Clarence Wong

Maintenance of clinical benefit in Crohn's disease patients after discontinuation of infliximab: long-term follow-up of a single centre cohort

Aliment Pharmacol Ther 2010; 32: 1129–1134

Increased Risk of Colorectal Cancer in Ulcerative Colitis Patients Diagnosed after 40 Years of Age

BACKGROUND The association between ulcerative colitis (UC) and colorectal cancer (CRC) is well established. Retrospective data show a 5.4% CRC incidence rate among patients with pancolitis and suggest that cancer surveillance should be provided to patients following eight to 10 years of extensive UC. AIM To identify premalignant risk factors for UC patients and to determine whether current recommendations for cancer surveillance need reviewing. PATIENTS AND METHODS A retrospective audit was conducted of adult patients with UC who were diagnosed with CRC between 1991 and 2002 in five hospitals in Edmonton, Alberta. RESULTS Thirty-one cases of CRC (68% male) were identified. In this group, the mean ages at diagnosis were 44.4 years for UC patients and 60.1 years for CRC patients. For patients in whom the initial data of diagnosis of UC could be determined (n=29), the median duration of UC at the time of CRC diagnosis was 16 years. Patients diagnosed with UC after 40 years of age (n=15, mean age 64 years) progressed more rapidly to CRC than patients diagnosed before 40 years of age (n=14, mean age 23 years). The median durations of UC before development of CRC were 22 years and 10 years, respectively, for patients with a diagnosis of UC before and after 40 years of age (OR 11.5, 95% CI 2.41 to 20.16; P=0.00029). Only four patients (13%) were enrolled in an appropriate cancer-screening program. Nine of these UC patients (29%) who were older than 40 years of age developed CRC before the 10-year point. CONCLUSIONS In the present study, patients diagnosed with UC after 40 years of age developed CRC more rapidly than those diagnosed before 40 years of age. This finding suggests that patients who are diagnosed with UC after 40 years of age should undergo CRC surveillance earlier than current recommendations.

A prospective audit of patient experiences in colonoscopy using the Global Rating Scale: A cohort of 1187 patients

BACKGROUND The Global Rating Scale (GRS) comprehensively evaluates the quality of an endoscopy department, providing a patient-centred framework for service improvement. OBJECTIVE To assess patient experiences during colonoscopy and identify areas that need service improvement using the GRS. METHODS Consecutive outpatients undergoing colonoscopy were asked to complete a pre- and postprocedure questionnaire. Questions were based on GRS items and a literature review. The preprocedure questionnaire addressed items such as patient characteristics and information provision. The postprocedure questionnaire contained questions regarding comfort, sedation, the attitude of endoscopy staff and aftercare. RESULTS The preprocedure questionnaire was completed by 1,187 patients, whereas the postprocedure part of the questionnaire was completed by 851 patients (71.9%). Fifty-four per cent of patients were first seen in the outpatient clinic. The indication for colonoscopy was explained to 85% of the patients. Sixty-five per cent of the patients stated that information about the risks of colonoscopy was provided. Sedation was used in 94% of the patients; however, 23% judged the colonoscopy to be more uncomfortable than expected. Ten per cent of patients rated the colonoscopy as (very) uncomfortable. Preliminary results of the colonoscopy were discussed with 87% of patients after the procedure. Twenty-one per cent of the patients left the hospital without knowing how to obtain their final results. Being comfortable while waiting for the procedure (OR 9.93) and a less uncomfortable procedure than expected (OR 2.99) were important determinants of the willingness to return for colonoscopy. CONCLUSIONS The present study provided evidence supporting the GRS in identifying service gaps in the quality of patient experiences for colonoscopy in a North American setting. Assessing experiences is useful in identifying areas that need improvement such as the provision of pre- and postprocedure information.

Crohn's disease genotypes of patients in remission vs relapses after infliximab discontinuation.

