Anti-TNF Therapeutic Drug Monitoring in Postoperative Crohn's Disease.

BACKGROUND: Anti-TNF prevents postoperative Crohn's disease recurrence in most patients but not all. This study aimed to define the relationship between adalimumab pharmacokinetics, maintenance of remission and recurrence. METHODS: As part of a study of postoperative Crohn's disease management, some patients undergoing resection received prophylactic postoperative adalimumab. In these patients, serum and fecal adalimumab concentration and serum anti-adalimumab antibodies [AAAs] were measured at 6, 12 and 18 months postoperatively. Levels of Crohn's disease activity index [CDAI], C-reactive protein [CRP] and fecal calprotectin [FC] were assessed at 6 and 18 months postoperatively. Body mass index and smoking status were recorded. A colonoscopy was performed at 6 and/or 18 months. RESULTS: Fifty-two patients [32 on monotherapy and 20 on combination therapy with thiopurine] were studied. Adalimumab concentration did not differ significantly between patients in endoscopic remission vs recurrence [Rutgeerts ≥ i2] [9.98µg/mL vs 8.43 µg/mL, p = 0.387]. Patients on adalimumab monotherapy had a significantly lower adalimumab concentration [7.89 µg/mL] than patients on combination therapy [11.725 µg/mL] [p = 0.001], and were significantly more likely to have measurable AAA [31% vs 17%, p = 0.001]. Adalimumab concentrations were lower in patients with detectable AAA compared with those without [3.59 µg/mL vs 12.0 µg/mL, p < 0.001]. Adalimumab was not detected in fecal samples. Adalimumab serum concentrations were lower in obese patients compared with in non-obese patients [p = 0.046]. CONCLUSION: Adalimumab concentration in patients treated with adalimumab to prevent symptomatic endoscopic recurrence postoperatively is, for most patients, well within the therapeutic window, and is not significantly lower in patients who develop recurrence compared with in those who remain in remission. Mechanisms of anti-TNF failure to prevent postoperative recurrence remain to be determined in these patients.

Serologic antibodies in relation to outcome in postoperative Crohn's disease.

BACKGROUND AND AIM: Disease recurs frequently after Crohn's disease resection. The role of serological antimicrobial antibodies in predicting recurrence or as a marker of recurrence has not been well defined. METHODS: A total of 169 patients (523 samples) were prospectively studied, with testing peri-operatively, and 6, 12 and 18 months postoperatively. Colonoscopy was performed at 18 months postoperatively. Serologic antibody presence (perinuclear anti-neutrophil cytoplasmic antibody [pANCA], anti-Saccharomyces cerevisiae antibodies [ASCA] IgA/IgG, anti-OmpC, anti-CBir1, anti-A4-Fla2, anti-Fla-X) and titer were tested. Quartile sum score (range 6-24), logistic regression analysis, and correlation with phenotype, smoking status, and endoscopic outcome were assessed. RESULTS: Patients with ≥ 2 previous resections were more likely to be anti-OmpC positive (94% vs 55%, ≥ 2 vs < 2, P = 0.001). Recurrence at 18 months was associated with anti-Fla-X positivity at baseline (49% vs 29%; positive vs negative, P = 0.033) and 12 months (52% vs 31%, P = 0.04). Patients positive (n = 28) for all four antibacterial antibodies (anti-CBir1, anti-OmpC, anti-A4-Fla2, and anti-Fla-X) at baseline were more likely to experience recurrence at 18 months than patients negative (n = 32) for all four antibodies (82% vs 18%, P = 0.034; odds ratio 6.4, 95% confidence interval 1.16-34.9). The baseline quartile sum score for all six antimicrobial antibodies was higher in patients with severe recurrence (Rutgeert's i3-i4) at 18 months, adjusted for clinical risk factors (odds ratio 1.16, 95% confidence interval 1.01-1.34, P = 0.039). Smoking affected antibody status. CONCLUSIONS: Anti-Fla-X and presence of all anti-bacterial antibodies identifies patients at higher risk of early postoperative Crohn's disease recurrence. Serologic screening pre-operatively may help identify patients at increased risk of recurrence.

Effect of intestinal resection on quality of life in Crohn's disease.

