Proton pump inhibitor resistance, the real challenge in gastro-esophageal reflux disease

Gastro-esophageal reflux disease(GERD)is one of the most prevalent chronic diseases.Although proton pump inhibitors(PPIs)represent the mainstay of treatment both for healing erosive esophagitis and for symptom relief,several studies have shown that up to 40%of GERD patients reported either partial or complete lack of response of their symptoms to a standard PPI dose once daily.Several mechanisms have been proposed as involved in PPIs resistance,including ineffective control of gastric acid secretion,esophageal hypersensitivity,ultrastructural and functional changes in the esophageal epithelium.The diagnostic evaluation of a refractory GERD patients should include an accurate clinical evaluation,upper endoscopy,esophageal manometry and ambulatory pH-impedance monitoring,which allows to discriminate non-erosive reflux disease patients from those presenting esophageal hypersensitivity or functional heartburn.Treatment has been primarily based on doubling the PPI dose or switching to another PPI.Patients with proven disease,not responding to PPI twice daily,are eligible for anti-reflux surgery.

Gastro-esophageal reflux disease and obesity, where is the link?

The confluence between the increased prevalence of gastro-esophageal reflux disease(GERD)and of obesity has generated great interest in the association between these two conditions.Several studies have addressed the potential relationship between GERD and obesity,but the exact mechanism by which obesity causes reflux disease still remains to be clearly defined.A commonly suggested pathogenetic pathway is the increased abdominal pressure which relaxes the lower esophageal sphincter,thus exposing the esophageal mucosal to gastric content.Apart from the mechanical pressure,visceral fat is metabolically active and it has been strongly associated with serum levels of adipocytokines including interleukin-6 and tumor necrosis factorα,which may play a role in GERD or consequent carcinogenesis.This summary is aimed to explore the potential mechanisms responsible for the association between GERD and obesity,and to better understand the possible role of weight loss as a therapeutic approach for GERD.

Gender difference in gastro-esophageal reflux diseases

The incidence of esophageal adenocarcinoma(EAC) has risen sharply in western countries over the past 4 decades. This type of cancer is considered to follow a transitional process that goes from gastro-esophageal reflux disease(GERD) to Barrett's esophagus(BE,a metaplastic condition of the distal esophagus), a precursor lesion and ultimately adenocarcinoma. This spectrum of GERD is strongly predominant in males due to an unidentified mechanism. Several epidemiologic studies have des cribed that the prevalence of GERD, BE and EAC in women is closely related to reproductive status, which suggests a possible association with the estrogen level. Recently, we revealed in an in vivo study that the inactivation of mast cells by the anti-inflammatory function of estrogen may account for the gender difference in the GERD spectrum. Other studies have described the contribution of female steroid hormones to the gender difference in these diseases. Estrogen is reported to modulate the metabolism of fat, and obesity is a main risk factor of GERDs. Moreover, estrogen could confer esophageal epithelial resistance to causative refluxate. These functions of estrogen might explain the approximately 20-year delay in the incidence of BE and the subsequent development of EAC in women compared to men, and this effect may be responsible for the male predominance. However, some observational studies demonstrated that hormone replacement therapy exerts controversial effects in GERD patients. Nevertheless, the estrogen-related endocrine milieu may prevent disease progression toward carcinogenesis in GERD patients. The development of innovative alternatives to conventional acid suppressors may become possible by clarifying the mechanisms of estrogen.

Transoral incisionless fundoplication for gastro-esophageal reflux disease: Techniques and outcomes

Gastro-esophageal reflux disease(GERD)is a verycommon disorder that results primarily from the loss of an effective antireflux barrier,which forms a mechanical obstacle to the retrograde movement of gastric content.GERD can be currently treated by medical therapy,surgical or endoscopic transoral intervention.Medical therapy is the most common approach,though concerns have been increasingly raised in recent years about the potential side effects of continuous longterm medication,drug intolerance or unresponsiveness,and the need for high dosages for long periods to treat symptoms or prevent recurrences.Surgery too may in some cases have consequences such as longlasting dysphagia,flatulence,inability to belch or vomit,diarrhea,or functional dyspepsia related to delayed gastric emptying.In the last few years,transoral incisionless fundoplication(TIF)has proved an effective and promising therapeutic option as an alternative to medical and surgical therapy.This review describes the steps of the TIF technique,using the Esophy X®device and the MUSETM system.Complications and their management are described in detail,and the recent literature regarding the outcomes is reviewed.TIF reconfigures the tissue to obtain a full-thickness gastroesophageal valve from inside the stomach,by serosato-serosa plications which include the muscle layers.To date the procedure has achieved lasting improvement of GERD symptoms(up to six years),cessation or reduction of proton pump inhibitor medication in about 75%of patients,and improvement of functional findings,measured by either p H or impedance monitoring.

