Pathological and Histological Aspects of Biliary Reflux After Mini-Gastric Bypass

Abstract

Background:

One anastomosis gastric bypass/mini-gastric bypass (OAGB/MGB) is considered to be the best alternative to Roux-en-Y gastric bypass due to the shorter operative time and fewer possible complications.

Objectives:

The purpose of this study is to determine biliary reflux in patients who undergo OAGB/MGB with a hand-sewn gastroenteroanastomosis, and OAGB/MGB with a linear stapled gastroenteroanastomosis.

Materials and Methods:

This prospective-retrospective study includes the results of treatment of 122 obese patients who underwent laparoscopic OAGB/MGB. Patients were divided into two clinical groups depending on the method of performing gastroenteroanastomosis. In the postoperative period, the possibility of developing biliary reflux was assessed using fibrogastroscopy with biopsy of the gastric mucosa. Histopathology of biopsy materials was evaluated. Microscopy of biopsy specimens was performed by a pathologist who evaluated each sample of gastric tissue in accordance with the system for determining the biliary reflux index (BRI).

Results:

With fibrogastroscopy, 9 (15.5%) cases in the study group and 16 (26.6%) cases in the control group, biliary reflux was diagnosed. In the study group of patients, BRI >14 was determined in 3 patients (5.153%). In the control group of patients, BRI >14 was found in 7 cases (10.94%). The difference is significant (p < 0.05).

Conclusion:

Determination of the BRI index in patients undergoing an OAGB/MGB can be used as a screening method to diagnose biliary reflux for its prevention and the development of tactics for the further management of patients with a high risk of complications associated with the toxic effects of aggressive bile. Hand-sewn gastroenteroanastomosis carries less risk of bile reflux gastritis and anastomositis than stapled gastroenteroanastomosis. Clinical Trial Registration number NCT04845438

Introduction

One Anastomosis gastric bypass/mini-gastric bypass (OAGB/MGB) is a modification of gastric bypass, proposed in 1967 by Edward Mason, but with a longer stomach stump formed on the lesser curvature, as well as the imposition of a side-to-side gastroenteroanastomosis with the small intestine, performed at a distance of about 200 cm from the Treitz ligament.^1,2 It is believed that OAGB/MGB is the best alternative to Roux-en-Y gastric bypass (RYGB) due to a shorter duration of operative time, a lower number of possible complications associated with the anastomotic leak, the development of internal hernias, and the simplicity of revision and reverse interventions, with equivalent or even superior results in terms of weight loss and correction of associated diseases.^3–5 However, despite these benefits, concerns remain about the high risk of chronic or symptomatic biliary reflux gastritis and reflux esophagitis, and therefore gastric and/or esophageal cancer.

These risks arise from the formation of a long gastric stump, in which the gastrin-producing zone of the stomach is preserved, creating an anastomosis with the small intestine at a distance of more than 200 cm from the Treitz ligament, as well as the development of gastrostasis during the formation of a narrow gastroenteroanastomosis, which is especially important in patients with type 2 diabetes mellitus and neurogastropathy.⁶ According to Salama and Hassan, in a study of 50 cases of OAGB/MGB 18 months after surgery using fibrogastroscopy with biopsy and 24-h pH-metry, reflux esophagitis was detected in 3 (6%) cases; in 2 (4%) cases, it was associated with acid reflux and in 1 (2%)—with alkaline gastroesophageal biliary reflux. No endoscopic signs of dysplasia or metaplasia were found.⁷ In contrast, Saarinen et al., studying the phenomena of biliary reflux using hepatobiliary scintigraphy, determined that 55.5% of patients in the study, who underwent mini-gastric bypass surgery, had transient bile reflux, which was detected in the gastric stump.⁸ The need for a more thorough study of biliary reflux is a serious problem in connection with the growing popularity of mini-gastric bypass surgery in the world bariatric community.⁹

It is also important to note that duodenogastric reflux is a physiological phenomenon. However, excessive biliary reflux can lead to symptomatic gastritis and/or esophagitis, intestinal metaplasia (IM), damage to the mucous membrane of the stomach and esophagus, Barrett's esophagus, and finally to stomach or esophageal cancer.¹⁰

The instrumental diagnostic methods used at the moment do not allow to fully judge the effect of biliary reflux on the state of the mucous membrane of the gastric stump. The only accurate method to assess the consequences of biliary reflux is to determine the biliary reflux index (BRI). The use of this method in the assessment of alkaline biliopancreatic reflux after OAGB/MGB, on the one hand, is necessary to understand the danger of the development of pathomorphological changes in the gastric stump mucosa in our patients; on the other hand, it is necessary to identify indications for performing revision bile diverting interventions.

