As a result of hiatus hernia (HH), both the esophagogastric junction and a portion of the proximal stomach migrate through the esophageal hiatus into the posterior mediastinum. Despite the intrathoracic location of the stomach, its anatomical remains are unaltered. Sliding HH is often associated with reflux esophagitis (RE); patients with HH may also have symptoms of RE.1–3 Changes in esophageal motility are important in the pathogenesis of RE. Lower esophageal sphincter (LES) pressure, esophageal peristalsis, acid and bilirubin reflux into the esophagus, and gastric dysfunction are all considered to be important factors in HH combined with RE.4–11 The role esophageal motility plays in a barium meal examination has recently been an interesting research area.
The aim of the present study was to investigate motility changes in patients with RE and HH by using a barium meal examination, 24-hour pH and bilirubin monitoring and an esophageal manometry.12–14
Patients who had experienced persistent heartburn or acid regurgitation symptoms for at least three months were considered eligible for the study. Patients with pervious esophageal, gastric, or biliary surgery; abdominal or thoracic radiotherapy; active gastrointestinal bleeding; esophageal or fundic varice; diabetus mellitus; Zollinger-Ellison syndrome; progressive systemic sclerosis; Raynaud's syndrome or other connective tissue diseases; and neurological disorders or malignant tumors were excluded. The patients were asked to fill out a detailed questionnaire regarding the severity and frequency of four symptoms: heartburn, acid regurgitation, food regurgitation, and retrosternal pain. Each symptom was to be graded with the level of severity (0=absent, 1=mild, 2=mild to moderate, 3=moderate, 4=moderate to severe and 5=severe) and frequency (0=absent, 1=less than one day per week, 2=one day per week, 3=two to three days per week, 4=four to five days per week, and 5=almost everyday). Patients who received a total score of 12 or more were suspected of having gastroesophageal reflux disease (GERD).3 Such patient was confirmed to have HH and RE through an endoscopy and a barium meal examination.
Upper gastrointestinal endoscopy
All selected subjects underwent an examination using a classical upper gastrointestinal endoscopy. The reflux esophagitis was observed and graded according to the classical criteria of grading A-D (Los Angeles Classification System).13
Simultaneous ambulatory esophageal pH and bilirubin monitoring, and esophageal manometry data analysis
A simultaneous ambulatory 24-hour esophageal pH monitoring, an esophageal manometry (Digitrapper Mk III 2000, Synetice Medical, Sweden), and an esophageal 24 hours bilirubin monitoring (Bilitic 2000, Synetice Medical, Sweden) were performed as reported by our laboratories13 in China. The recorded data were analyzed using the Synectics PM Software.13 Pathological acid reflux was considered if the percentage of the time with the intraesophageal pH being less than four was greater than 4%, the number of reflux episodes was greater than 50 or the DeMeester value was greater than 14.72. Pathological duodenal gastroesophageal reflux (DGER) was considered if the esophageal bilirubin absorbance was less than 0.14, the percentage of the time with the intraesophageal bilirubin absorbance being less than 0.14 was greater than 2.53%. Pathological acid reflux and DGER were quantified separately with the following variables obtained for computerized analysis: the number of reflux episodes lasting longer than 5 minutes, and the percentage of time with acid reflux or duodenoesophageal reflux. The patients were allowed to go home and to carry out normal daily activities. We recorded changes in 24-hour pH and bilirubin relative to the occurrences of epigastric pain and nausea, and relative to the time of getting up in the following morning, the time of being awake, and the time of sleep consecutively. The data were to graph daily changes in pH and bilirubin for each patient.
Esophageal manometry showed that information on the LES resting pressure was collected once; the information included the length of the LES, antegrade and retrograde peristalses, and synchronous and isolated contractile waves. Peristalsis was considered to be antegrade if the duration of the interwave peak was 0.25 to 7.0 seconds, or retrograde if the duration was -0.25 to -1.0 seconds. Contractions were considered to be synchronous if the duration of the intracontraction wave was <0.25 seconds, or isolated if the contraction wave was present in any location irregularly.