INTRODUCTION: Patients with Crohn's disease have poorer health-related quality of life [HRQoL] than healthy individuals, even when in remission. Although HRQoL improves in patients who achieve drug-induced or surgically induced remission, the effects of surgery overall have not been well characterised. METHODS: In a randomised trial, patients undergoing intestinal resection of all macroscopically diseased bowel were treated with postoperative drug therapy to prevent disease recurrence. All patients were followed prospectively for 18 months. C-reactive protein [CRP], Crohn's Disease Activity Index [CDAI], and faecal calprotectin [FC] were measured preoperatively and at 6, 12, and 18 months. HRQoL was assessed with a general [SF36] and disease-specific [IBDQ] questionnaires at the same time points. RESULTS: A total of 174 patients were included. HRQoL was poor preoperatively but improved significantly [p < 0.001] at 6 months postoperatively. This improvement was sustained at 18 months. Females and smokers had a poorer HRQoL when compared with males and non-smokers, respectively. Persistent endoscopic remission, intensification of drug treatment at 6 months, and anti-tumour necrosis factor therapy were not associated with HRQoL outcomes different from those when these factors were not present. There was a significant inverse correlation between CDAI, [but not endoscopic recurrence, CRP, or FC] on HRQoL. CONCLUSION: Intestinal resection of all macroscopic Crohn's disease in patients treated with postoperative prophylactic drug therapy is associated with significant and sustained improvement in HRQoL irrespective of type of drug treatment or endoscopic recurrence. HRQoL is lower in female patients and smokers. A higher CDAI, but not direct measures of active disease or type of drug therapy, is associated with a lower HRQoL.

A prospective dual-center proof-of-principle study evaluating the incremental benefit of narrow-band imaging with a fixed zoom function in real-time prediction of polyp histology. Can we resect and discard?

BACKGROUND: Advancements in endoscopic technology have increased the ability to distinguish neoplastic polyps during colonoscopy. If a minimum accuracy can be achieved, then a resect-and-discard model can be implemented, although studies to date have demonstrated limited success, especially in the assessment of serrated polyps. OBJECTIVE: To perform a proof-of-principle study assessing the accuracy of narrow-band imaging with near focus in predicting polyp histology including serrated polyps and to determine whether the minimum requirements can be achieved for a resect-and-discard policy. DESIGN: Dual-center, prospective case series. SETTING: Two tertiary-care referral endoscopic centers in Australia. PATIENTS: Two hundred consecutive patients undergoing colonoscopy for routine indications were recruited. INTERVENTIONS: Any polyps identified were assessed by using standard white light followed by narrow-band imaging with near focus for Kudo pit patterns and modified Sano capillary patterns. Based on this assessment and the macroscopic appearance, the polyp histology was predicted and subsequently compared with histopathology results. MAIN OUTCOME MEASUREMENTS: Correlation in postpolypectomy surveillance intervals between endoscopic and pathologic assessments as well as negative predictive value for rectosigmoid hyperplastic polyps. RESULTS: There was a 96% agreement for surveillance intervals between endoscopic assessment and histology by using the American Society for Gastrointestinal Endoscopy guidelines. There was a 96% negative predictive value in assessing rectosigmoid hyperplastic polyps. LIMITATIONS: Because this was a proof-of-principle study, there was no control arm, and there were small numbers, especially in assessing subgroups. The results have limited generalizability with the training requirements for polyp recognition, with confidence to be determined. CONCLUSION: Narrow-band imaging with near focus can predict polyp histology (including serrated polyps) accurately in the hands of trained endoscopists. Further studies with larger numbers are required to further validate this practice.

Measurement of fecal calprotectin improves monitoring and detection of recurrence of Crohn's disease after surgery.

