Andreas Franke

Alcohol-related diseases of the esophagus and stomach

The present review summarizes the clinically relevant effects of acute and chronic alcohol consumption on motility, mucosal inflammation and cancer of the esophagus and the stomach. Alcohol consumption results in a significant increase in the morbidity of these two organs, the most important probably being the significant increase in the development of esophageal cancer. This review refers to epidemiologic and systematic experimental data to elucidate the clinical impact of alcohol consumption as well as the underlying alcohol-induced pathophysiologic mechanisms for these esophageal and gastric diseases. Much research is still needed to clarify the effects of alcohol itself and the byproducts that result during the production of the different types of alcoholic beverages on dismotility and mucosal injury to the esophagus and stomach.

Effect of Ethanol and Some Alcoholic Beverages on Gastric Emptying in Humans

Background: There is a paucity of detailed and controlled studies on the action of ethanol and alcoholic beverages on gastric emptying in humans. This study was designed to compare the effect of beer, red wine, whisky and their comparable pure ethanol solutions on gastric emptying in a controlled and randomized investigation. Methods: On separate days, 10 healthy, fasted subjects received the following solutions, in random order, through a gastric tube: 500 mL beer, red wine, comparable pure ethanol solutions (4% and 10% v/v), glucose (5.5% and 11.4% w/v) and water, 125 mL whisky and 40% (v/v) ethanol (both followed by 125 mL water) and 250 mL water. Gastric emptying of the test solutions was assessed using ultrasonography of the antrum. Results: As measured by ultrasonography of the antrum, half emptying times of the ethanol solutions (4%, 10% and 40% v/v) were significantly (P < 0.05) longer (22.6 ± 4.8, 22.7 ± 4.3 and 27.8 ± 3.3 min, respectively, n = 10) than those of water (14.6 ± 1.9 min (500 mL) and 13.2 ± 1.7 min (250 mL), respectively). The half emptying times of beer (39.3 ± 4.3 min) and red wine (72.6 ± 7.6 min) were significantly longer than those of the corresponding ethanol concentrations, whereas whisky was emptied at nearly the same rate (26.4 ± 5.9 min) as 40% (v/v) ethanol. Emptying of glucose 5.5% and 11.4% (w/v) was significantly and dose dependently slower (29.7 ± 4.5 and 64.8 ± 8.9 min) than water. Conclusions: 1) Pure ethanol in concentrations of 4%, 10% and 40% (v/v) inhibits gastric emptying. 2) The inhibitory effect of beer and red wine, but not of whisky, is stronger than that of their comparable ethanol concentrations. 3) Caloric content and non‐alcoholic ingredients in alcoholic beverages produced by fermentation (beer and wine), but not in those produced by distillation (whisky), are most likely responsible for this effect.

Circulating fibronectin isoforms predict the degree of fibrosis in chronic hepatitis C.

Abstract Objective. Hepatic stellate cells only produce fibronectin isoforms in disease states. The isoform-defining domains can be detected in the blood circulation. This study examines whether circulating levels of fibronectin isoforms show a relationship with liver fibrosis on histology in patients with chronic hepatitis C. Material and methods. In a prospective study, 50 patients with chronic hepatitis C who underwent a liver biopsy were compared to 50 matched controls and 35 patients with other liver conditions. Results. Circulating levels of the fibronectin isoforms were significantly higher in patients with chronic hepatitis C compared to healthy controls [oncofetal fibronectin (oFN) 2.45 ± 0.17 versus 1.76 ± 0.16 mg/l, P < 0.005; extra domain-A (EDA) 1.05 ± 0.06 versus 0.86 ± 0.06 mg/l, P < 0.05; and extra domain-B (EDB) 14.55 ± 0.74 versus 9.31 ± 0.58 mg/l, P < 0.001], even though total fibronectin was lower (198.9 ± 3.5 versus 343.6 ± 14.5 mg/l, P < 0.001). A correlation with the fibrosis score was found for both oFN (r = 0.46, P < 0.005) and EDA (r = 0.51, P < 0.001). The combination of an elevation in both markers (oFN and EDA) in the upper quartile was associated with a specificity of > 99% for predicting significant fibrosis (stages 2–4) and 95% for predicting advanced fibrosis (stages 3–4). A combination of decreased values in the lowest tertile for both markers had a specificity of 94% for excluding significant fibrosis. Based on these findings, 30% of the patients scheduled for a liver biopsy could be correctly classified as having or not having significant fibrosis. The remainder would have to proceed with a biopsy. Conclusion. Circulating fibronectin isoforms produced by activated stellate cells represent a viable marker for the presence of significant fibrosis or a lack thereof.

