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Biomedical subjects

Robin S McLeod

Publications and source records attributed to Robin S McLeod.

At least 19 recordsLinked to original sources

Surveillance colonoscopy in individuals at risk for hereditary nonpolyposis colorectal cancer: an evidence-based review.

PURPOSE: Surveillance colonoscopy plays an important role in the management of asymptomatic patients known to carry and suspected of carrying hereditary nonpolyposis colorectal cancer gene mutations. Although the shortest interval between surveillance examinations may seem to offer the most benefit to patients, excessive use of this procedure may have unwanted consequences. This study was designed to evaluate the evidence and make recommendations regarding the optimal frequency of surveillance colonoscopy and the age at which to initiate surveillance based on the best available evidence. METHODS: MEDLINE was searched for all articles assessing surveillance colonoscopy from 1966 to 2004 by using the MESH terms "hereditary nonpolyposis colorectal cancer" and "screening." The evidence was systematically reviewed and a critical appraisal of the evidence was performed. RESULTS: There are no randomized, controlled, clinical trials examining the frequency of surveillance colonoscopy in hereditary nonpolyposis colorectal cancer. Three cohort studies were identified for review. There is one cohort study of good quality that provides evidence that surveillance colonoscopy every three years in patients with hereditary nonpolyposis colorectal cancer reduces the risk of developing colorectal cancer and the risk of death. The two remaining cohort studies provide poor evidence on which to make a recommendation. CONCLUSIONS: The best available evidence supports surveillance with complete colonoscopy to the cecum every three years in patients with hereditary nonpolyposis colorectal cancer (B recommendation). There is no evidence to support or refute more frequent screening. Further research is required to examine the potential harms and benefits of more frequent screening. However, given the potential for rapid progression from adenoma to carcinoma and missing lesions at colonoscopy, there is consensus that screening more frequently than every three years is required.

Colonoscopy↗

The impact of surgery for colorectal cancer on quality of life and functional status in the elderly.

PURPOSE: Colorectal cancer is a common diagnosis in the elderly. Frequently concerns arise about outcomes after surgery, and little is known about postoperative quality of life in this older group after major bowel surgery. The objective of this study was to compare quality of life and functional status of elderly patients (older than aged 80 years) who have undergone surgery for colorectal cancer with a younger (younger than aged 70 years), procedure-matched control group. METHODS: Patients in the case (older than aged 80 years) and control groups (younger than aged 70 years) were identified from the colorectal cancer database at Mount Sinai Hospital, Toronto, Canada. All had treatment for colorectal cancer within the last five years. Patients were surveyed by mail using the European Organization for Research and Treatment of Cancer quality of life scales specific to cancer and colorectal cancer (EORTC-C30 and EORTC-CR38) and the Short Form-36. Student's t-test was used to test differences. RESULTS: There were 29 patients in each of the groups. The current average ages were 83.2 (standard deviation=2.79) years, and 67.7 (standard deviation=5.1) years, respectively. The two groups scored similarly on the European Organization for Research and Treatment of Cancer quality of life scales in all domains except physical functioning, functional role, micturition, and stoma-related problems. Similarly, the mean scores of the Short Form-36 were similar with the exception of the vitality domain. Most patients did not require special assistance or alternate living arrangements after discharge from the hospital, and most patients seemed to be able to return to their preoperative level of functioning. However, stoma care was a greater concern to the elderly. CONCLUSIONS: Elderly patients older than aged 80 years who are selected for surgery have a quality of life comparable to younger patients in most respects. Therefore, colorectal cancer surgery may be offered to the highly functioning elderly with the expectation of a good quality of life postoperatively.

Activities of Daily Living↗

Phenotype-stratified genetic linkage study demonstrates that IBD2 is an extensive ulcerative colitis locus.

OBJECTIVES: The complete elucidation of genetic variants that contribute to inflammatory bowel disease (IBD) will likely include variants that increase risk to both Crohn's disease and ulcerative colitis as well as variants that increase risk for particular phenotypic subsets. The purpose of this study was to assess phenotypic subsets that contribute to the major IBD susceptibility loci. METHODS: This linkage study encompassed 904 affected relative pairs, representing the largest combined phenotyped cohort to date, and allowing for meaningful subset analyses. Genetic linkage data were stratified by disease location and age at diagnosis. RESULTS: We establish that some loci, notably the IBD3 and chromosome 3q linkage regions demonstrate contributions from both small intestine and colon cohorts, whereas others, notably the IBD1 (NOD2/CARD15) and IBD2 regions increase risk for small intestine or colon inflammation, respectively. The strongest linkage evidence in this study was for the subset of extensive ulcerative colitis in the region of IBD2 (lod 3.27; p < 0.001). Evidence for linkage in the region of NOD2/CARD15 (IBD1) was stronger for the subset of Crohn's patients with ileal disease (lod 2.56; p= 0.035) compared to the overall Crohn's group, consistent with previous findings that NOD2/CARD15 variants are associated with ileal disease. CONCLUSIONS: Analyses incorporating disease location in IBD increase the power and enhance the accuracy of genomic localization. Our data provide strong evidence that extensive ulcerative colitis represents a pathophysiologic subset of IBD.

