Sex Differences in Neoplastic Progression in Barrett's Esophagus: A Multicenter Prospective Cohort Study.

Recommendations in Barrett's esophagus (BE) guidelines are mainly based on male patients. We aimed to evaluate sex differences in BE patients in (1) probability of and (2) time to neoplastic progression, and (3) differences in the stage distribution of neoplasia. We conducted a multicenter prospective cohort study including 868 BE patients. Cox regression modeling and accelerated failure time modeling were used to estimate the sex differences. Neoplastic progression was defined as high-grade dysplasia (HGD) and/or esophageal adenocarcinoma (EAC). Among the 639 (74%) males and 229 females that were included (median follow-up 7.1 years), 61 (7.0%) developed HGD/EAC. Neoplastic progression risk was estimated to be twice as high among males (HR 2.26, 95% CI 1.11-4.62) than females. The risk of HGD was found to be higher in males (HR 3.76, 95% CI 1.33-10.6). Time to HGD/EAC (AR 0.52, 95% CI 0.29-0.95) and HGD (AR 0.40, 95% CI 0.19-0.86) was shorter in males. Females had proportionally more EAC than HGD and tended to have higher stages of neoplasia at diagnosis. In conclusion, both the risk of and time to neoplastic progression were higher in males. However, females were proportionally more often diagnosed with (advanced) EAC. We should strive for improved neoplastic risk stratification per individual BE patient, incorporating sex disparities into new prediction models.

Comparison of hypersensitivity reactions of intravenous iron: iron isomaltoside-1000 (Monofer® ) versus ferric carboxy-maltose (Ferinject® ). A single center, cohort study.

AIMS: Intravenous iron supplementation is widely used to treat iron deficiency and iron deficiency anemia when oral iron administration is ineffective or poorly tolerated. Hypersensitivity reactions (HSRs) during infusions are rare, but can be life-threatening. This study aimed to compare the risk for HSRs with the intravenous administration of iron isomaltoside-1000 and ferric carboxymaltose for the treatment of iron deficiency and iron deficiency anemia. METHODS: This was a single-centre cohort study. Nurses and physicians were instructed to fill out an HSR registration form with every administration of intravenous iron. HSRs were distinguished into serious and non-serious HSRs using the Ring and Messmer classification. RESULTS: HSRs occurred in 18/836 (2.1%) ferric carboxymaltose and 43/496 (8.7%) iron isomaltoside-1000 administrations. The crude risk for HSRs was 75% lower after ferric carboxymaltose treatment (RR = 0.248, 95% CI: 0.145-0.426, P < 0.0001). The risk for grade II HSRs was 88% lower after ferric carboxymaltoside (RR = 0.123, 95% CI: 0.051-0.294). The likelihood of HSRs was 3.4 times higher after the administration of iron isomaltoside-1000 (95% CI: 1.910-6.093, P < 0.0001). Regardless of the type of intravenous iron, patients with comorbidities have a factor 3.6 higher risk (95% CI: 1.899-6.739, P < 0.0001). CONCLUSIONS: Ferric carboxymaltose is associated with a 75% lower risk for HSRs compared with iron isomaltoside-1000 in our population. The presence of a comorbidity raises the likelihood of an HSR by a factor of three regardless of the type of intravenous iron infusion. Further research is needed to clarify the underlying mechanism in various patient groups.

Decision making and outcome of pregnancies in female patients with inflammatory bowel disease: findings from a community-based practice.

