Robotic Surgery: An Effective Treatment Option for Epiphrenic Diverticulum Associated with Nutcracker Esophagus

Background: Epiphrenic Diverticulum is frequently associated with esophageal motility disorders, such as nutcrackers esophagus. The diagnosis is usually made using imaging studies such as a Barium esophagogram, and esophageal manometry. Surgical treatment options for epiphrenic diverticulum and EN include diverticulectomy and wide myotomy. Aim: The resection of three epiphrenic diverticula and extensive myotomy were performed by robotic thoracoscopy uneventfully. Case presentation: A 65-year-old female complaining of dysphagia for solid foods, Chest pain and regurgitation. Esophagogastroduodenoscopy (EDG) with difficulty in advancing the endoscope at 25 cm and demonstrating an ED, no hiatal hernia and normal stomach and duodenum. Barium Esophagogram showed multiple diverticula and tortuosity throughout the esophagus. Conclusion: With robotic surgery, surgeons can perform highly precise operations with enhanced 3D vision and control. Through this cutting-edge approach, the treatment of ED associated with EN can be drastically changed, promising better outcomes for patients.

Myocardial metastasis from ZEB1-and TWIST-positive spindle cell carcinoma of the esophagus:A case report

BACKGROUND Metastatic cardiac tumors are known to occur more frequently than primary cardiac tumors,however,they often remain asymptomatic and are commonly dis-covered on autopsy.Malignant tumors with a relatively high frequency of cardiac metastasis include mesothelioma,melanoma,lung cancer,and breast cancer,whereas reports of esophageal cancer with cardiac metastasis are rare.CASE SUMMARY The case of a 60-year-old man who complained of dysphagia is presented.Upper gastrointestinal endoscopy showed a submucosal tumor-like elevated lesion in the esophagus causing stenosis.Contrast-enhanced computed tomography showed left atrial compression due to the esophageal tumor,multiple liver and lung metastases,and a left pleural effusion.Pathological examination of a biopsy speci-men from the esophageal tumor showed spindle-shaped cells,raising suspicion of esophageal sarcoma.The disease progressed rapidly,and systemic chemotherapy was deemed necessary,however,due to his poor general condition,adminis-tration of cytotoxic agents was considered difficult.Given his high Combined Positive Score,nivolumab was administered,however,the patient soon died from the disease.The autopsy confirmed spindle cell carcinoma(SCC)of the esophagus and cardiac metastasis with similar histological features.Cancer stem cell markers,ZEB1 and TWIST,were positive in both the primary tumor and the cardiac metastasis.CONCLUSION To the best of our knowledge,there have been no prior reports of cardiac metastasis of esophageal SCC.This case highlights our experience with a patient with esophageal SCC who progressed rapidly and died from the disease,with the autopsy examination showing cardiac metastasis.

Advancements in Barrett's esophagus detection:The role of artificial intelligence and its implications

Artificial intelligence(AI)is making significant strides in revolutionizing the detection of Barrett's esophagus(BE),a precursor to esophageal adenocarcinoma.In the research article by Tsai et al,researchers utilized endoscopic images to train an AI model,challenging the traditional distinction between endoscopic and histological BE.This approach yielded remarkable results,with the AI system achieving an accuracy of 94.37%,sensitivity of 94.29%,and specificity of 94.44%.The study's extensive dataset enhances the AI model's practicality,offering valuable support to endoscopists by minimizing unnecessary biopsies.However,questions about the applicability to different endoscopic systems remain.The study underscores the potential of AI in BE detection while highlighting the need for further research to assess its adaptability to diverse clinical settings.

