Relationship between straining, transient lower esophageal sphincter relaxation, and gastroesophageal reflux in children

OBJECTIVE: Physical straining such as deep inspiration or coughing may induce gastroesophageal reflux (GER) by overcoming feeble lower esophageal sphincter (LES) pressure. The role of straining as a provocant of GER has not been analyzed systematically in children. It was our aim to examine the contribution of straining to the occurrence of GER with particular attention to its relationship to transient LES relaxations, which are a major mechanism of the occurrence of GER in pediatric patients. METHODS: Concurrent esophageal manometry and pH monitoring was performed for 4 h postprandially in six children with esophagitis (age 9 months to 12 yr). Analysis was performed on isolated single strain episodes, defined as an increased intragastric pressure > 10 mm Hg. When a drop of esophageal pH < 4.0 was noted within 15 sec after any part of a strain, this strain was defined as related to the reflux episode. RESULTS: The median value of basal LES pressure was 10 mm Hg (range 1-18). In all, 134 analyzable strains and 87 analyzable reflux episodes were recorded. Isolated strains were associated with 20 reflux episodes (23%). Reflux was observed more frequently with strains that occurred during transient LES relaxations (12/40) than straining when the LES was contracted (8/94) (p < 0.01). Sustained strain (35%) and inspiratory strain (25%) were the major patterns of straining related to reflux. CONCLUSION: Straining provoked reflux infrequently and simultaneous occurrence of straining and transient LES relaxation was important in determining the occurrence of strain-related reflux in pediatric patients with reflux esophagitis.     

胆碱能神经对反流性食管炎食管动力的影响

目的研究内源性胆碱能神经在反流性食管炎食管动力机制异常中的作用.方法经下食管括约肌切开制备反流性食管炎的猫模型,用连续水灌注测压系统检测正常猫及反流性食管炎的猫食管体部动力;用分光光度法分别测定正常猫及反流性食管炎的猫食管中段、远段肌组织中的乙酰胆碱转移酶和乙酰胆碱酯酶活力.结果反流性食管炎组食管远段平均收缩波幅度明显低于正常对照组(P＜0.0001),食管远段传导速度低于正常对照组(P＜0.05);反流性食管炎时食管中段及远段肌组织中乙酰胆碱转移酶活力均低于正常对照组的中段及远段(P＜0.05及P＜0.0001),以远段更明显(P＜0.0001).反流性食管炎组食管中段及远段肌组织中的乙酰胆碱酯酶活力与对照组比较差异均无显著性(P＞0.05).结论反流性食管炎可导致食管远段动力低下,内源性胆碱能神经功能异常是其重要机制之一.     

Lower esophageal sphincter reacts against intraabdominal pressure in children with symptoms of gastroesophageal reflux

Studies of the effect of increased intraabdominal pressure on the lower esophageal sphincter (LES) are controversial. This study aimed to verify the LES competence against extrinsic abdominal compression in children with and without symptoms of gastroesophageal reflux (GER). Eighteen children ages 6–20 months were evaluated, 11 of them with symptoms of GER (group I) and 7 without symptoms of GER (group II). Manometry of the esophagus, LES, and stomach was performed in all children who underwent extrinsic abdominal compressions of 20, 40, 60, and 80 mm Hg. The pressure gradients in the esophagus, LES, and stomach were measured. The pressure gradient showed a significant difference only in the esophagus after extrinsic abdominal compressions of 60 mm Hg [group I median (range): 7.6mm Hg (2.7–20.0) vs group II: 2.8 mm Hg (1.4–9.6), P < 0.05], and 80 mm Hg [group I median (range): 7.7 mm Hg (3.7–28.9) vs group II: 3.8 mm Hg (1.2–21.1), P < 0.05]. It was concluded that the competence of LES to contain increased intraabdominal pressure might be an important factor in the pathophysiology of GER in children.     

