Normal values and regional differences in oesophageal impedance-pH metrics: a consensus analysis of impedance-pH studies from around the world.

OBJECTIVE: Limitations of existing impedance-pH thresholds include small sample size of normative studies, inclusion of artefactual pH drops and incorrect identification of impedance reflux events. We aimed to obtain new impedance-pH thresholds from expert consensus analysis of tracings from a large number of healthy subjects. DESIGN: Of 541 studies performed worldwide using two different systems (Diversatek, USA, and Laborie, Netherlands), 150 tracings with oesophageal diagnoses, behavioural disorders and study-related artefacts were excluded. The remainder studies were subject to two reviewer consensus analysis, in-person or through video conference, consisting of editing meals and pH drops, identification of impedance reflux and postreflux swallow-induced peristaltic wave (PSPW) using strict pre-established criteria and measurement of distal mean nocturnal baseline impedance (MNBI). RESULTS: Consensus analysis was performed in 391 tracings (age 32.7 years, range 18-71, 54.2% female). Normative thresholds were significantly different between Diversatek and Laborie (total acid exposure time: 2.8% and 5%; reflux episodes: 55 and 78; MNBI at 3 cm: 1400 and 1500 ohms, at 5 cm: 1400 and 1800 ohms). Males had higher acid exposure, more reflux episodes and lower MNBI. Significant regional differences were identified, including higher PSPW scores in Western countries, and higher MNBI in Asia using Diversatek, and higher acid exposure in the Netherlands, higher MNBI in Asia and South Africa, and lower MNBI in Turkey using Laborie. CONCLUSION: Normal impedance-pH monitoring thresholds have regional and system-related differences. Clinical interpretation needs to use normal thresholds valid for the system used and world region, following careful editing of the tracings.

24-Hour Measurement of Gastric pH in Rural South Africa.

Background. Previous studies have established norms of 24-hour gastric pH profiles for western countries. This study was designed to establish the pattern for a rural African population with a high incidence of oesophageal cancer. Methods. After lower oesophageal manometry a probe was placed 10 cm distal to the lower oesophageal sphincter. We carried out 24-hour ambulatory monitoring of gastric pH on 59 healthy subjects. This was satisfactorily completed on 26 female and 18 male (age 21-64, median 35) subjects in the Transkei region of South Africa. Results. The mean 24 hour gastric pH was 2.84 and the mean night-time pH was 3.7. 40 volunteers recorded a night-time pH reaching over 4. 33 volunteers recorded a night-time pH over 7. Night-time alkalinisation was present for 136.4 minutes (25th centile 22.8, 75th centile 208.1) at pH4 or over, and 79.3 (2.5, 122.7) minutes at pH7 or over. Episodes of rapid alkaline rise were 17 (10, 47). 21.1% of these occurred while supine. 35 of 36 tested subjects were positive for H. pylori IgG. Conclusion. Gastric alkalinisation is common in Transkei, at a higher pH than that reported in other studies, and is sustained longer. Nighttime alkalinisation is frequent. This suggests a high level of duodenogastric reflux.

Molecular basis for maize as a risk factor for esophageal cancer in a South African population via a prostaglandin E2 positive feedback mechanism.

The incidence of squamous cancer of the esophagus varies up to a hundredfold in different regions of the world. In Transkei, South Africa, a particularly high incidence of the disease is observed. We have previously proposed an association between a maize-rich diet and elevated levels of intragastric prostaglandin E2 production (PGE(2)). Here we investigate the molecular mechanisms by which a high-maize diet could lead to increased incidence of squamous cancer of the esophagus. We confirm that levels of PGE(2) are high (606.8 pg/ml) in the gastric fluid of individuals from Transkei. We also show that treatment of esophageal cells with linoleic acid, which is found at high levels in maize and is a precursor to PGE(2), leads to increased cell proliferation. Similarly, treatment of cells with PGE(2) or with gastric fluid from Transkeians also leads to increased proliferation. Our data suggest that the high levels of PGE(2) associated with a maize-rich diet stimulate cell division and induce the enzyme COX 2, resulting in a positive feedback mechanism that predisposes the esophagus to carcinoma.

Carcinogens and endemic squamous cancer of the oesophagus in Transkei, South Africa. Environmental initiation is the dominant factor; tobacco or other carcinogens of low potency or concentration are sufficient for carcinogenesis in the predisposed mucosa.

Oesophageal cancer is common in Africa, and is a major cause of death in Transkei, South Africa. The cause of this endemic disease has been debated for many decades. A continuing focus of research has been identification of a single potent carcinogen. I argue that endemic incidence of oesophageal cancer is associated with potent initiation, not with potent carcinogenesis. Tobacco is a known oesophageal carcinogen, and there is very strong evidence that it is causally involved in a significant proportion of victims. Other potential carcinogens present in the environment include fungal mycotoxins, human papillomavirus, Solanum nigrum and nitrosamines. These are all of lower carcinogenic potential for the oesophagus, and do not have strong evidence associating them with the disease. In the presence of potent environmental initiation, any oesophageal carcinogen even if of low potency or of low concentration may cause the disease. Any or all of the substances named above may be involved, any one of them the cause of the final carcinogenic change in the individual. Tobacco exemplifies this point. It is of relatively low concentration/usage in Transkei, yet has an undeniable association with oesophageal cancer. Carcinogenesis for the oesophagus in Transkei is solely or predominantly due to agents which are already known, including tobacco, acting on a predisposed mucosa. The search for further carcinogens is of low importance, and the search for a single potent carcinogen is misguided. What is of importance is the development of methods to reduce the risks associated with predisposing factors and with known carcinogens.

Dietary fat and salivary prostaglandin E2.

A study of the relation between dietary fat intake and salivary prostaglandin E2 was undertaken in Transkei, South Africa. Samples of saliva were obtained from (1) Transkeians on a very low fat diet, (2) Transkeians on a low fat diet, (3) Transkeians on a medium fat diet, (4) British patients. Salivary PGE2 means for the groups were (1) 2357 pg/ml, (2) 2020 pg/ml, (3) 733 pg/ml, (4) 312.5 pg/ml. Differences between groups 1 and 3, 1 and 4, and 2 and 4 were significant. Rural Transkeians on a low-fat diet have an elevated level of PGE2 in saliva. As fat increases in the diet, PGE2 in saliva tends towards the level found in those who eat a western diet. An increase in the level of PGE2 production in the upper gastrointestinal tract and in the tissues of the body may be a factor in promoting cancer of the esophagus and diseases favored by Th1 immune dysfunction.