oesophageal mucosal resistance

The human oesophagus is lined by a moist, partially keratinized, stratified squamous epithelium, one important property of which is to serve as a barrier between the outside (luminal) world and the internal world of the organism. This phenomenon in clinical parlance is known as 'oesophageal mucosal resistance'. This article details the structure and functions of the oesophageal mucosa that contribute to its defence against injury upon exposure to refluxed gastric acid.     

Medication-induced oesophageal disorders

Medication-induced oesophageal distress and injury have become increasingly common conditions. First, smooth muscle relaxants may worsen or produce symptoms of pre-existing gastro-oesophageal reflux disease; notable examples include certain calcium antagonists (nifedipine), nitrates, sildenafil, nicotine, theophylline, and substances with antimuscarinic potential. Second, drugs with local toxicity may produce de novo damage including inflammation, strictures, ulcers, and bleeding. Notorious examples are alendronate, certain antibiotics including tetracyclines and clindamycin, all NSAIDs/aspirin, quinidine, potassium chloride, and ferrous sulfate. Cyclooxygenase-2 inhibitors may be devoid of such toxicity, but may damage the mucosa by interfering with regenerative cell proliferation. The galenic formulation can modulate the risk of oesophageal injury. For this reason, medicines containing the same potentially toxic ingredient may be less exchangeable than commonly thought. Diagnostic gold standard is endoscopy. The best treatment is removal of the offending drug and supportive care. Prevention requires a re-appraisal of the drug’s indication and adherence to guidelines of optimal drug intake including ingestion in an upright position and swallowing with enough fluid. The clinical relevance of drug-induced oesophageal injury and the feasibility of therapeutic alternatives are individually addressed.     

Medication-induced oesophageal disorders

Medication-induced oesophageal distress and injury have become increasingly common conditions. First, smooth muscle relaxants may worsen or produce symptoms of pre-existing gastro-oesophageal reflux disease; notable examples include certain calcium antagonists (nifedipine), nitrates, sildenafil, nicotine, theophylline, and substances with antimuscarinic potential. Second, drugs with local toxicity may produce de novo damage including inflammation, strictures, ulcers, and bleeding. Notorious examples are alendronate, certain antibiotics including tetracyclines and clindamycin, all NSAIDs/aspirin, quinidine, potassium chloride, and ferrous sulfate. Cyclooxygenase-2 inhibitors may be devoid of such toxicity, but may damage the mucosa by interfering with regenerative cell proliferation. The galenic formulation can modulate the risk of oesophageal injury. For this reason, medicines containing the same potentially toxic ingredient may be less exchangeable than commonly thought. Diagnostic gold standard is endoscopy. The best treatment is removal of the offending drug and supportive care. Prevention requires a re-appraisal of the drug's indication and adherence to guidelines of optimal drug intake including ingestion in an upright position and swallowing with enough fluid. The clinical relevance of drug-induced oesophageal injury and the feasibility of therapeutic alternatives are individually addressed.     

The effect of healing oesophagitis on oesophageal motor function as determined by oesophageal scintigraphy and ambulatory oesophageal motility/pH monitoring

Background:

Oesophagitis has been shown by standard manometry to be associated with impaired oesophageal motility, but it remains unclear if this abnormality improves with healing of oesophagitis.

Aim:

To determine if healing of oesophagitis improves oesophageal motility using solid bolus oesophageal transit scintigraphy and combined ambulatory oesophageal motility/pH monitoring.

Methods:

Patients with grade II–III oesophagitis underwent ambulatory motility/pH monitoring (using a Konigsberg catheter with four pressure transducers at 5 cm intervals) and solid bolus scintigraphy before and after treatment with omeprazole 20 mg b.d. for 8–14 weeks.

Results:

Three (11%) of the 28 patients failed to heal. Initial scintigraphy was abnormal in 18 (67%) of 27 patients (one refused scintigraphy). Twenty-three of the 25 healed patients had repeat studies showing no significant change in the number which were abnormal (16 (64%), P = 1.0) or the overall oesophageal transit time (P = 0.65). Due to intolerance of the technique, only 11 patients had ambulatory motility/pH performed both before and after healing, giving the study 90% power to detect a 5 mmHg increase in peristaltic amplitude. No significant improvement was seen in any motility or pH parameter after healing of oesophagitis.

Conclusion:

Analysis of oesophageal motility showed no improvement in peristaltic activity after healing of oesophagitis, suggesting that the abnormal motility is either a primary disorder or an irreversible consequence of mucosal damage.

     

Managing diffuse oesophageal spasm

Non-cardiac chest pain is common,1 affecting around 25% of the population during their lifetime and accounting for about 2-5% of presentations to hospital accident and emergency departments.2 Around 10% of patients presenting with such pain, and up to 13% of those presenting with functional dysphagia, have diffuse oesophageal spasm (DOS), an oesophageal motility disorder.3,4 DOS is often recognised and treated only after patients have attended hospital emergency departments and specialist clinics for years, because of the non-specific nature of their symptoms and difficulty in diagnosis (features common to motility disorders).5 Here we discuss the diagnosis and further management of patients with DOS.     

