INDEX
EFFECT OF CHOLECYSTECTOMY ON DUODENOGASTRIC REFLUX, GASTRIC MUCOSA AND SERUM GASTRIN LEVEL
Atilla Soran, MD
Nilufer Erverdi, MD
Cavit Col, MD
Kessaf Aslar, MD
Mukerrem Cete, MD
Suleyman Hengirmen, MD
Ankara Numune Teaching and Research Hospital, Ankara 06100, Turkey
Running Title: Reflux after cholecystectomy
Key words: cholecystectomy, reflux, gastrin
Address: Atilla Soran, MD
Birlik Mah.7.Cad. Yesil Cankaya Sitesi B/17
Cankaya, 06610 Ankara, Turkey
Fax: 90 312 3103460
Tel: 90 312 4951304
E.Mail: asoran@mailcity.com
Total number of pages and tables: 12
SUMMARY
Cholecystectomy is associated with an increase in the incidence of gastritis and may contribute to the post-cholecystectomy syndrome. In this prospective study we evaluated of the relationship of duodenogastric reflux (DGR) with gastric mucosal changes, serum gastrin level and dyspeptic symptomis in cholecystomized patients. Gastritis rate was 31 times more in DGR (+) when compared with DGR (-) patients, and gastritis rate is 24 times more in patients with dyspeptic symptoms than patients without. But there was no difference between serum gastrin levels of the groups according to DGR, gastritis and dyspeptic symptoms (p>0.05). Therefore, this prospective study suggests that excessive DGR may be responsible for persistence of symptoms after cholecystectomy by causing gastric mucosal damage.
INTRODUCTION
Patients underwent cholecystectomy for symptomatic gallstone may have still dyspeptic symptoms. Gastric mucosal changes related to duodenogastric reflux (DGR) are accused for this if other gastrointestinal pathologic lesions are eliminated (1). Gastric alkaline episodes after cholecystectomy especially in symptomatic patients is suggested to be related with these symptoms (2,3).
The aim of this prospective study was to investigate the rates of DGR, gastric mucosal changes and dyspeptic symptomis in cholecystomized patients. The change in preoperative and postoperative serum gastrin levels and the relation between DGR and gastric mucosal changes with dyspeptic symptoma are also evaluated.
MATERIALS AND METHODS
Forty patients operated for uncomplicated gallstone in Ankara Numune Teaching and Research Hospital General Surgery Department were included in the study. Ultrasonography was the main diagnostic tool. Patients with common bile duct stones, previous gastric surgery and a history of any type of pathology of digestive tract were not included in the study. The ones who have reasons to evaluate serum gastrin levels were also excluded. Mean age of the patients was 51 years (range 21-82 years; 2 male and 38 female). Preoperatively besides routine laboratory examinations, oesefagogastroduedenoscopy (OGD) was performed and multiple biopsies obtained from antrum of the stomach without macroscopic recognized pathology. Biopsy speicmens were fixed in buffered 12 hours formalin embedded in paraffin and stained with hematoxylin and eosin. These sections wee examined by a pathologist, who was not informed of the endoscopic diagnosis. Fasting serum gastrin levels were measured by using ﾒGammaDab gastrin I RIA kit from INCSTAR Minnesota, USAﾓ. Two years after the operation endoscopy and antral biopsies were repeated and fasting serum gastrin levels were measured. Furthermore, abdominal ultrasound was done to evaluate the biliary system. Dyspeptic symptoms were defined as epigastric pain and burns upset, belch problems, gastric distension, fullness, nausea and bilious vomiting.
Statystical analyses were done by using Mann Whitney U and Fisher Exact tests.
RESULTS
Presence of large amounts of bile was associated with abnormal appearance of gastric mucosa during endoscopy of 22 (55%) of the 40 patients with cholecystectomy two years after the operation. Histologically proven gastritis was present in 19 (86%) of these 22 patients. Chronic superficial gastritis was detected in 3 (16%) of them. Mean serum gastrin levels of these patients was 56.6ｱ3.3pg/ml preoperatively and 54.8ｱ5.5pg/ml postoperatively. (Normal value: 25-125pg/ml).
DGR was not present in other 18 (45%) cholecystectomized patients. Histological findings were reported as chronic superficial gastritis in three (17%) of these patients while others were reported as normal. Mean serum gastrin levels was 51.7ｱ7.4pg/ml preoperatively and 41.7ｱ4.1pg/ml postoperatively. The difference between preoperative and postoperative gastrin levels was not statistically significant in DGR (+) and DGR (-) groups (p>0.05).
When we evaluated the relation between DGR and gastritis it was seen that 86% of DGR (+) patients had histologically proven gastritis while only 17% of DGR (-) patients had. The difference was found to be statistically significant (p<0.01). Gastritis rate was 31 times more when compared with DGR (-) patients (OR=31.67).
Ten of the 22 DGR (+) patients and four of the eighteen DGR (-) patients had dyspeptic symptoms: The difference was not significant statistically (p>0.05).
Dyspeptic symptoms were determined in 13 of 22 patients who gastritis were histologicaly proven. One of the 18 patients who had not gastritis histologically complained about dyspeptic symptoms. According to these findings in patients who have dyspeptic symptoms, gastritis rate is 24 times more than patients without symptoms. Also there was no difference between serum gastrin levels of the groups according to DGR, gastritis and dyspeptic symptoms (p>0.05).
