Blankenstein, M. van

The minimal incubation period from the onset of Barrett's oesophagus to symptomatic adenocarcinoma (Article)

2011-07-12T00:00:00Z

Background:The interval between the onset of Barrett's oesophagus (BO) and oesophageal adenocarcinoma (OAC) can be termed the incubation period. However, the unrecorded onset of BO precludes its direct observation.Methods:Determining the range of intervals between BO diagnosis and OAC within the longest observational BO follow-up study. Exclusion criteria were presence of high-grade dysplasia (HGD) or OAC at baseline, death within <2 years of BO diagnosis, oesophagectomy without HGD/OAC and loss to follow-up. A total of 133 patients (M/F 73/60) were taken into account.Results:In 1967 person years of follow-up there were 13 cases of HGD/OAC, (0.66% p.a.; 95% CI 0.58-0.74), 96 patients died without HGD/OAC and 24 survived without HGD/OAC. The mean intervals between BO diagnosis and either HGD/OAC, death or end of follow-up were 10.8, 12.6 and 25.5 years, respectively, and the mean ages at endpoint were 72.5, 80.0 and 68.3 years, respectively. The survivors without HGD/OAC had a lower age at BO diagnosis (mean 42.8 vs 61.2 and 67.4 years, P=0.001). Baseline presence of low-grade dysplasia was associated with progression to HGD/OAC (log rank P=0.001).Conclusion:The Rotterdam BO follow-up cohort revealed a long incubation period between onset of BO and development of HGD/OAC, in patients without HGD/OAC at baseline as illustrated by 24 patients diagnosed with BO at a young age and followed for a mean period of 25.5 years. Their tumour-free survival established a minimum incubation period, suggesting a true incubation period of three decades or more.

Risk of malignant progression in patients with Barrett's oesophagus: A Dutch nationwide cohort study (Article)

2010-08-01T00:00:00Z

Background: Reported incidence rates of oesophageal adenocarcinoma (OAC) in Barrett's oesophagus (BO) vary widely. As the effectiveness of BO surveillance is crucially dependent on this rate, its clarification is essential. Methods: To estimate the rate of malignant progression in patients with BO, all patients with a first diagnosis of BO with no dysplasia (ND) or low-grade dysplasia (LGD) between 1991 and 2006 were identified in the Dutch nationwide registry of histopathology (PALGA). Follow-up data were evaluated up to November 2007. Results: 42 207 patients with BO were included; 4132 (8%) of them had LGD. Re-evaluation endoscopies at least 6 months after initial diagnosis were performed in 16 365 patients (39%), who were significantly younger than those not re-examined (58±13 vs 63±16 years, p<0.001). These patients were followed-up for a total of 78 131 person-years, during which 666 (4%) high-grade dysplasia (HGD)/OACs occurred, affecting 4% of the surveillance patient population (mean age: 69±12 years, 76% male). After excluding HGD/OAC cases detected within 1 year after BO diagnosis (n=212, 32%), incidence rates per 1000 person-years were 4.3 (95% CI 3.4 to 5.5) for OAC and 5.8 (95% CI 4.6 to 7.0) for HGD/ OAC combined. Risk factors for HGD/OAC were increased age (eg, >75 years HR 12; 95% CI 8.0 to 18), male sex (2.01; 1.68 to 2.60) and presence of LGD at baseline (1.91; 1.53 to 2.40). Conclusion: In this largest reported cohort of unselected patients with BO, the annual risk of OAC was 0.4%. Male sex, older age and LGD at diagnosis are independent predictors of malignant progression, and should enable an improved risk assessment in BO

Increased risk of esophageal squamous cell carcinoma in patients with gastric atrophy: Independent of the severity of atrophic changes (Article)

2009-05-01T00:00:00Z

An association between gastric atrophy and esophageal squamous cell carcinomas (ESCC) has been described. However, the mechanism of this association is unknown. In this study, we aimed to examine this relationship in a cohort of patients with varying grades of gastric atrophy to increase the understanding about the causality of the association. Patients diagnosed with gastric atrophy between 1991 and 2005 were identified in the Dutch nationwide histopathology registry (PALGA). The incidence of ESCC and, presumably unrelated, small cell lung carcinomas (SCLC) observed in these patients was compared with that in the general Dutch population. Relative risks (RRs) and 95% confidence intervals were calculated by a Poisson model. At baseline histological examination, 97,728 patients were diagnosed with gastric atrophy, of whom 23,278 with atrophic gastritis, 65,934 with intestinal metaplasia and 8,516 with dysplasia. During follow-up, 126 patients were diagnosed with ESCC and 263 with SCLC (overall rates 0.19, respectively 0.39/1,000 person-years at risk). Compared with the general Dutch population, patients with gastric atrophy ran a RR of developing ESCC of 2.2 [95% CI 1.8-2.6] and of SCLC of 1.8 [95% CI 1.6-2.1]. The risk of ESCC did not increase with increasing severity of gastric atrophy (p = 0.90). In conclusion, this study found an association between gastric atrophy and both ESCC and SCLC, but the risk of ESCC did not increase with the severity of gastric atrophy. Therefore, a causal relationship seems unlikely. Confounding factors, such as smoking, may explain both associations.

