Gastroesophageal reflux disease and salivary pepsin in patients with heterotopic gastric mucosa in the upper esophagus

Summary Background Heterotopic gastric mucosa in the upper esophagus (HGMUE) is reported to be related to gastroesophageal reflux disease (GERD). This study investigated the prevalence of GERD and the use of salivary pepsin to diagnose gastroesophageal reflux, especially proximal reflux, in HGMUE patients. Methods One hundred and fifty-three HGMUE patients and 50 healthy volunteers were studied. All subjects took a reflux symptom index questionnaire (RSI); underwent endoscopy, barium esophagogram, high-resolution manometry (HRM), and 24-hour multichannel intraluminal impedance-pH-metry (MII-pH); and salivary pepsin test. Results Ninety-five (62.1%) HGMUE patients but no control subjects were diagnosed with GERD. The salivary pepsin concentration, RSI score, DeMeester score, acid exposure time (AET), total reflux episodes, proximal acidic reflux episodes, and proximal weakly acidic reflux episodes were significantly higher in the HGMUE group than in the control group (P < 0.05). The salivary pepsin test showed a sensitivity of 85.9% and specificity of 56.9% for diagnosing GERD using the optimal cut-off value of 75 ng/mL. One hundred and seven (69.9%) and 46 (30.1%) HGMUE patients were categorized as pepsin (+) and pepsin (−), respectively when 75 ng/mL was used as a cut-off value. Male sex, RSI, AET, and proximal acid reflux episodes were positive predictive factors for the occurrence of pepsin (+) in HGMUE patients. Conclusions GERD, especially GERD with proximal acid reflux and related symptoms, was common in HGMUE patients. The salivary pepsin test could be an additional useful test for testing reflux in HGMUE patients, but it will not replace the MII-pH.

Determining oncogenic patterns and cancer predisposition through the transcriptomic profile in Mitchell–Riley syndrome with heterotopic gastric mucosa and duodenal atresia: a case report

Background Homozygous mutations in the transcription factor RFX6 are the cause of the Mitchell–Riley syndrome (MRS) associating neonatal diabetes, congenital digestive system, such as biliary atresia, pancreatic hypoplasia, duodenal and/or jejunal atresia, intestinal malrotation, gallbladder aplasia, cholestasis. A constitutive inactivation of RFX6 leads also to gastric heterotopia. Application of RNA-seq in human diseases may help to better understand pathogenic mechanism of diseases and to predict the risk of developing chronic disorders and personalizing their prevention and treatment. We evaluated oncogenic patterns and cancer predisposition using the transcriptomic profile in a case of MRS with neonatal diabetes, duodenal atresia, and extensive intestinal tract gastric heterotopia. Results We signalled the interactors of RFX6 with other up and downregulated genes, that may be interested in severity of diabetic condition, in multi-organs impairment and cancer predisposition. Furthermore, several dysregulated genes are involved in biological processes that can lead to promote cancer including “Evading apoptosis” (BAD, BBC3, EGF, FGFR2, FLT3LG, HMOX1, HRAS, IFNAR2, IGF1R, IL12RB1, IL13RA1, IL15, IL2RB, IL2RG, IL6R, KEAP1, MGST1, PDGFA, PDGFRB, PIK3R3, RALB, RALGDS, RASSF1, SOS1, TGFA, TXNRD3), “Proliferation” (APC, BRAF, CCND2, CCND3, CCNE2, FGFR2, FLT3LG, FZD1, FZD6, HMOX1, HRAS, IGF1R, KEAP1, LRP6, MAPK3, MGST1, PDGFA, PDGFB, PDGFRB, RB1, SOS1, TGFA, TXNRD3, WNT10B), “Sustained angiogenesis” (BRAF, FGFR2, FLT3LG, HRAS, IGF1R, JAG1, MAPK3, NOTCH2, PDGFA, PDGFB, PDGFRB, SOS1, TGFA, TGFB1), “Genomic instability” (BAD, BBC3) and “Insensitivity to anti-growth signals” (SMAD2, TGFB1). We also inspected the signalings and their related genes in cancer, such as “PI3K signaling”, “ERK signaling”, “JAK-STAT signaling”, “Calcium signaling”, “Other RAS signaling”, “WNT signaling”. Conclusions In our MRS patient, we signaled the interactors of RFX6 with other up- and downregulated genes that may be related to severe diabetic condition, multi-organ impairment, and cancer predisposition. Notably, many dysregulated genes may lead to triggering carcinogenesis. The possibility of the patient developing cancer degeneration in heterotopic gastric mucosa and/or additional long-term tumoral sequelae is not excluded. Personalized prevention and treatment strategies should be proposed.