Large isolated fibrous tumors in the upper esophagus: A case report

BACKGROUND Solitary fibrous tumors(SFT)are rare spindle cell tumors that are usually benign.A total of 10 cases of SFTs in the upper esophagus have ever been reported.Here,we report the anesthetic management of a patient with a large isolated fibrous tumor of the upper esophagus compressing the tracheal membrane.We also provide a literature review of the current research.CASE SUMMARY We report the case of a 49 year old male with“cough aggravation and wheezing after exercise”,who underwent esophagectomy for a large isolated fibrous tumor compressing the tracheal membrane in the upper esophagus.We advise the use of a single-lumen tube with a blocker in patients with difficult airways to reduce the incidence of airway injury and fibrinoscopy at all stages of the perioperative period to guide airway management.This case study is the first report of the anesthetic management of a large,isolated fibrous tumor compressing the tracheal membrane in the upper esophagus.CONCLUSION This rare case emphasizes the importance of perioperative management of anesthesia in patients with large isolated fibrous tumors of the upper esophagus that compress the tracheal membrane.The use of blocker reduce the incidence of airway injury and fibrinoscopy at the perioperative period to guide airway mana-gement.

Socioeconomic traits and the risk of Barrett’s esophagus and gastroesophageal reflux disease: A Mendelian randomization study

BACKGROUND Previous observational studies have shown that the prevalence of gastroesophageal reflux disease(GERD)and Barrett’s esophagus(BE)is associated with socioeconomic status.However,due to the methodological limitations of traditional observational studies,it is challenging to definitively establish causality.AIM To explore the causal relationship between the prevalence of these conditions and socioeconomic status using Mendelian randomization(MR).METHODS We initially screened single nucleotide polymorphisms(SNPs)to serve as proxies for eight socioeconomic status phenotypes for univariate MR analysis.The inverse variance weighted(IVW)method was used as the primary analytical method to estimate the causal relationship between the eight socioeconomic status phenotypes and the risk of GERD and BE.We then collected combinations of SNPs as composite proxies for the eight socioeconomic phenotypes to perform multivariate MR(MVMR)analyses based on the IVW MVMR model.Furthermore,a two-step MR mediation analysis was used to examine the potential mediation of the associations by body mass index,major depressive disorder(MDD),smoking,alcohol consumption,and sleep duration.RESULTS The study identified three socioeconomic statuses that had a significant impact on GERD.These included household income[odds ratio(OR):0.46;95% confidence interval(95%CI):0.31-0.70],education attainment(OR:0.23;95%CI:0.18-0.29),and the Townsend Deprivation Index at recruitment(OR:1.57;95%CI:1.04-2.37).These factors were found to independently and predominantly influence the genetic causal effect of GERD.Furthermore,the mediating effect of educational attainment on GERD was found to be mediated by MDD(proportion mediated:10.83%).Similarly,the effect of educational attainment on BE was mediated by MDD(proportion mediated:10.58%)and the number of cigarettes smoked per day(proportion mediated:3.50%).Additionally,the mediating effect of household income on GERD was observed to be mediated by sleep duration(proportion mediated:9.75%)CONCLUSION This MR study shed light on the link between socioeconomic status and GERD or BE,providing insights for the prevention of esophageal cancer and precancerous lesions.

Artificial intelligence system for the detection of Barrett’s esophagus

BACKGROUND Barrett’s esophagus(BE),which has increased in prevalence worldwide,is a precursor for esophageal adenocarcinoma.Although there is a gap in the detection rates between endoscopic BE and histological BE in current research,we trained our artificial intelligence(AI)system with images of endoscopic BE and tested the system with images of histological BE.AIM To assess whether an AI system can aid in the detection of BE in our setting.METHODS Endoscopic narrow-band imaging(NBI)was collected from Chung Shan Medical University Hospital and Changhua Christian Hospital,resulting in 724 cases,with 86 patients having pathological results.Three senior endoscopists,who were instructing physicians of the Digestive Endoscopy Society of Taiwan,independently annotated the images in the development set to determine whether each image was classified as an endoscopic BE.The test set consisted of 160 endoscopic images of 86 cases with histological results.RESULTS Six pre-trained models were compared,and EfficientNetV2B2(accuracy[ACC]:0.8)was selected as the backbone architecture for further evaluation due to better ACC results.In the final test,the AI system correctly identified 66 of 70 cases of BE and 85 of 90 cases without BE,resulting in an ACC of 94.37%.CONCLUSION Our AI system,which was trained by NBI of endoscopic BE,can adequately predict endoscopic images of histological BE.The ACC,sensitivity,and specificity are 94.37%,94.29%,and 94.44%,respectively.