The informative value of the morphological diagnosis of changes in the gastric mucosa in biliary reflux is very high. Due to the stereotypical nature of changes in the gastric mucosa, it became possible to develop a BRI, based on histological data. This index was introduced by Sobala et al.¹¹ in 1993 based on biopsy data from the antrum of the stomach or the distal stump of the stomach. The index is derived based on the presence and severity of certain histological parameters: edema in the lamina propria of the gastric mucosa (indicated as E in the formula below), IM, chronic inflammation (CI in the formula below), and Helicobacter pylori (Hp) colonization in the stomach. Each histological parameter is assigned a score from 0 to 3 by the pathologist, which corresponds to the following levels: no parameter, mild, moderate, or high presence, respectively. The formula for determining the BRI was derived based on stepwise logistic regression analysis: $B R I = (7 \times E) + (3 \times I M) + (4 \times C I) - (6 \times H p) .$

According to Sobala et al., a BRI above 14 indicates biliary reflux (which corresponds to a bile acid level of more than 1 mM, that is, above the upper limit of the physiological norm) with 70% sensitivity and 85% specificity. Based on these data, as well as on the fact that other methods for diagnosing duodenogastric reflux, primarily 24-h pH-metry, do not have high accuracy today, this index is used by several authors as a diagnostic criterion in clinical trials.^12,13 As a result, we decided to use the BRI index in our work.

To determine the causes of duodenogastric biliary reflux, its effect on the mucous membrane of the stomach and esophagus, as well as the search for a solution to this problem due to the development of new modifications of the mini-gastric bypass surgery are of primary importance in validating this method as the most promising in the treatment of severe obesity. This would increase the adoption of this promising procedure for the treatment of severe obesity and associated comorbid conditions. The study aims to compare BRI after hand-sewn (HS) anastomosis with BRI after linear stapled anastomosis.

Materials and Methods

This prospective-retrospective cohort study includes the results of treatment of 122 obese patients with metabolic syndrome, who underwent laparoscopic mini-gastric bypass surgery from 2014 to 2018 at the NHI “Railway Clinical Hospital at the “Rostov-Glavnyi” station, Russian Railways, OJSC” Rostov-on-Don, Russian Federation. All patients were divided into two groups: patients who underwent mini-gastric bypass surgery using HS anastomosis, 58 people (group 1), and the control group of patients (group 2), who underwent a standard mini-gastric bypass surgery with linear stapled anastomosis¹—64 people (Table 1).⁶

Table 1.

General Characteristics of Patient Groups

Index	Study group	Control group	Statistical significance of differences^a
Average age, years	46.603 ± 9.8	49.953 ± 10.5	p = 0.33
Male	10 (17.24%)	14 (21.875%)
Female	48 (82.76%)	50 (78.125%)
Body mass index (average), kg/m²	49.035 ± 6.4	46.475 ± 8.1	p = 0.76
ASA Anesthetic Risk Scale Index
ASA I	15 (25.862%)	15 (23.437%)
ASA II	35 (60.344%)	39 (60.937%)
ASA III	8 (13.794%)	10 (15.626%)
Concomitant pathology
Arterial hypertension	31 (53.4%)	32 (50%)
Respiratory failure	11 (19.0%)	9 (14.1%)
Osteoarthritis	9 (15.5%)	10 (15.6%)
Gallstone	7 (12.1%)	6 (9.4%)
Diabetes mellitus, type 2	47 (81.0%)	51 (79.7%)
Impaired glucose tolerance	11 (19.0%)	13 (20.3%)
Hernia	4 (6.9%)	5 (7.8%)
Ovarian dysfunction or impaired potency in men	15 (25.9%)	15 (23.4%)
Others	7 (12.1%)	5 (7.8%)
Combination of two or more diseases	28 (48.3%)	27 (42.2%)

Differences are statistically significant at p < 0.05.

