Pathological and immunohistochemical analysis of gastric mucosa after one anastomosis gastric bypass surgery.

BACKGROUND: One anastomosis gastric bypass (OAGB) is now the third most common bariatric surgery worldwide. This procedure is garnering increasing attention, but its complication of bile reflux and the associated risk of gastric carcinogenesis remains controversial. OBJECTIVE: The study aims to assess the impact of bile reflux on the gastric mucosa by comparing pathological and immunohistochemical results of gastric mucosa before and 2 years after OAGB surgery. METHODS: This retrospective study analyzed gastric lesions observed in gastroscopy before and after OAGB surgery. Pathological examinations were conducted on mucosal samples from proximal, middle and distal part of stomach, with a particular focus on the expression of Ki-67, P53, and CDX2 in immunohistochemistry. Ki-67 indicates cellular proliferation, P53 is a tumor suppressor protein, and CDX2 is a marker for intestinal differentiation. RESULTS: A total of 16 patients completed the follow-up. Regarding gastritis, presurgery nonerosive gastritis was found in two cases (12.5%), and postsurgery in six cases (37.5%). Erosive gastritis increased from one case (6.2%) presurgery to three cases (18.7%) postsurgery, totaling an increase from three to nine cases (p = .028). Bile reflux in the stomach increased from one case (6.2%) presurgery to three cases (18.7%) postsurgery. Most lesions in the proximal, middle, and distal part of stomach were relatively mild, with normal tissue states being predominant. Mild inflammation was found in all three areas, whereas moderate inflammation, intestinal metaplasia, and glandular atrophy were less common. No cases of severe inflammation were noted. The expression of gastric biomarkers CDX-2, Ki67, and P53 showed no significant statistical variation in different areas. CONCLUSION: Bile reflux does occur after OAGB, but its incidence is not high. Based on the immunohistochemical and pathological results of the gastric mucosa 2 years post-OAGB, there seems to be no significant causal relationship between OAGB and oncogenic inflammation around the gastric tube.

Incomplete Intestinal Metaplasia of the Stomach Is more Related to Bile Reflux than Chronic Gastritis.

OBJECTIVE: Incomplete intestinal metaplasia (IIM) of the stomach is associated with higher risk of progression to dysplasia and gastric cancer than complete intestinal metaplasia (CIM). Whether the causative factors underlying IIM are different from those underlying CIM is currently unknown. In a recent study, bile acids were found to induce gastric intestinal metaplasia (IM) in mice by activating STAT3 signaling and accelerated the development of dysplasia. The aim of this study was to determine whether there are differences in associations between IIM and CIM and clinicopathologic features known to be associated with intestinal metaplasia, bile reflux, and activated STAT3. METHODS: Fifty-two consecutive gastric biopsies with IM were examined for the type of metaplasia, presence of inflammation, and Helicobacter pylori (H. pylori) status. Immunohistochemical staining was performed for phospho-STAT3 (p-STAT3) and evaluated by image analysis. The type of IM was then correlated with relevant clinicopathologic variables and p-STAT3 expression. RESULTS: Seven cases had IIM only, 31 had CIM only, and 14 had both CIM and IIM (CIIM). Significantly fewer cases with IIM had chronic gastritis than either CIM or CIIM (43%, 93%, 79%, respectively, p=0.005). H. pylori was not detected in any of the IIM cases but was positive in 29% of CIM and 29% of CIIM. Fifty-seven percent of patients with IIM had a history of cholecystectomy compared to 25% of those with CIM and 23% of those with CIIM. The mean BMI was 32.3 kg/m2 for patients with IIM compared to 28 kg/m2 for those with CIM and 31.2 kg/m2 for those with CIIM. Median p-STAT3 for biopsies with was IIM was 6.36 compared to 3.54 for CIM and 6.27 for CIIM. Reactive gastropathy was present in 57% of biopsies with IIM, 39% of CIM and 50% of CIIM. CONCLUSION: In contrast to CIM, IIM is significantly less likely to be associated with chronic gastritis. CIIM also tended to be less associated with H. pylori infection and more associated with reactive gastropathy, history of cholecystectomy, higher BMI, and higher median p-STAT3. These results tend to suggest that IIM is probably more likely to be associated with bile reflux than H. pylori-associated gastritis. Larger studies are needed to confirm these findings.Presented in part at Digestive Disease Week 2023, Chicago, IL, May 6, 2023.