Breast cancer metastasizing to the upper gastrointestinal tract(the esophagus and the stomach):A comprehensive review of the literature

Breast cancer can infrequently metastasize to the upper gastrointestinal(GI)tract but the exact incidence is not well established-there is considerable variation between incidence reported from clinical studies and incidence noted in autopsy series.Clinical presentation can be very non-specific and often mimics primary gastrointestinal conditions.Endoscopy alone may not be sufficient to make a diagnosis and misdiagnosis is also common.A high degree of awareness and clinical suspicion is required to establish metastases to the upper GI tract.We undertook a comprehensive review of the available literature on breast cancer metastases to the esophagus and stomach including the clinical symptoms and presentation,endoscopic features,additional diagnostic imaging modalities,treatment and outcomes.

Giant myxofibrosarcoma of the esophagus treated by endoscopic submucosal dissection:A case report

BACKGROUND Myxofibrosarcoma(MFS)is a fibroblast-derived sarcoma that mainly occurs in subcutaneous tissue.MFS rarely occurs in the gastrointestinal tract,especially in the esophagus.CASE SUMMARY A 79-year-old male patient was admitted to our hospital for dysphagia for a week.Computed tomography and electronic gastroscopy showed that a giant mass was located 30 cm from the incisor and extended to the cardia.There was incomplete esophageal stenosis.Endoscopic pathology showed spindle cell lesions,which were considered inflammatory myofibroblast like hyperplasia.Considering the strong demands of the patient and his family,and the fact that most inflammatory myofibroblast tumors are benign,we decided to perform endoscopic submucosal dissection(ESD)even if the tumor size was giant(9.0 cm×3.0 cm).Postoperative pathological examination resulted in a final diagnosis of MFS.MFS rarely occurs in the gastrointestinal tract,especially in the esophagus.Surgical resection and local adjuvant radiotherapy are the first choices to improve the prognosis.This case report firstly described the ESD for esophageal giant MFS.It suggests that ESD may be an alternative treatment for primary esophageal MFS.CONCLUSION This case report for the first time describe the successful treatment of a giant esophageal MFS by ESD,suggesting that ESD may be an alternative treatment for primary esophageal MFS,especially in elderly high-risk patients with obvious dysphagia symptoms.

Systemic treatments for resectable carcinoma of the esophagus

One of the most prevalent malignancies in the world is esophageal cancer(EC).The 5-year survival rate of EC remains pitiful despite treatment advancements.Neoadjuvant chemoradiotherapy in conjunction with esophagectomy is the standard of care for patients with resectable disease.The pathological complete response rate,however,is not acceptable.A distant metastasis or a locoregional recurrence will occur in about half of the patients.To increase the clinical effectiveness of therapy,it is consequently vital to investigate cutting-edge and potent therapeutic modalities.The approach to the management of resectable EC using immunotherapy has been considerably altered by immune checkpoint inhibitors.Systemic immunotherapy has recently been shown to have the potential to increase the survival of patients with resectable EC,according to growing clinical data.A combination of chemotherapy,radiation,and immunotherapy may have a synergistic antitumor impact because,according to mounting evidence,these treatments can stimulate the immune system via a number of different pathways.In light of this,it makes sense to consider the value of neoadjuvant immunotherapy for patients with surgically treatable EC.In this review,we clarify the rationale for neoadjuvant immunotherapy in resectable EC patients,recap the clinical outcomes of these approaches,go through the upcoming and ongoing investigations,and emphasize the difficulties and unmet research requirements.

Primary malignant melanoma of the esophagus:A case report

BACKGROUND Primary malignant melanoma of the esophagus(PMME)is a rare malignant disease whose clinical and molecular pathological features,origin and pathoge-nesis,diagnosis and treatment have not been elucidated.CASE SUMMARY In this paper,we report a case of a 73-year-old male with PMME.The patient complained of progressive dysphagia accompanied by substantial weight loss.Gastroscopy revealed a purple black bulging-type mass in the lower esophagus with easy bleeding on contact and scattered satellite lesions in the stomach.Histopathological biopsy revealed melanocytes in the esophageal mucosa.Physical examination and multidisciplinary consultation led to diagnostic exclusion of melanoma originating in other organs,such as the skin.Through this case report and literature review,we aimed to describe the clinical and molecular pathological features of PMME and summarize possible pathways of pathoge-nesis as well as cutting-edge therapeutic advances.CONCLUSION PMME is a rare malignancy of the esophagus with a poor prognosis.Clinicians should raise their awareness and be able to identify early lesions.