AIM To investigate genetic differences between Crohns disease (CD) patients with a sustained remission vs relapsers after discontinuing infliximab while in corticosteroid-free remission. METHODS Forty-eight CD patients received infliximab and were in full corticosteroid-free clinical remission but then discontinued infliximab for reasons other than a loss of response, were identified by review of an electronic database and charts. Infliximab-associated remission was defined as corticosteroid-free plus normalization of clinical disease activity [CD activity index (CDAI) < 150] during follow-up visits based on physician global assessments. A CD relapse (loss of infliximab-induced remission) was clinically defined as a physician visit for symptoms of disease activity (CDAI > 220) and a therapeutic intervention with CD medication(s), or a hospitalization with complications related to active CD. Genetic analyses were performed on samples from 14 patients (n = 6 who had a sustained long term remission after stopping infliximab, n = 8 who rapidly relapsed after stopping infliximab). Nucleotide-binding oligomerization domain 2 (NOD2)/caspase activation recruitment domain 15 (CARD15) polymorphisms (R702W, G908R and L1007fs) and the inflammatory bowel disease 5 (IBD5) polymorphisms (IGR2060a1 and IGR3081a1) were analyzed in each group. RESULTS Five single nucleotide polymorphisms of IBD5 and NOD2/CARD15 genes were successfully analyzed for all 14 subjects. There was no significant increase in frequency of the NOD2/CARD15 polymorphisms (R702W, G908R and L1007fs) and the IBD5 polymorphisms (IGR2060a1 and IGR3081a1) in either group of patients; those whose disease relapsed rapidly or those who remained in sustained long term remission following the discontinuation of infliximab. Nearly a third of patients in full clinical remission who stopped infliximab for reasons other than loss of response remained in sustained clinical remission, while two-thirds relapsed rapidly. There was a marked difference in the duration of clinical remission following discontinuance of infliximab between the two groups. The patients who lost remission did so after 1.0 years ± 0.6 years, while those still in remission were at the time of this study, 8.1 years ± 2.6 years post-discontinuation of infliximab, P < 0.001. The 8 patients who had lost remission after discontinuing infliximab had a mean number of 5 infusions (range 3-7), with a mean treatment time of 7.2 mo (range 1.5 mo-15 mo). The mean duration of time from the last infusion of infliximab to the time of loss of remission was 382 d (range 20 d-701 d). The 6 patients who remained in remission after discontinuing infliximab had a mean number of 6 infusions (range 3-12), with a mean treatment duration of 12 mo (range 3.6 mo-32 mo) (P = 0.45 relative to those who lost remission). CONCLUSION There are no IBD5 or NOD2/CARD15 mutations that predict which patients might have sustained remission and which will relapse rapidly after stopping infliximab.

The Appropriateness of Surveillance Colonoscopy Intervals after Polypectomy

BACKGROUND Adherence to surveillance colonoscopy guidelines is important to prevent colorectal cancer (CRC) and unnecessary workload. OBJECTIVE To evaluate how well Canadian gastroenterologists adhere to colonoscopy surveillance guidelines after adenoma removal or treatment for CRC. METHODS Patients with a history of adenomas or CRC who had surveillance performed between October 2008 and October 2010 were retrospectively included. Time intervals between index colonoscopy and surveillance were compared with the 2008 guideline recommendations of the American Gastroenterological Association and regarded as appropriate when the surveillance interval was within six months of the recommended time interval. RESULTS A total of 265 patients were included (52% men; mean age 58 years). Among patients with a normal index colonoscopy (n=110), 42% received surveillance on time, 38% too early (median difference = 1.2 years too early) and 20% too late (median difference = 1.0 year too late). Among patients with nonadvanced adenomas at index (n=96), 25% underwent surveillance on time, 61% too early (median difference = 1.85) and 14% too late (median difference = 1.1). Among patients with advanced neoplasia at index (n=59), 29% underwent surveillance on time, 34% too early (median difference = 1.86) and 37% later than recommended (median difference = 1.61). No significant difference in adenoma detection rates was observed when too early surveillance versus appropriate surveillance (34% versus 33%; P=0.92) and too late surveillance versus appropriate surveillance (21% versus 33%; P=0.11) were compared. CONCLUSION Only a minority of surveillance colonoscopies were performed according to guideline recommendations. Deviation from the guidelines did not improve the adenoma detection rate. Interventions aimed at improving adherence to surveillance guidelines are needed.