[Expert consensus on endoscopic diagnosis and treatment of the benign pancreaticobiliary junction disease (2023 edition)].

The pancreaticobiliary junction (PBJ) stands as a pivotal "hub" where the bile and pancreatic ductsmerge, directing the flow rate and direction of bile and pancreatic juice. Benign pancreaticobiliary junction diseases(BPBJD) can lead to compromised outflow of bile and pancreatic secretions, resulting in elevated pressures within the bile and pancreatic ducts, causing ductal dilation, secretion stasis, and stone formation.Furthermore, BPBJD can shift the direction of bile and pancreatic juice, inducing pancreaticobiliary reflux, bile-pancreatic reflux, or enterobiliary reflux, thereby causing both acute and chronic inflammation and tumors in the biliopancreatic system. Owing to the unique anatomical position of the PBJ and the often intricate and elusive symptoms of benign diseases in this region, clinicians might mainly address standard biliary and pancreatic diseases, overlooking the primary issues associated with the PBJ.Such oversight can yield less-than-optimal clinical outcomes. In response to this, the Gallbladder-Preserving Surgery Committee, Endoscopy Specialist Branch of Chinese Medical Doctor Association and the editorial board of the National Medical Journal of China assembled renowned domestic experts from the fields of hepatobiliary and pancreatic surgery and digestive endoscopy. Drawing upon the latest domestic and international research findings, as well as the clinical expertise of specialists from related fields within China, they have collaboratively developed an expert consensus on the endoscopic diagnosis and treatment of BPBJD. The overarching aim is to propagate and standardize the diagnosis and treatment approaches for BPBJD.

The relationship between bile reflux and common bile duct diameter after cholecystectomy: a clinical case-control study.

OBJECTIVE: The present study aims to investigate the relationship between bile reflux (BR) and diameter of the common bile duct (CBD) in patients after cholecystectomy. MATERIALS AND METHODS: In our case series analysis, according to the endoscopy results, the patients who underwent cholecystectomy were divided into two groups as those with BR and those non-BR. Age, sex, CBD diameter measured on ultrasonography, computed tomography, magnetic resonance cholangiopancreatography, and endoscopic biopsy results of the patients were statistically analyzed. RESULTS: In a total of 188 patients included in the study, BR was detected in 93 patients, it was not observed in 95 patients. The CBD diameter of the patients was observed to be 7 mm or less in 70.9% (n = 66) in the BR group, and 23% (n = 22) in the non-BR group. The statistical analysis revealed that while there was a significant difference between the two groups in terms of CBD diameter and intestinal metaplasia, the results were similar in both groups in terms of inflammation, activity, atrophy, and Helicobacter pylori. CONCLUSION: We believe that CBD diameter may be a predictive factor in the detection of BR after cholecystectomy.

OBJETIVO: Investigar la relación entre el reflujo biliar y el diámetro del colédoco después de la colecistectomía. MÉTODO: Estudio retrospectivo en el que, de acuerdo con los resultados de la endoscopia, los pacientes que se sometieron a colecistectomía se dividieron en dos grupos: con reflujo biliar y sin reflujo biliar. Se analizaron estadísticamente la edad, el sexo, el diámetro del conducto biliar común medido por ultrasonografía, tomografía computarizada y colangiopancreatografía por resonancia magnética, y los resultados de la biopsia endoscópica. RESULTADOS: En un total de 188 pacientes incluidos en el estudio, se detectó reflujo biliar en 93 pacientes y no se observó en 95 pacientes. Se vio que el diámetro del conducto biliar común de los pacientes era de 7 mm o menos en el 70.9% (n = 66) del grupo con reflujo biliar y en el 23% (n = 22) del grupo sin reflujo biliar. El análisis estadístico reveló que, si bien hubo una diferencia significativa entre los dos grupos en términos de diámetro del conducto biliar común y metaplasia intestinal, los resultados fueron similares en ambos grupos en términos de inflamación, actividad, atrofia y presencia de Helicobacter pylori. CONCLUSIONES: Creemos que el diámetro del colédoco puede ser un factor predictivo en la detección de reflujo biliar después de la colecistectomía.