BACKGROUND & AIMS: Crohn's disease (CD) usually recurs after intestinal resection; postoperative endoscopic monitoring and tailored treatment can reduce the chance of recurrence. We investigated whether monitoring levels of fecal calprotectin (FC) can substitute for endoscopic analysis of the mucosa. METHODS: We analyzed data collected from 135 participants in a prospective, randomized, controlled trial, performed at 17 hospitals in Australia and 1 hospital in New Zealand, that assessed the ability of endoscopic evaluations and step-up treatment to prevent CD recurrence after surgery. Levels of FC, serum levels of C-reactive protein (CRP), and Crohn's disease activity index (CDAI) scores were measured before surgery and then at 6, 12, and 18 months after resection of all macroscopic Crohn's disease. Ileocolonoscopies were performed at 6 months after surgery in 90 patients and at 18 months after surgery in all patients. RESULTS: Levels of FC were measured in 319 samples from 135 patients. The median FC level decreased from 1347 µg/g before surgery to 166 µg/g at 6 months after surgery, but was higher in patients with disease recurrence (based on endoscopic analysis; Rutgeerts score, ≥i2) than in patients in remission (275 vs 72 µg/g, respectively; P < .001). Combined 6- and 18-month levels of FC correlated with the presence (r = 0.42; P < .001) and severity (r = 0.44; P < .001) of CD recurrence, but the CRP level and CDAI score did not. Levels of FC greater than 100 µg/g indicated endoscopic recurrence with 89% sensitivity and 58% specificity, and a negative predictive value (NPV) of 91%; this means that colonoscopy could have been avoided in 47% of patients. Six months after surgery, FC levels less than 51 µg/g in patients in endoscopic remission predicted maintenance of remission (NPV, 79%). In patients with endoscopic recurrence at 6 months who stepped-up treatment, FC levels decreased from 324 µg/g at 6 months to 180 µg/g at 12 months and 109 µg/g at 18 months. CONCLUSIONS: In this analysis of data from a prospective clinical trial, FC measurement has sufficient sensitivity and NPV values to monitor for CD recurrence after intestinal resection. Its predictive value might be used to identify patients most likely to relapse. After treatment for recurrence, the FC level can be used to monitor response to treatment. It predicts which patients will have disease recurrence with greater accuracy than CRP level or CDAI score.

Crohn's disease management after intestinal resection: a randomised trial.

BACKGROUND: Most patients with Crohn's disease need an intestinal resection, but a majority will subsequently experience disease recurrence and require further surgery. This study aimed to identify the optimal strategy to prevent postoperative disease recurrence. METHODS: In this randomised trial, consecutive patients from 17 centres in Australia and New Zealand undergoing intestinal resection of all macroscopic Crohn's disease, with an endoscopically accessible anastomosis, received 3 months of metronidazole therapy. Patients at high risk of recurrence also received a thiopurine, or adalimumab if they were intolerant to thiopurines. Patients were randomly assigned to parallel groups: colonoscopy at 6 months (active care) or no colonoscopy (standard care). We used computer-generated block randomisation to allocate patients in each centre to active or standard care in a 2:1 ratio. For endoscopic recurrence (Rutgeerts score ≥i2) at 6 months, patients stepped-up to thiopurine, fortnightly adalimumab with thiopurine, or weekly adalimumab. The primary endpoint was endoscopic recurrence at 18 months. Patients and treating physicians were aware of the patient's study group and treatment, but central reading of the endoscopic findings was undertaken blind to the study group and treatment. Analysis included all patients who received at least one dose of study drug. This trial is registered with ClinicalTrials.gov, number NCT00989560. FINDINGS: Between Oct 13, 2009, and Sept 28, 2011, 174 (83% high risk across both active and standard care groups) patients were enrolled and received at least one dose of study drug. Of 122 patients in the active care group, 47 (39%) stepped-up treatment. At 18 months, endoscopic recurrence occurred in 60 (49%) patients in the active care group and 35 (67%) patients in the standard care group (p=0.03). Complete mucosal normality was maintained in 27 (22%) of 122 patients in the active care group versus four (8%) in the standard care group (p=0.03). In the active care arm, of those with 6 months recurrence who stepped up treatment, 18 (38%) of 47 patients were in remission 12 months later; conversely, of those in remission at 6 months who did not change therapy recurrence occurred in 31 (41%) of 75 patients 12 months later. Smoking (odds ratio [OR] 2.4, 95% CI 1.2-4.8, p=0.02) and the presence of two or more clinical risk factors including smoking (OR 2.8, 95% CI 1.01-7.7, p=0.05) increased the risk of endoscopic recurrence. The incidence and type of adverse and severe adverse events did not differ significantly between patients in the active care and standard care groups (100 [82%] of 122 vs 45 [87%] of 52; p=0.51) and (33 [27%] of 122 vs 18 [35%] of 52; p=0.36), respectively. INTERPRETATION: Treatment according to clinical risk of recurrence, with early colonoscopy and treatment step-up for recurrence, is better than conventional drug therapy alone for prevention of postoperative Crohn's disease recurrence. Selective immune suppression, adjusted for early recurrence, rather than routine use, leads to disease control in most patients. Clinical risk factors predict recurrence, but patients at low risk also need monitoring. Early remission does not preclude the need for ongoing monitoring. FUNDING: AbbVie, Gutsy Group, Gandel Philanthropy, Angior Foundation, Crohn's Colitis Australia, and the National Health and Medical Research Council.

