Bengt Wallner

The Esophageal Z-Line Appearance Correlates to the Prevalence of Intestinal Metaplasia

BACKGROUND Intestinal metaplasia at the gastroesophageal junction is associated with Barrett esophagus, gastric cardiac cancer, and gastritis. The aim of this study was to determine the prevalence of intestinal metaplasia among patients with symptoms suggestive of gastroesophageal reflux disease (GERD) and to study clinical, endoscopic, and histologic associations with intestinal metaplasia at the squamocolumnar junction. METHODS One hundred and eighty-six patients with symptoms indicating gastroesophageal reflux were included in the study. A new classification of the Z-line appearance was used. RESULTS The Z-line appearance was found to correlate with the prevalence of intestinal metaplasia at the squamocolumnar junction (P = 0.0001). Intestinal metaplasia at the squamocolumnar junction was found in 15.0% of the patients. There was a statistically significant association between intestinal metaplasia at the squamocolumnar junction and tongues of columnar epithelium at the Z-line (P = 0.020), intestinal metaplasia in the cardia (P = 0.020), positive CLO test (P = 0.026), smoking (P = 0.041), and age (P = 0.050). There was no association with endoscopic or histologic signs of esophagitis or with the severity or duration of GERD symptoms. CONCLUSION Intestinal metaplasia at the squamocolumnar junction correlates with the Z-line appearance, which would justify a new classification.Background: Intestinal metaplasia at the gastroesophageal junction is associated with Barrett esophagus, gastric cardiac cancer, and gastritis. The aim of this study was to determine the prevalence of intestinal metaplasia among patients with symptoms suggestive of gastroesophageal reflux disease (GERD) and to study clinical, endoscopic, and histologic associations with intestinal metaplasia at the squamocolumnar junction. Methods: One hundred and eighty-six patients with symptoms indicating gastroesophageal reflux were included in the study. A new classification of the Z-line appearance was used. Results: The Z-line appearance was found to correlate with the prevalence of intestinal metaplasia at the squamocolumnar junction (P = 0.0001). Intestinal metaplasia at the squamocolumnar junction was found in 15.0% of the patients. There was a statistically significant association between intestinal metaplasia at the squamo-columnar junction and tongues of columnar epithelium at the Z-line (P = 0.020), intestinal metaplasia in the cardia (P = 0.020), positive CLO test (P = 0.026), smoking (P = 0.041), and age (P = 0.050). There was no association with endoscopic or histologic signs of esophagitis or with the severity or duration of GERD symptoms. Conclusion: Intestinal metaplasia at the squamocolumnar junction correlates with the Z-line appearance, which would justify a new classification.

General and abdominal obesity and risk of esophageal and gastric adenocarcinoma in the European Prospective Investigation into Cancer and Nutrition

General obesity, as reflected by BMI, is an established risk factor for esophageal adenocarcinoma (EAC), a suspected risk factor for gastric cardia adenocarcinoma (GCC) and appears unrelated to gastric non‐cardia adenocarcinoma (GNCC). How abdominal obesity, as commonly measured by waist circumference (WC), relates to these cancers remains largely unexplored. Using measured anthropometric data from 391,456 individuals from the European Prospective Investigation into Cancer and Nutrition (EPIC) study and 11 years of follow‐up, we comprehensively assessed the association of anthropometric measures with risk of EAC, GCC and GNCC using multivariable proportional hazards regression. One hundred twenty‐four incident EAC, 193 GCC and 224 GNCC were accrued. After mutual adjustment, BMI was unrelated to EAC, while WC showed a strong positive association (highest vs. lowest quintile HR = 1.19; 95% CI, 0.63–2.22 and HR = 3.76; 1.72–8.22, respectively). Hip circumference (HC) was inversely related to EAC after controlling for WC, while WC remained positively associated (HR = 0.35; 0.18–0.68, and HR=4.10; 1.94‐8.63, respectively). BMI was not associated with GCC or GNCC. WC was related to higher risks of GCC after adjustment for BMI and more strongly after adjustment for HC (highest vs. lowest quintile HR = 1.91; 1.09–3.37, and HR = 2.23; 1.28–3.90, respectively). Our study demonstrates that abdominal, rather than general, obesity is an indisputable risk factor for EAC and also provides evidence for a protective effect of gluteofemoral (subcutaneous) adipose tissue in EAC. Our study further shows that general obesity is not a risk factor for GCC and GNCC, while the role of abdominal obesity in GCC needs further investigation.