应用食管气囊扩张法建立胃食管反流病动物模型研究

目的探讨应用微创方法建立胃食管反流病动物模型的可行性。方法对10只新西兰兔实施食管气囊扩张术,气囊中部定位于胃食管交界处,压力为10Psi（1Psi=6．89kPa）,维持10min,扩张2次,每次间隔3min,以建立胃食管反流病动物模型。实验动物在扩张前1周及扩张后1周行食管测压及食管下段pH值检测,对扩张前后的食管压力及胃食管反流进行比较。对气囊扩张后实验兔的食管进行病理检查并与正常食管进行比较。结果气囊扩张前后食管下括约肌的压力分别为（11．2±1．56）mmHg与（7．89±2．99）mmHg,两者差异有统计学意义（t=3．67,P=0．006）。扩张前后的反流率分别为（1．07±0．93）％与（9．36±7．79）％,两者差异有统计学意义（t=3．10,P=0．015）。病理结果示扩张后食管有明显的病理改变。术后6只动物出现明显的反流,造模的成功率为60％。结论食管气囊扩张法是一种新的、简单可靠和微创的建立胃食管反流病动物模型的方法。     

High vasoactive intestinal polypeptide plasma levels in patients with Barrett's esophagus

We have evaluated the correlation between vasoactive intestinal polypeptide (VIP) plasma concentration and severity of gastroesophageal reflux in patients with Barrett's esophagus and the possible differences in the VIP values of these patients compared with healthy volunteers. We also evaluated the relation between VIP plasma concentration and lower esophageal sphincter (LES) pressure in 24 patients with Barrett's esophagus. The mean VIP plasma concentration in 14 patients with severe gastroesophageal reflux was 25.6 +/- 0.75 pg/ml, significantly higher than the mean value observed in 10 patients with moderate reflux (18.9 +/- 0.67 pg/ml) (p less than 0.01). The mean LES resting pressure was significantly lower in the group of patients with severe gastroesophageal reflux than that observed in patients with moderate reflux (3 +/- 0.64 and 10.3 +/- 0.69 mm Hg, respectively; p less than 0.01). The mean VIP plasma concentration in 11 healthy volunteers (20.6 +/- 0.65 pg/ml) was significantly lower than the mean value observed in the subgroup of patients with severe gastroesophageal reflux (p less than 0.01). VIP values in patients with moderate reflux were not significantly different from those observed in our volunteers. There was a significant correlation between LES pressure and VIP plasma level (r = -0.9253; p less than 0.01). In conclusion, it is possible that the decreased LES resting pressure observed in patients with Barrett's esophagus and severe gastroesophageal reflux may be due to impairment of the VIPergic innervation, resulting in an increased local VIP release with possible overflow to peripheral plasma.     

Clinical and manometric findings in benign peptic strictures of the esophagus

To determine the possible factors that may contribute to the development of peptic stricture of the esophagus, clinical and manometric features were compared in patients with symptomatic gastroesophageal reflux and those with peptic strictures of the esophagus. Patients with stricture were older and had a longer duration of heartburn than patients without a stricture. Most importantly, patients with stricture had a more marked decrease in lower esophageal sphincter (LES) pressure, 4.9±0.5 mm Hg, than patients without a stricture, 7.5±0.6 mm Hg, P<0.01. The LES pressure in all patients with stricture was below 8 mm Hg, and did not overlap with normal values. Patients with stricture had either a nonspecific motor abnormality or aperistalsis (64%), compared to patients with symptomatic reflux (32%), P<0.05. Thus, peptic stricture of the esophagus is commonly associated with a long duration of reflux symptoms in patients with a very low LES pressure and esophageal motor disorder.     

Inversed Y cardioplasty plus a truncal vagotomy‐antrectomy and a Roux‐en‐Y gastrojejunostomy performed in patients with stricture of the esophagogastric junction after a failed cardiomyotomy or endoscopic procedure in patients with achalasia of the esophagus

