Susan Galandiuk

Smoking and Inflammatory Bowel Disease: A Meta-analysis

OBJECTIVE To assess whether there is a true effect of smoking on the 2 most prevalent forms of inflammatory bowel disease (IBD): Crohn disease (CD) and ulcerative colitis (UC). METHODS For this meta-analysis, we searched multiple health care databases, including MEDLINE and EMBASE (January 1980 to January 2006), to examine the relationship between smoking and IBD. Keywords searched included smoking, Inflammatory bowel disease, Crohns disease, and ulcerative colitis. Data were abstracted using predefined inclusion and exclusion criteria. An odds ratio (OR) was recalculated for each study using the random-effects model, and a combined OR was calculated. RESULTS A total of 245 articles were obtained through an electronic search of health care databases. Thirteen studies examined the relationship between UC and smoking, whereas 9 examined the relationship between CD and smoking. We found evidence of an association between current smoking and CD (OR, 1.76; 95% confidence interval [CI], 1.40-2.22) and former smoking and UC (OR, 1.79; 95% CI, 1.37-2.34). Current smoking had a protective effect on the development of UC when compared with controls (OR, 0.58; 95% CI, 0.45-0.75). CONCLUSION This is the first meta-analysis, to our knowledge, to evaluate the relationship between smoking and IBD using accepted quality standards for meta-analysis reporting. Our meta-analyses confirm that smoking is an important environmental factor in IBD with differing effects in UC and CD. By using predefined inclusion criteria and testing for homogeneity, the current analysis provides an estimate of the effect of smoking on both these forms of IBD.

Plasma miR-21: a potential diagnostic marker of colorectal cancer.

Objectives:The main objective of this study was to investigate the potential use of circulating microRNAs (miRNAs) as biomarkers of sporadic colorectal cancer (CRC). Background:CRC, a leading cause of death, is curable if detected early. There is an unmet need for an accurate, noninvasive biomarker of CRC. MiRNAs are non–protein-coding RNAs regulating gene expression that play a role in CRC development. Methods:Levels of 380 miRNAs were determined using microfluidic array technology (Applied Biosystems) in a “training” set of 30 CRC patients from whom cancer and adjacent normal tissue were collected. The 4 most dysregulated miRNAs (P < 0.05, false discovery rate (FDR): 10%) were then validated in a second blinded “test” set of 16 CRC patients from whom cancer and normal adjacent tissue had been collected. Validated tissue miRNAs were then evaluated in a plasma “test” set consisting of 30 CRC patients and 30 individuals without CRC. The most dysregulated tissue miRNAs were then validated in an independent new plasma test set consisting of 20 CRC patients with 20 age-, -, and race-matched subjects without CRC. Results:Nineteen of 380 miRNAs were dysregulated in CRC tissue in the tissue “training” set (P < 0.05, FDR: 10%). The 2 most upregulated (miR-31; miR-135b) and most downregulated (miR-1; miR-133a) miRNAs identified CRC in our “test” set with 100% sensitivity and 80% specificity. MiR-31 was more upregulated in stages III and IV compared with stages I and II (P < 0.05). In the “plasma” group, miR-21 differentiated CRC patients from controls with 90% specificity and sensitivity. Conclusions:Plasma miRNAs provide reliable and noninvasive markers for CRC. Plasma miR-21 warrants study in larger cohorts. It seems uniquely promising as a plasma biomarker for CRC.

Ileal Pouch—anal Anastomosis: Reoperation for Pouch-related Complications

The aim was to assess the value of reoperative surgery for pouch-related complications after ileal pouch-anal anastomosis (IPAA) for chronic ulcerative colitis and familial adenomatous polyposis. Between January 1981 and August 1989, 114 of 982 IPAA patients (12%) seen at the Mayo Clinic had complications directly related to IPAA that required reoperation. Among the 114 patients, the complications prevented initial ileostomy closure in 33 patients (25%), occurred after ileostomy closure in 68 patients (60%), and delayed ileostomy closure in the remaining patients. The salvage procedures performed included anal dilatation under anesthesia for anastomotic strictures, placement of setons and/or fistulotomy for perianal fistulae, unroofing of anastomotic sinuses, simple drainage and antibiotics for perianal abscesses, abdominal exploration with drainage of intra-abdominal abscesses with or without establishment of ileostomy, and complete or partial reconstruction of the reservoir for patients with inadequate emptying. None of the reoperated patients died. Reoperation led to restoration of pouch function in two thirds of patients and, of these, 70% had an excellent clinical outcome. However approximately 20% of the 114 pouches required excision. Excision was common, especially among patients who had pelvic sepsis. Salvage procedures for pouch-specific complications can be done safely and will restore pouch function in two thirds of patients. Complications after reoperation, however, may ultimately lead to loss of the reservoir in one in five patients.