Test-based exclusion diets in gastro-esophageal reflux disease patients:A randomized controlled pilot trial

AIM: To investigate the clinical response of gastro-esophageal reflux disease (GERD) symptoms to exclusion diets based on food intolerance tests.

Symptoms of Gastro-Esophageal Reflux Disease: A Comparative Study between Elderly and Younger Patients in Japan

The difference in gastro-esophageal reflux disease (GERD) symptoms between elderly and younger GERD patients has not been fully studied. Our aim was to examine if there was any difference in the degree of GERD symptoms between elderly and younger patients with reflux esophagitis. Patients who were diagnosed by endoscopic examination as having reflux esophagitis and who answered the questionnaire on the frequency scale for the symptoms of GERD (FSSG) were included. Elderly and younger adult patients were defined as patients aged 65 and over or less than 65, respectively. 596 subjects were included. 184 subjects (mean 71.1 years;114 males) were classified into the Elderly group, and 412 subjects (mean 51.2 years;307 males) into the Younger group. The mean FSSG score of the Elderly and Younger groups was 6.7 and 8.4, respectively (p = 0.0024). Among those with severe esophagitis, the mean FSSG score of the Elderly and Younger groups was 8.5 and 8.7, respectively (p = 0.58). Although elderly patients tended to have less degree of GERD symptoms than younger patients, these findings suggest that there may be no significant age-related difference in complaints of GERD symptoms among severe reflux esophagitis patients.

Anesthetic management of the SRS^(TM) endoscopic stapling system for gastro-esophageal reflux disease

The SRS TM Endoscopic Stapling System(Medigus,Tel Aviv,Israel) is a new tool capable of creating a totally endoscopic fundoplication,combined with an endoscope,endoscopic ultrasound and a surgical stapler.SRS TM endoscopic stapling for gastro-esophageal reflux disease is a minimally invasive,outpatient procedure,which requires general anesthesia with positive-pressure ventilation.Keeping the patient on positive endexpiratory pressure(PEEP) may minimize the pressure gradient between the esophagus and the mediastinum,as well as help to prevent air from leaking around the screws and causing pneumomediastinum.In addition,in patients with hiatal hernia,higher PEEP levels may be required to increase intra-thoracic pressure and to force the stomach to slide into the abdomen for ease of endoscopy.We advise smoother emergence from anesthesia,taking precautions for retching,postoperative nausea and vomiting(PONV),while coughing and gagging during extubation and PONV may affect the success of the procedure.Total intravenous anesthesia with propofol and remifentanil seems to be a good choice for these reasons.

Sensitivity of Esophageal Scintigraphy (Milk Scans) in Detecting Gastro-Esophageal Reflux

Gastro-esophageal scintigraphy (milk scan) is an accurate technique for detecting gastro-esophageal reflux that can be performed rapidly with minimal patient discomfort. A retrospective study was performed to find out to how much radionuclide milk scan is sensitive for detecting gastro-esophageal reflux (GER) for 89 patients who subjected to milk scan within Years 2010 to 2013. The study group age is ranging from one month old to four years old. Milk scan was performed using PHILIPS and SEIMENS machine. Tc 99-m sulfur colloid with milk administrated orally or through nasogastric tube to the patient. The highest frequency for milk scan study was in age group of 0 - 6 months old with 77% positive finding. Patients who suffer repeated vomiting represented the highest reason of examination for milk scan (46% of overall cases), while chocking attacks, pulmonary aspiration, and congenital heart disease, were 26%, 16%, 12% respectively of the overall cases. Seventy-nine percent of patients who prepared to be examine using nasogastric tube found with positive finding, 50% of GER patients have abnormal tracer activity in the mid of esophagus;on the other hand, 50% of GER patients divided equally between the lower and upper esophagus. The study show that infants especially in age of 0 - 6 months old and with repeated vomiting symptoms are strongly recommended to milk scan study rather than fluoroscopy to avoid unnecessary dose to the patients.