Comparison of magnetic resonance imaging and video capsule enteroscopy in diagnosing small-bowel pathology: localization-dependent diagnostic yield.

Abstract Objective. New technology has considerably advanced the diagnosis of small-bowel pathology. However, its significance in clinical algorithms has not yet been fully assessed. The aim of the present analysis was to compare the diagnostic utility and yield of video-capsule enteroscopy (VCE) to that of magnetic resonance imaging (MRI) in patients with suspected or established Crohns disease (Group I), obscure gastrointestinal blood loss (Group II), or suspected tumors (Group III). Material and methods. Forty-six out of 182 patients who underwent both modalities were included: 21 in Group I, 20 in Group II, and five in Group III. Pathology was assessed in three predetermined sections of the small bowel (upper, middle, and lower). The McNemar and Wilcoxon tests were used for statistical analysis. Results. In Group I, lesions were found by VCE in nine of the 21 patients and by MRI in six. In five patients, both modalities showed pathology. In Group II, pathological changes were detected in 11 of the 20 patients by VCE and in eight patients by MRI. In five cases, pathology was found with both modalities. In Group III, neither modality showed small-bowel pathology. For the patient groups combined, diagnostic yield was 43% with VCE and 30% with MRI. The diagnostic yield of VCE was superior to that of MRI in the upper small bowel in both Groups I and II. Conclusion. VCE is superior to MRI for the detection of lesions related to Crohns disease or obscure gastrointestinal bleeding in the upper small bowel.

Reliability of the [13C]-acetate breath test in the measurement of gastric emptying of ethanol solutions: a methodological study

Background: The [ 13 C]‐acetate breath test is a clinically well‐established test for measuring gastric emptying of liquids and correlates significantly with scintigraphy. However, no studies have been undertaken to examine the relationship between gastric emptying measured by the [ 13 C]‐acetate breath test and ultrasonography. Furthermore, it is not known how ethanol may affect gastric emptying as measured by the [ 13 C]‐acetate breath test. This is particularly important because of the additional steps of absorption, metabolism and exhalation of the tracer involved in the [ 13 C]‐acetate breath test compared to the simple measurement of gastric emptying by ultrasonography. The aim of the present study was to examine the relationship between the gastric half emptying times measured by the [ 13 C]‐acetate breath test and by ultrasonography and to determine the effect of ethanol on the comparability between both methods. Methods: On separate days, 10 healthy, fasted randomly selected subjects received the following solutions by gastric tube: 500 mL water, 4% and 10% (v/v) ethanol, 5.5% and 11.4 % (w/v) glucose. Gastric half emptying times of the test solutions were simultaneously determined using the [ 13 C]‐acetate breath test and ultrasonography of the fundus and the antrum. Results: The gastric emptying rates determined by ultrasonography of the fundus correlated significantly with the results obtained using the [ 13 C]‐acetate breath test for all test solutions (r = 0.64–0.92, P < 0.05 for all), whereas ultrasonography of the antrum correlated significantly with the breath test only when water (r = 0.94, P = 0.001) was used. The difference between the mean half‐emptying times obtained using the [ 13 C]‐acetate breath test and ultrasonography of the fundus was 55 ± 1.8 min. This difference was significantly longer when 4% and 10% (v/v) ethanol solutions were given (61.2 ± 3.3 and 71.2 ± 2.9 min) compared to water (P < 0.05). Conclusions: A good correlation was found between gastric emptying as measured by the [ 13 C]‐acetate breath test and ultrasonography of the fundus. Measurements that were obtained using the [ 13 C]‐acetate breath test demonstrate a longer gastric half emptying time compared with those obtained using ultrasonography. This difference is even more marked when ethanol solutions are used. Presumably, this is because ethanol affects the absorption and/or the hepatic metabolism of the tracer. The [ 13 C]‐acetate breath test is therefore not a reliable gastric emptying test for comparison of different solutions, especially when ethanol‐containing liquids are used.