[Clinical and gastroscopic features of children with cyclic vomiting syndrome: an analysis of 63 cases]. / 儿童周期性呕吐综合征63例临床与胃镜分析.

OBJECTIVES: To study the clinical and gastroscopic features of children with cyclic vomiting syndrome. METHODS: A retrospective analysis was performed on the medical data of 63 children with cyclic vomiting syndrome who were hospitalized and followed up in Beijing Tsinghua Changgung Hospital, School of Clinical Medicine, Tsinghua University from August 2019 to March 2022. RESULTS: Among the 63 children, there were 30 boys and 33 girls, with a mean age of 6.11 years, a mean course of disease of 2.57 years, and a mean vomiting period of 4.04 days. The most common accompanying symptom was listlessness or somnolence (55/63, 87%), followed by anorexia (45/63, 71%), abdominal pain or abdominal discomfort (40/63, 63%), constipation (19/63, 30%), salivation (12/63, 19%), nausea (11/63, 17%), headache (11/63, 17%), fever (6/63, 10%), and rash (1/63, 2%). All 63 children underwent gastroscopy, among whom 3 had no marked abnormalities, 22 (35%) had chronic superficial gastritis or chronic non-atrophic gastritis alone, and 38 (60%) had other abnormal changes aside from chronic gastritis (16 children with reflux esophagitis, 12 with bile reflux gastritis, 13 with duodenitis, 10 with erosive gastritis, and 5 with gastric or duodenal ulcer). Among the 63 children, 42 underwent pathological examinations of gastric mucosa, among whom 5 had no marked abnormalities, 34 had mild chronic gastritis, 2 had moderate chronic gastritis, and 1 had severe chronic gastritis. Among the 63 children, 15 received 24-hour dynamic esophageal pH monitoring during the interictal period, among whom 9 children were found to have pathological acid reflux. CONCLUSIONS: In addition to recurrent vomiting, most children with cyclic vomiting syndrome also have the symptoms such as somnolence or listlessness, anorexia, and abdominal pain. The main manifestation on gastroscopy is chronic gastritis, and most children may also have reflux esophagitis, bile reflux gastritis, and erosive gastritis. Mild chronic gastritis is the main pathological change of gastric mucosa.

Bile reflux and bile acids in the progression of gastric intestinal metaplasia.

ABSTRACT: Gastric intestinal metaplasia (GIM) is a precancerous lesion of gastric cancer (GC) and is considered an irreversible point of progression for GC. Helicobacter pylori infection can cause GIM, but its eradication still does not reverse the process. Bile reflux is also a pathogenic factor in GIM and can continuously irritate the gastric mucosa, and bile acids in refluxed fluid have been widely reported to be associated with GIM. This paper reviews in detail the relationship between bile reflux and GIM and the mechanisms by which bile acids induce GIM.

Bile Acid-Microbiome Interaction Promotes Gastric Carcinogenesis.

Bile reflux gastritis (BRG) is associated with the development of gastric cancer (GC), but the specific mechanism remains elusive. Here, a comprehensive study is conducted to explore the roles of refluxed bile acids (BAs) and microbiome in gastric carcinogenesis. The results show that conjugated BAs, interleukin 6 (IL-6), lipopolysaccharide (LPS), and the relative abundance of LPS-producing bacteria are increased significantly in the gastric juice of both BRG and GC patients. A secondary BA, taurodeoxycholic acid (TDCA), is significantly and positively correlated with the LPS-producing bacteria in the gastric juice of these patients. TDCA promotes the proliferation of normal gastric epithelial cells (GES-1) through activation of the IL-6/JAK1/STAT3 pathway. These results are further verified in two mouse models, one by gavage of TDCA, LPS, and LPS-producing bacteria (Prevotella melaninogenica), respectively, and the other by bile reflux (BR) surgery, mimicking clinical bile refluxing. Moreover, the bile reflux induced gastric precancerous lesions observed in the post BR surgery mice can be prevented by treatment with cryptotanshinone, a plant-derived STAT3 inhibitor. These results reveal an important underlying mechanism by which bile reflux promotes gastric carcinogenesis and provide an alternative strategy for the prevention of GC associated with BRG.