Indications for bariatric surgery were determined according to the National clinical guidelines for the treatment of morbid obesity in adults¹⁴ and European clinical guidelines for the treatment of obesity in adults.¹⁵ The criteria for inclusion of patients in this study were as follows: the presence of indications and the absence of contraindications to bariatric surgery according to the National clinical guidelines for the treatment of morbid obesity in adults; voluntary consent of patients to participate in the study; and absence of pathological bile reflux and associated reflux gastritis in the preoperative period. The criteria for excluding patients were as follows: lack of patient compliance in postoperative follow-up and treatment, as well as refusal to undergo control examinations, and the presence of clinical and endoscopic signs of atrophic gastritis, duodenal reflux, during the prehospital examination.

When selecting patients in the experimental groups, 32 subjects with clinical and endoscopic signs of gastritis underwent an antral gastric biopsy, followed by histological assessment of the degree of pathomorphological changes and determination of the BRI index. The median BRI was 7 points and the mean BRI was 7.8; the distribution width was 0–14 points, 95% confidence interval = 6.3–9.1.

Surgical technique

All operations were performed under general anesthesia using standard five-port laparoscopy. After carbon dioxide insufflation, an 18-cm-long gastric tube division was made along the lesser curvature starting below at the crow's foot with Echelon Flex™ linear stapler (Ethicon EndoSurgery™, Berkshire, United Kingdom) and calibrated with a 36 Fr bougie. A jejunal loop was lifted 200–250 cm from the Treitz ligament depending on BMI.

In the first group, an HS gastrojejunostomy (GJ) antecolic anastomosis was performed using a running 2/0 PDS (Ethicon, Livingston, United Kingdom) suture (single layer posteriorly and 2 layers anteriorly) sized over the orogastric tube. This resulted in a gastroenterostomy diameter of ∼3 cm.

In the control group, GJ anastomosis was performed antecolic with a 45 mm (Blue) linear stapler Echelon Flex. The remaining anastomotic defect was sewn with a running 2/0 PDS (Ethicon, Somerville, NJ) suture intra-abdominally.

An intraoperative air/methylene blue leak test was performed at the end of the procedure, and an abnormal intraoperative leak test. No abdominal drainage, urinary catheter, or nasogastric tube was left for any of the patients. All patients were mobilized and received oral liquids within 2 h after the operation.

Postoperative pathway

In the long-term postoperative period (9–18 months), all patients were interviewed to identify the following clinical symptoms: epigastric pain; belching; nausea; regurgitation of food with bile, vomiting; and heartburn. Also, in the postoperative period, the possibility of developing biliary reflux, the occurrence of ulcers in the area of gastroenteroanastomosis was assessed using fibrogastroscopy with biopsy of the gastric stump mucosa, microscopy of biopsy materials. Fibrogastroscopy with targeted biopsy was performed on the OLYVPUS GIF-Q510 device (Japan). During the study, two biopsy materials were obtained, one from the stump of the stomach and the other from the area of the gastroenteroanastomosis. Special attention was paid to the determination of morphological changes in the gastric stump mucosa as the most accurate indicators of the development of pathological enterogastric biliary reflux. Microscopy of the biopsies was performed using a Leica DM 4000B light microscope. Staining of the preparations was performed using Hematoxylin-Eosin. The pathologist, who was “blinded,” that is, had no idea about the clinical data of patients, evaluated each sample of gastric tissue according to the above-mentioned BRI system (Fig. 1). When determining these indicators, visual analog scales were used (Figs. 2 and 3)

FIG. 1.

Light microscopy of biopsy material of the gastric mucosa from the area of gastroenteroanastomosis. (Hematoxylin-Eosin staining, magnification × 200). This picture corresponds to the edema of the lamina propria (E)—1; intestinal metaplasia (IM)—2; chronic inflammation (CI)—2, Helicobacter pylori (HP) colonization—0; and corresponds to the BRI index—21. BRI, biliary reflux index.

FIG. 2.

Visual analog scale of infiltration severity gradation of the epithelium and the lamina propria of gastric mucosa by mononuclear cells and neutrophilic leukocytes [cit. by Ref.²⁷].

FIG. 3.

Visual analog scale of atrophy severity gradation of gastric mucosa [cit. by Ref.²⁷].

Statistics

The research results were processed by statistical methods using MS Excel 2010 and Statistica 8.0 software. When analyzing quantitative indicators (body weight, height, BMI, glycemic level, duration of surgery, etc.), the statistical significance of the differences was determined using the Student's t-test. To calculate the significance of the obtained differences for qualitative indicators (complication rate, frequency of biliary reflux, etc.), we applied Pearson's χ² test and Fisher's exact two-sided test using four-field tables.