Hybrid laparo-endoscopic access:New approach to surgical treatment for giant fibrovascular polyp of esophagus:A case report and review of literature

BACKGROUND Fibrovascular polyps are rare type of esophageal submucosal neoplasms.They are highly vascularized and can cause difficulty swallowing and even fatal complications such as uncontrolled bleeding and death caused by asphyxiation in case of tumor migration to oropharynx.In the article we describe a novel hybrid technique to surgical treatment–an endoscopic submucosal dissection with laparoscopic removal of the tumor.CASE SUMMARY The patient with a giant fibrovascular esophageal polyp presented with cough,discomfort in the throat,difficulty swallowing,and an episode of tumor migration into oropharynx.The patient was investigated with several imaging studies and was diagnosed with a giant highly vascularized esophageal fibrovascular polyp.The follow-up period of eight months accompanied with no complications.CONCLUSION This method has been shown to have comparable rates of recurrence and a low risk of complications.

Graft dilatation and Barrett’s esophagus in adults after gastric pullup and jejunal interposition for long-gap esophageal atresia

BACKGROUND Esophageal replacement(ER)with gastric pull-up(GPU)or jejunal interposition(JI)used to be the standard treatment for long-gap esophageal atresia(LGEA).Changes of the ER grafts on a macro-and microscopic level however,are unknown.AIM To evaluate long-term clinical symptoms and anatomical and mucosal changes in adolescents and adults after ER for LGEA.METHODS A cohort study was conducted including all LGEA patients≥16 years who had undergone GPU or JI between 1985-2003 at two tertiary referral centers in the Netherlands.Patients underwent clinical assessment,contrast study and endoscopy with biopsy.Data was collected prospectively.Group differences between JI and GPU patients,and associations between different outcome measures were assessed using the Fisher’s exact test for bivariate variables and the Mann-Whitney U-test for continuous variables.Differences with a P-value<0.05 were considered statistically significant.RESULTS Nine GPU patients and eleven JI patients were included.Median age at follow-up was 21.5 years and 24.4 years,respectively.Reflux was reported in six GPU patients(67%)vs four JI patients(36%)(P=0.37).Dysphagia symptoms were reported in 64%of JI patients,compared to 22%of GPU patients(P=0.09).Contrast studies showed dilatation of the jejunal graft in six patients(55%)and graft lengthening in four of these six patients.Endoscopy revealed columnar-lined esophagus in three GPU patients(33%)and intestinal metaplasia was histologically confirmed in two patients(22%).No association was found between reflux symptoms and macroscopic anomalies or intestinal metaplasia.Three GPU patients(33%)experienced severe feeding problems vs none in the JI group.The median body mass index of JI patients was 20.9 kg/m^(2) vs 19.5 kg/m^(2) in GPU patients(P=0.08).CONCLUSION The majority of GPU patients had reflux and intestinal metaplasia in 22%.The majority of JI patients had dysphagia and a dilated graft.Follow-up after ER for LGEA is essential.

Role of artificial intelligence in Barrett’s esophagus

The application of artificial intelligence(AI)in gastrointestinal endoscopy has gained significant traction over the last decade.One of the more recent applications of AI in this field includes the detection of dysplasia and cancer in Barrett’s esophagus(BE).AI using deep learning methods has shown promise as an adjunct to the endoscopist in detecting dysplasia and cancer.Apart from visual detection and diagnosis,AI may also aid in reducing the considerable interobserver variability in identifying and distinguishing dysplasia on whole slide images from digitized BE histology slides.This review aims to provide a comprehensive summary of the key studies thus far as well as providing an insight into the future role of AI in Barrett’s esophagus.