The effects of itopride on oesophageal motility and lower oesophageal sphincter function in man

Aliment Pharmacol Ther 2011; 33: 99–105

Summary

Background Itopride is a new prokinetic agent that combines antidopaminergic and cholinesterase inhibitory actions. Previous studies suggested that itopride improves heartburn in functional dyspepsia, and decreases oesophageal acid exposure in gastro‐oesophageal reflux disease. It remains unclear whether this effect is due to effects of itopride on the lower oesophageal sphincter (LES). Aims To study the effects of itopride on fasting and postprandial LES function in healthy subjects. Methods Twelve healthy volunteers (five men; 32.6 ± 2.0 years) underwent three oesophageal sleeve manometry studies after 3 days premedication with itopride 50 mg, itopride 100 mg or placebo t.d.s. Drug was administered after 30 min and a standardized meal was administered after 90 min, with measurements continuing to 120 min postprandially. Throughout the study, 10 wet swallows were administered at 30‐min intervals, and gastrointestinal symptoms were scored on 100 mm visual analogue scales at 15‐min intervals. Results Lower oesophageal sphincter resting pressures, swallow‐induced relaxations and the amplitude or duration of peristaltic contractions were not altered by both doses of itopride, at all time points. Itopride pre‐treatment inhibited the meal‐induced rise of transient LES relaxations (TLESRs). Conclusions Itopride inhibits TLESRs without significantly affecting oesophageal peristaltic function or LES pressure. These observations support further studies with itopride in gastro‐oesophageal reflux disease.     

A novel diagnostic tool for detecting oesophageal pathology: the PillCam oesophageal video capsule

BACKGROUND: Gastro-oesophageal reflux disease is a common entity. Erosive oesophagitis, ulcers and Barrett's oesophagus, which is found in up to 10% of gastro-oesophageal reflux disease patients, characterize severe gastro-oesophageal reflux disease. Patients with Barrett's oesophagus have 0.5% per patient-year risk of developing oesophageal adenocarcinoma. Currently, it appears that a minority of those at risk for Barrett's oesophagus undergo screening in part because of the costs associated with endoscopy as well as risks of sedation. A new ingestible PillCam oesophageal capsule developed may offer an alternative office-based approach to visualize the oesophagus without sedation. AIM: To compare the oesophageal capsule to conventional upper endoscopy for detection of oesophageal pathologies. METHODS: A newly developed capsule, which acquires video images from both ends of the device at a 4 frame/s rate, was ingested by 17 fasting patients with suspected oesophageal disorders. An ingestion procedure aimed to lengthen capsule transit time in the oesophagus was utilized. Subsequently, a standard upper endoscopy was carried out. The investigator interpreting the capsule findings was blinded to the endoscopy results and vice versa. Patients with dysphagia, known Zenker's diverticulum, intestinal obstruction, cardiac pacemaker or pregnancy were excluded. RESULTS: Twelve of the 17 patients examined had oesophageal findings using the endoscope as the gold standard. Capsule endoscopy identified oesophageal pathology in all 12 of these patients and an additional pathology in one patient that was missed during endoscopy. For the purpose of this study, this finding was regarded as a false-positive. The mean oesophageal passage time was 189 +/- 280 s. The positive predictive value of the oesophageal capsule for any oesophageal pathology was 92% and the negative predictive value was 100%. Oesophageal capsule sensitivity was 100% and specificity 80%. There were neither swallowing difficulties nor complications subsequent to ingestion in any subjects. Seventy-three percentage of patients preferred the oesophageal capsule procedure on conventional endoscopy. Only one patient preferred oesophagogastroduodenoscopy. CONCLUSIONS: This pilot study has shown that oesophageal capsule endoscopy is an accurate, convenient, safe and well-tolerated method to screen patients for significant oesophageal disorders. No sedation is required, which may allow simple, office-based screening and assessment. Further, large-scale studies are necessary to more fully assess this novel diagnostic tool.     

The molecular mechanisms of oesophageal cancer

Apoptosis is a process of programmed cell death, which is as essential as cell growth, for the maintenance of homeostasis. When these processes loose integration such as cancer, then uncontrolled cell growth occurs. Cancer of the oesophagus ranks as the ninth most common malignancy in the world, and recent evidence shows that its incidence is increasing. Prognosis of this disease is poor, with an overall 5-year survival rate of less than 10%. Unraveling the mechanisms or developing animal models for oesophageal carcinoma have thus far not been successful. It is believed that oesophageal cancer has an intricate molecular mechanism of evading apoptosis by the down-regulation of Bax, up-regulation of Bcl-2, Bcl-xl and Survivin, mutation of p53 and alteration in Fas expression. A great deal of research has been performed in order to determine the key genes that initiate and promote the growth of oesophageal cancer. This review focuses on apoptosis and candidate genes linked to the development of oesophageal cancer, which it is hoped may provide diagnostic and therapeutic tools, and potential therapeutic strategies for the management of this carcinoma.