Development and Validation of a Highly Sensitive Urine-Based Test to Identify Patients with Colonic Adenomatous Polyps

Objectives:Adenomatous polyps are precursors of colorectal cancer; their detection and removal is the goal of colon cancer screening programs. However, fecal-based methods identify patients with adenomatous polyps with low levels of sensitivity. The aim or this study was to develop a highly accurate, prototypic, proof-of-concept, spot urine-based diagnostic test using metabolomic technology to distinguish persons with adenomatous polyps from those without polyps.Methods:Prospective urine and stool samples were collected from 876 participants undergoing colonoscopy examination in a colon cancer screening program, from April 2008 to October 2009 at the University of Alberta. Colonoscopy reference standard identified 633 participants with no colonic polyps and 243 with colonic adenomatous polyps. One-dimensional nuclear magnetic resonance spectra of urine metabolites were analyzed to define a diagnostic metabolomic profile for colonic adenomas. A urine metabolomic diagnostic test for colonic adenomatous polyps was established using 67% of the samples (un-blinded training set) and validated using the other 33% of the samples (blinded testing set). The urine metabolomic diagnostic test’s specificity and sensitivity were compared with those of fecal-based tests.Results:Using a two-component, orthogonal, partial least-squares model of the metabolomic profile, the un-blinded training set identified patients with colonic adenomatous polyps with 88.9% sensitivity and 50.2% specificity. Validation using the blinded testing set confirmed sensitivity and specificity values of 82.7% and 51.2%, respectively. Sensitivities of fecal-based tests to identify colonic adenomas ranged from 2.5 to 11.9%.Conclusions:We describe a proof-of-concept spot urine-based metabolomic diagnostic test that identifies patients with colonic adenomatous polyps with a greater level of sensitivity (83%) than fecal-based tests.

Prospective phase II study of tomotherapy based chemoradiation treatment for locally advanced anal cancer

BACKGROUND AND PURPOSE To evaluate toxicity, local control, and survival of anal cancer patients treated with helical tomotherapy (HT) and concurrent 5-fluorouracil and mitomycin-C (5FU/MMC). MATERIALS AND METHODS Fifty-seven patients were treated with HT and concurrent 5FU/MMC. The planning objectives were to deliver 54 Gy to the tumor (PTV54) and 45 Gy to the nodes at risk (PTV45) in 30 fractions. Patients were reviewed for toxicity weekly during HT, every 6 weeks for 3 months, and then every 3-4 months for 5 years. RESULTS The median follow-up was 40 months. The median age was 58 years (range: 37-83). Stage distribution: stage II-48%, IIIA-18%, IIIB-34%. The majority of patients developed ⩽ grade 2 acute toxicity scores. The most common ⩾ grade 3 acute toxicity was neutropenia (40%). Common late toxicities were grade 2 anal incontinence (16%) and telangiectasia (12%). The 3 year colostomy-free survival rate was 77% (95% CI: 61-87%), 3 year disease-free survival rate was 80% (CI: 66-89%), and 3 year overall survival was 91% (CI: 77-96%). CONCLUSIONS Incorporation of HT with concurrent 5FU/MMC had low treatment-related acute and late morbidity with few treatment breaks. However, the expected dosimetric benefit for hematological toxicity was not experienced clinically.

Patient reported quality of life after helical IMRT based concurrent chemoradiation of locally advanced anal cancer

BACKGROUND AND PURPOSE Concurrent chemoradiation (CCRT) is the standard treatment for locally advanced anal canal carcinoma, although treatment-related side effects can affect patient quality of life (QOL). The purpose was to prospectively evaluate the effects of Tomotherapy (HT) based CCRT on patient reported QOL in locally advanced anal cancer. PATIENTS AND METHODS Fifty-four patients treated with HT and concurrent 5-fluorouracil/mitomycin-C underwent QOL evaluation at baseline, after treatment, and during follow-up with EORTC core (QLQ-C30) and colorectal (QLQ-CR29) questionnaires. The QOL scores at baseline and post-treatment were compared. RESULTS All C30 functional symptoms, except emotional and cognitive functioning, were impaired end-of-treatment and recovered by 3months follow-up. The majority of symptom scores were worse end-of-treatment but recovered by 3months except for fecal incontinence (FI), diarrhea, urinary incontinence (UI), and dyspareunia which persisted. FI returned to baseline at 12months while diarrhea, UI, and dyspareunia persisted. CONCLUSIONS Most impaired functions and symptoms following HT based CCRT were temporary and improved by 3months post-therapy. Late complications affecting QOL were FI, sexual function, UI, and diarrhea. Our observations support routine use of IMRT and emphasize the significance of precise evaluation of sexual, urinary, and anorectal functions before starting CCRT and routine incorporation of QOL evaluations.