Clinicopathological characterization of ten patients with primary malignant melanoma of the esophagus and literature review

BACKGROUND Primary malignant melanoma of the esophagus(PMME) is a rare malignant disease and has not been well characterized in terms of clinicopathology and survival.AIM To investigate the clinical features and survival factors in Chinese patients with PMME.METHODS The clinicopathological findings of ten cases with PMME treated at Henan Provincial People’s Hospital were summarized. Moreover, the English-and Chinese-language literature that focused on Chinese patients with PMME from 1980 to September 2021 was reviewed and analyzed. Univariate and multivariate analyses were employed to investigate the clinicopathologic factors that might be associated with survival.RESULTS A total of 290 Chinese patients with PMME, including ten from our hospital and 280 from the literature were enrolled in the present study. Only about half of the patients(55.8%) were accurately diagnosed before surgery. Additionally, 91.1% of the patients received esophagectomy, and 88 patients(36.5%) received adjuvant therapy after surgery. The frequency of lymph node metastasis(LNM) was 51.2%(107/209), and LNM had a positive rate of 45.3% even when the tumor was confined to the submucosal layer. The risk of LNM increased significantly with the p T stage [P < 0.001, odds ratio(OR): 2.47, 95% confidence interval(CI): 1.72-3.56] and larger tumor size(P = 0.006, OR: 1.21, 95%CI: 1.05-1.38). The median overall survival(OS) was 11.0 mo(range: 1-204 mo). The multivariate Cox analysis showed both the p T stage [P = 0.005, hazard ratio(HR): 1.70, 95%CI: 1.17-2.47] and LNM(P = 0.009, HR: 1.78, 95%CI: 1.15-2.74) were independent prognostic factors for OS. The median disease-free survival(DFS) was 5.3 mo(range: 0.8-114.1 mo). The multivariate analysis indicated that only the advanced p T stage(P = 0.02, HR: 1.93, 95%CI: 1.09-3.42) was a significant independent indicator of poor RFS in patients with PMME.CONCLUSION The correct diagnosis of PMME before surgery is low, and physicians should pay more attention to avoid a misdiagnosis or missed diagnosis. Extended lymph node dissection should be emphasized in surgery for PMME even though the tumor is confined to the submucosal layer. Both the LNM and p T stage are independent prognosis factors for OS, and the p T stage is the prognosis factor for DFS in patients with PMME.

Progression from low-grade dysplasia to malignancy in patients with Barrett's esophagus diagnosed by two or more pathologists

AIM To evaluate annual incidence of low grade dysplasia(LGD) progression to high grade dysplasia(HGD) and/or esophageal adenocarcinoma(EAC) when diagnosis was made by two or more expert pathologists.METHODS Studies evaluating the progression of LGD to HGD or EAC were included. The diagnosis of LGD must be made by consensus of two or more expert gastrointestinal pathologists. Articles were searched in Medline, Pubmed, and Embase. Pooled proportions were calculated using fixed and random effects model. Heterogeneity among studies was assessed using the I2 statistic. RESULTS Initial search identified 721 reference articles, of which 53 were selected and reviewed. Twelve studies(n = 971) that met the inclusion criteria were included in this analysis. Among the total original LGD diagnoses in the included studies, only 37.49% reached the consensus LGD diagnosis after review by two or more expert pathologists. Total follow up period was 1532 patient-years. In the pooled consensus LGD patients, the annual incidence rate(AIR) of progression to HGD and or EAC was 10.35%(95%CI: 7.56-13.13) and progression to EAC was 5.18%(95%CI: 3.43-6.92). Among the patients down staged from original LGD diagnosis to No-dysplasia Barrett's esophagus, the AIR of progression to HGD and EAC was 0.65%(95%CI: 0.49-0.80). Among the patients down staged to Indefinite for dysplasia, the AIR of progression to HGD and EAC was 1.42%(95%CI: 1.19-1.65). In patients with consensus HGD diagnosis, the AIR of progression to EAC was 28.63%(95%CI: 13.98-43.27). CONCLUSION When LGD is diagnosed by consensus agreement of two or more expert pathologists, its progression towards malignancy seems to be at least three times the current estimates, however it could be up to 20 times the current estimates. Biopsies of all Barrett's esophagus patients with LGD should be reviewed by two expert gastroenterology pathologists. Follow-up strict surveillance programs should be in place for these patients.