Long-term follow-up reveals low incidence of colorectal cancer, but frequent need for resection, among Australian patients with inflammatory bowel disease.

BACKGROUND & AIMS: Inflammatory bowel disease can require surgical resection and also lead to colorectal cancer (CRC). We investigated the cumulative incidence of resection surgeries and CRC among patients with ulcerative colitis (UC) or Crohn's disease (CD). METHODS: We analyzed data from a cohort of patients who participated in an inflammatory bowel disease study (504 with UC and 377 with CD) at 2 academic medical centers in Sydney, Australia from 1977 to 1992 (before the development of biologic therapies). We collected follow-up data on surgeries and development of CRC from hospital and community medical records or via direct contact with patients during a median time period of 14 years. Cumulative incidences of resection surgeries and CRC were calculated by competing risk survival analysis. RESULTS: Among patients with UC, CRC developed in 24, for a cumulative incidence of 1% at 10 years (95% confidence interval [CI], 0%-2%), 3% at 20 years (95% CI, 1%-5%), and 7% at 30 years (95% CI, 4%-10%). Their cumulative incidence of colectomy was 15% at 10 years (95% CI, 11%-19%), 26% at 20 years (95% CI, 21%-30%), and 31% at 30 years (95% CI, 25%-36%). Among patients with CD, 5 of 327 with colon disease developed CRC, with a cumulative incidence of CRC of 1% at 10 years (95% CI, 0%-2%), 1% at 20 years (95% CI, 0%-2%), and 2% at 30 years (95% CI, 0%-4%). Among all patients with CD, the cumulative incidence of resection was 32% at 5 years (95% CI, 27%-37%), 43% at 10 years (95% CI, 37%-49%), and 53% at 15 years (95% CI, 46%-58%). Of these 168 subjects, 42% required a second resection within 15 years of the first surgery (95% CI, 33%-50%). CONCLUSIONS: Patients with UC have a low incidence of CRC during a 30-year period (7% or less); the incidence among patients with CD is even lower. However, almost one-third of patients with UC and about 50% of those with CD will require surgery.

Relationship between disease severity and quality of life and assessment of health care utilization and cost for ulcerative colitis in Australia: a cross-sectional, observational study.

BACKGROUND & AIMS: The burden of ulcerative colitis (UC) in relation to disease severity is not well documented. This study quantitatively evaluated the relationship between disease activity and quality of life (QoL), as well as health care utilization, cost, and work-related impairment associated with UC in an Australian population. METHODS: A cross-sectional, noninterventional, observational study was performed in patients with a wide range of disease severity recruited during routine specialist consultations. Evaluations included the Assessment of Quality of Life-8-dimension (AQoL-8D), EuroQol 5-dimension, 5-level (EQ-5D-5L), the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ), and the Work Productivity and Activity Impairment (WPAI) instrument. The 3-item Partial Mayo Score was used to assess disease severity. Health care resource utilization was assessed by chart review and patient questionnaires. RESULTS: In 175 patients, mean (SD) AQoL-8D and EQ-5D-5L scores were greater for patients in remission (0.80 [0.19] and 0.81 [0.18], respectively) than for patients with active disease (0.70 [0.20] and 0.72 [0.19], respectively, both Ps<0.001). IBDQ correlated with both AQoL-8D (r=0.73; P<0.0001) and EQ-5D-5L (0.69; P<0.0001). Mean 3-month UC-related health care cost per patient was AUD $2914 (SD=$3447 [mean for patients in remission=$1970; mild disease=$3736; moderate/severe disease=$4162]). Patients in remission had the least work and activity impairment. CONCLUSIONS: More severe UC disease was associated with poorer QoL. Substantial health care utilization, costs, and work productivity impairments were found in this sample of patients with UC. Moreover, greater disease activity was associated with greater health care costs and impairment in work productivity and daily activities.