Uncharted Territory: Frequent Relapsing, Steroid Sensitive Secondary Minimal Change Nephrotic Syndrome Cause by Solid Tumor of the Gastro-Esophageal Junction —(Case Presentation and Review of the Literature)

We reported a biopsy proved case of minimal change nephrotic syndrome in a 72-year-old patient. The minimal change nephrotic syndrome has been steroid sensitive, but the patient had 7 relapses over a span of 5 years. Each time the dose of steroid is tapered, a relapse of the nephrotic syndrome occurred. Eventually, the patient was complaining of dysphagia and difficulty swallowing. Hospital work-up with barium swallow, endoscopy, and CT of the chest, abdomen and pelvis, revealed a focal stenotic lesion with mild to moderate esophageal dysmotility 7/15/2022. A diagnosis of an ulcerating lesion with biopsy confirmed a neuro-endocrine carcinoma of the gastro-esophageal junction was entertained. The CT of the chest/abdomen/pelvis, 7/19/2022, has shown, an esophageal mass of 5.1 × 5.6 × 7 cm of the gastro-esophageal junction with ulceration. No evidence of spread beyond the esophagus and stomach. The histology revealed a poorly differentiated neuroendocrine tumor of the gastro-esophageal junction. The patient underwent several rounds of chemotherapy, radiation, and surgery culminating in tumor control. His nephrotic syndrome was resolved after the tumor has been controlled by surgery and chemotherapy.

Suppression of esophageal cancer cell growth using curcumin,(-)-epigallocatechin-3-gallate and lovastatin

AIM:To determine the effects of curcumin,(-)-epigallocatechin-3-gallate (EGCG),lovastatin,and their combinations on inhibition of esophageal cancer.METHODS:Esophageal cancer TE-8 and SKGT-4 cell lines were subjected to cell viability methyl thiazolyl tetrazolium and tumor cell invasion assays in vitro and tumor formation and growth in nude mouse xenografts with or without curcumin,EGCG and lovastatin treatment.Gene expression was detected using immunohistochemistry and Western blotting in tumor cell lines,tumor xenografts and human esophageal cancer tissues,respectively.RESULTS:These drugs individually or in combinations significantly reduced the viability and invasion capacity of esophageal cancer cells in vitro.Molecularly,these three agents reduced the expression of phosphorylated extracellular-signal-regulated kinases (Erk1/2),c-Jun and cyclooxygenase-2 (COX-2),but activated caspase 3 in esophageal cancer cells.The nude mouse xenograft assay showed that EGCG and the combinations of curcumin,EGCG and lovastatin suppressed esophageal cancer cell growth and reduced the expression of Ki67,phosphorylated Erk1/2 and COX-2.The expression of phosphorylated Erk1/2 and COX-2 in esophageal cancer tissue specimens was also analyzed using immunohistochemistry.The data demonstrated that 77 of 156 (49.4%) tumors expressed phosphorylated Erk1/2 and that 121 of 156 (77.6%) esophageal cancers expressed COX-2 protein.In particular,phosphorylated Erk1/2 was expressed in 23 of 50 (46%) cases of esophageal squamous cell carcinoma (SCC) and in 54 of 106 (50.9%) cases of adenocarcinoma,while COX-2 was expressed in 39 of 50 (78%) esophageal SCC and in 82 of 106 (77.4%) esophageal adenocarcinoma.CONCLUSION:The combinations of curcumin,EGCG and lovastatin were able to suppress esophageal cancer cell growth in vitro and in nude mouse xenografts,these drugs also inhibited phosphorylated Erk1/2,c-Jun and COX-2 expression.

miR-93-5p Transferred by Exosomes Promotes the Proliferation of Esophageal Cancer Cells via Intercellular Communication by Targeting PTEN

Objective To investigate the relationship between plasma miR-93-5p and the risk of esophageal cancer, as well as the influence of miR-93-5p on the biological function of esophageal cancer cells,exerted through exosomes.Methods The expression of plasma miR-93-5p in esophageal cancer patients and healthy controls was analysed by real-time quantitative PCR. The influence of miR-93-5p on the risk and prognosis of esophageal carcinoma was analyzed by conditional logistic regression and survival analysis. The effect of miR-93-5p on the biological function of recipient cells was investigated by establishing an in vitro donor cell co-culture model. The target gene of miR-93-5p was validated by luciferase reporter assay and Western Blotting.Results Upregulation of plasma miR-93-5p expression significantly increases the risk of esophageal cancer and is associated with poor prognosis. miR-93-5p transferred by exosomes promotes the proliferation of recipient esophageal cancer cells and affects the expression of PTEN and its downstream proteins p21 and cyclin D1.Conclusion Our study provides a reference for the identification of biomarkers for the diagnosis and prognosis of esophageal cancer.