Immunohistochemical markers for Barrett's esophagus and associations to esophageal Z-line appearance.

Background: Data from previous studies on intestinal metaplasia at the gastroesophageal junction have been conflicting, which makes the diagnosis of Barretts esophagus less obvious. This may partly be due to the lack of a reliable classification of the Z-line appearance. We previously proposed such a classification (the ZAP classification) that was shown to correlate with the prevalence of intestinal metaplasia. The use of different immunohistochemical techniques has increased in the study of intestinal metaplasia. In the present study our aim was to 1) evaluate the impact of different antibodies, namely cytokeratin (CK) 7, 13, and 20, CaCO3/73, and FBB2/29, in order to differentiate between Barretts esophagus and cardia intestinal metaplasia, and 2) explore the staining patterns in different ZAP grades. Methods: Thirty-nine specimens with intestinal metaplasia were compared - 9 from Barretts esophagus, 6 from cardia, and 24 from the Z-line. The Z-line specimens were evaluated with respect to ZAP grade. Results: No differences were encountered regarding staining patterns for CK13 and CaCO3/73 in Barretts esophagus and cardia. The staining pattern of CK7/20 was significantly different between Barretts esophagus and cardia. CK7/20 showed a rising frequency of Barretts esophagus staining pattern with rising ZAP grade. Conclusion: CK7/20 is a feasible marker for Barretts esophagus. Intestinal metaplasia in different ZAP grades differs regarding expression of immunohistochemical markers.BACKGROUND Data from previous studies on intestinal metaplasia at the gastroesophageal junction have been conflicting, which makes the diagnosis of Barretts esophagus less obvious. This may partly be due to the lack of a reliable classification of the Z-line appearance. We previously proposed such a classification (the ZAP classification) that was shown to correlate with the prevalence of intestinal metaplasia. The use of different immunohistochemical techniques has increased in the study of intestinal metaplasia. In the present study our aim was to 1) evaluate the impact of different antibodies, namely cytokeratin (CK) 7, 13, and 20, CaCO3/73, and FBB2/29, in order to differentiate between Barretts esophagus and cardia intestinal metaplasia, and 2) explore the staining patterns in different ZAP grades. METHODS Thirty-nine specimens with intestinal metaplasia were compared--9 from Barretts esophagus, 6 from cardia, and 24 from the Z-line. The Z-line specimens were evaluated with respect to ZAP grade. RESULTS No differences were encountered regarding staining patterns for CK13 and CaCO3/73 in Barretts esophagus and cardia. The staining pattern of CK7/20 was significantly different between Barretts esophagus and cardia. CK7/20 showed a rising frequency of Barretts esophagus staining pattern with rising ZAP grade. CONCLUSION CK7/20 is a feasible marker for Barretts esophagus. Intestinal metaplasia in different ZAP grades differs regarding expression of immunohistochemical markers.

Healthy lifestyle index and risk of gastric adenocarcinoma in the EPIC cohort study

Several modifiable lifestyle factors, including smoking, alcohol, certain dietary factors and weight are independently associated with gastric cancer (GC); however, their combined impact on GC risk is unknown. We constructed a healthy lifestyle index to investigate the joint influence of these behaviors on GC risk within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. The analysis included 461,550 participants (662 first incident GC cases) with a mean follow‐up of 11.4 years. A healthy lifestyle index was constructed, assigning 1 point for each healthy behavior related to smoking status, alcohol consumption and diet quality (represented by the Mediterranean diet) for assessing overall GC and also body mass index for cardia GC and 0 points otherwise. Risk of GC was calculated using Cox proportional hazards regression models while adjusting for relevant confounders. The highest versus lowest score in the healthy lifestyle index was associated with a significant lower risk of GC, by 51% overall (HR 0.49 95% CI 0.35, 0.70), by 77% for cardia GC (HR 0.23 95% CI 0.08, 0.68) and by 47% for noncardia GC (HR 0.53 (95% CI 0.32, 0.87), p‐trends<0.001. Population attributable risk calculations showed that 18.8% of all GC and 62.4% of cardia GC cases could have been prevented if participants in this population had followed the healthy lifestyle behaviors of this index. Adopting several healthy lifestyle behaviors including not smoking, limiting alcohol consumption, eating a healthy diet and maintaining a normal weight is associated with a large decreased risk of GC.