Results

Clinical signs of enterogastric biliary reflux were found in both groups, but the severity of these symptoms was higher in the control group of patients, which was confirmed statistically (Fig. 4).

FIG. 4.

Frequency of occurrence of clinical symptoms in the study and control groups.

We carried out a histological examination of biopsy materials of mucous membrane of the gastric stump and the area of gastroenteroanastomosis obtained during fibrogastroscopy. The study was carried out from 9 to 36 months after surgery; the mean duration was 16.3 ± 5.7 months. During fibrogastroscopy, biliary reflux was diagnosed in 9 (15.5%) cases in the experimental group and in 16 (26.6%) cases in the control group. At the same time, frothy bile was found in the stomach stump, and there was an abundant flow of bile into the stomach stump through the gaping lumen of the gastroenteroanastomosis. In 18 (31.0%) cases in the experimental group and 26 (40.6%) cases in the control group, signs of active gastritis of the gastric stump were observed; the mucous membrane was edematous and hyperemic, with an increase in the vascular pattern. Somewhat more often, in 41.4% of cases in the experimental group and in 46.9% of cases in the control, similar signs were observed in the area of gastroenteroanastomosis. In 10 cases (17.2%) in the experimental group and 15 cases (23.4%) in the control group, multiple surface defects of the mucous membrane of the anastomotic area were found to be rounded or oval ranging from 0.1 to 0.5 cm in size, with a pale pink bottom covered with translucent, whitish-gray overlays in the form of thin films, regarded as acute erosion. Ulcers in the area of the gastroenteroanastomosis were detected in one case (1.7%) in the experimental group and in three cases (4.7%) in the control mini-gastric group, and were localized in the jejunum at the site of its anastomosis with the stomach or near the anastomosis. These were deep defects of the mucous membrane with raised edges, ranging in size from 0.5 to 2.5 cm, covered with dense fibrin overlays (Table 2).

Table 2.

Endoscopic Criteria for Assessing the State of the Mucous Membrane of the Gastric Stump and Gastroenteroanastomosis in the Long-Term Postoperative Period

Symptoms	First group, N = 58, n (%)	Second group, N = 64, n (%)
Gastritis of the stomach stump	18 (31.0)	26 (40.6)
No anastomositis (anastomotic inflammation)	23 (39.7)	16 (26.7)
Superficial anastomositis	15 (25.8)	15 (23.4)
Erosive anastomositis	10 (17.2)	14 (21.8)
Gastroenteric anastomosis ulcer	1 (1.7)	3 (4.7)
Enterogastric reflux, presence of bile in the lumen of the stomach	9 (15.5)	16 (25.0)

In the experimental group of patients, the BRI >14 was determined in 3 patients (5.15%). In the control group of patients, BRI >14 was found in 7 patients (10.94%). The difference is significant (p < 0.05) (Table 3).

Table 3.

BRI Value in the Experimental Groups in the Late Postoperative Periods

Clinical groups	n	BRI ≤14	BRI >14
Study group	58	55	3 (5.15%)
Control group	64	57	7 (10.94%)

BRI, biliary reflux index.

Thus, the number of patients with a BRI index of more than 14 points was significantly higher in the control group of patients with instrumental gastroenteroanastomosis.

Discussion

Since the very first mini-gastric bypass (OAGB/MGB) operation in 1997, this operation has become more popular due to its simplicity, shorter operative time, few complications, and excellent results. For a long time, mini-gastric bypass surgery has been criticized by bariatric surgeons, due to the theoretically high risk of potential development of gastroesophageal cancer due to biliary reflux. Literature data show that Billroth II gastric resection is not reliably associated with an increase in the incidence of gastric cancer.^16–18 More than 43 gastric and esophageal cancers have been reported after all bariatric surgeries; at the same time, no case of gastric or esophageal stump cancer was detected after OAGB/MGB.^20–23 However, the controversy over the development of biliary reflux after mini-gastric bypass surgery and the associated risk of developing gastric and esophageal cancer continues to this day.

Clinical diagnosis of biliary reflux after OAGB/MGB is difficult unless the patient experiences biliopancreatic regurgitation and/or vomiting of bile, especially at night. Other symptoms may include bloating, heartburn, nausea, belching, epigastric pain, or signs of bile aspiration.