Risk of Colorectal Cancer in Patients With Barrett's Esophagus: A Dutch Population-Based Study (Article)

2009-01-01T00:00:00Z

OBJECTIVES:The association between Barrett's esophagus (BE) and colorectal cancer (CRC) is controversial. Population-based studies on the risk of CRC in BE are scarce. The aim of this study was to determine the risk of CRC in a nationwide cohort of patients with BE in the Netherlands with long-term follow-up.METHODS:Patients diagnosed with BE between 1991 and 2006 were identified in the Dutch nationwide histopathology registry (Pathologisch Anatomisch Landelijk Geautomatiseerd Archief (PALGA)). The incidence of CRC observed in these patients was compared with that in the general Dutch population aged >40 years. Relative risks (RRs) and 95% confidence intervals (95% CIs) were calculated using a Poisson model.RESULTS:A total of 42,207 patients with a first diagnosis of BE were included in this study. During a mean follow-up of 5.6 years (s.d. 4), 713 patients (1.7%) were diagnosed with CRC (overall rate: 3.4/1,000 person-years at risk), at a mean age of 73.7 years (s.d. 10). All CRCs occurred in BE patients aged >40 years, and the majority (96%) in those over 50 years of age. Of those CRCs, 317 (44%) were detected within the first year after initial BE diagnosis, and 396 (54%) thereafter. For all patients with BE, CRC risk was 1.70 (95% CI: 1.58-1.83), as compared with the general Dutch population aged >40 years. However, CRC risk within the first year of follow-up after BE diagnosis (RR: 4.76 (95% CI: 4.26-5.31)) was significantly higher than within 1-5 years of follow-up (RR: 0.99 (95% CI: 0.86-1.14)) or more than 5 years of follow-up (RR: 1.28 (95% CI: 1.11-1.47)) (P<0.001).CONCLUSIONS:This population-based study shows an overall increased risk of CRC in patients with BE as compared with the general Dutch population, which can for the greater part be explained by diagnostic bias. The magnitude of the association between BE and CRC does not merit a more extensive CRC screening strategy in BE patients than has currently been recommended for the general population.Am J Gastroenterol advance online publication, 1 September 2009; doi:10.1038/ajg.2009.503.

Trends in the incidence of adenocarcinoma of the oesophagus and cardia in the Netherlands 1989-2003 (Article)

2007-06-04T00:00:00Z

Over the 15-year period 1989-2003, the incidence of oesophagus-cardia adenocarcinoma in the Netherlands rose annually by 2.6% for males and 1.2% for females. This was the net outcome of annual increases in the incidence of adenocarcinoma of the oesophagus (ACO) of 7.2% for males and 3.5% for females and annual declines in the incidence of adenocarcinoma of the gastric cardia (AGC) of more than 1% for both genders. Nonlinear cohort patterns were found in females with ACO and for both genders in AGC; a nonlinear period pattern was observed only in males with AGC. These differing epidemiological patterns for ACO and AGC do not support a common aetiology. Proposed underlying factors for the rise in ACO incidence appear to have little effect on AGC incidence. This and the secular decline in smoking among males may have led to the decline in AGC incidence.

Modelling a population with Barrett's oesophagus from oesophageal adenocarcinoma incidence data (Article)

2007-02-28T00:00:00Z

Objective. A recent study of adenocarcinoma of the oesophagus (ACO) incidence rates in Denmark showed a steep fall in the over-80 population, interpreted as the result of a decline in the prevalence of Barrett's oesophagus (BO) in this age group, for which three hypotheses were advanced: the specific mortality from ACO and, superimposed, either excess mortality from causes of death unrelated to ACO or a birth cohort effect. The aim of this study was to create models estimating the BO population fitting each of these three hypotheses, in order to select the most plausible hypothesis and to gain insight into the Danish BO population. Material and methods. Models were designed for these three hypotheses, conforming to the generally accepted 0.4-0.5% annual ACO incidence in BO patients. These models employed expectation-maximization (EM) algorithms, Danish life tables and the observed ACO incidence rates. The models enabled the estimation of a BO population for each hypothesis. Results. After testing against set criteria, the most plausible model was found to be that describing a birth cohort effect which predicted a ±5% annual rise in the prevalence of BO and, consequently, in the incidence rate of ACO in Denmark. This prediction was borne out over the subsequent decade. Conclusions. This rising ACO incidence rate is likely to continue into the foreseeable future. The use of EM algorithms enabled a first estimate of the BO population at risk of ACO, although, owing to the limitations imposed by the models, the age- and gender-specific ACO risk for the entire Danish BO population could not as yet be ascertained.

Some Observations on the Epidemiology of Barrett's Oesophagus and Adenocarcinoma of the Oesophagus (Doctoral Thesis)

2006-11-22T00:00:00Z