Cause-specific mortality and 30-year relative survival of Crohn's disease and ulcerative colitis.

BACKGROUND: Data from the northern hemisphere suggest that patients with ulcerative colitis (UC) have similar survival to the general population, whereas mortality in Crohn's disease (CD) is increased by up to 50%. There is a paucity of data from the southern hemisphere, especially in Australia. METHODS: A prevalence cohort (1977-1992) of patients with inflammatory bowel disease (IBD) diagnosed after 1970 was studied. Survival status data and causes of death up to December 2010 were extracted from the National Death Index. Relative survival analysis was carried out separately for men and women. RESULTS: Of 816 cases (384 men, 432 women; 373 CD, 401 UC, 42 indeterminate colitis), 211 (25.9%) had died by December 2010. Median follow-up was 22.2 years. Relative survival of all patients with IBD was not significantly different from the general population at 10, 20, and 30 years of follow-up. Separate analyses of survival in CD and UC also showed no differences from the general population. There was no difference in survival between patients diagnosed earlier (1971-1979) or later (1980-1992). At least 17% of the deaths were caused by IBD. Fatal cholangiocarcinomas were more common in IBD (P < 0.001), and fatal colorectal cancers more common in UC (P = 0.047). CONCLUSIONS: In Australia, IBD patient survival is similar to the general population. In contrast to data from Europe and North America, survival in CD is not diminished in Australia. IBD caused direct mortality in 17%, especially as biliary and colorectal cancers are significant causes of death.

Inflammatory bowel disease and pregnancy: lack of knowledge is associated with negative views.

BACKGROUND: Enabling women with inflammatory bowel diseases (IBD) to have successful pregnancies requires complex decisions. The study aimed to assess patients' views on IBD and pregnancy and to evaluate any association with subject knowledge. METHODS: General attitudes of females with IBD were assessed on fertility, medication use, delivery mode and pregnancy outcomes. Attitudes regarding personal situation were assessed in participants nulliparous since IBD diagnosis. Knowledge of pregnancy-related issues in IBD was assessed by the Crohn's and Colitis Pregnancy Knowledge Score 'CCPKnow'. RESULTS: Of 145 participants 68% of participants agreed with need for medical therapy for flares during pregnancy, but 24% felt it more important to tolerate symptoms. 36% believed that all IBD medication is harmful to unborn children. Of 96 women nulliparous after IBD diagnosis, 46% were worried about infertility, 75% expressed concern about passing IBD to offspring and 30% considered not having children. Nearly all participants worried about the effects of IBD on pregnancy and the effects of pregnancy on IBD. General attitudes that 'medication should be stopped prior to conception' (P<0.001), 'pregnant women should avoid all IBD drugs' (P<0.001), and 'put up with symptoms' (P<0.001) were associated with significantly lower CCPKnow scores. CONCLUSION: Over a third of patients considered IBD medication harmful to unborn children. Fear of infertility and concerns about inheritance may explain high rates of voluntary childlessness. Attitudes contrary to medical evidence were associated with significantly lower knowledge. Young women with IBD, particularly those with poor knowledge, should be offered education and counselling about pregnancy-related issues.

Self-reported depressive symptoms and suicidal feelings in perianal Crohn's disease.

AIM: Crohn's disease is a chronic inflammatory condition that has been associated with high rates of mental illness. Perianal lesions are prevalent; however, their specific impact on depression has not been studied. The aim of our study was to investigate the prevalence and associations of self-reported depressive symptoms in the subset of Crohn's patients with perianal disease. METHOD: Patients with perianal Crohn's disease from one institution were surveyed to elicit the frequency of self-reported depressive symptoms. Patients completed a questionnaire and consented to medical records audit. RESULTS: Of the 130 patients invited, 69 (53%) returned a survey. Depressive symptoms were self-reported at very high rates, with 73% reporting feeling depressed and 13% reporting feeling suicidal at some point. Associations were found between depressive symptoms and duration of disease, prior surgery, past or present stoma, and anal stenosis. Patients who self-reported depressive symptoms had lower overall utilities, and were willing to trade very significant proportions (upwards of 15%) of their life expectancy for disease cure. CONCLUSION: This study suggests that many patients with perianal Crohn's disease experience significant emotional distress that impairs their overall quality of life. Further controlled studies are required to assess the impact of perianal disease and to address the need to target interventions to meet the mental health needs of this population.