Fibroscopy is the first instrumental method for studying patients who have clinical signs of biliary reflux. Although this study is not very sensitive, it enables visual documentation of bile present in the lumen of the gastric stump and/or esophagus and it can be used to determine some of the pathological changes observed in the mucous membrane of the stomach and esophagus (gastritis, erosions, acute ulcers, esophagitis, Barrett's esophagus, or presumptive tumor).

The next method for determining the reflux of biliopancreatic secretions is pH-metry. However, measuring the pH of the esophagus is unreliable and cannot provide an accurate diagnosis of alkaline reflux, due to the presence of many associated artifacts leading to nonspecific results.²⁴ Fiber-optic spectrophotometry (Bilitec, 2000), in combination with pH monitoring, according to several authors, is the most accurate method for diagnosing bile reflux. However, due to methodological limitations, the spectrometric method was not sufficiently developed and was replaced by pH impedance measurement, which experts consider to be a more reliable and suitable method.^25,26 Monitoring of multichannel intraluminal impedance allows the analysis of changes in electrical resistance and detection of all virtual episodes of reflux (liquid, gas, or both). In combination with monitoring the level of pH, impedance-pH can be used to characterize all reflux episodes, both acidic and alkaline. To date, only one study has been conducted using systematic pH impedance monitoring, manometry, and upper endoscopy.¹⁰ A study by Tolone et al. included 15 patients with preoperative reflux symptoms, who underwent mini-gastric bypass surgery. One (1) year after OAGB/MGB, there were no cases of esophageal-gastric junction dysfunction, but intragastric pressure significantly decreased from 15 to 9.5 (p < 0.01), the gastroesophageal pressure gradient decreased from 10.3 to 6.4 (p < 0.01), and the number of gastroesophageal reflux cases decreased from 41 to 7 (p < 0.01). However, in this case, no endoscopic sign of gastric mucosa and/or esophagus lesions, secondary to possible biliary reflux, was found.¹⁰ Regardless of these results, the small number of patients studied, as well as the short follow-up period, does not allow for definitive conclusions.

The most informative method for diagnosing biliary reflux is the determination of morphological changes in the gastric mucosa.²⁷ Therefore, in our study, we focused on identifying the morphological substrate of gastric mucosa damage due to the discharge of biliopancreatic secretions into the stomach.

In this prospective-retrospective cohort study, we conducted a comparative analysis of the mini-gastric bypass with a line-stapled and mini-gastric bypass, with a HS 3.0 cm long anastomosis technique.

The formation of a linear stapled gastroenteroanastomosis during mini-gastric bypass surgery has its own characteristics—a narrow thick-walled stomach stump is stapled with a small-diameter small-walled small intestine taken at a distance of 2 m from the Treitz ligament. Moreover, the diameter of the created anastomosis significantly exceeds the diameter of the small intestine, which creates anatomical conditions for biliary reflux. In this regard, we have developed a method in which a larger gastric stump is created, excluding its gastrin-producing zone, with the implementation of a relatively small gastroenteroanastomosis, 3.0 cm long. The anastomosis suture is single-row and is performed along the antimesenteric edge of the intestine, which leads to the effect of bowel sagging and improves the free passage of intestinal contents, preventing the development of biliary reflux.^17,25

An important point of prehospital selection of patients for mini-gastric bypass surgery is the exclusion of patients with clinical and endoscopic signs of biliary reflux, and signs of atrophic gastritis and esophagitis. In unclear cases, it is advisable to perform a biopsy of the gastric mucosa with a histological assessment of the biopsy according to the BRI system.

An analysis of the immediate results of mini-gastric bypass surgery in our study showed that using a manual sutured gastroenteroanastomosis did not significantly increase the risks of intraoperative and postoperative complications, as well as the duration of the operation.

A mathematical analysis of clinical indicators of biliary reflux confirmed an increase in the severity of clinical symptoms in the control group of patients. So, according to statistics, clinical symptoms of heartburn, nausea, and regurgitation of food with bile were significantly lower in the experimental group, which, in our opinion, is associated with the removal of the acid-producing zone of the stomach and the imposition of a narrower manual gastroenteroanastomosis.

When analyzing the incidence of endoscopic signs of biliary reflux in the period from 9 to 18 months after the operation, we did not obtain significant differences in the incidence of gastroenteroanastomotic ulcers; at the same time, a lower incidence of endoscopic signs of biliary reflux and anastomosis phenomena was statistically proven, which in this sample indicates the effectiveness of the proposed antireflux protection.