Adaptor Proteins, Signal Transducing↗

Pouch-vaginal fistula after ileal pouch-anal anastomosis: treatment and outcomes.

PURPOSE: Pouch-vaginal fistula is an uncommon but serious complication after ileal pouch anal anastomosis. The management of pouch-vaginal fistulas is challenging and a number of treatment options exist. The purpose of this study was to examine the outcomes after various procedures for pouch-vaginal fistula performed at our institution. METHODS: Patients who were treated for pouch-vaginal fistula at Mount Sinai Hospital were identified from a prospectively maintained database. Demographic, disease history, treatment, and outcomes data were obtained. Treatment success was defined as no recurrence of the fistula with a functioning pouch and no ileostomy. RESULTS: Since November 1982, 24 of 619 (3.9 percent) women who had primary ileal pouch-anal anastomosis performed at Mount Sinai Hospital developed a pouch-vaginal fistula. Five women had ileal pouch-anal anastomosis performed at another institution and were referred for management of their pouch-vaginal fistula. Local and/or combined abdominoperineal repairs were performed in 22 of 29 patients. Combined abdominoperineal repairs were associated with a higher success rate than that of local perineal repairs (52.9 vs. 7.9 percent, respectively, at 10 years after repair; p = 0.035). Overall, 50 percent (11/22) of patients who underwent surgical repair of a pouch-vaginal fistula had a successful result with a functioning pouch and no recurrence of the fistula, and 21 percent (6/29) of patients required pouch excision. CONCLUSIONS: The management of pouch-vaginal fistula after ileal pouch-anal anastomosis is associated with a high recurrence rate. Combined abdominoperineal repair appears to offer better results than those of local procedures.

Abdomen↗

Crohn's disease and indeterminate colitis and the ileal pouch-anal anastomosis: outcomes and patterns of failure.

PURPOSE: This study was designed to determine the outcome of patients with Crohn's disease and indeterminate colitis who have an ileal pouch-anal anastomosis. METHODS: Between 1982 and 2001, 1,270 patients underwent a restorative proctocolectomy at the Mount Sinai Hospital: 1,135 had ulcerative colitis, 36 had Crohn's disease, 21 had indeterminate colitis, and 78 had another diagnosis. Perioperative data were collected prospectively. Functional outcomes were assessed with a 35-question survey mailed to all patients with a functioning pouch of at least six months duration. RESULTS: Pouch complications were significantly more common in patients with Crohn's disease (64 percent) and indeterminate colitis (43 percent) compared with patients with ulcerative colitis (22 percent) (P < 0.05). Similarly, 56 percent of patients with Crohn's disease had their pouch excised or defunctioned, compared with 10 percent of patients with indeterminate colitis and 6 percent with ulcerative colitis (P < 0.01). In the subgroup of patients with a diagnosis of Crohn's disease, multivariate analysis revealed that the pathologist's initial designation of ulcerative colitis (based on the colectomy specimen) and an increasing number of pathologic, clinical, and endoscopic features of Crohn's disease were independently associated with pouch failure. The functional results in patients with Crohn's disease with a successful pouch were not significantly different from those with indeterminate colitis or ulcerative colitis. CONCLUSIONS: Although complication rates may be higher in patients with indeterminate colitis compared with ulcerative colitis, the overall pouch failure rate is similar. On the other hand, more than one-half of patients with Crohn's disease will require pouch excision or diversion. Our data suggest that it is difficult to identify patients with Crohn's disease who are likely to have a successful outcome after restorative proctocolectomy. Thus, Crohn's disease should remain a relative contraindication to restorative proctocolectomy, whereas ileal pouch-anal anastomosis is an acceptable alternative for patients with indeterminate colitis.

Adult↗

Prevalence of male and female sexual dysfunction is high following surgery for rectal cancer.