Laparoscopic anterior cardiomyotomy in addition to anterior Dor's fundoplication is the procedure of choice for achalasia of the esophagus with approximately 95% success rate. Redo cardiomyotomy is complicated and associated with rerecurrence of dysphagia. Twelve patients with failed redo myotomy were clinically evaluated with radiology, endoscopy, and manometry in whom achalasia type III or IV was confirmed. We propose as treatment for these selected cases an inversed Y cardioplasty + truncal vagotomy, a partial distal gastrectomy and Roux‐en‐Y gastrojejunostomy in order to facilitate esophageal emptying and avoid the appearance of postoperative gastroesophageal reflux as a side effect of this procedure. One patient was reoperated on in order to enlarge the cardioplasty. Disappearance of dysphagia was confirmed in all patients. Three patients presented reflux symptoms and were treated with 20 mg of Omeprazole 20 twice/day. No food retention, erosive esophagitis, or Barrett's esophagus were observed. The mean resting pressure decreased from 24.9 ± 8.5 mm Hg to 7.5 ± 2.5 mm Hg (P = 0.0001). Furthermore, esophageal diameter decreased significantly after a 5‐year follow‐up. This procedure could be an option for treating patients in which repeated Heller operations have failed.     

Antireflux surgery for symptomatic gastroesophageal reflux

To determine the effects of Nissen fundoplication upon the symptoms of reflux and the diagnostic tests employed to evaluate reflux and to examine the relationship between gastroesophageal reflux and lower esophageal sphincter pressure before and after fundoplication, 10 patients with symptomatic reflux were studied before and after operation. Clinical evaluation, barium esophagography, endoscopy with mucosal biopsy, esophageal manometry, acid-perfusion and acid-reflux testing, and gastroesophageal scintiscanning were performed on each patient before and after surgery. Following fundoplication, marked symptomatic, radiographic, endoscopic, and histologic improvement was observed. Serial acid-reflux tests at increasing gastroesophageal pressure gradients returned to normal after surgery. Lower-esophageal-sphincter (LES) pressure increased from 8.2±1.3 to 12.0±1.5 mm Hg (P<0.01). In addition, surgery resulted in a significant decrease in the gastroesophageal reflux index from 17.4±2.4 to 2.7±1.1% (P<0.001). Surprisingly, the pre- and postoperative resting LES pressures did not correlate significantly with corresponding gastroesophageal reflux indices for individual patients. We conclude that increased LES pressure alone does not explain adequately the functional and clinical improvement which follows fundoplication.     

正常人和胃食管反流病人的昼夜食管pH和动力变化

目的:为探讨正常人和胃食管反流病(gastroesophageal reflux disease,GERD)病人昼夜食管运动规律以及食管运动与酸反流的关系。方法:45例GERD病人和10名正常人均接受食管测压和动态食管pH及压力同步监测。结果:(1)下食管括约肌压、远端食管蠕动压及有效食管蠕动百分比在酸反流DeMeester高计分组明显低于低计分组(P<0.05),在反流性食管炎组也明显低于非反流性食管炎组(P<0.05)。(2)有GERD症状或食管炎的卧位有效蠕动百分比明显低于立位(P<0.05)。反流性食管炎组80％有夜间或伴有夜间反流,而不伴反流性食管炎的GERD无1例出现夜间反流。结论:昼夜食管pH和压力动态监测有利于进一步探讨GERD的运动病理,除LES功能外,食管清除功能在GERD发病中起重要作用。     

Surgical treatment of the non-complicated gastroesophageal reflux: fundoplication without division of the short gastric vessels

BACKGROUND: There is today a significant greater number of laparoscopic antireflux procedures for the surgical treatment of gastroesophageal reflux disease and there are yet controversies about the necessity of division of the short gastric vessels and full mobilization of the gastric fundus to perform an adequate fundoplication. AIM: To verify the results of the surgical treatment of non-complicated gastroesophageal reflux disease performing Rossetti modification of the Nissen fundoplication. Patients and Methods - Fourteen patients were operated consecutively and prospectively (mean age 44.07 years); all had erosive esophagitis without Barrett's endoscopic signals (grade 3, Savary-Miller) and they were submitted to the Rossetti modification of the Nissen fundoplication. Endoscopy, esophageal manometry and pHmetry were performed before the procedure and around 18 months postoperatively. RESULTS: There was no morbidity, transient dysphagia average was 18.42 days; there was no register of dehiscence or displacement of the fundoplication and only one patient revealed a light esophagitis at postoperative endoscopy; the others presented a normal endoscopic view of the distal esophagus. All noticed a marked improvement of preoperative symptoms. Lower esophageal sphincter pressure changed from 5.82 mm Hg (preoperative mean) to 12 mm Hg (postoperative mean); lower esophageal sphincter relaxing pressure, from 0.38 mm Hg to 5.24 mm Hg and DeMeester score, from 16.75 to 0.8. CONCLUSION: Rossetti procedure (fundoplication without division of the short gastric vessels) is an effective surgical method to treat gastroesophageal reflux disease.     