The morphological study of biopsies of the gastric stump mucosa after mini-gastric bypass with the study of the BRI is extremely informative for assessing its undesirable consequences. We have not found BRI studies of gastric mucosal biopsies after mini-gastric bypass surgery in English literature according to PubMed and Cochrane. Our study of long-term results of OAGB/MGB in the two groups with a median follow-up of 15 months revealed BRI greater than 14 in 3 patients (5.15%) of the experimental group and in 7 (10.94%) patients of the control group. These data indicate the need for monitoring patients during the following 15 months after the operation.

We recommend manual sutured gastroenteroanastomosis with a width corresponding to the diameter of the intestinal loop taken for the anastomosis. In our opinion, this technique provides a restrictive component and antireflux protection of the anastomosis.

If BRI is greater than 14 points in patients after mini-gastric bypass surgery, it is advisable to recommend revision intervention—RYGB.

Conclusion

(1)

Formation of HS endoscopic intracorporeal antireflux anastomosis in the experimental group of patients is more functional since it allows to reduce the frequency of endoscopic and histological signs of biliary reflux compared with the control group.

(2)

Applicants for mini-gastric bypass surgery need careful selection. Patients who have undergone mini-gastric bypass surgery need a thorough examination with fibrogastroscopy at least once a year to determine severe biliary reflux. In the future, such patients are recommended to perform revision operations.

Footnotes

Acknowledgments

A part of our scientific article was presented initially at The 8th Congress of the Federation for the Surgery of Obesity and Metabolic Disorders, Athens. 2018. “Long-term evaluation of biliary reflux after one anastomosis gastric bypass/A.G. Khitaryan, A.V. Mezhunts.”

Disclosure Statement

No competing financial interests exist.

Funding Information

No funding was received for this article.

References

Robert Rutledge. The mini-gastric bypass: experience with the first 1,274 cases. Obes Surg, 2001; 11:276–280.

Piazza

, Ferrara

, Leanza

, Coco

, Sarva

, Bellia

, et al. Laparoscopic mini-gastric bypass: short-term single-institute experience. Updates Surg, 2011; 63:39–42.

Mahawar

, Carr

, Balupuri

, Small

. Controversy surrounding ‘mini’ gastric bypass. Obes Surg, 2014; 24:24–33.

Georgiadou

, Sergentanis

, Nixon

, Diamantis

, Tsigris

, Psaltopoulou

. Efficacy and safety of laparoscopic mini-gastric bypass. A systematic review. Surg Obes Relat Dis, 2014; 10:84–91.

Mahawar

, Kumar

, Carr

, Jennings

, Schroeder

, Balupuri

, et al. Current status of mini-gastric bypass. J Minim Access Surg, 2016; 12:305–310.

Khitaryan

, Starzhinskaya

, Mezhunc

, Veliev

, Zavgorodnyaya

, Orekhov

. Gastroezofageal'naya reflyuksnayabolezn’ u pacientov s ozhireniem raznoj stepeni tyazhesti i saharnym diabetom. Tavricheskij mediko-biologicheskij vestnik, 2018; 21:129–137.

Salama

TMS

, Hassan

. Incidence of biliary reflux esophagitis after laparoscopic omega loop gastric bypass in morbidly obese patients. J Laparoendosc Adv Surg Tech A, 2017; 27:18–22.

Saarinen

, Rasanen

, Salo

, Loimaala

, Pitkonen

, Leivonen

, et al. Bile reflux scintigraphy after mini-gastric bypass. Obes Surg, 2017; 27:2083–2089.

Bruzzi

, Chevallier

, Czernichow

. One-anastomosis gastric bypass: why biliary reflux remains controversial?. Obes Surg, 2017; 27:545–547.

10.

Tolone

, Cristiano

, Savarino

, Lucido

, Fico

, Docimo

. Effects of omega-loop bypass on esophagogastric junction function. Surg Obes Relat Dis, 2016; 12:62–69.

11.

Sobala

, O' Connor

, Dewar

, King

, Axon

, Dixon

. Bile reflux and intestinal metaplasia in gastric mucosa. J Clin Pathol, 1993; 46:235–40.

12.

