A prospective study of endoscopist-blinded colonoscopy withdrawal times and polyp detection rates in a tertiary hospital.

BACKGROUND: Studies have suggested that a colonoscopy withdrawal time of at least 6 minutes is associated with an increased adenoma detection rate in patients undergoing colorectal cancer screening. AIMS: We aimed to determine colonoscopy withdrawal time and rate of polyp detection in a blinded study--conducted at Christchurch Hospital (Christchurch, New Zealand)--to determine if there was a relationship. METHODS: All 16 consultant endoscopists performing colonoscopy in a tertiary hospital had their withdrawal time from the caecum prospectively timed over 208 consecutive procedures between 11 April 2007 and 19 May 2007. The following data was collected: indication for procedure, final diagnosis, polypectomy rate, procedures performed and withdrawal time were recorded. Histology results were reviewed for all patients. RESULTS: 111 (53%) of colonoscopies were performed for symptom assessment and 97 (47%) for surveillance. There was significant heterogeneity between colonoscopists' withdrawal times (p<0.001). Polyps were diagnosed in 65 of all colonoscopies (31.3%). Of the screening colonoscopies polyps were found in 38 (39.1%) of which 14 were adenomas (adenoma detection rate of 14%). The median colonoscopy withdrawal time was 3 minutes 16 seconds when no polyps were found (range 5 seconds to 11 minutes 50 seconds). The median colonoscopy time when polyps were found was 8 minutes 31 seconds which included time taken for procedures (range 2 minutes 7 seconds to 35 minutes 40 seconds), p<0.001. COCNLUSIONS: This study confirms that more adenomas were found by those endoscopists who had slower withdrawal times. Also colonoscopy withdrawal times are inherently much faster than recommended and highlights the importance of regular adenoma detection rate and withdrawal time auditing.

Allopurinol might improve response to azathioprine and 6-mercaptopurine by correcting an unfavorable metabolite ratio.

BACKGROUND AND AIM: Allopurinol potentiates azathioprine and 6-mercaptopurine (6-MP) by increasing 6-thioguanine nucleotide (6-TGN) metabolite concentrations. The outcome might also be improved by adding allopurinol in individuals who preferentially produce 6-methylmercaptopurine nucleotides (6-MMPN), rather than 6-TGN. The aim of the present study was to investigate the effect of allopurinol on concentrations of 6-MMPN and 6-TGN in individuals with a high ratio of these metabolites (>20), which is indicative of a poor thiopurine response. METHODS: Sixteen individuals were identified who were taking azathioprine or 6-MP, and were commenced on allopurinol to improve a high 6-MMPN:TGN ratio. Metabolite concentrations were compared before and after commencing allopurinol, and markers of disease control were compared. RESULTS: The addition of 100-300 mg allopurinol daily and thiopurine dose reduction (17-50% of the original dose) resulted in a reduction of the median (and range) 6-MMPN concentration, from 11,643 (3,365-27,832) to 221 (55-844) pmol/8×10(8) red blood cells (RBC; P=0.0005), increased 6-TGN from 162 (125-300) to 332 (135-923) pmol/8×10(8) RBC (P=0.0005), and reduced the 6-MMPN:6-TGN ratio from 63 (12-199) to 1 (0.1-4.5) (P=0.0005). There was a significant reduction in steroid dose requirements at 12 months (P=0.04) and trends for improvement in other markers of disease control. One patient developed red cell aplasia that resolved upon stopping azathioprine and allopurinol. CONCLUSIONS: In those with a high 6-MMPN:6-TGN ratio (>20), response to thiopurine treatment might be improved by the addition of allopurinol, together with a reduced thiopurine dose and close hematological monitoring.

Population-based epidemiology study of autoimmune hepatitis: a disease of older women?

