BACKGROUND: Carriers of extended-spectrum ß-lactamase-producing Enterobacteriaceae (ESBL-PE) who receive cephalosporin-based prophylaxis have twice the risk of surgical site infection (SSI) following colorectal surgery as noncarriers. We tested whether ESBL-PE screening and personalized prophylaxis with ertapenem reduces SSI risk among carriers. METHODS: We conducted a prospective nonrandomized, nonblinded, interventional study in 3 hospitals in Israel, Switzerland, and Serbia. Patients were screened for ESBL-PE carriage before elective colorectal surgery. During the baseline phase, departmental guidelines advised prophylaxis with a cephalosporin plus metronidazole. In the intervention phase, guidelines were changed for ESBL-PE carriers to receive ertapenem. The primary outcome was any type of SSI within 30 days. We calculated adjusted risk differences (ARDs) following logistic regression. RESULTS: The intention-to-treat analysis compared 209 ESBL-PE carriers in the baseline phase to 269 in the intervention phase. SSI rates were 21.5% and 17.5%, respectively (ARD, -4.7% [95% confidence interval {CI}, -11.8% to 2.4%]). Unplanned crossover was high (15%), so to assess efficacy we performed an as-treated analysis comparing 247 patients who received cephalosporin-based prophylaxis with 221 who received ertapenem. SSI rates were 22.7% and 15.8%, respectively (ARD, -7.7% [95% CI, -14.6% to -.8%]), and rates of SSI caused by ESBL-PE were 6.5% and 0.9%, respectively (ARD, -5.6% [95% CI, -8.9% to -2.3%]). There was no significant difference in the rate of deep SSI. The number needed to treat to prevent 1 SSI in ESBL-PE carriers was 13. CONCLUSIONS: Screening for ESBL-PE carriage before colorectal surgery and personalizing prophylaxis for carriers is efficacious in reducing SSI.

Carriage of Extended-spectrum Beta-lactamase-producing Enterobacteriaceae and the Risk of Surgical Site Infection After Colorectal Surgery: A Prospective Cohort Study.

BACKGROUND: Antibiotic prophylaxis that covers enteric pathogens is essential in preventing surgical site infections (SSIs) after colorectal surgery. Current prophylaxis regimens do not cover extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-PE). We aimed to determine whether the risk of SSI following colorectal surgery is higher in ESBL-PE carriers than in noncarriers. METHODS: We conducted a prospective cohort study of patients who underwent elective colorectal surgery in 3 hospitals in Israel, Switzerland, and Serbia between 2012 and 2017. We included patients who were aged ≥18 years, were screened for ESBL-PE carriage before surgery, received routine prophylaxis with a cephalosporin plus metronidazole, and did not have an infection at the time of surgery. The exposed group was composed of ESBL-PE-positive patients. The unexposed group was a random sample of ESBL-PE-negative patients. We collected data on patient and surgery characteristics and SSI outcomes. We fit logistic mixed effects models with study site as a random effect. RESULTS: A total of 3600 patients were screened for ESBL-PE; 13.8% were carriers SSIs occurred in 55/220 carriers (24.8%) and 49/440 noncarriers (11.1%, P < .001). In multivariable analysis, ESBL-PE carriage more than doubled the risk of SSI (odds ratio [OR], 2.36; 95% confidence interval [CI], 1.50-3.71). Carriers had higher risk of deep SSI (OR, 2.25; 95% CI, 1.27-3.99). SSI caused by ESBL-PE occurred in 7.2% of carriers and 1.6% of noncarriers (OR, 4.23; 95% CI, 1.70-10.56). CONCLUSIONS: ESBL-PE carriers who receive cephalosporin-based prophylaxis are at increased risk of SSI following colorectal surgery.

Prevalence and risk factors for carriage of extended-spectrum ß-lactamase-producing Enterobacteriaceae among patients prior to bowel surgery.

Prophylactic antibiotics are an important measure in preventing perioperative infection, Failure to cover multidrug-resistant pathogens may place carriers at increased risk of infection. We conducted a prospective, cross-sectional study in patients prior to bowel surgery to measure the carriage prevalence of extended-spectrum ß-lactamase-producing Enterobacteriaceae and identify risk factors for carriage in this population. During an 11-month period, 150 patients were eligible for inclusion. 27 patients (18%) were found to be carriers of extended-spectrum ß-lactamase-producing Enterobacteriaceae. Factors independently associated with carriage were immunosuppressive therapy (OR, 4.09; 95% CI 1.55-10.81; P = 0.005) and receipt of antibiotics in the prior 3 months (OR, 2.59; 95% CI 1.08-6.24; P = 0.033). Detection of a population at risk for carriage may help in devising and modifying appropriate antibiotic regimens for surgical prophylaxis in carriers of multidrug-resistant bacteria.

