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Neurogastroenterology and Motility Jan 2021Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two... (Review)
Review
Chicago Classification v4.0 (CCv4.0) is the updated classification scheme for esophageal motility disorders using metrics from high-resolution manometry (HRM). Fifty-two diverse international experts separated into seven working subgroups utilized formal validated methodologies over two-years to develop CCv4.0. Key updates in CCv.4.0 consist of a more rigorous and expansive HRM protocol that incorporates supine and upright test positions as well as provocative testing, a refined definition of esophagogastric junction (EGJ) outflow obstruction (EGJOO), more stringent diagnostic criteria for ineffective esophageal motility and description of baseline EGJ metrics. Further, the CCv4.0 sought to define motility disorder diagnoses as conclusive and inconclusive based on associated symptoms, and findings on provocative testing as well as supportive testing with barium esophagram with tablet and/or functional lumen imaging probe. These changes attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of peristalsis and obstruction at the EGJ.
Topics: Esophageal Achalasia; Esophageal Motility Disorders; Esophageal Spasm, Diffuse; Esophagogastric Junction; Humans; Manometry
PubMed: 33373111
DOI: 10.1111/nmo.14058 -
World Journal of Emergency Surgery :... 2019The esophagus traverses three body compartments (neck, thorax, and abdomen) and is surrounded at each level by vital organs. Injuries to the esophagus may be classified... (Review)
Review
The esophagus traverses three body compartments (neck, thorax, and abdomen) and is surrounded at each level by vital organs. Injuries to the esophagus may be classified as foreign body ingestion, caustic ingestion, esophageal perforation, and esophageal trauma. These lesions can be life-threatening either by digestive contamination of surrounding structures in case of esophageal wall breach or concomitant damage of surrounding organs. Early diagnosis and timely therapeutic intervention are the keys of successful management.
Topics: Caustics; Esophageal Perforation; Esophagoscopy; Esophagus; Foreign Bodies; Humans; Tomography, X-Ray Computed
PubMed: 31164915
DOI: 10.1186/s13017-019-0245-2 -
Advances in Respiratory Medicine 2017The diaphragm is the primary muscle involved in active inspiration and serves also as an important anatomical landmark that separates the thoracic and abdominal cavity.... (Review)
Review
The diaphragm is the primary muscle involved in active inspiration and serves also as an important anatomical landmark that separates the thoracic and abdominal cavity. However, the diaphragm muscle like other structures and organs in the human body has more than one function, and displays many anatomic links throughout the body, thereby forming a 'network of breathing'. Besides respiratory function, it is important for postural control as it stabilises the lumbar spine during loading tasks. It also plays a vital role in the vascular and lymphatic systems, as well as, is greatly involved in gastroesophageal functions such as swallowing, vomiting, and contributing to the gastroesophageal reflux barrier. In this paper we set out in detail the anatomy and embryology of the diaphragm and attempt to show it serves as both: an important exchange point of information, originating in different areas of the body, and a source of information in itself. The study also discusses all of its functions related to breathing.
Topics: Diaphragm; Esophagogastric Junction; Humans; Posture; Respiratory Mechanics; Work of Breathing
PubMed: 28871591
DOI: 10.5603/ARM.2017.0037 -
Gut Jun 2022Gastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies...
Multitrait genetic association analysis identifies 50 new risk loci for gastro-oesophageal reflux, seven new loci for Barrett's oesophagus and provides insights into clinical heterogeneity in reflux diagnosis.
OBJECTIVE
Gastro-oesophageal reflux disease (GERD) has heterogeneous aetiology primarily attributable to its symptom-based definitions. GERD genome-wide association studies (GWASs) have shown strong genetic overlaps with established risk factors such as obesity and depression. We hypothesised that the shared genetic architecture between GERD and these risk factors can be leveraged to (1) identify new GERD and Barrett's oesophagus (BE) risk loci and (2) explore potentially heterogeneous pathways leading to GERD and oesophageal complications.