Duodenal infusion of different nutrients and the site of gaseous stimulation influence intestinal gas dynamics

Objective. Excessive intestinal gas can be involved in postprandial abdominal symptom generation, but whether the small bowel influences intestinal gas dynamics, depending on the ingested meal, remains to be demonstrated. We compare the intestinal response to a proximal and distal small intestinal gas challenge during different duodenal nutrient components. Material and methods. We randomly studied 32 healthy subjects, twice, on different days with a gas mixture infused at 12 ml/min either directly into the proximal jejunum or into the ileum; during duodenal lipids, amino acids, glucose, at 1 kcal/min each, or saline (n=8 for each group). Gas evacuation was monitored continuously and abdominal perception and girth changes were assessed. Results. In response to the jejunal gas challenge, duodenal lipids delayed intestinal gas clearance more potently than amino acids (733±26 ml and 541±108 ml final gas retention; p<0.001), but when gas was directly infused into the ileum the retained volumes were much smaller (271±78 ml and 96±51 ml; p<0.001). During duodenal glucose, intestinal gas clearance following jejunal or ileal gas infusion was not significantly influenced. Abdominal perception in response to the jejunal and ileal gas challenge only increased slightly during duodenal lipids (2.0±0.3 score and 2.3±0.6 score; p<0.05 versus control). Conclusion. Postprandial intestinal gas clearance is hampered by duodenal lipids and amino acids but not by glucose. Specific inhibitory effects are more pronounced when gas is infused into the jejunum, which underlines the importance of the small intestine in postprandial gas retention.

Effect of High- and Low-Caloric Mixed Liquid Meals on Intestinal Gas Dynamics

High-caloric meals can evoke postprandial abdominal complaints involving disturbances in intestinal gas balance. We aimed to determine the influence of the caloric content of meals on intestinal gas dynamics. Eight healthy subjects (five women, three men; age range, 25–43 years) underwent paired studies with low (1 kcal/min)- and high (3 kcal/min)-caloric meal infusion 35% fat, (45% carbohydrate, 20% protein) into the duodenum in random order and proximal jejunal gas infusion. Gas evacuation, perception, and abdominal girth were assessed. The low-caloric meal caused neither gas retention (–7 ± 58 ml) nor girth changes (0 ± 0 mm). In contrast, the high-caloric meal led to significant gas retention (705 ± 56 ml) and increased abdominal perimeter (7 ± 1 mm; P < 0.001 vs. the low-caloric meal for both). Thus, a high caloric load of nutrients arriving at the duodenum modulates both intestinal gas transit and abdominal perimeter.