Heterotopic Gastric Mucosa in Gastric Propria Muscularis Treated by Endoscopic Submucosal Dissection: A Case Report and Literature Review.

Background: Heterotopic gastric mucosa（HGM）is a congenital anatomical variation. It can occur in various tissues and organs of the gastrointestinal tract. Part of the HGM appeared as a solitary, sessile submucosal lesions covered with normal mucosa, and because it was relatively rare, thereby resulting in some HGM to be easily missed or misdiagnosed. We report on a case of heterotopic gastric mucosa in gastric propria muscularis.Case presentation: A 32-year-old man with abdominal distension for one month. Upper gastrointestinal endoscopy revealed hemispherical lesion covered with smooth mucosa located in gastric antrum. Endoscopic ultrasound (EUS) revealed that it might be derived from the submucosa, with no echogenic nodules, and a partition is visible inside. Endoscopic submucosal dissection (ESD) was performed and histological examination revealed scattered heterotopic mucosal glands (HGG) located in the propria muscularis. Regular follow-up, the patient's abdominal distension was significantly relieved.Conclusion: HGM of the type of submucosal tumor-like lesion is rare. EUS is a well-established method for submucosal lesion. On EUS, these lesions showed cystic anechoic central core in the submucosa with no solid component,which is similar to gastric cyst. Therefore, this requires us to be alert to the possibility of HGM in order to further evaluate and treat, and if necessary, it can be removed by ESD.

Prevalencia de mucosa gástrica heterotópica cervical y su relación con síntomas de reflujo gastroesofágico. Estudio observacional

Introduction. The heterotopic gastric mucosal patch or inlet patch is the presence of gastric columnar mucosa outside the stomach, most frequently located in the proximal esophagus. Its manifestations vary from esophageal and extraesophageal reflux symptoms to major complications, most of them being asymptomatic. Aim. To determine the prevalence of cervical heterotopic gastric mucosa in our environment and its association with esophageal and extraesophageal reflux symptoms. Material and methods. Prospective cross-sectional and observational study; consecutive patients who came to our institution between December 2018 and October 2019 for diagnostic upper gastrointestinal videoendoscopy were included, following a questionnaire on clinical manifestations. Results. A total of 1,408 patients were included. In 89 (6.3%), a cervical heterotopic gastric mucosal patch was described. The mean age of the patients without this condition was 54.6 and 55.5 in patients with it. The esophageal symptoms of gastroesophageal reflux (heartburn, regurgitation, and chest pain) in patients with cervical heterotopic gastric mucosa was observed in 40 (44.9% / p = 0.473), 12 (13.5% / p = 0.783) and 4 (4.5% / p = 0.199) patients respectively. The presence of extraesophageal symptoms (globus, chronic cough, dysphonia, and throat clearing) in patients with cervical heterotopic gastric mucosa was: 9 (10.1% / p = 0.011); 7 (7.9% / p = 0.155); 4 (4.5% / p = 0.458) and 9 (10.1% / p = 0.036) respectively. Conclusions. A statistically significant association was found between the presence of cervical heterotopic gastric mucosal patch and symptoms of globus (p = 0.011) and throat clearing (p = 0.036). It could be interpreted that this group of patients would benefit from the research and treatment of this condition with the intention of improving their symptoms.

Symptomatic Heterotopic Gastric Mucosa in Distal Esophagus

Introduction Heterotopic gastric mucosa (HGM) in esophagus is commonly noted as an inlet patch at endoscopy. We describe a rare patient with symptomatic distal esophageal HGM. Case Report A 40-year-old male presented with retrosternal pain and marked odynophagia for the last 4 weeks without any history of ingestion of antibiotics, foreign body, or corrosive. Endoscopy showed abrupt circumferential transition to salmon pink mucosa at 35 cm from incisors. From 35 to 41 cm, there were areas of polypoid edematous thickening with few superficial ulcers of 1 to 3 mm. Squamous epithelium was visualized at narrow band imaging from 41 cm to the Z-line at 43 cm with no hiatus hernia. Biopsy showed gastric-type mucosa with parietal cells without dysplasia. Serology for cytomegalovirus and human immunodeficiency virus was negative. He was managed with proton pump inhibitors (PPIs) and prokinetics and improved symptomatically. Follow-up endoscopy at 3 months demonstrated healing of ulcers with persistence of HGM and pseudopolyps. He remains well on maintenance with PPI at 1-year follow-up. Conclusion Symptomatic HGM in distal esophagus is rare and can be differentiated from Barrett’s esophagus histologically and by presence of squamous epithelium between HGM and stomach. Inflammatory mass lesions may develop and mimic esophageal malignancy. Symptoms are largely due to acid production and usually respond to PPI.