INTRODUCTION: The aim of this study was to evaluate information provided on pregnancy, personal decision making, disease course, and outcome of pregnancy from a patient's perspective in a population of patients with inflammatory bowel disease (IBD) attending two general hospitals. PATIENTS AND METHODS: A questionnaire was sent to all female patients with IBD in two general hospitals in the Netherlands. The questionnaire comprised four sections: (i) demographic data and medication use (ii) details on previous pregnancies and reasons for not becoming pregnant, (iii) outcome of pregnancies before IBD diagnosis, and (iv) outcome of pregnancies after IBD diagnosis. If necessary, medical records were reviewed to verify responses or for further medical details. RESULTS: In total, 385 women returned the questionnaire, 501 completed pregnancies were reported, and 113 women had never been pregnant. In 272 women with at least one pregnancy, 334 pregnancies occurred before IBD diagnosis, 157 after IBD diagnosis, and in 10 cases, IBD was diagnosed during pregnancy. Medication for IBD was used in 67% of pregnancies after IBD diagnosis, mainly 5-ASA preparations (54%). Women with ulcerative colitis experienced more IBD-related complaints during pregnancy compared with women with Crohn's disease (25 vs. 14%, P=0.016). Additional medication (n=21) or surgery (n=2) for IBD during pregnancy was indicated in 14% of cases. Most women reported an uneventful pregnancy course (79%). Preterm birth occurred in 13% of pregnancies. CONCLUSION: Pregnancy in women with IBD seen in a general hospital can be managed with a good outcome. Step-up therapy is needed in a minority of cases, and severe complications are rare.

Benefit of Earlier Anti-TNF Treatment on IBD Disease Complications?

BACKGROUND: Anti-tumour necrosis factor [anti-TNF] treatment was demonstrated to have disease-modifying abilities in inflammatory bowel disease [IBD]. In this study, we aimed to determine the effect of anti-TNF treatment timing on IBD disease complications and mucosal healing [MH]. METHODS: The following IBD-related complications were tested in relation to timing of anti-TNF therapy start in newly diagnosed IBD patients [n = 413]: fistula formation, abscess formation, extra-intestinal manifestations [EIM], surgery, referral to academic centre, and MH. RESULTS: A total of 85 patients [21%] received anti-TNF (66 Crohn's disease [CD], 16 ulcerative colitis [UC], 3 inflammatory bowel disease unclassified [IBDU]) of whom 57% [48 patients] were treated < 16 months after diagnosis. Patients receiving anti-TNF early [< 16 months] did not differ from patients receiving anti-TNF late [> 16 months] regarding gender, age, smoking status, and familial IBD. More importantly, patients receiving anti-TNF early did not suffer less IBD-related complications during follow-up as compared with patients started on anti-TNF late, nor was more MH observed. Similar results were obtained when anti-TNF treated patient were stratified more stringently, ie < 12 months [40 patients] vs >2 4 months [24 patients]. Cox regression analysis showed no beneficial correlations between anti-TNF timing and IBD-related complications. Anti-TNF treated patients achieving MH were 11 times less likely to develop EIMs compared with patients who did not achieved MH while on anti-TNF. CONCLUSIONS: This study was unable to confirm a benefit of earlier anti-TNF treatment on IBD disease complications. This could be explained by more aggressive treatment earlier in disease, resulting in fewer IBD complications. However, it seems more likely that inappropriate selection of patients for therapy leads to suboptimal treatment and subsequently suboptimal outcome.

Determinants of fatigue in Crohn's disease patients.

OBJECTIVE: Crohn's disease (CD) is often associated with severe fatigue. Little is known about patients who may be at the highest risk for fatigue. Therefore, we assessed the disease phenotype and factors related to fatigue in the presence of CD in two different populations. METHODS: Patients presenting at the clinic of a referral hospital and a general hospital were included in the study. They completed questionnaires including the Checklist Individual Strength, the Hospital Anxiety and Depression Scale, a questionnaire on disease activity, and one on medication use. The Montreal classification and sociodemographics were obtained from medical records. Hemoglobin and C-reactive protein levels were measured at baseline. RESULTS: In total, 425 patients were included (276 women, mean age: 42 years). Compared with patients from the general hospital, patients at the referral hospital had worse disease activity, worse disease behavior, more bowel resections, and a higher percentage of side-effects to medication and use of anti-tumor necrosis factor (TNF). The prevalence of fatigue was significantly higher in the referral patients compared with the general patients (65.7 vs. 52.5%, respectively; P=0.01). Similar results were found in patients in remission (53.3 vs. 40.5%; P=0.061). Factors related to fatigue were the use of anti-TNF at baseline, side-effects to 5-aminosalicylic acid, disease activity, female sex, and shorter disease duration. Furthermore, we found improvement in fatigue and a trend toward lower disease activity after 1 year of anti-TNF use. CONCLUSION: A high percentage of CD patients suffer from fatigue. As a more aggressive phenotype seems to be associated with more severe fatigue and patients in remission still suffer from fatigue, a multidimensional approach for fatigue is warranted in these patients.