Separation and Enrichment of Alkaloids from Coptidis Rhizoma and Euodiae Fructus by Macroporous Resin and Evaluation of the Effect on Bile Reflux Gastritis Rats.

The Zuojin Pill consists of Coptidis Rhizoma (CR) and Euodiae Fructus (EF). It has been a classic prescription for the treatment of gastrointestinal diseases in China since ancient times. Alkaloids are considered to be its main pharmacologically active substances. The authors of the present study investigated the feasibility of preparing high purity total alkaloids (TAs) from CR and EF extracts separately and evaluated the effect for the treatment of bile reflux gastritis (BRG). Coptis chinensis Franch. and Evodia rutaecarpa (Juss.) Benth. were used in the study. An optimized method for the enrichment and purification of TAs with macroporous resin was established. Furthermore, qualitative analysis by using ultra-high performance liquid chromatography coupled with electrospray ionization and quadrupole-time of flight mass spectrometry (UHPLC-ESI-QTOF-MS) was explored to identify the components of purified TAs. Thirty-one compounds, thirty alkaloids and one phenolic compound, were identified or tentatively assigned by comparison with reference standards or literature data. A method of ultra-high performance liquid chromatography coupled with diode array detector (UHPLC-DAD) for quantitative analysis was also developed. The contents of nine alkaloids were determined. Moreover, a rat model of BRG was used to investigate the therapeutic effect of the combination of purified TAs from CR and EF. Gastric pathologic examination suggested that the alkaloids' combination could markedly attenuate the pathological changes of gastric mucosa.

Evaluation of esophageal pathology in a group of patients 2 years after one-anastomosis gastric bypass (OAGB) - Cohort study.

BACKGROUND: One-anastomosis gastric bypass (OAGB) is a well established surgical procedure for morbid obesity. There are ongoing speculations and a debate regarding biliary reflux (BR) following OAGB. Studies considered OAGB as a risk for symptomatic and asymptomatic BR and marginal ulceration. The aim of the study was to evaluate the rate of gastroesophageal reflux disease (GERD) and esophagitis in microscopic and macroscopic evaluations among post OAGB patients diagnosed by means of upper endoscopy (UE) with a mucosal biopsy, and to assess the influence of comorbidities and medical history on endoscopic findings. METHODS: Patients operated between 1st January 2016 to 31st December 2017 were schedule, two years after OAGB for UE with a biopsy. In all cases, biopsies from the distal esophagus were obtained. All patients received a validated GERD-Health-Related Quality of Life questionnaire to assess their current symptoms. RESULTS: Fifty patients were finally enrolled in the study. Twenty-four (48%) had grade A or B esophagitis. Four patients (8%) had endoscopically suspected esophageal metaplasia (ESEM). 34/50 (68%) patients had various histopathological esophageal changes, based on the conducted endoscopy, among which four cases of Barrett's esophagus were observed. CONCLUSIONS: Despite the high rates of esophagitis in our cohort, most of the patients did not report any symptoms which confirm the thesis of the essential role of asymptomatic bile reflux following OAGB. Theoretically, chronic bile reflux can degenerate Barrett's esophagus into esophageal cancer.

Bile reflux and hypopharyngeal cancer (Review).

Laryngopharyngeal reflux, a variant of gastroesophageal reflux disease, has been considered a risk factor in the development of hypopharyngeal cancer. Bile acids are frequently present in the gastroesophageal refluxate and their effect has been associated with inflammatory and neoplastic changes in the upper aerodigestive tract. Recent in vitro and in vivo studies have provided direct evidence of the role of acidic bile refluxate in hypopharyngeal carcinogenesis and documented the crucial role of NF­κB as a key mediator of early oncogenic molecular events in this process and also suggested a contribution of STAT3. Acidic bile can cause premalignant changes and invasive squamous cell cancer in the affected hypopharynx accompanied by DNA damage, elevated p53 expression and oncogenic mRNA and microRNA alterations, previously linked to head and neck cancer. Weakly acidic bile can also increase the risk for hypopharyngeal carcinogenesis by inducing DNA damage, exerting anti­apoptotic effects and causing precancerous lesions. The most important findings that strongly support bile reflux as an independent risk factor for hypopharyngeal cancer are presented in the current review and the underlying mechanisms are provided.