DESIGN
We applied multitrait GWAS models combining GERD (78 707 cases; 288 734 controls) and genetically correlated traits including education attainment, depression and body mass index. We also used multitrait analysis to identify BE risk loci. Top hits were replicated in 23andMe (462 753 GERD cases, 24 099 BE cases, 1 484 025 controls). We additionally dissected the GERD loci into obesity-driven and depression-driven subgroups. These subgroups were investigated to determine how they relate to tissue-specific gene expression and to risk of serious oesophageal disease (BE and/or oesophageal adenocarcinoma, EA).
RESULTS
We identified 88 loci associated with GERD, with 59 replicating in 23andMe after multiple testing corrections. Our BE analysis identified seven novel loci. Additionally we showed that only the obesity-driven GERD loci (but not the depression-driven loci) were associated with genes enriched in oesophageal tissues and successfully predicted BE/EA.
CONCLUSION
Our multitrait model identified many novel risk loci for GERD and BE. We present strong evidence for a genetic underpinning of disease heterogeneity in GERD and show that GERD loci associated with depressive symptoms are not strong predictors of BE/EA relative to obesity-driven GERD loci.
Topics: Barrett Esophagus; Esophageal Neoplasms; Esophagitis, Peptic; Gastroesophageal Reflux; Genome-Wide Association Study; Humans; Obesity
PubMed: 34187846
DOI: 10.1136/gutjnl-2020-323906 -
EBioMedicine Jul 2021Esophageal squamous cell carcinoma (ESCC) is among the most prevalent causes of cancer-related death in adults. Tumor microenvironment (TME) has been associated with...
BACKGROUND
Esophageal squamous cell carcinoma (ESCC) is among the most prevalent causes of cancer-related death in adults. Tumor microenvironment (TME) has been associated with therapeutic failure and lethal outcomes for patients. However, published reports on the heterogeneity and TME in ESCC are scanty.
METHODS
Five tumor samples and five corresponding non-malignant samples were subjected to scRNA-seq analysis. Bulk RNA sequencing data were retrieved in publicly available databases.
FINDINGS
From the scRNA-seq data, a total of 128,688 cells were enrolled for subsequent analyses. Gene expression and CNV status exhibited high heterogeneity of tumor cells. We further identified a list of tumor-specific genes and four malignant signatures, which are potential new markers for ESCC. Metabolic analysis revealed that energy supply-related pathways are pivotal in cancer metabolic reprogramming. Moreover, significant differences were found in stromal and immune cells between the esophagus normal and tumor tissues, which promoted carcinogenesis at both cellular and molecular levels in ESCC. Immune checkpoints, regarded as potential targets for immunotherapy in ESCC were significantly highly expressed in ESCC, including LAG3 and HAVCR2. Eventually, we constructed a cell-to-cell communication atlas based on cancer cells and immune cells and performed the flow cytometry, qRT-PCR, immunofluorescence, and immunohistochemistry analyses to validate the results.
INTERPRETATION
This study demonstrates a widespread reprogramming across multiple cellular elements within the TME in ESCC, particularly in transcriptional states, cellular functions, and cell-to-cell interactions. The findings offer an insight into the exploration of TME and heterogeneity in the ESCC and provide new therapeutic targets for its clinical management in the future.
FUNDING
The work was supported by the Shanghai Pujiang Program (2020PJD009) and Research Development Fund of Zhongshan Hospital, Fudan University (2019ZSFZ002 and 2019ZSFZ19).
Topics: Adaptor Proteins, Signal Transducing; Animals; Antineoplastic Agents; Apoptosis; Carcinoma, Squamous Cell; Cell Line; Cell Line, Tumor; Dasatinib; Drug Resistance, Neoplasm; Esophageal Neoplasms; Esophagus; Histone Deacetylase Inhibitors; Humans; Isocitrate Dehydrogenase; Mice; Mice, Inbred NOD; Single-Cell Analysis; Transcriptome; YAP-Signaling Proteins
PubMed: 34192657
DOI: 10.1016/j.ebiom.2021.103459 -
Nature Communications May 2017Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and...