The Global Rating Scale in clinical practice: a comprehensive quality assurance programme for endoscopy departments.

BACKGROUND: The Global Rating Scale is an endoscopy quality assurance programme, successfully implemented in England. It remains uncertain whether it is applicable in another health care setting. AIM: To assess the applicability of the Global Rating Scale as benchmark tool in an international context. METHODS: Eleven Dutch endoscopy departments were included for a Global Rating Scale-census, performed as a cross-sectional evaluation, July 2010. Two Global Rating Scale-dimensions - 'clinical quality' and 'patient experience' - were assessed across six items using a range of levels: from level-D (basic) to level-A (excellent). Construct validity was assessed by comparing department-specific colonoscopy audit data to GRS-levels. RESULTS: For 'clinical quality', variable scores were achieved in items 'safety' (9%=B, 27%=C, 64%=D) and 'communication' (46%=A, 18%=C, 36%=D). All departments achieved a basic score in 'quality' (100%=D). For 'patient experience', variable scores were achieved in 'timeliness' (18%=A, 9%=B, 73%=D) and 'booking-choice' (36%=B, 46%=C, 18%=D). All departments achieved basic scores in 'equality' (100%=D). Departments obtaining level-C or above in 'information', 'comfort', 'communication', 'timeliness' and 'aftercare', achieved significantly better audit outcomes compared to those obtaining level-D (p<0.05). CONCLUSION: The Global Rating Scale is appropriate to use outside England. There was significant variance across departments in dimensions. Most Global Rating Scale-levels were in line with departments' audit outcomes, indicating construct validity.

The incidence of 30-day adverse events after colonoscopy among outpatients in the Netherlands.

OBJECTIVES: Colonoscopy is the gold standard for visualization of the colon. It is generally accepted as a safe procedure and major adverse events occur at a low rate. However, few data are available on structured assessment of (minor) post-procedural adverse events. METHODS: Consecutive outpatients undergoing colonoscopy were asked for permission to be called 30 days after their procedure. A standard telephone interview was developed to assess the occurrence of (i) major adverse events (hospital visit required), (ii) minor adverse events, and (iii) days missed from work. Adverse events were further categorized in definite-, possible-, and unrelated adverse events. Patients were contacted between January 2010 and September 2010. RESULTS: Out of a total of 1,528 patients who underwent colonoscopy and gave permission for a telephone call, 1,144 patients were contacted (response: 75%), 49% were male, the mean age was 59 years (s.d.: 14). Thirty-four patients (3%) reported major adverse events. These were definite-related in nine (1%) patients, possible-related in 6 (1%), and unrelated in 19 patients (2%). Minor adverse events were reported by 466 patients (41%). These were definite-related in 336 patients (29%), possible-related in 36 (3%), and unrelated in the remaining 94 patients (8%). Female gender (odds ratio (OR): 1.5), age <50 years (OR: 1.5), colonoscopy for colorectal cancer screening/surveillance (OR: 1.6), and fellow-endoscopy (OR: 1.7) were risk factors for the occurrence of any definite-related adverse event. Patients who reported definite-related adverse events were significantly less often willing to return for colonoscopy (81 vs. 88%, P<0.01) and were less often positive about the entire colonoscopy experience (84 vs. 89%, P=0.04). CONCLUSIONS: Structured assessment of post-colonoscopy adverse events shows that these are more common than generally reported. Close to one-third of patients report definite-related adverse events, which are major in close to 1 in 100 patients. The occurrence of adverse events does have an impact on the willingness to return for colonoscopy.

Quality evaluation of colonoscopy reporting and colonoscopy performance in daily clinical practice.