Overlapping gastroesophageal reflux disease and irritable bowel syndrome:Increased dysfunctional symptoms

AIM:To investigate the association of gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS) in Iranian patients and examine the prevalence of functional symptoms of the gastrointestinal tract in patients presenting with either IBS, GERD or both.METHODS: Six thousand four hundred and seventy six patients presented to the Gastro-intestinal (GI) clinic with symptoms of functional dysfunction of GI tract, 1419 patients (62.0% women, 38.0% men; mean age: 37.4±11.5 years) met Rome or Rome criteria(depending on the year of diagnosis)for IBS.2658 patients were diagnosed with GERD based on clinical presentation and endoscopic findings.We assessed other functional symptoms(epigastric pain,nausea,vomiting,belching,constipation and diarrhea)in patients suffering from GERD,IBS or both.RESULTS: Among IBS subjects, 63.6% (69.0% women, 31.0% men; mean age: 36.4±10.3 years) also hadGERD, whereas 34.7% of the non-IBS patients had GERD [odds ratio (OR) =3.2, 95% confidence interval (CI): 2.9-3.7, P<0.0001]. Among patients with GERD, 33.9% of subjects met Rome criteria compared to 13.5% of non-GERD patients (OR=3.6, 95% CI: 3.1-4.3, P<0.0001). Prevalence of all functional symptoms was higher in overlapping GERD and IBS subjects, when compared with their prevalence in the IBS subjects without GERD or GERD only subjects (P<0.05).CONCLUSION: This finding shows that in overlapping GERD and IBS, other functional abnormalities of the GI tract are also highly prevalent, suggesting a common underlying dysfunction.

Circular RNA AKT3 governs malignant behaviors of esophageal cancer cells by sponging miR-17-5p

BACKGROUND Recent studies have demonstrated that circular RNA AKT3(circAKT3)plays a crucial role in regulating the malignant phenotypes of tumor cells.However,the potential effects of circAKT3 on esophageal cancer have not been investigated.AIM To illuminate the role of circAKT3 in malignant behaviors of esophageal cancer cells and its underlying mechanism.METHODS Clinical samples were collected to detect the expression of circAKT3.The role of circAKT3 in proliferation,migration,invasion,and apoptosis of esophageal cancer cells was evaluated using Cell Counting Kit-8,wound healing assays,Transwell assays,and fluorescence analysis,respectively.The target of circAKT3 was screened and identified using an online database and luciferase reporter assay.A xenograft nude mouse model was established to investigate the role of circAKT3 in vivo.RESULTS In vitro assays showed that proliferative,migratory,and invasive capacities of esophageal cancer cells were significantly enhanced by circAKT3 overexpression.Furthermore,miR-17-5p was screened as the target of circAKT3,and miR-17-5p antagonized the effects of circAKT3 on esophageal cancer cells.Moreover,we identified RHOC and STAT3 as the direct target molecules of miR-17-5p,and circAKT3 facilitated expression of RHOC and STAT3 by inhibiting miR-17-5p.In vivo assays showed circAKT3 knockdown inhibited growth of esophageal cancer.CONCLUSION CircAKT3 contributed to the malignant behaviors of esophageal cancer in vitro and in vivo by sponging miR-17-5p thus providing a potential target for treatment of esophageal cancer.

Overlap of functional heartburn and gastroesophageal reflux disease with irritable bowel syndrome

Several studies indicate a significant degree of overlap between irritable bowel syndrome(IBS)and gastroesophageal reflux disease(GERD).Likewise,both functional heartburn(FH)and IBS are functional digestive disorders that may occur in the same patients.However,data establishing a solid link between FH and IBS are lacking,mainly because the clinical definition of FH has undergone substantial changes over the years.The available literature on the overlap between GERD or FH and IBS highlights considerable heterogeneity in terms of the criteria and diagnostic procedures used to assess heartburn and IBS.In particular,several epidemiological studies included patients with concomitant IBS and GERD without any attempt to distinguish FH(as defined by the RomeⅢcriteria)from GERD via pathophysiological investigations.Independent of these critical issues,there is preliminary evidence supporting a significantdegree of FH-IBS overlap.This underscores the need for studies based on updated diagnostic criteria and accurate pathophysiological classifications,particularly to distinguish FH from GERD.This distinction would represent an essential starting point to achieving a better understanding of pathophysiology in the subclasses of patients with GERD and FH and properly assessing the different degrees of overlap between IBS and the subcategories of heartburn.The present review article intends to appraise and critically discuss current evidence supporting a possible concomitance of GERD or FH with IBS in the same patients and to highlight the pathophysiological relationships between these disorders.