Incidence and mortality of esophagus cancer in China, 2008-2012

Objective: To analyze the incidence and mortality rates of esophagus cancer in China from 2008 to 2012.Methods: Incident and mortality cases of esophagus cancer were retrieved from the National Central Cancer Registry(NCCR) database collecting from 135 cancer registries in China during 2008-2012. The incidence and mortality rates of esophagus cancer were calculated by area(urban/rural), region(eastern, middle, western), gender and age group(0, 1-4, 5-84 by 5 years and 85+ years). China census in 2000 and Segi’s world population were applied for age-standardized rates. Joinpoint model was used for time-trend analysis.Results: The crude incidence rate of esophagus cancer was 22.57/100,000. The age-standardized incidence rates by China standard population(ASIRC) and by world standard population(ASIRW) were 14.58/100,000 and14.80/100,000, respectively. The crude mortality rate of esophagus cancer was 17.19/100,000. The agestandardized mortality rates by Chinese standard population(ASMRC) and by world standard population(ASMRW) were 10.80/100,000 and 10.86/100,000 respectively. Incidence and mortality rates of esophagus cancer were higher in males than in females and higher in rural areas than in urban areas. The crude incidence rate in middle areas was the highest among all areas, followed by western areas and eastern areas. The age-specific incidence rate of esophagus cancer was relatively low in age groups before 40 years old and then increased after 45 years old. It peaked in the age group of 80-84 years. The patterns of age-specific mortality rates of esophagus cancer were close to those of age-specific incidence rates. The ASIRC of esophagus cancer decreased dramatically by 29.87% between 2003 and 2012, from 14.33/100,000 to 10.05/100,000. The esophagus cancer incidence rate decreased by 3.76% per year(P>0.05). The mortality rate of esophagus cancer decreased annually over the decades from 2003 to 2012 in China(P>0.05). In females, the annual percentage change(APC) of mortality rate was-5.43%[95% confidence intervals(95% CI):-6.50%,-4.30%](P<0.05) and the mortality rate of esophagus cancer in rural females was statistically significant(APC:-3.20%, 95% CI:-4.20%,-2.20%)(P<0.05).Conclusions: The focus of prevention and treatment for esophagus cancer is strengthening primary prevention of esophageal cancer, and promoting esophagus cancer secondary prevention to reduce incidence and mortality rates of esophagus cancer, prolong survival rate of patients and decline the burden of esophagus cancer in China.

Alteration of the esophageal microbiota in Barrett's esophagus and esophageal adenocarcinoma

The incidence of esophageal adenocarcinoma(EAC) has increased in recent decades, and its 5-year survival rate is less than 20%. As a well-established precursor, patients with Barrett's esophagus(BE) have a persistent risk of progression to EAC. Many researchers have already identified some factors that may contribute to the development of BE and EAC, and the identified risks include gastroesophageal reflux(GER), male sex, older age, central obesity,tobacco smoking, Helicobacter pylori(H. pylori) eradication, and the administration of proton pump inhibitors(PPIs) and antibiotics. The human gut harbors trillions of microorganisms, the majority of which are bacteria. These microorganisms benefit the human host in many ways, such as helping in digestion, assisting in the synthesis of certain vitamins, promoting the development of the gastrointestinal immune system, regulating metabolism and preventing invasion by specific pathogens. In contrast, microbial dysbiosis may play important roles in various diseases, such as inflammation and cancers. The composition of the microbiota located in the normal esophagus is relatively conserved without distinct microbial preferences in the upper, middle and lower esophagus. Six major phyla constitute the esophageal microbiota, including Firmicutes,Bacteroides, Actinobacteria, Proteobacteria, Fusobacteria and TM7, similar to the oral microbiota. Streptococcus dominates the esophageal microbiota. However, the microbiota varies in different esophageal diseases compared to that in the healthy esophagus. The type Ⅰ microbiota, which is primarily composed of gram-positive bacteria, is closely associated with the normal esophagus, while type Ⅱ microbiota has enriched gram-negative bacteria and is mainly associated with the abnormal esophagus. These increased gram-negative anaerobes/microaerophiles include Veillonella, Prevotella, Haemophilus, Neisseria, Granulicatella and Fusobacterium, many of which are associated with BE. The microbial diversity in the esophagus is decreased in EAC patients, and Lactobacillus fermentum is enriched compared to that in controls and BE patients. Furthermore, the microbiota may be associated with BE and EAC by interacting with their risk factors, including central obesity, GER, H. pylori, administration of PPIs and antibiotics. Therefore, a large gap in research must be bridged to elucidate the associations among these factors. Some studies have already proposed several potential mechanisms by which the microbiota participates in human carcinogenesis by complicated interactions with the human host immune system and signaling pathways. The activation of the LPS-TLR4-NF-κB pathway may contribute to inflammation and malignant transformation. This exciting field of gastrointestinal microbiota allows us to unravel the mystery of carcinogenesis from another perspective. Further studies are needed to explore whether the microbiota changes before or after disease onset, to improve our understanding of the pathogenesis, and to find novel targets for prevention, diagnosis and therapy, which could offer more cost-effective and relatively safe choices.