Tea and coffee consumption and risk of esophageal cancer: The European prospective investigation into cancer and nutrition study

Epidemiological data regarding tea and coffee consumption and risk of esophageal cancer (EC) is still inconclusive. We examined the association of tea and coffee consumption with EC risk among 442,143 men and women without cancer at baseline from 9 countries of the European Prospective Investigation into Cancer and Nutrition. Tea and coffee intakes were recorded using country‐specific validated dietary questionnaires. Cox regression models were used to analyze the relationships between tea and coffee intake and EC risk. During a mean follow‐up of 11.1 years, 339 participants developed EC, of which 142 were esophageal adenocarcinoma (EAC) and 174 were esophageal squamous cell carcinoma (ESCC). In the multivariable models, no significant associations between tea (mostly black tea), and coffee intake and risk of EC, EAC and ESCC were observed. In stratified analyses, among men coffee consumption was inversely related to ESCC (HR for comparison of extreme tertiles 0.42, 95% CI 0.20–0.88; p‐trend = 0.022), but not among women. In current smokers, a significant and inverse association was observed between ESCC risk and tea (HR 0.46, 95% CI 0.23–0.93; p‐trend = 0.053) and coffee consumption (HR 0.37, 95% CI 0.19–0.73; p‐trend = 0.011). However, no statistically significant findings were observed using the continuous variable (per 100 mL/d). These data did not show a significant association between tea and coffee consumption and EC, EAC and ESCC, although a decreased risk of ESCC among men and current smokers is suggested, but need to be confirmed in further prospective studies including more cases.

Towards a healthy stomach? Helicobacter pylori prevalence has dramatically decreased over 23 years in adults in a Swedish community

Background In Western countries the prevalence of Helicobacter pylori (H. pylori) infection may be declining but there is a lack of recent longitudinal population studies. We evaluated the changing epidemiology over a 23-year period in Sweden. Materials and methods In 1989, the validated Abdominal Symptom Questionnaire (ASQ) was mailed to a random sample of inhabitants (ages 22–80 years) in a Swedish community, and 1097 (87%) responded. H. pylori serology was analysed in a representative subsample (n = 145). Twenty-three years later, the ASQ was mailed again using similar selection criteria, and 388 out of 1036 responders had an upper endoscopy with assessment of H. pylori and corpus atrophy status. Results The prevalence of positive H. pylori serology decreased from 37.9% (1989) to 15.8% (2012), corresponding to a decrease in odds of 75% per decade (odds ratio (OR): 0.25; 95% confidence interval (CI): 0.11–0.59, p = 0.001) independent of age, gender, body mass index (BMI) and level of education, with a pattern consistent with a birth cohort effect. The prevalence increased with increasing age (p = 0.001). The prevalence of H. pylori on histology in 2012 was 11.4% (95% CI 8.6–15.0). The prevalence of corpus atrophy on serology and/or histology in 2012 was 3.2% (95% CI 1.8–5.5); all cases were ≥57 years old. Conclusion The stomach is healthier in 2012 compared with 1989. H. pylori prevalence in adults has decreased over the last two decades to a level where clinical management might be affected.

Balloon dilation of benign esophageal rings or strictures : a randomized clinical trial comparing two different inflation times

Although balloon dilatation is the primary treatment for benign dysphagia, information about the optimal inflation time is lacking. The aim of the current pilot study was to compare 10 seconds inflation time with 2 minutes inflation time, regarding the efficacy. Twenty patients with symptomatic strictures were prospectively studied in a randomized fashion. The 10-second group required an average of 1.4 dilations per patient; the 2-minute group required an average of 1.5 dilations per patient. This pilot study indicates that 10 seconds inflation time is as effective as 2 minutes. Because the treatment is both painful and unpleasant, this is an important finding.