OBJECTIVE: To measure sexual function and quality of life (QOL) after rectal cancer treatment. SUMMARY BACKGROUND DATA: Previous studies on sexual function after rectal cancer treatment have focused on males and have not used validated instruments. METHODS: Patients undergoing curative rectal cancer surgery from 1980 to 2003 were administered a questionnaire, including the Female Sexual Function Index (FSFI) or International Index of Erectile Function (IIEF), and the EORTC QLQ-C30/CR-38. Multiple logistic regression was used to test associations of clinical factors with outcomes. RESULTS: Eighty-one women (81.0%) and 99 men (80.5%) returned the questionnaire; 32% of women and 50% of men are sexually active, compared with 61% and 91% preoperatively (P < 0.04); 29% of women and 45% of men reported that "surgery made their sexual lives worse." Mean (SD) FSFI and IIEF scores were 17.5 (11.9) and 29.3 (22.8). Specific sexual problems in women were libido 41%, arousal 29%, lubrication 56%, orgasm 35%, and dyspareunia 46%, and in men libido 47%, impotence 32%, partial impotence 52%, orgasm 41%, and ejaculation 43%. Both genders reported a negative body image. Patients seldom remembered discussing sexual risks preoperatively and seldom were treated for dysfunction. Current age (P < 0.001), surgical procedure (P = 0.003), and preoperative sexual activity (P = 0.001) were independently associated with current sexual activity. Gender (male, P = 0.014), surgical procedure (P = 0.005), and radiation therapy (P = 0.0001) were independently associated with the outcome "surgery made sexual life worse." Global QOL scores were high. CONCLUSIONS: Sexual problems after surgery for rectal cancer are common, multifactorial, inadequately discussed, and untreated. Therefore, sexual dysfunction should be discussed with rectal cancer patients, and efforts to prevent and treat it should be increased.

Aged↗

Surgical management of entero and colocutaneous fistulae in Crohn's disease: 17 year's experience.

BACKGROUND AND AIMS: Fistulous disease is common in Crohn's disease, and entero- and colocutaneous fistulae are particularly debilitating and difficult to manage. We present the results of surgical management of these fistulas. PATIENTS AND METHODS: Retrospective chart review of all 51 patients with Crohn's disease (56 surgical procedures) undergoing surgery for cutaneous fistulae between 1983 and 2000. RESULTS: Previous surgery for Crohn's disease had been carried out in 43 patients (84%). The fistula site was enterocutaneous in 36 patients (64%), colocutaneous in 12 (21%), and anastomotic in 8 (14%); 9 patients (16%) also had associated enteroenteric fistulas. The onset of the fistula followed abscess drainage in 15 (27%) and occurred at the site of recurrent disease in 41 (73%). Forty patients (71%) initially underwent conservative management prior to surgery; 16 (28%) underwent surgery directly. Surgical procedures were: 25 ileocolic resections, 8 stoma revisions with resection, 8 small bowel resections 7 subtotal colectomies, 4 partial colectomies, 3 proctocolectomies, and one fistula tract excision. Mean total length of stay was 18 days (postoperative 10.7 days). Six (11%) patients had eight postoperative complications. Mean follow-up was 48.6 months (range 3-187). Recurrence as defined by either clinical examination or reoperation was documented in nine fistulas (16%), with a mean time to recurrence of 27 months. CONCLUSION: Entero-and colocutaneous fistulae usually occur from a site of active disease. Surgical management with bowel resection, including the fistula, is the preferred method of treatment. Morbidity has been low and recurrence rate lower than expected.

Adult↗

Azathioprine or ileocolic resection for steroid-dependent terminal ileal Crohn's disease? A Markov analysis.

INTRODUCTION: The objective of this study was to determine whether initial azathioprine therapy, followed by ileocolic resection if azathioprine fails, or initial ileocolic resection without a trial of azathioprine is the preferred treatment strategy in steroid-dependent, terminal ileal Crohn's disease. METHODS: A Markov, decision analytic model was developed to simulate a 36-month course for a patient with steroid-dependent, terminal ileal Crohn's disease who would initially take azathioprine or have ileocolic resection. Clinically important outcomes in the model included side effects and effectiveness of azathioprine and postoperative complications, mortality, and recurrence following ileocolic resection. The probabilities and utilities for these variables were derived from previously published studies. RESULTS: Initial azathioprine therapy offered a relatively small benefit of 0.45 quality-adjusted life-months over initial ileocolic resection. The model was sensitive to utility for being symptom-free on azathioprine and utility for being symptom-free postoperatively. CONCLUSIONS: Initial azathioprine therapy and initial ileocolic resection are both reasonable treatment strategies in this setting. The preferred treatment strategy is highly dependent on the quality of life that can be achieved with each treatment option. Therefore, individual response and symptom control with each treatment must be strongly considered in this treatment decision.