Antisecretory drugs (H2 blockers or proton pump inhibitors) and prokinetics were discontinued at least 72 hours before the monitoring began.
Radiography (Philips 93D) was carried out by an experienced radiologist, who was only aware of the patients’ symptoms. The RE diagnosis was made according to Christiansen's method.11 HH was diagnosed if the gastric folds extended above the hiatus. The occurrence of barium reflux from the stomach to the esophagus was regarded. When the esophagus was fully distended with barium, the axial length of the sliding hiatus hernia was measured during a mid-swallow. Esophageal motility was evaluated for the presence or absence of nonperistaltic contractions12 and other esophageal dysfunctions.
At the end of the study, the patients were routinely evaluated as they were rotated from a supine position to a right lateral recumbent position while assessed for spontaneous gastroesophageal reflux. The radiological criteria for esophagitis included mucosal granularity or nodularity, thickened folds, inflammatory esophagogastric polyps, and ulceration. The gastroesophageal reflux types were classified as sucking, intermittent, or dump. Sucking reflux means reflux of sucking accompanied by respiration; intermittent reflux means refluxing inconsecutively; and dump reflux happens in a trendelenburg position. The clearance types were classified as passive, delayed or alternating. Passive clearance occurrs when the esophagus expands passively and then clears. Delayed clearance occurrs when barium remains within the esophagus for more than 1 minute without contractile wave. Alternating clearance occurrs when there is an alternation between antegrade and retrograde reflux.
Data were expressed as mean ± standard deviation (SD). Statistical analysis was performed using the Student's t test or χ2 test. Differences among numerical variables were assessed using the t test, and differences among categorical variables were assessed using the χ2 test. A simple pearson correlation analysis was used to establish correlations. Differences were considered to be statistically significant at P <0.05.
From October 2003 to January 2005, 55 patients with RE and HH were referred to Changhai Hospital, Second Military Medical University, Shanghai, China, and enrolled in the study. The study group comprised 29 males and 26 females; the patients’ mean age was (61.3±24.8) years. All patients’ scores from the reflux disease questionnaire were greater than 12.8% of the patients complained of heartburn, 88.9% of acid regurgitation, 75.6% of retrosternal pain, and 62.2% of food regurgitation. In the control group, there were 15 healthy subjects, comprised 9 males and 6 females, whose mean age was (28.5±10.7) years.
Upper gastrointestinal endoscopy
Endoscopic results showed that the esophageal mucosa was normal in the control group. According to the Los Angeles Classification of esophagitis, patients in the HH group were divided into two groups according to the degree of their esophagitis: (1) HH1 (grades A and B, n=30, 16 males and 14 females, mean age of (60.3±21.5) years); and (2) HH2 (grades C and D, n=25, 13 males and 12 females, mean age of (58.5±27.7) years). There was no statistically significant difference between the subgroup HH1 and HH2 with regard to distribution of age, sex, and symptom pattern.
Esophageal motility on barium meal examination
In the control group, esophageal peristalsis was smooth, and no reflux and clearance types were found. Contrarily, we assessed the spasms, constrictions, and changes in the coarseness of the mucosa as either granular or nodular in all RE patients with HH. 13.3% (4/30) of HH1 group, and 52% (13/25) of HH2 group had a small esophageal inflammatory ulcer and no esophageal strictures. Dump reflux and delayed clearance were greater in patients in the HH2 group than those in the HH1 group (P <0.05) (Table 1). In 9 patients in the HH2 group with delayed clearance, the width of the hernia sac was > 5 cm.
Ambulatory 24-hour esophageal pH monitoring
The percentages of total, supine, and upright acid exposure times were greater in patients with HH than in patients of the control group (P <0.01), but the differences between patients in the HH1 and HH2 groups were not statistically significant (Table 2).
Ambulary 24-hour esophageal bilirubin monitoring
The three-value parameters of the HH2 group were significantly higher than those of the HH1 group (P <0.05) (Table 3); those parameters were zero in the control group.