Missed inadvertent gastrointestinal injuries during abdominal operations: characteristics, diagnosis, and treatment.

Inadvertent gastrointestinal tract injuries (IGITI) during abdominal operations increase postoperative morbidity. Common mechanisms for this type of injury are not well-defined. The risk factors associated with an increase in missed IGITI during elective abdominal surgery and a possible strategy that may contribute to early diagnosis were not previously evaluated. Between 1998 and 2006, all the patients who underwent a subsequent laparotomy within 30 days of an index operation were identified. Patients reoperated for missed IGITI, defined as perforation at sites other than previous anastomosis or bowel repair, were collected. Data pertaining to patients, disease, and primary operations' characteristics, as well as reoperation findings and outcomes were studied. Methods of diagnosis of perforation for each particular patient were assessed. Thirty-two patients (15 females, 17 males) underwent a second operation for gastrointestinal tract leak within 30 days of an index surgery due to missed IGITI. The mean age was 59.5 ± 18.2 years (range 21-87). The average time between the first and second operation was 5.3 ± 3.5 days (range 1-13). Adhesions (27 patients), previous operations (20 patients), and laparoscopic approach (13 patients) were the most commonly documented factors that may result in missed IGITI. Diagnosis of gastrointestinal leak due to missed IGITI was made clinically in 12 patients. Twenty patients underwent contrast study before reoperation. Careful selection of patients and type of surgery in addition to awareness of this rare complication may decrease the frequency of missed IGITI, lead to earlier diagnosis, and possibly improve outcomes.

Backwash ileitis does not affect pouch outcome in patients with ulcerative colitis with restorative proctocolectomy.

BACKGROUND & AIMS: There has been controversy over the significance of active inflammation of the terminal ileum (also known as backwash ileitis) in patients with ulcerative colitis (UC) and idiopathic inflammatory bowel disease of indeterminate type for diagnosis and pouch construction. We investigated the impact of backwash ileitis on pouch outcome after restorative proctocolectomy with ileoanal pouch anastomosis. METHODS: Data from patients with backwash ileitis (n = 132) were compared with those from 132 matched controls without ileal inflammation for age, sex, and type of proctocolectomies with ileal pouch construction (1- or 2-stage). We evaluated terminal ileal sections from original colectomies of 2213 patients with either UC or idiopathic inflammatory bowel disease of indeterminate type, collected during a 21-year period, for extent and severity of chronic and active ileitis. Clinical pouch outcomes were assessed through a longitudinally maintained clinical outcome database that systematically catalogued all short-term and long-term pouch complications, including pouchitis, sepsis, impaired long-term pouch survival, and conversion to Crohn's disease. RESULTS: Regardless of severity or extent, backwash ileitis was not correlated with any clinical outcome examined, short-term or long-term. CONCLUSIONS: Ileal inflammation is not a contraindication for restorative proctocolectomy with ileal pouch construction in patients with UC or idiopathic inflammatory bowel disease of indeterminate type. Ileal inflammation with pancolitis is not a useful criterion for classifying otherwise typical UC as colitis of indeterminate type, because pouch outcomes are not affected.

Preoperative colorectal neoplasia increases risk for pouch neoplasia in patients with restorative proctocolectomy.

BACKGROUND & AIMS: Restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) has substantially reduced the risk for ulcerative colitis (UC)-associated dysplasia or cancer (neoplasia). We characterized features, risk factors, and outcomes of pouch neoplasia in patients with inflammatory bowel disease in a historical cohort study. METHODS: A total of 3203 patients with a preoperative diagnosis of inflammatory bowel disease underwent restorative proctocolectomy with IPAA from 1984 to 2009 at the Cleveland Clinic. Demographic, clinical, and endoscopic data were reviewed and samples were examined by histological analyses. Univariable and Cox regression analyses were performed. RESULTS: Cumulative incidences for pouch neoplasia at 5, 10, 15, 20, and 25 years were 0.9%, 1.3%, 1.9%, 4.2%, and 5.1%, respectively. Thirty-eight patients (1.19%) had pouch neoplasia, including 11 (0.36%) with adenocarcinoma of the pouch and/or the anal-transitional zone (ATZ), 1 (0.03%) with pouch lymphoma, 3 with squamous cell cancer of the ATZ, and 23 with dysplasia (0.72%). In the Cox model, the risk factor associated with pouch neoplasia was a preoperative diagnosis of UC-associated cancer or dysplasia, with adjusted hazard ratios of 13.43 (95% confidence interval: 3.96-45.53; P < .001) and 3.62 (95% confidence interval: 1.59-8.23; P = .002), respectively. Mucosectomy did not protect against pouch neoplasia. CONCLUSIONS: Risk for neoplasia in patients with UC and IPAA is small and not eliminated by colectomy or mucosectomy. A preoperative diagnosis of dysplasia or cancer of colon or rectum is a risk factor for pouch dysplasia or adenocarcinoma.