Adult↗

Assessment of critical appraisal skills.

BACKGROUND: Studies have provided little evidence that critical appraisal skills improve with focused courses. However, outcome measures in these studies have been questionable. The goal of this study was to develop a feasible, reliable, and valid assessment of critical appraisal skills. METHODS: Forty-four surgery residents read three articles and then responded to short answer questions and provided 7-point ratings regarding various methodological aspects of each article. Reliability and validity of the examination were assessed. RESULTS: The mean score was 52.4% (SD 8.6%). Internal consistency of the 55-question examination was 0.77. Interrater reliability of clinician markers was 0.91. Mean score for residents with more intensive critical appraisal training was significantly higher than for those with little or no training (56.6% versus 49.3%, t(35) = 2.31, P = 0.02), suggesting construct validity. CONCLUSIONS: This examination has promising psychometric properties, and may be useful in evaluating critical appraisal curricula.

Clinical Competence↗

Teaching practicing surgeons critical appraisal skills with an Internet-based journal club: A randomized, controlled trial.

BACKGROUND: The effectiveness of interventions for developing critical appraisal skills in practicing physicians has not been studied, despite the documented importance of reading the literature in caring for patients and in continuing professional development. The objective of this study was to evaluate whether an Internet-based intervention would lead to enhanced critical appraisal skills in practicing surgeons. METHODS: General surgeons who agreed to participate were randomized into 2 groups. The intervention was a curriculum in critical appraisal skills that included a clinical and methodologic article, a listserve discussion, and clinical and methodologic critiques. The control group received only the clinical articles. The primary outcome measure was a previously validated 2-hour test of critical appraisal. RESULTS: Of the 55 surgeons who completed the examination, subjects in the intervention group performed better on the test of critical appraisal skills than those in the control group (mean score: intervention group, 58% +/- 8 vs control group, 50% +/- 8), with a large effect size of 1.06 standard deviation units (t+3.92, P <.0001). Training conditions accounted for 22% of the variance in total scores. CONCLUSIONS: A multifaceted, Internet-based intervention resulted in improved critical appraisal skills of practicing general surgeons.

Adult↗

CARD15 and HLA DRB1 alleles influence susceptibility and disease localization in Crohn's disease.

OBJECTIVES: Crohn's disease (CD) is a chronic inflammatory disease of the gut associated with allelic variants of CARD15 and HLA-DRB1 genes. We investigated the prevalence and effects of these variants in a Canadian CD cohort. METHODS: 507 unrelated CD patients were genotyped for the three major CD-associated variants (Arg702Trp, Gly908Arg, and Leu1007fsinsC) and for thirteen HLA-DRB1 alleles. RESULTS: At least one CARD15 variant was present in 32.5% of the CD patients compared with 20% of controls. The prevalence of CARD15 mutation was similar in both sporadic and familial and Jewish and non-Jewish CD patients. The Gly908Arg variant was significantly higher and the Arg702Trp variant significantly lower in Jewish compared to non-Jewish patients. A positive association between the HLA-DRB1*0103 allele and CD was detected in non-Jewish, familial cases (p = 0.0002), with risk for CD increased by 6.7 fold by the presence of an HLA-DRB1*0103 allele as compared to 1.9 fold and 19 fold by a single or two CARD15 variant alleles, respectively. We show a significant association of ileal involvement with CARD15 variants (OR = 1.8; p = 0.02), HLA-DRB1*0701 (OR = 1.9; p = 0.006) and DRB1*04 (OR = 1.7; p = 0.02) alleles and demonstrate the capacity of combined CARD15 and HLA-DRB1 genotyping to predict ileal disease in CD patients. By contrast, the HLA-DRB1*0103 allele was associated with later age of diagnosis (p = 0.02) and pure colonic disease (p = 0.000013). CONCLUSIONS: These observations confirm the influence of CARD15 and HLA-DRB1 alleles on both CD susceptibility and site of disease and identify genotyping of these variants as a potential tool for improved diagnosis and risk prediction in CD.

Adolescent↗

Current awareness in Canada of clinical practice guidelines for colorectal cancer screening.