Acid-induced esophageal shortening in humans: a cause of hiatus hernia?

BACKGROUND: Hiatus hernia and gastroesophageal reflux disease commonly coexist, and there is pathophysiological evidence that the presence of a hiatus hernia contributes to abnormal acid reflux. However, the cause of hiatus hernia remains unclear. In an animal model, it has been shown that acute acid injury to the esophagus results in esophageal shortening, raising the possibility that reflux esophagitis per se can contribute to the formation of hiatus hernia by inducing esophageal shortening. AIM: To determine whether luminal acid produces esophageal shortening in humans. METHODS: Twelve volunteers were each studied on two occasions, one week apart, in a double-blind, crossover trial. The location of the lower esophageal sphincter (LES), as well as the LES resting pressure and axial length were determined at baseline and then again after 20 min of either acid or saline perfusion. RESULTS: Acid perfusion did not induce significant changes in resting LES pressure but resulted in proximal migration of the LES (ie, esophageal shortening) by an average of 0.5 cm, with the largest proximal migration being 1.8 cm. In contrast, saline perfusion resulted in slight distal migration of the LES (ie, esophageal lengthening). CONCLUSIONS: Intraluminal acid perfusion causes longitudinal axis shortening of the esophagus and suggests that gastroesophageal acid reflux may contribute to the cause of hiatus hernia.     

Lower esophageal sphincter pressure as an index of gastroesophageal acid reflux

The purpose of this study was to determine the relationship of lower esophageal sphincter (LES) pressure and the volume of acid placed into the stomach required to induce gastroesophageal reflux in man. LES pressure was recorded continuously and by station pull-through by three radially oriented catheters in both symptomatic and asymptomatic subjects during the graded infusions of 0.1 N HCl acid into the stomach. Sumptomatic subjects had a mean LES pressure of 7.5±0.7 mm Hg and refluxed at a volume of 140.0±21.0 ml. Fifty-five percent of asymptomatic subjects refluxed at a mean volume of 380.0±24.7 ml, and had a mean LES pressure of 13.8±0.4 mm Hg. Asymptomatic nonrefluxers at a volume of 500 ml of 0.1 HCL acid had a mean LES pressure of 18.9±1.1 mm Hg. The mean LES pressure and acid volumes showed statistical significance between the three groups (P<0.01). There was an excellent overall correlation between LES pressure and acid volume required to produce reflux in all subjects (r=0.91,P<0.001). Following reflux, asymptomatic but not symptomatic subjects showed a significant increase in LES pressure. These studies suggest that: (1) LES pressure does provide an accurate index of the gastroesophageal antireflux mechanism, provided that acid volume is considered; and (2) asymptomatic subjects showing acid reflux have higher LES pressures, reflux at higher volumes, and develop an LES contractile response after the reflux episode.This work was supported by a grant from the Smith Kline & French Laboratories, Philadelphia, Pennsylvania.     

Factors that influence induction of gastroesophageal reflux in normal human subjects

Findings from recent studies indicate that transient relaxation of the lower esophageal sphincter (LES) is an important contributory mechanism to spontaneous episodes of gastroesophageal reflux (GER) in normal subjects as well as in patients with reflux esophagitis. Our study aim was to evaluate the interrelationship between reduction of LES pressure and elevation of intraabdominal pressure in the induction of GER in healthy subjects. Seven volunteers were studied supine after gastric loading with 0.1 N HCl. A pH probe recorded acid GER. Leg raising (LR) or abdominal compression (AC) were used as stress maneuvers to increase intraabdominal pressure, either alone or in combination with stimuli that concurrently lowered LES pressure, namely multiple rapid swallows (RS) or intraesophageal balloon distention (BD). Each individual stimulus and stimulus combination was tested three times, giving a total of 24 test maneuvers per subject. The test maneuvers elicited 2-12 GERs in each subject. The GER incidence for single maneuvers was: AC, 0%; LR, 0%; RS, 19%; and BD, 24%. LR in combination with RS or BD did not increase the incidence of GER above that induced by RS or BD alone. In contrast, AC concurrent with RS and BD increased the incidence of GER to 52% and 81%, respectively. For all test conditions, a prerequisite for the occurrence of GER was a fall in LES pressure to a minimal value of 3 mm Hg or less. GER never occurred when LES pressure was greater than or equal to 4 mm Hg, even during intervals of increased intraabdominal pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Correlation of esophageal pH and motor abnormalities with endoscopic severity of reflux esophagitis