Perianal Crohn Disease: Predictors of Need for Permanent Diversion

Objective:Fissures, fistulas, abscesses, and anal canal stenosis are manifestations of perianal Crohn disease (CD). There are no known predictors of which patients will fail sphincter-sparing surgical therapy and ultimately require fecal diversion. Methods:Of 356 consecutive patients with CD, 24% (86) had perianal CD (age range, 14–83 years), and women were slightly more frequently affected. Clinical variables were examined for factors predictive of the need for permanent fecal diversion. Results:CD associated with perianal CD was limited to the small bowel and/or ileocolic area in 23% of patients; the remainder had colorectal CD. Eighty-six patients underwent 344 operations. Forty-two patients (49%) ultimately required permanent diversion; among them were 21 of 32 patients (66%) with anal stricture and 12 of 20women (60%) with rectovaginal fistula. Univariate analyses of clinical variables were performed with respect to need for permanent fecal diversion. Significant univariate predictors were the presence of colonic CD (P = 0.0045, odds ratio [OR] 5.4), avoidance of ileocolic resection (P = 0.0147, OR 0.4), and the presence of an anal stricture (P = 0.0165, OR 3.0). In multivariate logistic regression, the presence of colonic disease and anal canal stricture were predictors of permanent diversion. The OR associated with the risk of permanent diversion in the presence of colonic disease and in the absence of anal stricture was 10 (P = 0.0345). In the presence of both colonic disease and anal canal stenosis, the OR associated with permanent stoma was 33 (P = 0.0023). Conclusions:The management of perianal CD continues to be challenging. Roughly half of patients required permanent fecal diversion, which was even more frequently true for patients with colonic CD and anal stenosis. Recognizing these tendencies will assist both patients and surgeons in planning optimal treatment.

Fournier's gangrene

Fourniers gangrene can still be a life-threatening condition with a high mortality rate. Diagnosis and treatment should be prompt and adequate. Radiological studies may help to define the extent of the disease preoperatively in cases in which this is unclear. Surgery with extensive debridement of all necrotic tissue is the mainstay of treatment.

Meta‐analysis: antibiotic prophylaxis to prevent peristomal infection following percutaneous endoscopic gastrostomy

Despite numerous guidelines recommending prophylactic antibiotics prior to percutaneous endoscopic gastrostomy, their use remains controversial.