INTRODUCTION: The Canadian Task Force on Preventive Health Care (CTF-PHC) recently revised its screening recommendations for colorectal cancer (CRC). We wished to assess the effect of this change on the screening beliefs and clinical practice of primary care physicians. METHODS: We surveyed 160 primary-care physicians, quasi-randomly sampled, in June-July 2001 and again in April-July 2002, 9 months after publication of the guidelines. Descriptive statistics and McNemar chi2 analyses were carried out on data from physicians who responded to both surveys. RESULTS: Of the those sampled, 47% responded to both surveys. After the publication of the CTF-PHC guidelines, the proportion reporting that they recommend CRC screening to their patients at average risk increased from 43% to 60% (p = 0.02). Before publication of the revised guidelines 48% stated that the CTF-PHC did not support screening, compared with 24% afterward (p = 0.01). CTF-PHC guidelines were acknowledged by 30% to be a source of CRC screening information. Around 9 months post-publication, 24% of the physicians stated their awareness of the revised screening guidelines. The most commonly cited reasons for not recommending CRC screening to average-risk patients were that the evidence is inconclusive and that CTF-PHC guidelines do not support screening. CONCLUSIONS: After publication of the revised CTF-PHC guidelines more primary-care physicians reported that they recommend CRC screening to their average-risk patients. The belief that the evidence is inconclusive nevertheless remains a considerable barrier to implementation. To increase the use of screening for CRC, additional strategies are required.

Adult↗

A population- and family-based study of Canadian families reveals association of HLA DRB1*0103 with colonic involvement in inflammatory bowel disease.

The aim of this study was to identify major histocompatibility complex alleles associated with the development and clinical features of inflammatory bowel disease (IBD). Genotyping at the human leukocyte antigen (HLA) DRB1 and DQB1 loci was performed on individuals from 118 Caucasian IBD sibling pair families and on 216 healthy controls. Both population- and family-based association tests were used to analyze data obtained on the entire study population and on clinical subgroups stratified by diagnosis, ethnicity, and disease distribution. HLA DRB1*0103 was significantly associated with IBD (OR = 6.0, p = 0.0001) in a case-control analysis of non-Jewish IBD-affected individuals. This association was apparent among both Crohn's disease (OR = 5.23, p = 0.0007) and ulcerative colitis (OR = 7.9, p = 0.0001) patients and was confirmed in the non-Jewish IBD population by results of family-based association analysis using the transmission disequilibrium test. HLA DQB1*0501 was also associated with IBD (OR = 1.64, p = 0.02) in the non-Jewish population. but statistically significant association of this allele with disease was not detected for Crohn's disease and ulcerative colitis separately. No significant associations were identified among the Jewish patients. In the non-Jewish IBD families, IBD was as strongly associated with the DRB1*0103 DQB1*0501 haplotype as with the DRB1*0103 allele alone. The carrier frequency of the DRB1*0103 allele was found to be 10-fold higher in Crohn's disease patients with pure colonic involvement than in healthy controls (38.5% vs. 3.2%; p = 0.0002). These data demonstrate the association of the HLA DRB1*0103 allele with both Crohn's disease and ulcerative colitis and with large intestine-restricted disease in non-Jewish IBD patients and therefore identify HLA DRB1*0103 as a potentially important contributor to disease susceptibility and to expression of colonic involvement in IBD.

Canada↗

Surgery for inflammatory bowel diseases.

Surgery is required in many patients with inflammatory bowel disease at some point in their disease. In patients with ulcerative colitis, surgery is potentially curative whereas recurrence of Crohn's disease following surgery is a common occurrence. As a result, the indications and surgical management of the two diseases may be quite different. Surgery is usually reserved for the management of complications or failure of medical treatment in Crohn's disease. Resection of the diseased segment is the usual procedure performed. While surgery usually results in an improvement in quality of life, recurrence of disease occurs frequently with reported rates of 5-90% at 1 year, depending on the criteria used. To date, there have been no surgical maneuvers which have been shown to decrease the risk of recurrence. Over the past few decades, several advances have been made in the surgical management of Crohn's disease: use of strictureplasty for extensive disease; use of laparoscopic techniques to perform surgery and the performance of the ileal pouch procedure in very selected patients. Significant advances in the surgical management of ulcerative colitis have been made in the past 50 years. Although there are several options available to patients, the preferred option now is the ileal pouch procedure. With technical modifications and with experience, this procedure can now be performed with a low complication rate, with good functional results and quality of life and excellent long-term outcome.

Anastomosis, Surgical↗