Analysis of simultaneous 24 hours esophageal pH and bilirubin monitoring
Acid reflux and DGER occurred simultaneously in 54.3% (30 of 55) of HH with RE patients, 43.3% (13 of 30) of HH1 patients, and a greater 68% (17 of 25) of HH2 patients (P <0.05). The incidence of DGER in patients with grades A, B, C, and D reflux esophagitis was 60% (18/30) in the HH1 group and 80% (20/25) in the HH2 group. The results showed that the prevalence of DGER rose with the increased severity of esophageal lesions.
The relationship between barium studies and 24 hours esophageal pH and bilirubin monitoring
24-hour pH and bilirubin monitoring were evaluated in RE, but were correlated with those on barium studies findings. Of all the patients, 54.3% (30 of 55) with simultaneously occurring acid reflux and DGER in the HH group showed that the reflux of barium from the stomach to the esophagus was regarded in the recumbent position, and 5 cases exhibited the sucking reflux in the erect position, for which the degree of esophagitis was grades C and D.
The average LES resting pressure and the length of the LES in the HH1 group ((2.10±0.86) kPa; (2.11±0.63) cm) and HH2 group ((1.81±0.93) kPa; (1.96±0.84) cm) were less than those of the control group ((3.15±0.71) kPa; (2.61±0.73) cm) (P <0.05). However, there were no differences between the two HH groups for the LESP and the length of the LES. During episodes of acid reflux in the HH groups, the percentage of antegrade peristalsis was less than that in the control group (P <0.05), but there were no differences among the percentages of retrograde peristalsis, and synchronized and isolated contractions in the two HH groups and the control group (Table 4).
The frequency and amplitude of the peristalsis and the percentage of the normal primary esophageal peristalsis were less in HH patients than in the patients of the control, and the duration of the esophageal peristalsis was longer in HH patients than in the patients of the control (P <0.05). There was no difference between the HH1 and HH2 groups (Table 5).
The relationship between barium studies and esophageal peristalses
On the barium examination, the results showed that 17 cases (4 in the HH1 group and 13 in the HH2 group) with esophageal ulcer showed esophageal dysmotility, 23.5% (4 in 17) with dump reflux, and 29.4% (5 in 17) with delayed clearance in the HH group. The result of those 17 cases showed that the frequency and amplitude of peristalsis (0.91±0.47, 3.12±1.53) were less than those of the RE patients without esophageal ulcer (1.23±0.62, 5.01±1.74) (P <0.05), the duration of esophageal peristalsis was longer than that of the RE patients without esophageal ulcer. The results of the barium studies showed that the prevalence of reflux rose and clearance delayed were correlated with that of the frequency and amplitude of peristalsis were less and the duration of esophageal peristalsis was longer with the esophageal peristalses examination.
Sliding HH is a type of diaphragmatic hernia of the esophageal hiatus. The development of RE combined with HH is related to esophageal dysmotility; decreased LES function and peristaltic disturbance of the stomach and duodenum can cause gastric acid, bile and pancreatic juices to reflux into the esophagus, and then cause esophagitis in approximately 90% of cases. The most frequent symptoms of HH with RE are retrosternal pain, heartburn, regurgitation, nausea, and vomiting.10,11 A few patients even have hemorrhage of the upper gastrointestinal tract. In the past, many patients' progressed to a precancerous Barrett's esophagus (BE), which is a pre-malignant condition of the esophagus characterized by the presence of a specialized intestinal metaplasia in the esophagus.15
Esophageal-24-hour pH and bilirubin monitoring were acknowledged as the diagnosis standards of reflux esophagitis.16,17 In our study, 24-hour esophageal pH monitoring showed that the percentages of the total, supine, and upright acid exposure time were greater in HH patients than in the patients of the control (P <0.01), and that there was no difference between the patients of the HH1 and HH2 groups. We suggest that there is no direct correlation between the degree of esophageal acid exposure and the severity of the esophagitis. Xu et al13 have suggested that unconjugated bile acid was harmful and have found that bile reflux could cause cell membrane damage and consequently, increased esophageal mucosal permeability. Nehra et al18 reported that the concentration of bile acid was found to be significantly higher in RE patients.