Patients undergoing colorectal cancer screening underestimate their cancer risk and delay presentation for screening

BACKGROUND Colorectal cancer (CRC) is the third most common cancer in Canada. Screening guidelines recommend that first-time screening should occur at 50 years of age for average-risk individuals and at 40 years of age for those with a family history of CRC. OBJECTIVE To examine whether persons with a positive CRC family history were achieving screening at 40 years of age and whether average-risk persons were achieving screening at 50 years of age. METHODS The present study was a cross-sectional analysis of subjects who entered a colon cancer screening program and were undergoing CRC screening for the first time. RESULTS A total of 778 individuals were enrolled in the present study: 340 (174 males) with no family history of CRC, and 438 (189 males) with a positive family history of CRC. For the group with a positive family history, the mean (± SD) age for primary screening was 54.4 ± 8.5 years, compared with 58.2 ± 6.4 years for the group with no family history. On average, those with a positive family history initiated screening 3.8 years (95% CI 2.8 to 4.8; P<0.05) earlier than those without. Adenoma polyp detection rate for the positive family history group was 20.8% (n=91) compared with 23.5 % (n=80) for the group with no family history. CONCLUSIONS Individuals with a positive CRC family history are initiating screening approximately four years earlier than those without a family history; nevertheless, both groups are undergoing screening well past current guideline recommendations.

Follow-up of past participants of the Canadian Association of Gastroenterology Scholars’ Program (2001 to 2005) – Where are they now?