Quality of life in perianal Crohn's disease: what do patients consider important?

BACKGROUND: Perianal Crohn's disease can affect quality of life across physical, functional, and psychosocial domains. Little is known about how patients prioritize factors affecting their quality of life. OBJECTIVE: This study aimed to determine which factors are considered by patients to be the most important and most unfavorable to their quality of life, and to gauge the relative impact of perianal and nonperianal symptoms. DESIGN: This cross-sectional study involves a mailed questionnaire and medical records audit. SETTINGS: Recruitment was from the database of 2 specialists at a single tertiary-level teaching hospital. Surveys were completed in the community. PATIENTS: Patients with Crohn's disease who had been seen in the preceding 10 years with documented perianal disease were recruited to participate. Of 130 patients invited, 69 (53%) returned a survey. MAIN OUTCOME MEASURES: Patients rated the importance of 16 quality-of-life factors spanning multiple domains. Patient utility was also elicited through use of trade-off scenarios. RESULTS: The mean age of participants was 42.7 years and 62% were female. Eighty percent of patients had undergone prior surgery. Anal pain or discomfort was considered the most important factor for patients, rated highly important by 40%. Physical symptoms were rated more important and adverse than functional, psychosocial, and body image factors. The presence of a long-term perianal drain was predictive of high ratings of importance for the majority of factors investigated. Perianal symptoms did not contribute more than nonperianal symptoms to overall utility. LIMITATIONS: This study was limited by its small sample size, single-institution bias, self-completion questionnaire, and response rate. CONCLUSIONS: Patients with perianal Crohn's disease experience significant impairment of quality of life. Physical symptoms are felt to be the most important and unfavorable. The patient experience of long-term perianal drains warrants further study.

Capsule endoscopy versus positron emission tomography for detection of small-bowel metastatic melanoma: a pilot study.

BACKGROUND: Melanoma is the most common tumor to metastasize to the GI tract, where it mainly involves the small bowel. OBJECTIVE: To compare capsule endoscopy (CE) and (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)-CT scanning, the current standard and most sensitive investigation modality, in detecting small-bowel metastases in patients with metastatic melanoma. DESIGN: A prospective study of patients with metastatic melanoma who were undergoing FDG PET-CT scanning. CE was performed and the results read by two independent observers without knowledge of the other investigation results. SETTING: Tertiary care centers. PATIENTS: This study involved 21 patients with a median age of 52 years (range 22-88 years). INTERVENTION: CE. MAIN OUTCOME MEASUREMENTS: Detection of small-bowel melanoma. RESULTS: FDG PET-CT scanning showed increased abdominal uptake in 12 patients, but only 5 of these patients were found to have small-bowel melanoma on CE. Importantly, in 1 patient with a bleeding small-bowel tumor on CE, the FDG PET-CT scan result was negative. One patient with positive FDG PET-CT scan results and negative CE results subsequently developed symptomatic small-bowel melanoma 10 months after CE. LIMITATIONS: Small-bowel melanoma could not be excluded entirely in 7 patients with positive FDG PET-CT scan results and negative CE results, and follow-up is ongoing. The number of patients in this study was small. CONCLUSION: CE was better than FDG PET-CT scanning in localizing small-bowel melanoma. This study suggests that CE is an ideal complementary investigation modality for patients with known metastatic melanoma undergoing preoperative work-ups and in those with unexplained anemia or GI symptoms.

The inability to visualize the ampulla of Vater is an inherent limitation of capsule endoscopy.