Motility abnormalities, common in gastroesophageal reflux disease, are likely to be related to endoscopic esophagitis. We studied pH and manometry parameters in relation to the severity of esophagitis. Forty-seven patients with symptomatic gastroesophageal reflux disease for > 3 months were evaluated by: (i) endoscopy (grading of esophagitis by Savary-Miller classification); (ii) mucosal biopsy; (iii) manometry; and (iv) 24-h pH-metry. We found Savary-Miller's grades of: 0 (9 patients out of 47), I (16/47), II (16/47), III (4/47), IV (2/47). Distal esophageal contraction amplitude was lower in severe (grade II to IV) as compared with mild (grade 0 and I) esophagitis (49 [7-182] versus 83 [27-196] mmHg [P = 0.001]). The length and pressure in the lower esophageal sphincter (LES), duration and velocity of contraction in the body, number of episodes of reflux and long-duration reflux, longest reflux, median pH, per cent of time with pH < 4 and DeMeester scores were not significantly different between the two groups. The area under pH 4 showed a negative correlation with LES pressure and amplitude of distal esophageal contractions. We conclude that higher endoscopic grades of esophagitis are associated with lower amplitude of contraction in distal esophagus. Lower LES pressure and distal esophageal contraction amplitude are associated with greater area under curve for pH below 4.     

Is Barrett's esophagus characterized by more pronounced acid reflux than severe esophagitis?

Objective: Barrett's esophagus is related to gastroesophageal reflux disease (GERD). However, only a small fraction of patients with GERD develop Barrett's esophagus. We evaluated whether gastroesophageal acid reflux is more pronounced in Barrett's patients than in patients with moderate or severe endoscopic esophagitis.
Methods: Retrospective evaluation of results of esophageal manometry and 24 hour ambulatory pH monitoring performed between 1990 and 1996 at the Leiden University Medical Center in those patients who also underwent endoscopy ≤3 months before pH-metry. Included were 51 patients with Barrett's esophagus, 30 patients with severe esophagitis, 45 patients with moderate esophagitis, and 24 healthy control subjects.
Results: Patients with Barrett's esophagus had significantly increased acid reflux time (   p < 0.01  –0.05) compared to patients with moderate, but not compared to patients with severe esophagitis. Distal esophageal body motility and LES pressure were significantly (   p < 0.01  –0.05) reduced in patients with Barrett's esophagus compared to patients with moderate esophagitis but not compared to those with severe esophagitis.
Conclusion: Although acid reflux is increased in patients with Barrett's esophagus and esophageal motility is impaired, other factors apart from acid exposure and motility contribute to the development of Barrett's esophagus.     

Asymmetrical circumferential distribution of esophagogastric junctional lesions: anatomical and physiological considerations

Several components of the gastrointestinal tract including the esophagogastric junction (EGJ) show circumferential asymmetry in the formation of pathological lesions, which is caused by the morphological and functional asymmetry of the gastrointestinal tract. Pressure in the lower esophageal sphincter (LES) is higher on the left posterior side as compared to the right anterior side, which may partly explain why Mallory–Weiss tears frequently occur on the right side wall of the EGJ. Lower LES pressure in the right anterior wall may not effectively prevent gastroesophageal reflux on this side and may be a reason why esophageal erosions in patients with reflux esophagitis, short segment Barrett’s esophagus, and adenocarcinomas associated with short segment Barrett’s esophagus are frequently found in the right anterior wall of the esophagus. In addition, acidic gastroesophageal reflux may also cause rupture of esophageal varices predominantly on that side. Thus, asymmetrical LES pressure may be a cause of the right anterior side predominance of diseases found in this part of the gastrointestinal tract.     