The two-edged sword of large-dose steroids for spinal cord trauma

ObjectiveIn 1990, large-dose steroid administration was advocated in spine-injured patients to lessen neurologic deficits. The authors undertook both prospective and retrospective studies to evaluate the response of such profound pharmacologic intervention. Summary Background DataOf all sources of nonfatal injury, spinal cord trauma remains the most devastating in both cost and impact on the quality of the patients life. One study found that routine large-dose steroid administration after injury lessened the extent of neurologic injury. After uncommonly promp‡ and broad lay press publicity, this practice was widely accepted. Biased by knowledge of the known immunosuppressive effects of steroids, the authors suspected that pneumonia was both more frequent and severe in steroid-treated patients. MethodsThirty-two patients with cervical or upper thoracic spinal injuries (C3–6, 20 patients; C6–7, 6 patients; and T1–6 6 patients) were studied at an urban level I trauma center from January 1987 to February 1993. Complete spinal cord injury was present in 22 of 32 patients; 14 patients received steroids postinjury. There was no difference in mean age, cord level, age-adjusted injury severity score, or the percent of injury severity score caused by the spinal injury. ResultsThe length of hospital stay was longer in steroid-treated patients (S) than in nonsteroid (NS) patients, that is, 44.4 days versus 27.7 days, respectively (p = 0.065). Seventy-nine per cent of S patients had pneumonia compared with 50% of NS patients (p = 0.614). There was no statistical difference in the episodes of pneumonia per patient between the two groups (p > 0.05). Prospectively, the authors evaluated sequentially several parameters known to be important in human immune responses to bacterial challenges in nine S and five NS patients. In S patients, both the per cent and density of monocyte class II antigen expression and T-helper/ suppressor cell ratios were lower than in NS patients. However, S patients did have an initially higher, earlier boost in some host defense parameters that rapidly declined, and their subsequent response was both blunted and delayed. These differences became even clearer when stratified according to cord level and incomplete versus complete cord status. Not surprisingly, infected patients, whether S or NS, had lower levels of monocyte antigen expression, CR3, and helper/ suppressor ratios. ConclusionsThese data do not permit a judgment to be made whether neurologic status was improved by S administration. It is known that vital immune responses were adversely affected, that pneumonia was somewhat more prevalent, and that hospitalization was prolonged and costs therefore increased by an average of

Villous tumors of the duodenum.

51,504 per admission. Further clinical studies will be needed to determine to what extent these observations offset the putative benefits of large-dose steroids in the treatment of spinal trauma.

The importance of diagnostic accuracy in colonic inflammatory bowel disease

Records of 32 patients with 34 villous and tubulovillous adenomas of the duodenum, treated at the Cleveland Clinic over the past 21 years, were reviewed. Twenty-two patients (69%) had complete resection of the adenoma; the incidence of malignancy was 47%. Five patients underwent a Whipple procedure; 4 patients had segmental resection of the duodenum; 12 had wide local excision of the adenoma; 1 had both a segmental resection and a local excision for two separate adenomas; and 5 patients had endoscopic excision alone. The remaining five patients underwent exploratory laparotomy alone or with palliative bypass procedures. A 28% recurrence rate was observed, all of these after segmental resection, local excision, or endoscopic excision. The highest recurrence rate was associated with local excision. The 2− and 5-year survival rates for patients with adenomas containing invasive cancer were 22% and 0%, respectively, compared to 87% and 87%, respectively, for benign adenomas (including those with carcinoma in situ). Twenty-two per cent of patients had intestinal polyposis syndromes. Duodenal adenomas were diagnosed a mean of 17 years after colectomy for polyposis, indicating the need for continued surveillance in these patients.

A plasma microRNA panel for detection of colorectal adenomas: a step toward more precise screening for colorectal cancer.

OBJECTIVE:Crohns disease (CD) and ulcerative colitis (UC) may both affect the colon. However, in approximately 10–20% of these cases, it is impossible to distinguish between these two entities either clinically or histologically, and a diagnosis of indeterminate colitis (IC) is made. Correct diagnosis is important because surgical treatment and long-term prognosis differ for UC and CD. The purpose of this study was to determine the extent of interobserver agreement among board-certified pathologists and a specialist gastrointestinal (GI) pathologist regarding the histological diagnosis of colonic inflammatory bowel disease (IBD).METHODS:A total of 24 university medical center pathologists from eight institutions evaluated 84 colectomy specimens and 35 sets of biopsy specimens from 119 consecutive patients with colonic IBD. A specialist GI pathologist subsequently reviewed all cases without knowledge of clinical data and prior diagnosis.RESULTS:The GI pathologists diagnoses differed from the initial diagnoses in 45% of surgical specimens and 54% of biopsy specimens. Of 70 cases initially diagnosed as UC, 30 (43%) were changed to CD or IC, whereas 4 of 23 cases (17%) initially diagnosed as CD were changed to UC or IC. The κ coefficient for the overall agreement of initial diagnoses with the specialist GI pathologists diagnoses was −0.01 (p = 0.98).CONCLUSIONS:There is significant interobserver variation in the histological diagnosis of colonic IBD. This may have a profound effect on clinical patient care and, especially, on the choice of operation. More accurate diagnostic criteria are needed to facilitate patient care and to optimize treatment outcome.