The in vivo preventive and therapeutic properties of curcumin in bile reflux-related oncogenesis of the hypopharynx.

Bile at strongly acidic pH exerts a carcinogenic effect on the hypopharynx, based upon recent pre-clinical studies that support its role as an independent risk factor. We recently demonstrated in vitro that curcumin can prevent oncogenic profile of bile in human hypopharyngeal cells, by inhibiting NF-κB. We hypothesize that topically applied curcumin to the hypopharynx can similarly block early oncogenic molecular events of bile, by inhibiting NF-κB and consequently altering the expression of genes with oncogenic function. Using Mus musculus (C57Bl/6J), we topically applied curcumin (250 µmol/L; three times per day; 10 days) to the hypopharynx, 15 minutes before, 15 minutes after or in combination with bile acids (pH 3.0). Immunohistochemical analysis and qPCR revealed that topically applied curcumin either before, after or in combination with acidic bile exposure significantly suppressed its induced NF-κB activation in regenerating epithelial cells, and overexpression of Rela, Bcl2, Egfr, Stat3, Wnt5a, Tnf, Il6, Ptgs2. Akt1 was particularly inhibited by curcumin when applied simultaneously with bile. We provide novel evidence into the preventive and therapeutic properties of topically applied curcumin in acidic bile-induced early oncogenic molecular events in hypopharyngeal mucosa, by inhibiting NF-κB, and shaping future translational development of effective targeted therapies using topical non-pharmacologic inhibitors of NF-κB.

Increased levels of conjugated bile acids are associated with human bile reflux gastritis.

Bile acids (BAs) play essential roles in facilitating lipid digestion and absorption in the intestine. Gastric BAs were attributed to abnormal refluxing from duodenal compartments and correlated with the occurrence of gastric inflammation and carcinogenesis. However, the differences in gastric BAs between physiologically compromised and healthy individuals have not been fully investigated. In this study, gastric juice was collected from patients clinically diagnosed as gastritis with/without bile reflux and healthy subjects for BA profiles measurements. As a result, we found that the conjugated BAs became prominent components in bile reflux juice, whereas almost equal amounts of conjugated and unconjugated BAs existed in non-bile reflux and healthy juice. To investigate whether gastric BA changes were regulated by hepatic BA synthesis, C57BL/6J mice were intervened with GW4064/resin to decrease/increase hepatic BA synthesis. The results revealed that changes of gastric BAs were coordinated with hepatic BA changes. Additionally, gastric BAs were detected in several healthy mammals, in which there were no obvious differences between the conjugated and unconjugated BAs. Pigs were an exception. Thus, increased levels of conjugated BAs are associated with human bile reflux gastritis. Gastric conjugated BAs could become a panel of biomarkers to facilitate diagnosis of pathological bile reflux.

Long-term consequences of one anastomosis gastric bypass on esogastric mucosa in a preclinical rat model.

Although bariatric surgery is proven to sustain weight loss in morbidly obese patients, long-term adverse effects have yet to be fully characterized. This study compared the long-term consequences of two common forms of bariatric surgery: one-anastomosis gastric bypass (OAGB) and Roux-en-Y Gastric Bypass (RYGB) in a preclinical rat model. We evaluated the influence of biliopancreatic limb (BPL) length, malabsorption, and bile acid (BA) reflux on esogastric mucosa. After 30 weeks of follow-up, Wistar rats operated on RYGB, OAGB with a short BPL (15 cm, OAGB-15), or a long BPL (35 cm, OAGB-35), and unoperated rats exhibit no cases of esogastric cancer, metaplasia, dysplasia, or Barrett's esophagus. Compared to RYGB, OAGB-35 rats presented higher rate of esophagitis, fundic gastritis and perianastomotic foveolar hyperplasia. OAGB-35 rats also revealed the greatest weight loss and malabsorption. On the contrary, BA concentrations were the highest in the residual gastric pouch of OAGB-15 rats. Yet, no association could be established between the esogastric lesions and malabsorption, weight loss, or gastric bile acid concentrations. In conclusion, RYGB results in a better long-term outcome than OAGB, as chronic signs of biliary reflux or reactional gastritis were reported post-OAGB even after reducing the BPL length in a preclinical rat model.