Approximately half of the world's 500,000 new oesophageal squamous-cell carcinoma (ESCC) cases each year occur in China. Here, we show whole-genome sequencing of DNA and RNA in 94 Chinese individuals with ESCC. We identify six mutational signatures (E1-E6), and Signature E4 is unique in ESCC linked to alcohol intake and genetic variants in alcohol-metabolizing enzymes. We discover significantly recurrent mutations in 20 protein-coding genes, 4 long non-coding RNAs and 10 untranslational regions. Functional analyses show six genes that have recurrent copy-number variants in three squamous-cell carcinomas (oesophageal, head and neck and lung) significantly promote cancer cell proliferation, migration and invasion. The most frequently affected genes by structural variation are LRP1B and TTC28. The aberrant cell cycle and PI3K-AKT pathways seem critical in ESCC. These results establish a comprehensive genomic landscape of ESCC and provide potential targets for precision treatment and prevention of the cancer.
Topics: Adult; Aged; Alcohol Drinking; Asian People; Carcinoma, Squamous Cell; Cell Cycle; China; DNA Copy Number Variations; Esophageal Neoplasms; Esophageal Squamous Cell Carcinoma; Esophagus; Ethanol; Female; Genome, Human; Humans; Male; Middle Aged; Mutation; Phosphatidylinositol 3-Kinases; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-akt; Receptors, LDL; Signal Transduction; Whole Genome Sequencing
PubMed: 28548104
DOI: 10.1038/ncomms15290 -
American Journal of Physiology.... Aug 2015The esophagus is a relatively simple organ that evolved to transport food and liquids through the thoracic cavity. It is the only part of the gastrointestinal tract that... (Review)
Review
The esophagus is a relatively simple organ that evolved to transport food and liquids through the thoracic cavity. It is the only part of the gastrointestinal tract that lacks any metabolic, digestive, or absorptive function. The mucosa of the adult esophagus is covered by a multilayered squamous epithelium with a remarkable similarity to the epithelium of the skin despite the fact that these tissues originate from two different germ layers. Here we review the developmental pathways involved in the establishment of the esophagus and the way these pathways regulate gut-airway separation. We summarize current knowledge of the mechanisms that maintain homeostasis in esophageal epithelial renewal in the adult and the molecular mechanism of the development of Barrett's metaplasia, the precursor lesion to esophageal adenocarcinoma. Finally, we examine the ongoing debate on the hierarchy of esophageal epithelial precursor cells and on the presence or absence of a specific esophageal stem cell population. Together the recent insights into esophageal development and homeostasis suggest that the pathways that establish the esophagus during development also play a role in the maintenance of the adult epithelium. We are beginning to understand how reflux of gastric content and the resulting chronic inflammation can transform the squamous esophageal epithelium to columnar intestinal type metaplasia in Barrett's esophagus.
Topics: Animals; Cell Differentiation; Embryonic Stem Cells; Epithelium; Esophageal Diseases; Esophagus; Gene Expression Regulation, Developmental; Homeostasis; Humans
PubMed: 26138464
DOI: 10.1152/ajpgi.00088.2015 -
Thoracic Surgery Clinics Nov 2019Paraesophageal hernia represents a complex surgical problem involving significant distortion of the anatomy and function of the esophagus, stomach, gastroesophageal... (Review)
Review
Paraesophageal hernia represents a complex surgical problem involving significant distortion of the anatomy and function of the esophagus, stomach, gastroesophageal junction, mediastinum, lungs, and heart. Surgeons operating in the area must have deep understanding of the normal anatomy and pathologic derangements in patients with paraesophageal hernias. This article describes the normal anatomy and anatomic abnormalities in application to the various approaches used in the surgical repair of a paraesophageal hernia.
Topics: Diaphragm; Endoscopy, Digestive System; Esophageal Sphincter, Lower; Esophagus; Hernia, Hiatal; Herniorrhaphy; Humans; Laparoscopy; Radiography; Stomach; Tomography, X-Ray Computed
PubMed: 31564392
DOI: 10.1016/j.thorsurg.2019.07.008