Chromosome analysis of esophageal squamous cell carcinoma cell line KYSE 410-4 by repetitive multicolor fluorescence in situ hybridization

Chromosome aberrations are distinctive features of human malignant tumors. Analysis of chromosomal changes can illuminate the molecular mechanisms underlying the development and progression of cancer. To establish the technique of multicolor fluorescence in situ hybridization （M-FISH） for identifying chromosome aberrations in esophageal carcinoma cell line KYSE 410-4, four pools of 6-color whole-chromosome painting probes have been designed and hybridized on the same metaphase spread by four rounds of repetitive FISH. Repetitive 6-color M-FISH was successfully established and the cytogenetic abnormalities in KYSE 410-4 cells were characterized. Chromosome gains occurred at 2q, 3, 8, 17p, and X. An isochromosome 3q was visualized in the cell line, which might be one intermediate mechanism leading to 3p losses and/or 3q gains. Furthermore, 16 structural arrangements were detected, including four derivative chromosomes. The rearrangement of the centromeric regions accounted for approximately 44% of all rearrangements. The results added a more complete and accurate information of the genetic alterations to the classical cytogenetic description of KYSE 410-4 and provided a detailed cytogenetic background data for appropriate use of the cell line. The established 6-color M-FISH was useful for analyzing chromosomes in the whole genome of human tumors.

Detection of D2-40 monoclonal antibody-labeled lymphatic vessel invasion in esophageal squamous cell carcinoma and its clinicopathologic significance

Objective： This study aims to investigate the clinicopathologic significance of lymphatic vessel invasion （LVI） labeled by D2-40 monoclonal antibody in esophageal squamous cell carcinoma （ESCC）. Methods： Immunohistochemical assay was used to detect the expression of D2-40 and LVI in 107 ESCC patients. Then, the correlation between the clinicopathologic feature and the overall survival time of the patients was analyzed. Results： The lymph node metastasis rates were 70% and 21% in the LVI-positive and LVI-negative groups, respectively. The nodal metastasis rate was higher in the LVI-positive group than in the LVI-negative group. Multivariate regression analysis showed that LVI was related to nodal metastasis （P〈0.001）. The median survival time of the patients was 26 and 43 months in the LVI-positive and LVI-negative groups, respectively. Mthough univariate regression analysis showed significant difference between the two groups （P=0.014）, multivariate regression analysis revealed that LVI was not an independent prognostic factor for overall survival in the ESCC patients （P=0.062）. Lymphatic node metastasis （P=0.031）, clinical stage （P=0.019）, and residual tumor （P=0.026） were the independent prognostic factors. Conclusion： LVI labeled by D2-40 monoclonal antibody is a risk factor predictive of lymph node metastasis in ESCC patients.

N-linked glycoproteomic profiling in esophageal squamous cell carcinoma

BACKGROUND Mass spectrometry-based proteomics and glycomics reveal post-translational modifications providing significant biological insights beyond the scope of genomic sequencing.AIM To characterize the N-linked glycoproteomic profile in esophageal squamous cell carcinoma(ESCC)via two complementary approaches.METHODS Using tandem multilectin affinity chromatography for enrichment of N-linked glycoproteins,we performed N-linked glycoproteomic profiling in ESCC tissues by two-dimensional gel electrophoresis(2-DE)-based and isobaric tags for relative and absolute quantification(iTRAQ)labeling-based mass spectrometry quantitation in parallel,followed by validation of candidate glycoprotein biomarkers by Western blot.RESULTS 2-DE-based and iTRAQ labeling-based quantitation identified 24 and 402 differentially expressed N-linked glycoproteins,respectively,with 15 in common,demonstrating the outperformance of iTRAQ labeling-based quantitation over 2-DE and complementarity of these two approaches.Proteomaps showed the distinct compositions of functional categories between proteins and glycoproteins with differential expression associated with ESCC.Western blot analysis validated the up-regulation of total procathepsin D and high-mannose procathepsin D,and the downregulation of total haptoglobin,high-mannose clusterin,and GlcNAc/sialic acid-containing fraction of 14-3-3ζ in ESCC tissues.The serum levels of glycosylated fractions of clusterin,prolinearginine-rich end leucine-rich repeat protein,and haptoglobin in patients with ESCC were remarkably higher than those in healthy controls.CONCLUSION Our study provides insights into the aberrant N-linked glycoproteome associated with ESCC,which will be a valuable resource for future investigations.