OBJECTIVE: Lesions missed by capsule endoscopy (CE) have been reported and this may be partly because of the properties of the capsule. We aimed to compare the ability of Pillcam SB1, SB2, ESO1 and ESO2 to identify the ampulla of Vater (AoV). METHODS: Patients were divided into four groups: SB1 [single head capsule, 2 frames per second (fps), a 140° field of view, n=50], SB2 (single head, 2 fps, a wider field of view of 156°, n=50), ESO1 (double head, 14 fps, a 140° field of view, n=8) and ESO2 (double head, 18 fps, an extra wide field of view of 169°, n=12). Metoclopramide was administered in 25 out of 50 patients in SB1 group and all patients in SB2 group before CE. RESULTS: The AoV was not detected in any patients having SB1, irrespective of the use of metoclopramide. The AoV was identified in only nine out of 50 (18%) patients in the SB2 group confirming the benefit of a widened field of view, however, showed that even this capsule failed to visualize the AoV in more than three-quarters of cases. Double-headed capsules with faster frame rates did not improve the detection rate, the AoV was visualized in only one out of 12 (8%) patients in the ESO2 group but none in the ESO1 studies. CONCLUSION: Currently, CE is not reliable to visualize the AoV and by inference the proximal duodenum. This is most likely related to the speed at which the capsule passes through the fixed second part of the duodenum. Faster frame rates plus a wider field of view do not overcome this limitation, which could account for missed lesions elsewhere in the small bowel.

Prospective randomized controlled trial evaluating cap-assisted colonoscopy vs standard colonoscopy.

AIM: To study the significance of cap-fitted colonoscopy in improving cecal intubation time and polyp detection rate. METHODS: This study was a prospective randomized controlled trial conducted from March 2008 to February 2009 in a tertiary referral hospital at Sydney. The primary end point was cecal intubation time and the secondary endpoint was polyp detection rate. Consecutive cases of total colonoscopy over a 1-year period were recruited. Randomization into either standard colonoscopy (SC) or cap-assisted colonoscopy (CAC) was performed after consent was obtained. For cases randomized to CAC, one of the three sizes of cap was used: D-201-15004 (with a diameter of 15.3 mm), D-201-14304 (14.6 mm) and D-201-12704 (13.0 mm). All of these caps were produced by Olympus Medical Systems, Japan. Independent predictors for faster cecal time and better polyp detection rate were also determined from this study. RESULTS: There were 200 cases in each group. There was no significant difference in terms of demographic characteristics between the two groups. CAC, when compared to the SC group, had no significant difference in terms of cecal intubation rate (96.0% vs 97.0%, P = 0.40) and time (9.94 +/- 7.05 min vs 10.34 +/- 6.82 min, P = 0.21), or polyp detection rate (32.8% vs 31.3%, P = 0.75). On the subgroup analysis, there was no significant difference in terms of cecal intubation time by trainees (88.1% vs 84.8%, P = 0.40), ileal intubation rate (82.5% vs 79.0%, P = 0.38) or total colonoscopy time (23.24 +/- 13.95 min vs 22.56 +/- 9.94 min, P = 0.88). On multivariate analysis, the independent determinants of faster cecal time were consultant-performed procedures (P < 0.001), male patients (P < 0.001), non-usage of hyoscine (P < 0.001) and better bowel preparation (P = 0.01). The determinants of better polyp detection rate were older age (P < 0.001), no history of previous abdominal surgery (P = 0.04), patients not having esophagogastroduodenoscopy in the same setting (P = 0.003), trainee-performed procedures (P = 0.01), usage of hyoscine (P = 0.01) and procedures performed for polyp follow-up (P = 0.01). The limitations of the study were that it was a single-center experience, no blinding was possible, and there were a large number of endoscopists. CONCLUSION: CAC did not significantly different from SC in term of cecal intubation time and polyp detection rate.

Hepatitis C virus infection rates and risk factors in an Australian hospital endoscopy cohort.

OBJECTIVE: To determine the reservoir and risk factors of HCV infection in a hospital population. METHODS: The presence of anti-HCV in 2,119 endoscopy patients was related to putative risk factors for exposure using the SAS statistical package. RESULTS: Most of the 4.7% of anti-HCV positive patients had multiple risk factors for HCV exposure. The risk was significantly increased in patients; with a previous history of hepatitis (36.4 fold), past history of injecting drugs (IDU) (32.1 fold), those born in North Africa, Middle East and Mediterranean countries (4.3 fold), had been tattooed before 1980s (3.3 fold), from 1980s-1990s (5.9 fold), had acupuncture before 1980s (3.8 fold), had a blood transfusion (3.6 fold), had clotting factors or growth hormone (4 fold), had contact with someone diagnosed with hepatitis in 1990s (4.1 fold). Of the anti-HCV patients 38 had a history of IDU, 43 were migrants and 10 were both. CONCLUSION: Anti-HCV prevalence was five times higher than predicted by the passive surveillance scheme and 20% of patients were unaware of their infection. Only one of these patients reported IDU. The evidence of HCV intersecting epidemics between developing and developed countries in Australia was strongly supported. IMPLICATIONS: The study provides a rational basis for targeted programs to identify asymptomatic HCV carriers who might benefit from the new antiviral treatment.