The Canadian Association of Gastroenterology (CAG) Scholars’ Program, previously called the Bright Lights Course, is designed primarily for senior medical students, and first- and second-year internal medicine and pediatric residents. It was started in 2001 to encourage trainees to consider a subspecialty career in gastroenterology. Each university is asked to nominate students or residents to attend. The program is limited to a maximum of 32 candidates, one to three of whom are taken from each medical school across Canada. The two-day program, which is held before the Canadian Digestive Diseases Week conference, allows students the chance to work with and learn from an internationally recognized academic and clinical faculty who are respected leaders and role models in the field. Participants are provided with a view of the various careers that are possible in gastroenterology including basic science research, clinical research, medical education and community gastroenterology. The program also reviews ethical challenges, advances in gastroenterology, what it is like to be a gastroenterology fellow and emphasizes evidence-based gastroenterology. Participants have the opportunity to interact in small groups and to test their skills with an endoscopy challenge. Initial informal feedback has been positive (1) and suggests that the program has helped to entice residents to pursue gas-troenterology. To more formally assess the success of the program, we conducted a survey of the past participants of the CAG Scholars’ Program. A list of all past participants from 2001 to 2005 was compiled. Contact information was updated through the CAG, the Canadian Medical Directory and a Web-based search. Over a one-month period, each past participant was contacted through e-mail and telephone (a maximum of two e-mails and telephone calls) at their last known e-mail address and telephone number. In total, there have been 150 participants (56% male and 44% female) in the CAG Scholars’ Program (Table 1). At the time of participation, 22% were medical students and 78% were residents. Nineteen per cent were unable to be reached or did not respond to the messages. The current status is known in 81% (n=122) of the past participants. TABLE 1 Demographics of past participants of the Canadian Association of Gastroenterology Scholars’ Program (2001 to 2005) (n=150) Of those whose status is known, 70% are currently pursuing or planning to pursue gastroenterology, 26% are not pursuing or not planning to pursue gastroenterology, and 4% are still undecided. Of the 70% pursuing gastroenterology, 20% are currently gastroenterology consultants, 43% are gastroenterology fellows, and 7% are medical students or residents planning on applying to gastroenterology (Table 1). Of the 26% not pursuing gastroenterology, 24% are currently residents or consultants in a different specialty and 2% are medical students or residents not planning on applying to gastroenterology. The most common alternate specialty among those who are not pursuing gastroenterology include cardiology (2), anesthesia (3), medical oncology (4) and general internal medicine (4). To help assess the influence of the CAG Scholars’ Program, the survey asked the past participants whether they were planning on pursuing gastroenterology before and after the course (Figure 1). Before the course, 60% intended to pursue gas-troenterology, 5% did not intend to pursue gastroenterology and 35% were undecided. After the course, 70% intended to pursue gastroenterology, 26% did not intend to pursue gas-troenterology and 4% were undecided (P<0.001). Figure 1) “Were you planning to pursue gastroenterology?” Responses of past participants before and after the Canadian Association of Gastroenterology Scholars’ Program Finally, to help assess how the CAG Scholars’ Program factored into the trainees career decision-making process, the past participants were asked how important the course was in their decision-making process when choosing a specialty or subspecialty. On a scale of 1 to 5, an answer of 1 indicated that it was not important at all and an answer of 5 indicated that it was extremely important (Figure 2). The mean and median responses were 2.93 and 3, respectively. Figure 2) “How important was the Canadian Association of Gastroenterology Scholars’ Program in your decision-making process when choosing a specialty?” 1 = Not important, 5 = Extremely important In 2004, the CAG developed a five-year strategic plan for July 2004 to June 2009 (5). One of its principal initiatives was to “emphasize the development of the next generation of gastroenterology clinical practitioners, researchers, educators, and leaders” and to “attract, train, and retain the best and the brightest to gastroenterology”. The CAG Scholars’ Program is considered one of the means to achieve this end. While informal feedback has been positive (1), this is the first time it has been formally assessed. Even accounting for those who either did not reply and those lost to follow-up, the majority of past participants did end up training in gastroenterology. The CAG is proud to acknowledge its Benefactor Corporate Sponsors: Abbott Laboratories Ltd AstraZeneca Canada Inc Axcan Pharma Inc Janssen-Ortho Inc Nycomed (formerly ALTANA Pharma) Olympus Canada Inc Pentax Canada Inc Pfizer Canada Inc Procter & Gamble Pharmaceuticals Schering Canada Inc Most of the participants had an interest in gastroenterology before attending the course. The retention rate among this group was quite high. Of those who stated that they were interested in gastroenterology before attending the course, only 6% did not pursue gastroenterology or stated that they were not interested in pursuing gastroenterology after the course. In addition, among those who were initially undecided on a specialty before the course, another 39% ended up pursuing gastroenterology after the course. It would seem that in addition to confirming and reinforcing the desire of those participants who were already intending to pursue gastroenterology, the program also converted some of those who were initially undecided. The number of residents (78%) invited to the program greatly outnumbered the number of medical students (22%). Although this balance seems disproportionate, the program has been stated to be primarily for first- and second-year residents (4). In fact, by selecting more residents than medical students, the yield of attracting future gastroenterologists may be higher. Among medical students invited to the program, only 36% ended up pursuing or are planning to pursue gastroen-terology. By comparison, 82% of residents invited to the course ended up pursuing or are planning to pursue gastroenterology (P<0.001). This observation is supported by a recent survey of current gastroenterologists (3) in which 63% stated that it was during residency that they made the decision to pursue gas-troenterology. By comparison, only 15.8% decided on gastroen-terology during their clerkship years. Another observation from the survey was that the number of women being attracted to gastroenterology seemed to be increasing. In 2004, it was reported that only 15.6% of current practicing gastroenterologists were women (3). On the other hand, there was an almost equal participation rate between women (46%) and men (54%) in the CAG Scholars’ Program. This figure is close to the average number of females entering medicine, which is 56.9% (3). Approximately 10 years ago, it was reported that Canada had 1.1 gastroenterologists per 100,000 people (6). In comparison, the United Kingdom had 1.7 gastroenterologists per 100,000 people and the United States had 3.1 gastroen-terologists per 100,000 people. More recent data presented by Dr Paul Moayyedi (McMaster University, Hamilton, Ontario) at the 2006 Canadian Digestive Diseases Week conference (2) showed that Canada had 1.8 gastroenterologists per 100,000 people, which still ranks among the lowest in the western world. In fact, it was estimated that with the current number of trainees the number of gastroenterologists will actually decline by approximately 10% in the next five to 10 years. Through initiatives such as the CAG Scholars’ Program, we can hopefully reinforce the interests of trainees who are interested in gastroenterology, convert some of those that are undecided and continue to attract the best and the brightest to our field.