The relationship between gastric cancer, its precancerous lesions and bile reflux: A retrospective study.

OBJECTIVE: To evaluate the relationship between gastric cancer (GC) and precancerous lesions and bile reflux. METHODS: Medical records of 30 465 participants who underwent gastroscopy between January and December 2018 in our center were reviewed. Their age, sex, time of endoscopy, endoscopic/histologic diagnosis and grade of bile reflux were recorded. The participants were further divided into the chronic gastritis group (n = 27 807), a precancerous lesion group (n = 1943) and a GC group (n = 715). The χ2 tests and hierarchical analyses were performed. RESULTS: Patients aged 18-27 years had a higher bile reflux rate than those aged 28-37 and 68-75 years (P < 0.001), while it did not differ between patients aged <50 years and those over 50 years (P = 0.639). It was lower in men than in women (P < 0.001). The bile reflux rate did not differ in terms of months, seasons and half of the year (all P > 0.05), but differed between morning and afternoon when they underwent the endoscopy (P = 0.000). There was an interrelationship between the severity of gastric mucosal disease and bile reflux grade (r = 0.171). After excluding the effects of sex, age and time of endoscopy on bile reflux, bile reflux rate in chronic gastritis and precancerous lesions was lower than in gastric cancer (P < 0.01). CONCLUSIONS: Bile reflux may be a risk factor for gastric cancer and precancerous lesions. A high grade of bile reflux may be associated with the progression of gastric mucosal diseases.

The Effect of Primary Duodenogastric Bile Reflux on the Presence and Density of Helicobacter pylori and on Gastritis in Childhood.

Background and Objectives: Although there are many studies that investigate the relationship between duodenogastric reflux (DGR) and Helicobacter pylori in adult patients, the reported data are contradictory. In addition, there are very few studies in the literature investigating the relationship between DGR and H.pylori in the pediatric age group. In the present study, we investigated the effect of primary DGR on H.pylori and gastritis. Materials and Methods: A total of 361 patients who were referred to the clinic of our hospital with dyspeptic complaints who had an upper gastrointestinal system endoscopy and a gastric biopsy were included in the study. Results: DGR was detected in 45 cases, and 316 cases that did not have DGR were considered as the control group. Comparisons were made between the DGR cases and the control group in terms of risk factors (age, gender), the presence and density of H.pylori, and the presence and severity of gastritis. The average age of the patients who were included in the study was 11.6 ± 4.6 years. A total of 128 (36%) of the cases were male and 233 (64%) were female. DGR was present in 45 (13%) of the cases. The average age of the patients with DGR was 13.9 ± 3.1 years, the average age of the control group was 11.3 ± 4.7, and there were statistically significant differences (p < 0.001). No significant differences were detected in terms of gender between DGR and the control group (p > 0.05). H.pylori (+) was detected in 29 (64%) of patients with DGR, and in 202 (64%) of the control group. No significant differences were detected between H.pylori prevalence (p = 0.947). Gastritis was detected in 37 (82%) of the patients with DGR, and in 245 (77%) of the control group (p = 0.476). No significant differences were detected between the presence and density of H.pylori, gastritis presence, severity and DGR (p > 0.05). Conclusions: The ages of patients with DGR were significantly higher than in the control group, and advanced age was shown to be a risk factor for primary DGR. It was found that the presence of DGR has no effect on the presence and severity of H.pylori. Given this situation, we consider it is important to eradicate H.pylori infection, especially in the case where H.pylori is present together with DGR.

Biliary reflux as a causal factor in hypopharyngeal carcinoma: New clinical evidence and implications.