Effect of Acute Hyperglycemia on Intestinal Gas Transit and Tolerance in Nondiabetic Humans

Background: Acute hyperglycemia usually inhibits gastrointestinal motility and hyperinsulinemia may contribute to specific inhibitory effects. However, the influences on postprandial intestinal gas dynamics have not been investigated. Aims: To compare effects of euglycemic hyperinsulinemia and acute fasting hyperglycemia on intestinal gas dynamics in nondiabetics. Methods: On 3 separate days, 10 healthy volunteers were evaluated in randomized order with duodenal glucose, intravenous glucose or saline infusion. Rectal gas evacuation was continuously measured; perception and abdominal girth changes were separately evaluated. After 60 min equilibration, proximal jejunal gas infusion (12 ml/min) was started for 150 min. Results: Acute hyperglycemia failed to cause significant intestinal gas retention (72 ± 64 ml and 53 ± 29 ml final gas retention vs. saline); in contrast, gas clearance was expedited, with a maximal effect between 30 and 105 min (p < 0.001 vs. control). Euglycemic hyperinsulinemia did not significantly influence intestinal gas clearance and no relevant changes of abdominal girth or abdominal and rectal perception were seen, as compared to control (p > 0.05 for all parameters). Conclusion: Accelerated intestinal gas clearance under hyperglycemia is one physiologic factor to avoid postprandial intestinal gas accumulation. Specific underlying mechanisms, which need further investigation, may be disturbed in symptomatic patients.

Esomeprazole reduces gastroesophageal reflux after beer consumption in healthy volunteers.

Objective. Patients with gastroesophageal reflux disease (GERD) are advised to avoid alcoholic beverages since alcohol consumption induces gastroesophageal reflux in healthy volunteers and increases it in patients with GERD. Proton-pump inhibitors (PPIs) are frequently administered for reflux symptoms but their effect on gastroesophageal reflux after alcohol consumption has not yet been fully studied. The aim of the present study was therefore to investigate the effect of esomeprazole, an S-enantiomer of omeprazole, on gastroesophageal reflux after beer consumption. Material and methods. In this placebo-controlled, double-blind, crossover study, 16 healthy male volunteers received 20 mg esomeprazole daily for one week. On day 7, in an acute experiment, the subjects then consumed 500 ml beer within 5 min. Subsequently, gastroesophageal reflux was monitored by pH-metry over a period of 3 h. In addition, gastric emptying was measured by ultrasonography and blood concentrations of ethanol, cholecystokinin and gastrin were determined. Results. Gastroesophageal reflux was significantly (p=0.001) reduced by 93% after treatment with esomeprazole (0.2%, median percentage of time pH<4) as compared to placebo (2.6%), but gastric emptying, blood ethanol and cholecystokinin concentrations were not significantly different after esomeprazole treatment. Plasma gastrin levels were significantly (p=0.0003) higher after esomeprazole (98.6±19.7 pg/ml) than after placebo (22.7±3.8 pg/ml) before beer consumption. However, there was no difference in the increase in plasma gastrin after beer consumption between the esomeprazole treatment and placebo. Conclusions. Esomeprazole significantly reduces gastroesophageal reflux after beer consumption in healthy volunteers. Gastric emptying of beer is not prolonged after treatment with esomeprazole, although compared with placebo, this PPI induced significantly higher plasma gastrin concentrations. Moderate alcohol consumption does not worsen gastroesophageal reflux when a PPI is administered.

Role of the jejunum versus ileum on intestinal gas dynamics during a balanced meal in healthy subjects.

Under physiological conditions, the human gut adapts intestinal gas propulsion and evacuation to prevent intestinal gaseous complaints In this study we aimed to determine influences of the jejunum versus ileum on intestinal gas dynamics during a balanced meal. Paired studies were randomly performed with seven women and three men, ages 28–42. A mixed liquid meal was infused (1 kcal/min) into the duodenum. After 30 min, gas was infused (12 ml/min) into the jejunum or ileum for 150 min. Gas expulsion was measured, and perception and girth changes were assessed. Postprandial intestinal gas propulsion was uneventful and recovery complete, with −7± 58 and −92± 44 ml final intestinal gas retention for jejunal and ileal gas infusion, respectively. Neither significant differences in abdominal perception nor changes in abdominal girth were seen. During a balanced meal, intestinal gas is effectively propulsed aborally, and this does not depend on the site of the small intestinal stimulation.