BACKGROUND AND AIM: The etiology of autoimmune hepatitis (AIH) is unknown, and limited epidemiological data are available. Our aim was to perform a population based epidemiological study of AIH in Canterbury, New Zealand. METHODS: To calculate point prevalence, all adult and pediatric outpatient clinics and hospital discharge summaries were searched to identify all cases of AIH in the Canterbury region. Incident cases were recruited prospectively in 2008. Demographic and clinical data were extracted from case notes. Both the original revised AIH criteria and the simplified criteria were applied and cases were included in the study if they had definite or probable AIH. RESULTS: When the original revised criteria were used, 138 cases (123 definite and 14 probable AIH), were identified. Prospective incidence in 2008 was 2.0/100,000 (95% confidence interval [CI] 0.8-3.3/100,000). Point prevalence on 31 December 2008 was 24.5/100,000 (95% CI 20.1-28.9). Age-standardized (World Health Organization standard population) incidence and prevalence were 1.7 and 18.9 per 100,000, respectively. Gender-specific prevalence confirmed a female predominance, while ethnicity-specific prevalence showed higher prevalence in Caucasians. 72% of cases presented after 40 years of age and the peak age of presentation was in the sixth decade of life. CONCLUSIONS: This is the first and largest population-based epidemiology study of AIH in a geographically defined region using standardized inclusion criteria. The observed incidence and prevalence rates are among the highest reported. The present study confirms that AIH presents predominantly in older women, with a peak in the sixth decade, contrary to the classical description of the disease.

Effect of inflammatory bowel disease classification changes on NOD2 genotype-phenotype associations in a population-based cohort.

BACKGROUND: NOD2 mutations are associated with Crohn's disease (CD) in Caucasian clinic-based cohorts. Data from population-based cohorts are limited. Clinic-based studies may overestimate this association. Genotype-phenotype relationships are yet to be assessed using the Montreal classification. We hypothesized that the NOD2-CD association would be weaker in a population-based cohort, and that the Montreal classification would strengthen genotype-phenotype associations. METHODS: A population-based case-control study was performed including 91% of all people in Canterbury, New Zealand, with inflammatory bowel disease (IBD); NOD2 genotyping was performed and patients were phenotyped according to the Vienna and Montreal classification systems. RESULTS: The NOD2 genotype was available on 684 CD, 643 ulcerative colitis (UC), 36 indeterminate colitis/IBDU (IBD unclassified) patients, and 201 controls. Control frequencies for the 702W, 908R, and 1007fs alleles were 0.030, 0.012, and 0.010, respectively, compared with 0.074, 0.027, and 0.040 for CD. The 702W (P = 0.001) and 1007fs (P = 0.002) alleles were significantly associated with CD. Younger age of diagnosis (<17 years) was associated with 1 (odds ratio (OR) 1.9 [95% confidence intervals 0.98-3.6]) or 2 (OR 6.5 [2.3-18.6]) NOD2 mutations compared with diagnosis >40 years. Ileal disease was most strongly associated with NOD2 mutations (1 mutation OR 3.9 [2.4-6.3], 2 mutations OR 6.7 [2.4-18.5]). Penetrating disease was associated with NOD2 mutations using the Montreal but not the Vienna classification. CONCLUSIONS: The association between NOD2 mutations and CD was found to be weaker in our population-based cohort than in previous studies that used referral-based cohorts. Application of the Montreal classification led to a strengthening of the NOD2 genotype-phenotype association.

High incidence of Crohn's disease in Canterbury, New Zealand: results of an epidemiologic study.

BACKGROUND: Inflammatory bowel disease (IBD) has increased exponentially in industrialized nations over the last 50 years. Previous New Zealand studies have shown that IBD is less common than in other countries; however, clinical observations suggested a high incidence and prevalence of IBD in Canterbury, particularly Crohn's disease (CD). AIM: This study aimed to determine the descriptive epidemiology of IBD in Canterbury. METHODS: Canterbury IBD patients, recruited using multiple strategies, gave informed consent, permission for clinical record review, completed a questionnaire, and were bled for DNA extraction as part of the Canterbury IBD Project. Cases were confirmed using standard criteria, and completeness of recruitment was validated using capture-recapture methods. Demographic and phenotypic data were extracted from case notes. One thousand four hundred twenty patients (715 CD, 668 ulcerative colitis [UC]) were recruited (> 91% of Canterbury IBD patients). RESULTS: In 2004, age-standardized (World Health Organization World Standard Population) IBD, CD, and UC incidence rates were 25.2, 16.5, and 7.6/100,000/year, respectively. The IBD, CD, and UC point prevalences on 1 June, 2005 were 308.3, 155.2, and 145.0/100,000, respectively. CD patients were more likely than UC patients to be female (61.4% vs. 47.1%) and to be younger (median age, 39.9 years vs. 43.7 years). The percent of IBD patients who were white was 97.5%. CONCLUSION: IBD is at least as common in Canterbury as in other western regions. CD incidence and prevalence are amongst the highest ever reported and are higher than for UC. IBD population characteristics are otherwise similar to other countries. The Canterbury IBD Project will be a valuable tool for future population-based IBD epidemiology and genetics research.