MicroRNAs, development of Barrett’s esophagus, and progression to esophageal adenocarcinoma

Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esoph-ageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellular processes, and the role of miRNAs in disease development is be-coming increasingly evident. Understanding altered miRNA expression is likely to help unravel the molecular mechanisms that underpin the development of Barrett's esophagus and its progression to cancer.

From reflux esophagitis to Barrett's esophagus and esophageal adenocarcinoma

The occurrence of gastroesophageal reflux disease is common in the human population.Almost all cases of esophageal adenocarcinoma are derived from Barrett's esophagus,which is a complication of esophageal adenocarcinoma precancerous lesions.Chronic exposure of the esophagus to gastroduodenal intestinal fluid is an important determinant factor in the development of Barrett's esophagus.The replacement of normal squamous epithelium with specific columnar epithelium in the lower esophagus induced by the chronic exposure to gastroduodenal fluid could lead to intestinal metaplasia,which is closely associated with the development of esophageal adenocarcinoma.However,the exact mechanism of injury is not completely understood.Various animal models of the developmental mechanisms of disease,and theoretical and clinical effects of drug treatment have been widely used in research.Recently,animal models employed in studies on gastroesophageal reflux injury have allowed significant progress.The advantage of using animal models lies in the ability to accurately control the experimental conditions for better evaluation of results.In this article,various modeling methods are reviewed,with discussion of the major findings on the developmental mechanism of Barrett's esophagus,which should help to develop better prevention and treatment strategies for Barrett's esophagus.

Clinical significance of heterotopic gastric mucosal patch of the proximal esophagus

Heterotopic gastric mucosa of the proximal esophagus (HGMPE),also referred to as"inlet patch"or"cervical inlet patch",is a salmon colored patch that is usually located just distal to the upper esophageal sphincter. HGMPE is uncommon with endoscopic studies reporting a prevalence ranging from less than one percent to 18%.Most HGMPE are asymptomatic and are detected incidentally during endoscopy for evaluations of other gastrointestinal complaints.Most consider HGMPE as clinically irrelevant entity.The clinical significance of HGMPE is mainly acid related or neoplastic transformation.The reported prevalence of laryngopharyngeal reflux symptoms varies from less than 20%to as high as 73.1%.However,most of these symptoms are mild. Clinically significant acid related complications such as bleeding,ulcerations,structure and fistulization have been reported.Although rare,dysplastic changes and malignancies in association with HGMPE have also been reported.Associations with Barrett's esophagus have also been reported but the findings so far have been conflicting.There are still many areas that are unknown or not well understood and these include the natural history of HGMPE,risk factors for complications,role of Helicobacter pylori infection and factors associated with malignant transformations.Follow-up may need to be considered for patients with complications of HGMPE and surveillance if biopsies show intestinal metaplasia or dysplastic changes.Despite the overall low incidence of clinically relevant manifestations reported in the literature,HGMPE is a clinically significant entity but further researches are required to better understand its clinical significance.