Prophylactic fluconazole does not improve outcome in patients with purulent and fecal peritonitis due to lower gastrointestinal perforation.

The benefit of anticandida treatment in addition to standard antibiotic therapy in the presence of perforation/leakage of the lower gastrointestinal tract (LGIT) is still controversial. We retrospectively assessed the clinical effects of empiric anticandida treatment in patients with LGIT perforation who had undergone exploratory laparotomy due to perforated/leaking bowel or appendix between 1999 and 2004, including generalized fecal/purulent peritonitis. Two groups of patients emerged: those receiving empiric anticandida treatment (fluconazole, n = 24) and those who did not (n = 77). All the fluconazole-treated and 40/77 nonfluconazole-treated patients required intensive care unit care and were the subject of this assessment. Postoperative candida infection and mortality rates were similar in the critically-ill fluconazole-treated and nontreated patients (4% vs 7%, 21% vs 22.5%, respectively, P = NS); resistant candidiasis rates were also similar. Hospital and intensive care unit stays were longer in the treated group, however not reaching statistical difference (26.5 +/- 18 vs 21.4 +/- 18.3 days, 14.8 +/- 14.2 vs 9.3 +/- 14.1 days, respectively). The rates of morbidity, pneumonia, and multiorgan failure were significantly higher (P < 0.05) in the treated patients (87% vs 63%, 37% vs 7.5%, and 58% vs 35%, respectively). Empiric fluconazole in patients with peritonitis associated with LGIT perforation did not improve patients' outcome compared with those without empiric treatment.

Ileal pouch rectal anastomosis: a viable alternative to permanent ileostomy in Crohn's proctocolitis patients.

BACKGROUND: Ileal pouch rectal anastomosis (IPRA) is a possible alternative to permanent ileostomy when a short, normal-appearing rectal stump remains after total colectomy. Its outcomes in Crohn colitis (CC) patients have not been reported. STUDY DESIGN: CC patients who underwent IPRA from 1992 to 2004 were identified. Operative and morbidity data were collected. Functional outcomes and quality-of-life (QOL) data were obtained using a mailed questionnaire and compared with matched patients who underwent straight ileorectal anastomosis (SIRA). RESULTS: Twenty-three CC patients underwent IPRA. Perioperative complications included three pelvic septic fluid collections and five small bowel obstructions or ileus, and were treated nonoperatively. Twenty-two patients were available for longterm followup (median 98 months). Fourteen patients (64%) had disease recurrence. Two (9%) have lost a functioning anastomosis. Nine (41%) required additional operations. Matched SIRA patients had higher level of anastomosis (23.4 +/- 5.5 versus 9.0 +/- 4.1 cm above the dentate line; p < 0.0001). Bowel movement frequency (median 6.5/24 hours in both groups), incontinence, and urgency rates were similar. Nighttime seepage and pad usage were more frequent in IPRA. No differences were found in QOL parameters (Cleveland Global QOL score: 0.78 versus 0.73 [0 = worst, 1 = best], IPRA versus SIRA, respectively; p = 0.31). All patients with a functioning IPRA stated they would have their operation again if needed, and 94% would recommend it to others. CONCLUSIONS: IPRA offers durable preservation of bowel continuity and good function and QOL in selected CC patients who might otherwise require a permanent ileostomy.

Postoperative radiotherapy for stage IIIA rectal cancer: is it justified?