BACKGROUND: Recent preclinical explorations strongly support the tumorigenic potential of bile on laryngopharyngeal mucosa. Herein, the authors describe, in bile-related human hypopharyngeal squamous cell carcinoma (HSCC), NF-κB-related messenger RNA (mRNA) and microRNA (miRNA) oncogenic phenotypes similar to those previously identified in acidic bile-exposed premalignant murine hypopharyngeal mucosa. METHODS: In this pilot study, the authors included human HSCC specimens paired with their adjacent normal tissue (ANT) derived from 3 representative patients with documented biliary laryngopharyngeal reflux (bile[+]) compared with 5 control patients without signs of bile reflux disease (bile[-]). Immunohistochemical, quantitative polymerase chain reaction, and miRNA analyses were used to detect the levels of activated NF-κB and expression levels of STAT3, EGFR, BCL2, WNT5A, IL-6, IL-1B, ΔNp63, cREL, TNF-α, TP53, NOTCH1, NOTCH2, NOTCH3, miR-21, miR-155, miR-192, miR-34a, miR-375, miR-451a, miR-489, miR-504, and miR-99a. RESULTS: Bile(+) HSCC demonstrated an intense NF-κB activation accompanied by significant overexpression of RELA(p65), EGFR, STAT3, BCL-2, cREL, ΔNp63, WNT5A, IL-6, and IL1B; upregulation of oncomir miR-21; and downregulation of tumor suppressor miR-375 compared with their respective ANTs. Bile(+) HSCC demonstrated significantly higher mRNA levels of all the analyzed genes, particularly RELA(p65), IL-6, EGFR, and TNF-α compared with bile(-) tumors. The miR-21/miR-375 ratio, which previously has been linked to tumor aggressiveness, was found to be >260-fold and >30-fold higher, respectively, in bile(+) HSCCs compared with their ANTs and bile(-) tumors. CONCLUSIONS: Although limitations apply to this pilot study due to the small number of patients with HSCC, the novel findings suggest that a history of bile as a component of esophageal reflux disease may represent an independent risk factor for hypopharyngeal carcinogenesis.

Bile Gastritis Following Laparoscopic Single Anastomosis Gastric Bypass: Pilot Study to Assess Significance of Bilirubin Level in Gastric Aspirate.

INTRODUCTION: Laparoscopic single anastomosis gastric bypass (SAGB) is increasingly performed for morbidly obese patients. AIM OF WORK: This pilot study aims primarily at evaluating the incidence of bile gastritis after SAGB. The occurrence of reflux oesophagitis and reflux symptoms were also assessed. PATIENTS AND METHODS: This study included 20 patients having no reflux symptoms. All patients underwent a SAGB as a primary bariatric procedure by a single surgeon. Patients included consented to have an upper GI endoscopy done at 6 months postoperatively. Gastric aspirate was sent for bilirubin level assessment. Gastric and esophageal biopsies were submitted for histopathology and campylobacter-like organism (CLO) test. RESULTS: In our study, the rate of bile gastritis was 30%. In 18 patients, the level of bilirubin in gastric aspirate seems to be related to the degree of mucosal inflammation. The remaining two patients had microscopic moderate to severe gastritis with normal aspirate bilirubin level. Two patients with bilirubin level in aspirate more than 20 mg/dl had severe oesophagitis, gastritis with erosions, and metaplasia. Relationship between bilirubin level and histopathological findings of gastric biopsy examination was statistically significant with a P value of 0.001. CONCLUSION: The incidence of bile gastritis in this cohort is higher than reported in the literature, and this may be worrying. The correlation between endoscopic findings and patients' symptoms is poor. Bilirubin level and pH in aspirate might be useful tools to confirm alkaline reflux. Its level might help to choose candidates for revision surgery after SAGB. This needs further validation with larger sample size.

Pancreaticobiliary Juice Reflux in Patients With a Morphologically Normal Ductal System: Assessment Using Unenhanced MRI With Spin Labeling.

OBJECTIVE: The purpose of this article is to evaluate pancreaticobiliary reflux and to assess its correlation with clinical findings in patients without morphologic pancreaticobiliary maljunction by using a new MRI technique. MATERIALS AND METHODS: A total of 320 consecutive patients with suspected pancreaticobiliary diseases underwent MRCP and flow analysis by MRI. MRI flow analysis, clinical, and laboratory findings of each patient were retrospectively reviewed. The visible pancreaticobiliary reflux was graded on a 5-point confidence scale. RESULTS: Among all 320 patients with pancreatic juice reflux, 14.1% had reflux scored as grades 4 and 5 combined, and 5.0% had reflux scored as grade 5. By univariate analysis and multivariate analysis, a relatively long common channel was found to be the only significant causal factor for pancreatic juice reflux. Of patients with pancreatic juice reflux of grade 4 or 5, 11.1% (5/45) also had biliary malignancies; 18.8% (3/16) of those with pancreatic juice reflux of grade 5 had biliary malignancies. Conversely, pancreatic juice reflux of grade 4 or 5 occurred in 35.7% (5/14) of patients with biliary malignancies, and reflux of grade 5 occurred in 21.4% (3/14) of those patients. CONCLUSION: It was possible to evaluate pancreaticobiliary reflux using an MRI technique that may be suitable as a screening tool. Our results revealed that pancreaticobiliary reflux is relatively frequent in individuals without pancreaticobiliary maljunction.