Transient Lower Esophageal Sphincter Relaxations and Esophageal Body Muscular Contractile Response in Reflux Esophagitis

In patients with gastroesophageal reflux disease (GERD), transient lower esophageal sphincter relaxations (TLESRs) are more frequently accompanied by acid reflux than in normals. The role of esophageal tone during gastroesophageal reflux events is unknown. We studied the tonic motor activity in the body of the esophagus during TLESRs with and without acid reflux in 11 patients with erosive esophagitis and compared the results with those previously obtained in healthy subjects. Esophageal peristaltic contractions were recorded 13, 8, and 3 cm above a sleeve that measured LES pressure. An intraluminal balloon was inflated 8 cm above the sleeve to induce an esophageal tonic contraction [artificial high pressure zone (HPZ)]. The percentage of TLESRs with acid reflux was significantly higher in patients with esophagitis than in healthy controls (58.3% vs 37.3%, P < 0.05). TLESRs per se were not associated with an inhibition or increase in esophageal body contractility, which, however, changed substantially immediately after reflux. In patients with esophagitis the esophageal body tonic contractility was inhibited in 59.5% of TLESRs vs 36% in controls (P < 0.05). Esophageal contractions during TLESRs traveled down the esophagus in 77% of the instances in patients vs 96.5% in controls (P < 0.05). In conclusion, gastroesophageal reflux during TLESRs was more frequently associated with inhibition of esophageal body tonic contractility in patients with esophagitis than in normals. The different response of the esophageal body to reflux observed in GERD patients may partially contribute to the higher prevalence of reflux during TLESRs in these patients.     

Comparison of esophageal acid exposure distribution along the esophagus among the different gastroesophageal reflux disease (GERD) groups

BACKGROUND: Patients with nonerosive reflux disease (NERD) have the lowest esophageal acid exposure profile compared with the other gastroesophageal reflux disease (GERD) groups. AIM: To compare lower esophageal acid exposure recordings 1 cm above the lower esophageal sphincter (LES) with those 6 cm above the LES as well as to determine the characteristics of esophageal acid exposure along the esophagus among the different GERD groups. METHODS: Patients with classic heartburn symptoms were enrolled into the study. Patients were evaluated by a demographics questionnaire and the validated GERD Symptom Checklist. Upper endoscopy was performed to evaluate the presence of esophageal erosions and Barrett's esophagus (BE). Ambulatory pH testing was performed using a commercially available 4-sensor pH probe with sensors located 5 cm apart. The distal sensor was placed 1 cm above the LES. RESULTS: Sixty-four patients completed the study. Of those, 21 patients had NERD, 20 had erosive esophagitis (EE), and 23 had BE. All patient groups demonstrated greater esophageal acid exposure 1 cm above the LES than 6 cm above the LES. In NERD and EE, this phenomenon was primarily a result of a higher mean percentage of upright time with pH <4. Unlike patients with EE and BE, those with NERD had very little variation in esophageal acid exposure throughout the esophagus (total and supine). CONCLUSIONS: ALL GERD groups demonstrated significant greater esophageal acid exposure at the very distal portion of the esophagus, primarily as a result of short upright reflux events. Unlike erosive esophagitis and BE, NERD patients demonstrate a more homogenous acid distribution along the esophagus.     

Influence of surgically induced gastric and gastroduodenal content reflux on esophageal carcinogenesis – experimental model in Wistar female rats

