#oesophagus

Preserving Pipework

A protein called Troy (Tnfrsf19) defines a population of progenitor cells that have a key role in the maintenance of the lining of the oesophagus [food pipe]

Read the published research article here

Image from work by David Grommisch and colleagues

Department of Cell and Molecular Biology, Karolinska Institutet, Sweden

Image originally published with a Creative Commons Attribution – NonCommercial – NoDerivs (CC BY-NC-ND 4.0)

Published in bioRxiv, March 2024 (not peer reviewed)

                                            Eosinophilic Esophagitis 

Due to a compromised mucosal barrier in the oesophagus and a reverse immunological response mediated by Th2 interleukins, esophageal fissures/lesions, fibrosis, and dysmotility develop in Eosinophilic Esophagitis. There is a 7% chance that eosinophilic esophagitis will be genetically inherited. Eosinophilic esophageal disease is now a major contributor to food impaction and dysphagia due to its rise in prevalence in recent years. Because it is a chronic inflammatory disease, patients must continue to be managed in order to prevent symptoms from getting worse. EoE can be treated with anything from medication to a strict elemental diet. Foods that cause inflammation may need to be cut out of the diet. Their buildup at a specific site on the body indicates the presence of allergic disorders.

The patient's age may have an impact on the symptoms, which might vary greatly. Asthma instances linked to the condition are rising, and so are awareness of it and diagnosis rates. People with this illness may also develop eczema in addition to the symptoms.An excessive amount of eosinophils (a specific type of white blood cell) are found in the oesophagus in Eosinophilic Esophagitis  a chronic immunological illness of the digestive system. Food travels through the oesophagus, a tube, from the mouth to the stomach. The term "allergic esophagitis" also applies to eosinophilic esophagitis. The immune system of the body includes eosinophils. They are essential for immune system control and provide defence against some illnesses. Their buildup at a specific site on the body indicates the presence of allergic disorders.

Anonymous said to @ask-drferox:  Why are intra-thoracic esophagus surgeries a nightmare?

I have honestly never seen a patient survive oesophageal surgery, and have gone to great lengths to try to avoid patients needing one.

To begin with, most of the oesophagus is in the thorax, and there’s a reason ‘open chest surgery’ inspires a certain degree of awe and dread. You have to crack open those ribs, and as soon as you enter the chest cavity the patient can no longer breathe on their own.

Breathing in mammals works because of negative pressure. The lungs are kind of elastic, so when the chest wall moves outwards, or the diaphragm moves down, it causes them to expand to fill the larger space. When the chest cavity is open, that can’t happen, because air is sucked into the hole (outside the lungs) instead. The chest wall and diaphragm can move all you like, but the air doesn’t move in the lungs.

So instead, you either need a ventilator, or somebody has to sit there and breathe for the patient the entire time, pushing air into its lungs. And afterwards, if it all goes well, you gotta close up with a chest drain and manage that so that the patient will continue to breathe.

Next, you have to actually reach the oesophagus. This organ runs from the head, down the neck, into the chest, over the heart and then through the diaphragm to the heart. Guess where the three narrowest parts are that obstructions usually get stuck are? The entrance to the thorax, passing through the diaphragm, and directly over the heart. That beating mass of muscle that you don’t really want to mess with.

Now, if we’re going well, we need to cut into that oesophagus. And this is also a problem.

The rest of the gastrointestinal tract has wiggle room. You can cut out a third of the small intestine if you really want to, and large chunks of stomach or colon. You have basically no ‘excess’ in an oesophagus that you can remove without putting it under too much tension. There is a minimum distance that it simply must cover. If it’s under too much tension, the surgical site will simply break apart.

It also, unlike organs in the abdomen, has no serosa (except the little bit that’s inside the abdomen). This is the outer layer of the organ that makes the seal at the surgical site water proof, and without it the oesophagus is very, very prone to leaking.

And leaking into the thoracic cavity is going to be Bad News.

Considering the most common reason for needing to cut into the oesophagus is to remove a foreign object that’s stuck, there’s also a lot of damaged, compromised tissue there which might break down, especially if that object is hard or pointy like a bone.

Alternatives to oesophageal surgery are trying to pull the object back up the way it came, or push it into the stomach and cut out out of the good old reliable stomach, but both of those options have risks of causing further damage on the way up or down too.