Clinical significance of bile reflux into the pancreatic duct without pancreaticobiliary maljunction assessed by intraoperative cholangiography.

INTRODUCTION: Bile reflux into the pancreatic duct (BRPD) is sometimes demonstrated during intraoperative cholangiography (IOC) even in patients without pancreaticobiliary maljunction. However, the clinical significance of this finding in laparoscopic and open cholecystectomy is unclear. METHODS: Among 484 patients who underwent cholecystectomy (372 laparoscopic, 112 open), patients whose pancreatic duct was depicted in IOC were selected. The value of pancreatic amylase (p-amylase) of the gallbladder bile, histological changes, and the immunohistochemical expression of proliferating cell nuclear antigen (PCNA) in the gallbladder mucosa were analyzed in patients with BRPD. The data were then compared to those in patients without BRPD whose gallbladder bile p-amylase was measured (control group, n = 20). RESULTS: The success rate of IOC was 93.6%. The rate of BRPD in laparoscopic and open cholecystectomy was 5.2% and 5.7%, respectively. The value of gallbladder bile p-amylase in patients with BRPD was significantly higher than in the control group (790.5 vs 14.0 IU/L, P = 0.034). The value of the PCNA labeling index in patients with BRPD was significantly higher than that of the control group (15.4% vs 4.1%, P = 0.0026). Among the 24 patients with BRPD, pathological changes in the gallbladder mucosa were detected in five (two hyperplasia, three metaplasia), but there was no correlation between the presence of pathological change and PCNA labeling index or gallbladder bile p-amylase. CONCLUSIONS: IOC could detect BRPD both in laparoscopic and open cholecystectomy at a similar rate. Patients with BRPD had high levels of gallbladder bile p-amylase and PCNA labeling index, findings similar to those in patients with pancreaticobiliary maljunction.

Activity of mitogen-activated protein kinases in the esophageal epithelium of patients with Barrett's esophagus.

Barrett's esophagus (BE), a complication of gastroesophageal reflux disease, is associated with an increased risk of esophageal cancer. Mitogen-activated protein kinases may play an important role in the pathogenesis of this process. We aimed to evaluate mitogen-activated protein kinases activity in esophageal mucosa of patients with BE and find possible relationship between reflux type and BE. Twenty-four patients (mean age: 59 years) with gastroesophageal reflux disease symptoms and endoscopically suspected esophageal metaplasia (ESEM) were prospectively enrolled for testing by a multichannel intraluminal impedance monitoring along with a Bilitec 2000. Endoscopic biopsies were taken from methylene blue-positive pit patterns (sites suggesting specialized intestinal metaplasia [SIM]), from 2 cm above the Z-line and from cardial parts of the stomach. The biopsies were analyzed for extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 activity by Western blot. Seventeen ESEMs had histologically proven metaplasia: eight patients had SIM and nine had gastric-type epithelia (GE). Biliary reflux was more evident in SIM (P = 0.019) but not in GE (P = 0.019); non-biliary reflux was typical for GE (P = 0.005) but not for SIM (P = 0.04). Strong activations of ERK and p38 were found predominantly in SIM, but not in normal esophageal mucosa (NE) (P = 0.01 and P < 0.001 respectively). Strong signals for active JNK and p38 were detected in GE, but not in NE (P = 0.006 and P = 0.02 respectively). ERK activity was significantly higher than p38 activity in ESEM patients only with GE (P = 0.02). The strong activation of ERK, but not JNK is indicative of SIM. The presence of bile in gastroesophageal refluxate is predisposing to SIM, but not to GE in esophageal mucosa.