PURPOSE: Adjuvant radiotherapy is currently recommended for all node-positive rectal cancers to reduce local recurrence. This study evaluated if an adequate mesorectal excision can obviate the need for radiotherapy in early node-positive cancer. METHODS: Stage IIIA rectal cancer patients were identified in a prospectively maintained database. Patients who received postoperative radiotherapy (radiotherapy) and those who did not (no radiotherapy) were compared for recurrence, survival, bowel function, and quality of life. Quality of life was assessed using the Short Form-36 Medical Outcomes Survey. RESULTS: Eighty-six patients underwent proctectomy for T1-T2,N1 rectal cancers from 1978 to 2004. Patients receiving radiotherapy (n = 34) were younger and had a higher percentage of T1 tumors than patients who did not receive radiotherapy (n = 52). Other tumor characteristics, type of surgery, and number of involved lymph nodes were comparable. Estimated 5-year local recurrence was radiotherapy 3.4 percent and no radiotherapy 4.7 percent; distant recurrence was radiotherapy 13.5 percent and no radiotherapy 16.5 percent; and disease-specific mortality rates were similar 13.5 vs. 11.3 percent, for radiotherapy and no radiotherapy (all P > .05). Patients receiving radiotherapy had higher frequency of daytime bowel movements, urgency, and usage of pads and antidiarrheal medications. Age adjusted quality of life parameters were comparable between treatments. CONCLUSION: Postoperative radiotherapy did not reduce recurrence or mortality. Function but not quality of life was adversely affected. Routine postoperative radiotherapy for Stage IIIA rectal cancer should be reconsidered.

Clinical outcomes and cost analysis of a "fast track" postoperative care pathway for ileal pouch-anal anastomosis: a case control study.

PURPOSE: Traditional length of hospital stay after ileal pouch-anal anastomosis is 8 to 15 days. Fast track rehabilitation programs reduce stay, but there are concerns that readmission and complication rates may be increased. This study evaluated a fast track pathway after ileoanal pouch surgery. METHODS: One hundred three consecutive patients underwent ileal pouch-anal anastomosis on two colorectal services using a fast track protocol with early ambulation, diet, and defined discharge criteria. Direct hospital costs and 30-day and long-term complication data were collected. Patients were matched to controls managed with traditional care pathways by other colorectal staff. RESULTS: Matching was established for 97 patients. Fast track patients had shorter hospital stay than controls (median 4 vs. 5 days; mean 5.0 vs. 5.9, P = 0.012). Readmission and recurrent operation rates were similar (24 vs. 20 percent, P = 0.49, and 9 vs. 10 percent, P = 0.8, fast track vs. control, respectively). Median direct costs per patient (US$) within 30 days were lower with fast track (5692 vs. 6672, P = 0.001), primarily because of reductions in postoperative management expenses. Complication rates, including pouch failure, bowel obstruction, pouchitis, and anastomotic stricture were comparable. Early discharge (< or = 5 days from surgery) occurred in 79 (77 percent) fast track patients. Failure with early discharge was associated with male gender, reoperations, and anastomotic complications. CONCLUSIONS: Fast track protocol after ileoanal pouch surgery reduces length of stay and hospital costs without increasing complication rates. Successful early discharge usually signals a benign postoperative course.

Multivariable analysis of factors associated with hospital readmission after intestinal surgery.

BACKGROUND: Readmission rates after major abdominal surgery have a significant impact on hospital costs and quality of care. Identification of risk factors for readmission may improve postoperative care and discharge plans. METHODS: One hundred fifty consecutive patients readmitted within 30 days of discharge after intestinal surgery (RD) were compared with matched nonreadmitted patients. Patient-related (demographic, comorbidity, medications), disease-related (diagnosis, type of surgery), and perioperative course variables were collected for logistic regression analysis. RESULTS: RD was associated with chronic obstructive pulmonary disease (odds ratio [OR] 7.12 and 95% confidence interval [CI] 1.4-37.6), worse functional capacity class (OR 2.02 and CI 1.15-3.56), previous anticoagulant therapy (OR 4.85 and CI 1.2-19.7), steroid treatment, and discharge to a facility other than home (OR 4.35 and CI 0.97-20.0, P = .055). In patients with intestinal perforation, RD rate was decreased (OR 0.3 and CI 0.1-0.9), but this was associated with a longer primary hospital stay (median 8 vs. 6 days, P = .12). RD causes included surgical site septic complications (33%), ileus and/or small-bowel obstruction (23%), medical complications (24%), and others (20%). CONCLUSIONS: Functional capacity, chronic obstructive pulmonary disease, previous anticoagulant therapy, perioperative steroids, and discharge destination are independent predictors of RD. Disease-related factors have minor impact on RD rates. Improving functional status before surgery, decreasing the adverse impact of steroids, and/or stratifying perioperative anticoagulant use may decrease unexpected readmissions in this patient population.