BACKGROUND: Comprehensive monitoring of colonoscopy quality requires complete and accurate colonoscopy reporting. OBJECTIVE: This study aimed to assess the compliance with colonoscopy reporting and to assess the quality of colonoscopy performance. DESIGN: Consecutive colonoscopy reports were reviewed by hand. Four hundred reports were included from each department. SETTING: Daily clinical practice in 12 Dutch endoscopy departments. PATIENTS: Consecutive patients undergoing scheduled colonoscopy procedures. MAIN OUTCOME MEASUREMENTS: Quality of reporting was assessed by using the American Society for Gastrointestinal Endoscopy criteria for colonoscopy reporting. Quality of colonoscopy performance was evaluated by using the cecal intubation rate and adenoma detection rate (ADR). RESULTS: A total of 4800 colonoscopies were performed by 116 endoscopists: 70% by gastroenterologists, 16% by gastroenterology fellows, 10% by internists, 3% by nurse-endoscopists, and 1% by surgeons. The mean age of the patients was 59 years (standard deviation 16), and 47% were male. Reports contained information on indication, sedation practice, and extent of the procedure in more than 90%. Only 62% of the reports mentioned the quality of bowel preparation (range between departments 7%-100%); photographic documentation of the cecal landmarks was present in 71% (range 22%-97%). The adjusted cecal intubation rate was 92% (range 84%-97%). The ADR was 24% (range 13%-32%). LIMITATIONS: Dependent on reports, no intervention in endoscopic practice. No analysis for performance per endoscopist. CONCLUSION: Colonoscopy reporting varied significantly in clinical practice. Colonoscopy performance met the suggested standards; however, considerable variability between endoscopy departments was found. The results of this study underline the importance of the implementation of quality indicators and guidelines. Moreover, by continuous monitoring of quality parameters, the quality of both colonoscopy reporting and colonoscopy performance can easily be improved.

Awareness of surveillance recommendations among patients with colorectal adenomas.

BACKGROUND & AIMS: The efficacy of colorectal cancer screening programs depends on the rate of attendance at surveillance colonoscopy examinations. Increasing patients' awareness about the importance of surveillance might improve attendance, but it is not clear how much they know about their follow-up recommendations. We assessed the awareness of patients with adenomas about their surveillance recommendations. METHODS: Ten endoscopy departments provided access to their colonoscopy database for quality assurance; 2 datasets were obtained. We analyzed data from 4000 colonoscopies (400 per department) performed on patients with adenomas. All the patients were mailed a survey to determine how much information they had about their colonoscopy results and their follow-up recommendations. Data from 549 patients were included in the analysis. We also assessed surveillance attendance among 500 patients (50 per department) who had adenomas removed. RESULTS: Of the patients analyzed, 85% recalled retrieval of polyps during their colonoscopy, and 85% recalled whether they needed surveillance or not. The indication for surveillance was recalled by 69% of patients (range between departments, 55%-83%; P < .01). Factors that were associated with awareness of recommendations were younger age (odds ratio [OR], 1.06; 95% confidence interval [CI], 1.06-1.09), treatment by a gastroenterologist (OR, 5.53; 95% CI, 3.28-9.32), and presence of 3 or more adenomas (OR, 2.97; 95% CI, 1.29-6.85). Attendance among patients with adenomas varied among departments, from 60% to 89% (P < .01), and was not associated with awareness of patients about their recommendations per department (P = .59). CONCLUSIONS: Not enough patients (only 85%) who receive colonoscopies are aware of their results or surveillance recommendations. Although awareness of findings and recommendations did not correlate with follow-up attendance, patients should be better informed about findings and their need for surveillance.

Full-blown graft-versus-host disease presenting with skin manifestations, jaundice and diarrhoea: an unusual paraneoplastic phenomenon of a thymoma.

We describe a patient who presented with chronic diarrhoea, skin lesions and jaundice. Based on histopathological examinations of the affected organs combined with the clinical features, it appeared that the patient fulfilled the criteria for graft-versus-host disease (GVHD). GVHD occurs especially after allogeneic stem cell transplantation and sometimes after organ transplantations. However, this patient had never undergone such a procedure. Further examination revealed that the patient also suffered from a thymoma, which was concluded to be the cause of GVHD. Unfortunately, the patient died after resection of the thymoma. This patient is probably the second case with thymoma and full-blown GVHD and shows that GVHD can occur in the absence of a previous transplantation.