A successful practical application of Coverage with Evidence Development in Australia: Medical Services Advisory Committee interim funding and the PillCam Capsule Endoscopy Register.

BACKGROUND: In August 2002, an application for the listing on the Medicare Benefits Schedule (MBS) of PillCam Capsule Endoscopy (formally M2A) as a diagnostic procedure for obscure gastrointestinal bleeding (OGIB) was made to the Medical Services Advisory Committee (MSAC). As a result of this application, in May 2004 PillCam Capsule Endoscopy was approved with interim funding until April 2007. This funding was conditional on the collection of Australian data on the long-term safety, effectiveness, and cost-effectiveness of capsule endoscopy. METHODS: A review was conducted of how the data were collected, the methodological difficulties associated with the collection and analysis of the data, and the outcomes of the data. RESULTS: The PillCam Capsule Endoscopy Register ran from 2004 to 2007 and amassed data on 4,099 patients forming the largest database on PillCam in the world. Based on these data, in November 2007, MSAC recommended that full public funding be supported under the current MBS Item Number 11820 as capsule endoscopy is as safe as and more effective than comparable diagnostic tests. It is the preferred choice of patients and has the potential to reduce the number and cost of previous investigations. CONCLUSIONS: This form of CED proved to be ideally suited to PillCam Capsule Endoscopy. The PillCam Capsule Endoscopy Register provided data that made it possible to validate assumptions used in the economic modeling in the assessment carried out for MSAC in response to the application for funding. DISCUSSION: The use of interim funding requires both risk and cost sharing among the key players: industry, government, the medical profession, and the hospitals. Although the characteristics of PillCam Capsule Endoscopy proved to be suited to data collection, this may not be the case with other emerging health technologies. If interim funding coupled with data collection is to become an effective mechanism for bridging the evidence gap, work needs to be carried out by health technology assessment agencies to provide guidance on the design of registers so that they cater for the unique characteristics of individual procedures.

Are repeat upper gastrointestinal endoscopy and colonoscopy necessary within six months of capsule endoscopy in patients with obscure gastrointestinal bleeding?

BACKGROUND AND AIM: Medicare reimbursement for capsule endoscopy for the investigation of obscure gastrointestinal bleeding in Australia requires endoscopy and colonoscopy to have been performed within 6 months. This study aims to determine the diagnostic yield of repeating these procedures when they had been non-diagnostic more than 6 months earlier. METHODS: Of 198 consecutive patients who were referred for the investigation of obscure gastrointestinal bleeding, 50 underwent repeat endoscopy and colonoscopy solely to enable reimbursement (35 females and 15 males; mean age 59.4 [range: 21-82] years). The average duration of obscure bleeding was 50.16 (range: 9-214) months. The mean number of prior endoscopies was 3 (median: 2) and 2.8 colonoscopies (median: 2). The most recent endoscopy had been performed 18.9 (median: 14; range: 7-56) months, and for colonoscopy, 19.1 (median 14; range 8-51) months earlier. RESULTS: A probable cause of bleeding was found at endoscopy in two patients: gastric antral vascular ectasia (1) and benign gastric ulcer (1). Colonoscopy did not reveal a source of bleeding in any patient. Capsule endoscopy was performed in 47 patients. Twenty four (51%) had a probable bleeding source identified, and another five (11%) a possible source. These included angioectasia (17 patients), mass lesion (2), non-steroidal anti-inflammatory drug enteropathy (2), Cameron's erosions (2), and Crohn's disease (1). Four patients undergoing repeat capsule endoscopy had a probable bleeding source detected. CONCLUSION: The yield of repeat endoscopy and colonoscopy immediately prior to capsule endoscopy is low when these procedures have previously been non-diagnostic. Such an approach is also not cost-effective.