Barrett’s Oesophagus

efflux of gastric acid in to the lower oesophagus

produces burning pain known as heart burn

due to increased abdominal pressure e.g. over eating, pregnancy, poor posture

also factors rendering the lower oesophageal sphincter lax or incompetent e.g. hiatus hernia

the stomach acid damages the sensitive normal squamous epithelium of lower oesophagus

resulting in metaplasia from squamous epithelium to columnar glandular epithelium

the metaplastic columnar epithelium may resemble that of the small intestine, or that of the proximal region of the stomach

can progress from metaplastic glandular epithelium, to epithelial dysplasia then to adenocarcinoma  

patients with Barrett’s are kept under surveillance through endoscopy and biopsy to detect early neoplastic change

Oesophageal cancer

90-95% are squamous cell derived 

50-80% are adenocarcinomas 

Symptoms include dysphagia (difficulty swallowing) and pain 

small and localised tumors treated surgically with curative intent 

larger tumors tend to be inoperable = palliative care 

growth can still be delayed with chemo- or radio-therapy, which can render some larger tumors operable

prognosis depends on the extent of the disease and other medical problems, but is generally fairly poor 

Staging:

T1 – invades lamina propria & submucosa 

T2 – invades muscularis propria 

T3 - invades adventitia 

T4 – has invades adjacent structures 

Tough to Swallow

Sip a refreshing drink, or take a bite of yummy food and, for most of us, no thought is given to what happens next. Swallowing, like blinking and breathing, is automatic. But what if it isn’t, and one of life’s pleasures becomes uncomfortable and a serious choking risk? Swallowing disorders have a variety of causes that often include a neurological problem such as nerve damage from a degenerative disease, stroke or neurotoxic medication. Recently, researchers have identified in mice the particular oesophagus-targeting neurons (pictured) that sense the presence of food or liquid in the throat and relay signals to the brain to prompt peristalsis – the wave-like squeezing of oesophageal muscles that pushes food to the stomach. The hope is that knowledge of how these cells work and how they might be stimulated could ultimately lead to interventions for people where the simple act of swallowing has become difficult and dangerous.

Written by Ruth Williams

Image from work by Elijah D. Lowenstein and colleagues

Developmental Biology/Signal Transduction, Max Delbrück Center for Molecular Medicine, Berlin, Germany

Image copyright held by the original authors

Research published in Neuron, May 2023

Tube Driver

Many structures in our bodies, like the oesophagus and intestines, are tubes. Each starts off as very short structures, but by birth have lengthened substantially. But what drives these tube extensions? Most of our cells have a singular cilium protruding from its surface acting like an antenna waiting to receive signals. These ciliary structures must first receive signals from Hedgehog proteins to first create a layer of smooth muscle (green) in structures like the oesophagus (pictured). This muscle starts to exert mechanical forces onto mesenchymal cells – a type of stem cell – and triggers the accumulation of a protein called YAP (red) which promotes cell proliferation, resulting in tube elongation. By removing the cilium gene CILK1 (bottom row), smooth muscle organisation was disrupted and the amount of YAP was reduced in the intestines, but also in the developing oesophagus showing that Hedgehog signalling to the cilia is the tube driver.

Written by Sophie Arthur

Image from work by Ying Yang and colleagues

Department of Biochemistry and Biophysics, Cardiovascular Research Institute, University of California San Francisco, San Francisco, CA, USA

Image originally published with a Creative Commons Attribution 4.0 International (CC BY 4.0)

Published in Nature Communications, December 2021

Gateway for Infection

A year on from the COVID-19 pandemic beginning its spread across the globe, scientists continue to gather new insights about how the SARS-CoV-2 virus is transmitted. Recently, a research team showed how people with Barrett’s oesophagus, a chronic condition in which the tube connecting the mouth and stomach is damaged over time by acid reflux may be more vulnerable to COVID-19. The condition is characterised by the out-of-place growth of intestine-like cells in the food pipe. By building 'mini-organs' using oesophageal cells collected from these patients (example shown here), the team found the intestinal-type cells (in red) along with TMPRSS2 protein, one of the known receptors for the SARS-CoV-2 virus (in green). While this study does not provide evidence that COVID-19 can be transmitted through food and drink in most people, it does suggest that individuals with this relatively common gastrointestinal condition could be more vulnerable to the virus.

Written by Gaëlle Coullon

Image from work by Ramon U. Jin and colleagues, Washington University School of Medicine

Division of Gastroenterology, Department of Medicine, Washington University in St. Louis, School of Medicine, St. Louis, MO, USA

Image copyright held by the original authors

Research published in Gastroenterology, January 2021