Many results suggest that a long-term esophageal bile exposure plays an important role in the genesis of RE rather than in the absence of gastric acid.19–24 Therefore, it is reasonable to surmise that the coexistence of DGER and acid reflux might cause more severe damage and a greater risk of promoting the development of RE. In the present study, we found that 60% of HH1 patients had DGER, 80% had concurrent DGER and acid reflux, and the parameters of DGER in the HH2 group were significantly higher than in the HH1 group. Thus, we think that the incidence of DGER is correlated with the severity of esophagitis. Our results emphasize the importance of DGER in the causing of RE, especially synergistically with acid reflux.
The LESP was much lower in the HH group than in the control group, but the difference in two HH groups was not statistically significant. This showed that LESP is an important factor in the development of RE but not correlated with the severity of esophagitis. The result was in accordance with the results of other studies.25–29 Antegrade peristalsis was the main modality of a normal esophageal peristalsis; the percentage of antegrade peristalsis of the two HH groups were much lower than that of the control group. The decrease in the percentage of antegrade peristalsis, the synchronism waves, and the frequency of peristalsis were all important factors in intraesophageal acid and bilirubin clearance delayed in HH patients. There was no significant difference in the duration of peristalsis between the HH1 and HH2 groups, suggesting that the duration was not closely related to esophageal injury. This result was also in accordance with the results of other studies.25,26,29
A dynamic observation of the esophageal mucosa outpatients with RE was carried out through a barium meal examination. Anggiansah et al25 found that primary peristalsis is the most significant acid clearance mechanism in RE patients. Cuomo et al26 found that esophageal peristalsis correlated with esophageal manometry in HH. Pan et al14 reported that esophageal dysmotility was characterized by an intermittently decreased or absent primary peristalsis in the lower half of the thoracic esophagus with or without associated nonperistaltic contractions (NPCs). A decreased primary peristalsis was characterized through the barium studies.
In our study, we showed that many morphological changes took place. The coarseness of the mucosa was very common, and esophageal spasms in the inferior segment were also frequent in the HH groups. Sucking reflux and passive clearance were also very important factors in the HH groups. The dump reflux and delayed clearance were of greater significance in patients in the HH2 group than those in the HH1 group (P <0.05). In 9 patients of the HH2 group with delayed clearance, the width of the hernia sac was >5 cm, which suggested that changes in the structure of the esophagus itself were significant in the generation of reflux. In all patients, 54.3% (30 of 55) with simultaneously occurring acid reflux and DGER in the HH groups showed that the reflux of barium from the stomach to esophagus was regarded in the recumbent position, and 5 cases exhibited a sucking reflux in the erect position, for which the degree of the esophagitis was severe. It was indicated that barium reflux may be in accordance with the results of esophageal acid reflux and DGER.
The frequency and amplitude of peristalsis and the percentage of the normal primary esophageal peristalsis were less in the HH groups than in control group. It may be considered that esophageal motility as shown through the barium studies of reflux rose and clearance delayed was correlated with that of the frequency and amplitude of peristalsis were less and the duration of esophageal peristalsis was longer with the esophageal peristalses examination. Panebianco et al30 reported in a comparison of the evaluation of esophageal motility disorders with a magnetic resonance fluoroscopy to evaluations with manometry and a barium fluoroscopy, that a barium meal examination was an useful method of esophageal motility.
In summary, acid reflux and DGER, lowered LESP, decreased frequency, and the amplitude of peristalsis may play an important role in the development of RE combined with HH. The dump reflux and delayed clearance often appear on the barium meal examination of the HH groups. Esophageal motility results on the barium examination were in accordance with the results of the 24-hour pH, bilirubin monitoring, and esophageal manometry, but the radiologic method was the simplest to use.
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