Aprea

, Canfora

, Ferronetti

. Morpho-functional gastric pre-and post-operative changes in elderly patients undergoing laparoscopic cholecystectomy for gallstone related disease. BMC Surg, 2012; 12:5.

13.

Kuran

, Parlak

, Aydog

. Bile reflux index after therapeutic biliary procedures. BMC Gastroenterol, 2008; 8:4–11.

14.

Dedov

, Shestakova

, Melnichenko

, Mazurina

, Andreeva

, Bondarenko

, et al. National clinical guidelines for the treatment of morbid obesity in adults. 3rd revision (Treatment of morbid obesity in adults). [Nacional'nye klinicheskie rekomendacii po lecheniyu morbidnogo ozhireniya u vzroslyh. 3-ij peresmotr (Lechenie morbidnogo ozhireniya u vzroslyh)]. Obes Metab, 2018; 15:53–70. https://cyberleninka.ru/article/n/natsionalnye-klinicheskie-rekomendatsii-po-lecheniyu-morbidnogo-ozhireniya-u-vzroslyh-3-iy-peresmotr-lechenie-morbidnogo-ozhireniya-u/viewer

15.

Zaslavsky

AYu

, Kuprinenko

. Endocrinologist's summary. Part 4. Treatment of obesity in adults. European Clinical Guidelines (2008). 2011:32. [13. Konspekt endokrinologa. Ch. 4. Lechenie ozhireniya u vzroslyh. Evropejskie klinicheskierekomendacii (2008)]. https://www.gastroscan.ru/literature/authors/11571.

16.

Schafer

, Larson

, Melton

. The risk of gastric carcinoma after surgical treatment for benign ulcer disease: a population-based study in Olmsted County, Minnesota. N Engl J Med, 1983; 309:1210–1213.

17.

Clark

, Fresni

, Gledhill

. Cancer following gastric surgery. Br J Surg, 1985; 72:591–594.

18.

Luukkonen

, Kalima

, Kivilaako

. Decreased risk of gastric stump carcinoma after partial gastrectomy. Hepatogastroenterology, 1990; 37:392–396.

19.

Bassily

, Smallwood

, Crotty

. Risk of gastric cancer is not increased after partial gastrectomy. J Gastroenterol Hepatol, 2000; 15:762–767.

20.

Scozzari

, Trapani

, Toppino

, Morino

. Esophagogastric cancer after bariatric surgery: systematic review of the literature. Surg Obes Relat Dis, 2013; 9:133–142.

21.

Nau

, Rattner

, Meireles

. Linitus plastica presenting two years after elective Roux-en-Y gastric bypass for treatment of morbid obesity: a case report and review of the literature. Surg Obes Relat Dis, 2014; 10:15–17.

22.

Scheepers

, Schoon

, Nienhuijs

. Esophageal cancer after sleeve gastrectomy. Surg Obes Relat Dis, 2011; 7:11–12.

23.

Angrisani

, Santonicola

, Iovino

. Gastric cancer: a de novo diagnosis after laparoscopic sleeve gastrectomy. Surg Obes Relat Dis, 2014; 10:186–187.

24.

Champion

, Richter

, Vaezi

, Singh

, Alexander

. Duodenogastroesophageal reflux: relationship to pH and importance in Barrett's esophagus. Gastroenterology, 1994; 107:47–54.

25.

Sifrim

, Castell

, Dent

, Kahrilas

. Gastro-oesophageal reflux monitoring: review and consensus report on detection and definitions of acid, non-acid, and gas reflux. Gut, 2004; 53:1024–1031.

26.

Mezhunts

, Khitaryan

, Zavgorodnyaya

, et al. A method of surgical treatment of morbid obesity//RF Patent No. 2016134082, August 19, 2016. Published: January 11, 2018 Bul. No. 2. [Sposob hirurgicheskogo lecheniya morbidnogo ozhireniya//Patent RF No. 2016134082, August 19, 2016. Opublikovano: January 11, 2018 Byul. No. 2]. https://patenton.ru/patent/RU2640783C1/en

27.

Yanul

, Lyubutina

. OLGA-2008 system: modern international histological classification of chronic gastritis. [Sistema OLGA-2008: sovremennaya Mezhdunarodnaya gistologicheskayaklassifikaciya hronicheskih gastritov]. Mil Med, 2011; 3:32–35. https://cyberleninka.ru/article/n/sistema-olga-novyy-podhod-v-diagnostike-i-lechenii-hronicheskih-gastritov/viewer