Thiopurine drug adverse effects in a population of New Zealand patients with inflammatory bowel disease.

PURPOSE: The thiopurine drugs, azathioprine and 6-mercaptopurine are effective in the treatment of inflammatory bowel disease (IBD). However, their use is limited by serious adverse effects that can lead to cessation of therapy. The incidence of these adverse effects has been reported to be approximately 9% but in Christchurch it was felt that the incidence was higher. METHODS: We searched our letter database to identify all patients with IBD who had received a thiopurine drug between 1996 and 2002. The case notes were then reviewed to identify those patients who had suffered an adverse effect that required cessation of the drug. RESULTS: From a total of 216 patients with IBD taking a thiopurine drug, 56 (25.9%) had an adverse reaction requiring cessation of the drug. Adverse effects included allergic-type (25%), liver test abnormalities (34%), nausea/vomiting (6%), bone marrow suppression (7%), pancreatitis (7%) and other (9%). Males were significantly more likely than females to have an allergic-type reaction (p = 0.003). All adverse effects resolved with cessation of the drug, with a median of 7 days to resolution. Of the patients with liver test abnormalities on azathioprine, most were able to tolerate 6-mercaptopurine, however challenge with 6-mercaptopurine was not successful for most other patients. CONCLUSIONS: In Canterbury, New Zealand, patients with IBD have a high rate of therapy-limiting adverse effects to thiopurine drugs. There is a significant gender bias for allergic-type adverse effects. Mechanisms for both these observations are not clear.

Surveillance for dysplasia in patients with inflammatory bowel disease: a national survey of colonoscopic practice in New Zealand.

BACKGROUND: Patients with chronic ulcerative colitis and Crohn's colitis have an increased risk of colorectal cancer. Because of this, surveillance colonoscopy is practiced. AIMS: We aimed to describe the practice of surveillance colonoscopy in New Zealand, with comparison among specialties, and with practice internationally. SUBJECTS: New Zealand colonoscopists (both physicians and surgeons) looking after patients with inflammatory bowel disease were surveyed to evaluate attitudes about surveillance colonoscopy and ways in which colonoscopy results are interpreted. METHODS: A postal survey assessed the colonoscopist's understanding of how and why surveillance colonoscopy is undertaken and their interpretation of the results from such evaluations. RESULTS: Of the 196 physicians and surgeons surveyed, 180 responded (92 percent). Sixty responses were excluded. Only 24 of 120 respondents (20 percent) correctly defined dysplasia. The median number of biopsies taken at colonoscopy was 17. Eighty of 120 (67 percent) and 77 of 120 (64 percent) doctors underestimate the risk of invasive malignancy if low-grade or high-grade dysplasia, respectively, is identified. The colectomy referral rate for dysplasia-associated lesion or mass was 115/120 (96 percent); that for high-grade dysplasia was 110/120 (92 percent); and that for low-grade dysplasia was 26/120 (22 percent). Thirty of 120 (25 percent) doctors offer patients the option of colectomy after 20 years of colitis. Seventy of 120 (58 percent) doctors sought the opinion of a second pathologist if dysplasia was found. There were differences in responses between specialist groups, with colorectal surgeons most likely to correctly define dysplasia and appreciate the significance of low-grade dysplasia. CONCLUSIONS: Many New Zealand colonoscopists have a poor understanding of the definition and importance of dysplasia associated with colitis. Although colectomy referral rates are higher in this study than in similar studies, low-grade dysplasia is often not referred for colectomy. Improved education may improve surveillance practice.