Hill classification is superior to the axial length of a hiatal hernia for assessment of the mechanical anti-reflux barrier at the gastroesophageal junction

Background and study aims: The pathogenesis of gastroesophageal reflux disease (GERD) is multifactorial, including the mechanical anti-reflux barrier of the gastroesophageal junction. This barrier can be evaluated endoscopically in two ways: by measuring the axial length of any hiatal hernia present or by assessing the gastroesophageal flap valve. The endoscopic measurement of axial length is troublesome because of the physiological dynamics in the area. Grading the gastroesophageal flap valve is easier and has proven reproducible. The aim of the present study was to compare the two endoscopic grading methods with regard to associations with GERD. Patients and methods: Population-based subjects underwent endoscopic examination assessing the axial length of hiatus hernia, the gastroesophageal flap valve using the Hill classification, esophagitis using the Los Angeles (LA) classification, and columnar metaplasia using the Z-line appearance (ZAP) classification. Biopsies were taken from the squamocolumnar junction to assess the presence of intestinal metaplasia. Symptoms were recorded with the validated Abdominal Symptom Questionnaire. GERD was defined according to the Montreal definition. Results: In total, 334 subjects were included in the study and underwent endoscopy; 86 subjects suffered from GERD and 211 presented no symptoms or signs of GERD. Based on logistic regression, the estimated area under the curve statistic (AUC) for Hill (0.65 [95 %CI 0.59 – 0.72]) was higher than the corresponding estimate for the axial length of a hiatal hernia (0.61 [95 %CI 0.54 – 0.68]), although the difference was not statistically significant (P = 0.225). Conclusion: From our data, and in terms of association with GERD, the Hill classification was slightly stronger compared to the axial length of a hiatal hernia, but we could not verify that the Hill classification was superior as a predictor. The Hill classification may replace the axial length of a hiatal hernia in the endoscopic assessment of the mechanical anti-reflux barrier of the gastroesophageal junction.

A postfundoplication study on Z-line appearance and intestinal metaplasia in the gastroesophageal junction.

The purpose of this study was investigate the Z-line appearance by using a previously proposed classification, the ZAP classification, and to investigate the prevalence of intestinal metaplasia in the Z-line, among fundoplicated patients. Sixty patients, who had undergone fundoplication 2 to 17 years earlier, were included in the study. The prevalence of intestinal metaplasia was 20%. Intestinal metaplasia was found to be associated with age, more than 10 years of symptoms of gastroesophageal reflux disease preoperatively, tongues of columnar epithelium in the distal esophagus, carditis, and ZAP grade. ZAP grade, furthermore, was associated with male gender and more than 10 years of symptoms of gastroesophageal reflux disease preoperatively. Among patients with intestinal metaplasia, different ZAP grades can indicate different etiologic factors. Even among patients undergoing fundoplication (i.e., patients with an anatomically altered gastroesophageal junction), the ZAP classification is a feasible tool to characterize the Z-line appearance. The ZAP classification could prove valuable in selecting patients for follow-up treatment.

Identifying clinically relevant sliding hiatal hernias : a population-based endoscopy study

Abstract Objectives: The clinical relevance of small to moderate sliding hiatal hernias is controversial. The aims of the present study were to (1) investigate which symptoms are associated with sliding hiatal hernias and (2) define the length of a sliding hiatal hernia at which gastrointestinal symptoms occur. Methods: A study population representative of the general Swedish population answered a questionnaire regarding gastrointestinal symptoms and was investigated with an upper endoscopy. The length of any sliding hiatal hernia was measured. Results: Only reflux-related symptoms were associated with length of the hiatal hernia (acid regurgitation OR 1.46, CI 1.19–1.79, heartburn OR 1.27, CI 1.05–1.54), and the association did not become significant until an axial hiatal hernia length of 2 cm. Conclusions: Only reflux symptoms could be attributed to sliding hiatal hernias. Hiatal hernias less than 2 cm should be considered clinically insignificant.