DISCUSSION
Cholecystectomy is associated with an increase in the incidence of gastritis and may contribute to the post-cholecystectomy syndrome (4,5). It is shown that DGR has increased after cholecystectomy (6-9). It may be due to the absence of reservoir function of gallbladder causing a more continuous flow of bile in the duodenum and abnormal antroduodenal motilities. In addition, fasting bile acid concentration in the bile produced by the liver is increased after cholecystectomy and also reflux of especially the glucoconjugated bile acids (6,10). Bile acid is known to be harmful for gastric mucosa (11). Previous studies brought out that duodenal reflux may damage the gastric mucosa and cause symptoms like epigastric pain, nausea and bilious vomiting (2,5,12,13).
DGR is one of the important factors in gastritis etiology. The DGR rate of 86% in our cases with gastritis is found to be in accordance with the literature (4,14,15,16) (Tables 1 and 2). The relation between DGR occurrence with gastritis is statistically significant (p<0.01), and risk of gastritis in patients with DGR is 31 times more than the patients without DGR (OR=31.67). Presence of gastritis in 19 patients with normal gastric mucosa preoperatively and 10 of them complaining dyspeptic symptoms indicate that DGR is an important factor on gastric mucosal damage. Six months after surgical intervention a morphologic variation in the gastric mucosa with a decrease in parietal cells and a slight increase in gastrin cells was shown as a result of DGR (10). Despite DGR is a potential cause of hypergastrinemia, one might expect an increase in gastrin level after cholecystectomy but difference in gastrin levels of the patients were not statistically different when compared before and 2 years after cholecystectomy.
Recently some studies shown that 64-68 % of patients had chronic superficial gastritis, and 12% had chronic atrophic gastritis after cholecystectomy (9,17). In the present study 84% of the patients with gastritis had chronic superficial gastritis and 14 % had chronic atrophic gastritis. However, as seen also in our study, DGR does not always give rise to gastritis nor do patients with gastritis always have symptom (18).
The symptoms of clinical status named as post-cholecystectomy syndrome seen in cholecystectomized patients are defined as nausea, epigastric discomfort, burning pain, bilious vomiting, belching and feeling of fullness, indigestion, flatulence and eructation. Etiopathogenesis has not been classified yet but DGR may play a significant role in the postcholecystectomy syndrome (4,12,13,15,16,19,20). Dyspeptic symptoms disappear only in 46% of the patients underwent cholecystectomy (21). In the follow-up period twenty-six (65%) of our cholecystectomized patients didnﾕt complain about any dyspeptic symptoms anymore. The difference about gastritis in patients with and without dyspeptic symptoms is found to be statistically significant (p<0.01). The probability of complaining about dyspeptic symptoms is 24 times more in patients with gastritis than the group without gastritis.
In conclusion, this prospective study suggests that excessive DGR may be responsible for persistence of symptoms after cholecystectomy by causing gastric mucosal damage. In order to distinguish from the other causes of postcholecystectomy syndrome, patients with dyspeptic symptoms in the follow-up after cholecystectomy should evaluate by endoscopic for DGR related gastric mucosal changes.
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Table 1. The relationship of DGR and gastritis.
| |
|
Gastritis positive |
Gastritis negative |
Total |
|
DGR (+) |
n |
19 |
3 |
22 |
| |
% |
86 |
14 |
100 |
|
DGR(-) |
n |
3 |
15 |
18 |
| |
% |
17 |
83 |
100 |
|
Total |
n |
22 |
18 |
40 |
| |
% |
55 |
45 |
100 |
x2: 19.4 p<0.001 OR=31.67
Table 2. The relationship of DGR and dyspeptic symptoms.
| |
|
Symptomatic |
Asymptomatic |
Total |
|
DGR (+) |
n |
10 |
12 |
22 |
| |
% |
45 |
55 |
100 |
|
DGR (-) |
n |
4 |
14 |
18 |
| |
% |
22 |
78 |
100 |
|
Total |
n |
14 |
26 |
40 |
| |
% |
35 |
65 |
100 |
x2:2.35 p>0.05
Table 3. The relationship of gastritis and dyspeptic symptoms.
| |
|
Symptomatic |
Asymptomatic |
Total |
|
Gastritis (+) |
n |
13 |
9 |
22 |
| |
% |
60 |
40 |
100 |
|
Gastritis (-) |
n |
1 |
17 |
18 |
| |
% |
5 |
95 |
100 |
|
Total |
n |
14 |
26 |
40 |
| |
% |
35 |
65 |
100 |
x2:12.4 OR=24.5 p<0.001
Table 4. The relationship of DGR, gastritis and dyspeptic symptoms with serum gastrin levels
|
Group |
Serum gastrin level |
Statistic |
|
All patients (n=40) |
Preoperative 55.6 ±16.8 |
|
| |
Postoperative 49.8 ±20.2 |
p=0.272 |
|
Gastritis (+) (n=22) |
Preoperative 56.6 ± 3.3 |
|
| |
Postoperative 54.8 ± 5.5 |
p=0.75 |
|
Gastritis (-) (n=18) |
Preoperative 51.7 ± 7.4 |
|
| |
Postoperative 41.7 ± 4.1 |
p=0.065 |
|
DGR (+) (n=22) |
Preoperative 54.6 ± 13.7 |
|
| |
Postoperative 52.5 ± 20.9 |
p=0.76 |
|
DGR ( -) (n=18) |
Preoperative 51.7 ± 22.1 |
|
| |
Postoperative 46.9 ± 22.4 |
p=0.65 |
|
Symptom (+) (n=14) |
Preoperative 63.3 ± 19.6 |
|
| |
Postoperative 48.2 ± 20.5 |
p=0.079 |
|
Symptom ( -) (n=26) |
Preoperative 48.5 ± 9.8 |
|
| |
Postoperative 51.1 ± 20.7 |
p=0.067 |