Does a melatonin supplement alter the course of gastroesophageal reflux disease?

Symptomatic gastro-esophageal reflux disease(GERD) is a very common disease.The consequence of GERD is not only erosive esophagitis,but also esophageal stricture,Barrett's esophagus and extra-esophageal damage(including the lungs,throat,sinuses,middle ear and teeth).GERD and Barrett's esophagus are also identif ied as major risk factors for esophageal carcinoma.Therapy with melatonin prevents esophageal injury from acid-pepsin and acid-pepsin-bile exposure in animals,then further studies are required in humans to establish whether a melatonin supplement is able to protect the patients with GERD from erosions,Barrett's and neoplasia.

Irradiation-induced EMT is associated with activation of TGF-β and restriction of BMP signaling in esophageal cancer cells

Objective: Irradiation may enhance migration and/or invasiveness of cancer cells in vitro and in vivo, the mechanism of which may be associated with epithelial-mesenchymal transition (EMT). The present study explored the mechanisms of EMT induced by irradiation in esophageal cancer cells. Methods: Human esophageal cancer cell line EC109 was treated with increased doses of irradiation (0 Gy, 20 Gy, 40 Gy and 60 Gy). Cell morphology was observed. Expressions of E-cadherin and vimentin were determined by immunofluorescence assay or western blot. Secretion of transforming growth factor-β1 (TGF-β1) by cells was determined by enzyme-linked immunosorbent assay (ELISA), and the expressions of Smad2/3 and phosphorated Smad2 (p-Smad2) were also examined by Western blot. The mRNA expressions of BMP-4, a bone morphogenetic protein (BMP) ligand, and two secreted BMP antagonists (Chordin and Gremlin), were detected with reverse transcription-polymerase chain reaction (RT-PCR). Cell migratory capacity was evaluated. Results: Irradiation induced EMT in EC109 cells in a dose-dependent manner as evidenced by morphological changes, decreased expression of E-cadherin and increased expression of vimentin, and increased cell motility. The secretion of TGF-β1 and expression of p-Smad2 were gradually increased in an irradiation dose-dependent manner, but the Smad2/3 protein levels remained stable. The mRNA expression of BMP-4 was gradually down-regulated, but the expressions of Chordin and Gremlin were gradually up-regulated in cells treated with increased doses of irradiation. Conclusion: Irradiation can induce EMT in esophageal cancer cells in a dose-dependent manner, and the mechanism may be associated with activation of TGF-β and restriction of BMP signaling.

Research Progress of Different Acupuncture and Moxibustion Methods in the Treatment of GERD(Gastro Esophageal Reflux Disease)

Over the past decade,there have been many clinical reports on acupuncture and moxibustion in the treatment of gastro esophageal reflux disease,which has been an increasing trend year by year.The authors use"acupuncture","acupuncture and moxibustion"or"electric acupuncture"and"GERD"or"gastro esophageal reflux disease"as key words for retrieval.Through the clinical articles on acupuncture and moxibustion methods in the treatment of GERD indexed by China CNKI academic literature database,VPCS database and Wanfang database from 2006 to 2016,we find that:acupuncture and moxibustion methods in the treatment of GERD has definite curative effect and outstanding advantages.It can better improve the symptoms of patients and can effectively improve their quality of life.At present,in clinical applications,there are treatment ideas such as the method of acupuncture on governor vessel back segment,the old ten needles,and compatibility of five meridians in the aspect of acupoint selection;there are treatment ideas such as fire acupuncture,thread-embedding,and electric acupuncture in the aspect of method of needling and moxibustion;there are treatment ideas such as acupuncture and moxibustion combined with pinellia ternate Xiexin Decoction,Chinese herb bath,deanxit(flupentixol and melitracen tablets)in the aspect of acupuncture and medicinal treatment.This paper comb integration of the current variety of therapies,in order to allow readers to obtain a more comprehensive clinical diagnosis and treatment ideas of gastro esophageal reflux disease.