Studies in human beings and animals have shown that esophageal exposure to duodenal and gastric contents may be important for the development of Barrett's esophagus and its complications, including adenocarcinoma and epidermoid carcinoma. Diethylnitrosamine (DEN) is a carcinogen that stimulates the development of epidermoid carcinoma in the esophagus of mice. The aim of this study was to evaluate the effect of gastroduodenal and gastric content reflux on induction of esophageal carcinogenesis. Gastroesophageal reflux (GER) and gastroduodenoesophageal reflux (GDER) were produced by cardioplasty and esophagoduodenostomy. The chosen carcinogen was DEN, diluted in drinking water, given 3 days a week for 20 consecutive weeks. One hundred Wistar female rats were divided into six groups, as follows: group 1 (18 rats), cardioplasty without DEN; group 2 (18 rats), cardioplasty with DEN; group 3 (10 rats), only water; group 4 (17 rats), cardioplasty with DEN; group 5 (17 rats), esophagoduodenostomy with DEN; group 6 (20 rats), only DEN. GER in isolation induced papillomatosis or ulceration in 22.2% of rats and, when associated with DEN, induced papillomatosis in 61.1% of rats. GDER in isolation induced marked esophagitis in 61.1% of rats, Barrett's esophagus in 16.7% and esophageal adenocarcinoma in 16.7%; when associated with DEN, 23.5% of rats presented marked esophagitis, papillomatosis or ulceration, whereas 76.5% had esophageal carcinoma, with 70.6% epidermoid carcinoma and 5.9% adenocarcinoma. Rats treated with water alone did not show histologic abnormalities of the esophageal mucosa. Rats treated with DEN alone developed papillomas in 50.0% of the cases and remained histologically unchanged in 50.0%. There was no development of low- or high-grade dysplasia in any group. The conclusions are that (1) GDER is significantly more deleterious to esophageal mucosa than GER; (2) in this study, GER did not present carcinogenic potential in relation to the esophagus; (3) GDER in isolation is an esophageal carcinogen, producing Barrett's esophagus and esophageal adenocarcinoma; (4) esophageal oncogenesis caused by GDER is potentiated by DEN, inducing esophageal epidermoid carcinoma; (5) in this study, DEN in isolation did not generate tumors in the esophagus of rats.     

The prevalence of Helicobacter pylori infection and the status of gastric acid secretion in patients with Barrett's esophagus in Japan

OBJECTIVES: The acidity of the refluxate into the esophagus is a key factor for the pathogenesis of gastroesophageal reflux disease. Helicobacter pylori (H. pylori) infection can influence gastric acid secretion. We have reported that H. pylori infection prevents reflux esophagitis by decreasing gastric acid secretion in Japanese patients, but the role of this organism in Barrett's esophagus is unclear. The aim of this study was to investigate the prevalence of H. pylori infection and gastric acid secretion in Japanese patients with reflux esophagitis with or without Barrett's esophagus. METHODS: We enrolled 112 reflux esophagitis patients who were examined for the status of H. pylori and acid secretion in this study. They were divided into three groups, according to the presence or absence of Barrett's esophagus as follows: reflux esophagitis group without Barrett's esophagus (reflux esophagitis alone) (80 patients); short-segment Barrett's esophagus group (16 patients); and long-segment Barrett's esophagus group (LSBE) (16 patients). Age- and sex-matched control subjects were also assigned to the 80 patients with reflux esophagitis alone. The prevalence of H. pylori infection was determined by histology, rapid urease tests, and serum IgG antibodies. Gastric acid secretion was evaluated by the endoscopic gastrin test (EGT). RESULTS: The overall prevalence of H. pylori infection in the reflux esophagitis patient group (24.1%) was significantly lower than the control group (71.2%) (odds ratio 0.13, 95% confidence interval 0.07-0.24; p < 0.0001). The prevalence of H. pylori infection in the patients with Barrett's esophagus tended to be lower than that in the patients with reflux esophagitis alone (reflux esophagitis alone; 30.0%, SSBE; 18.7%, LSBE; 0%), especially in the patients with LSBE compared with the reflux esophagitis alone group (p < 0.01). The EGT value of the respective reflux esophagitis patient group was significantly higher than the control group. The EGT value in the patients with Barrett's esophagus tended to be higher than that in the patients with reflux esophagitis alone, but the difference was not statistically significant. When examined in H. pylori-negative subjects, no difference was found in the EGT value between the control subjects and the patients with reflux esophagitis alone, but it was significantly higher in patients with Barrett's esophagus than the control subjects (p < 0.05). On the other hand, when examined in the H. pylori-positive subjects, the EGT value was significantly higher in the patients with reflux esophagitis alone than in the control subjects (p < 0.01). CONCLUSIONS: H. pylori infection may play a protective role in the development of Barrett's esophagus, especially in the development of LSBE in Japan. Gastric acid hypersecretion may be concerned with the development of Barrett's esophagus in addition to the absence of H. pylori infection.