Unhealed Ulcers Research Articles

TREATMENT OF DUODENAL ULCER WITH CARBENOXOLONE SODIUM: A DOUBLE‐MASKED ENDOSCOPIC TRIAL

In a double-masked trial, 43 patients with an endoscopically confirmed, symptomatic duodenal ulcer were allocated at random to treatment with either carbenoxolone sodium or placebo, both provided in identical "positioned-release" capsules. The 40 patients who satisfactorily completed the trial were evenly distributed between the two treatment groups. The groups were well matched with regard to clinical features and initial ulcer size. Endoscopic review of ulcer healing after six weeks' treatment showed that 12 patients (60%) receiving carbenoxolone had healed ulcers, compared with five (25%) receiving placebo (P = 0.05). Symptomatic remission occurred by the fourth week in 17 patients (85%) receiving carbenoxolone, compared with six (30%) receiving placebo (P less than 0.001). The mean (geometric) serum carbenoxolone level in patients with healed ulcers was 31.11 microgram/mL compared with 17.75 microgram/mL in those with unhealed ulcers (P less than 0.005). Side effects of carbenoxolone therapy were observed, but they did not necessitate withdrawal of the drug and were readily controlled in every instance. These results confirm the therapeutic efficacy of carbenoxolone sodium in duodenal ulcer. In addition, a relationship between serum carbenoxolone levels and the occurrence of ulcer healing was observed.

2 - Peptic Ulceration and its Correlation with Symptoms

Studies in which the numbers of healed or unhealed ulcers and their correlation with symptoms are availabel are summarized in Table 1. A review of the data and inspection of the Table show that the correlation of GU or DU healing with symptomatic remission is generally poor. The reasons for this are unknown and reflect the very incomplete understanding of the mechanism of ulcer pain and of the pathways through which the pain is mediated. The pathogenesis of pain in GU or DU may be due to the action of acid and pepsin, or of bile, on the tissues exposed in the ulcer crater, to abnormal motility, to normal motility acting on inflamed tissue, to areas of inflammation surrounding the ulcer crater, or to a combination of these factors. The relative importance of each of these variables in DU or GU, or in individual patients (because the mechanism of pain may not be the same in each patient) is not known. Nor is it known how much the pathogenesis of ulcer pain is the result of local release of histamine, kinins, and prostaglandins. These biogenic factors are known to be associated with inflammation and produce, or enhance, somatic pain. Their importance in peptic ulcer in man needs to be studied. Relief of pain after neutralization or buffering of gastric contents with alkali or food suggests strongly that acid must play an important part in the pathogenesis of the ulcer symptoms. The rapidity with which relief of symptoms occurs points towards the direct involvement of hydrogen ions in at least one type of ulcer symptom. Lowering of intragastric acidity by histamine H2- receptor antagonists or high-dose alkali may contribute to the observed discrepancies between ulcer healing and the remission of pain, by creating an environment in the gastroduodenal lumen which favours symptomatic improvement, even in the presence of an unhealed crater. This idea, however, does not explain why there is a discordance between healing and symptoms in patients receiving placebo, or in those treated with other drugs, such as carbenoxolone sodium. In the absence of endoscopic evidence, the presence or absence of symptoms cannot be assumed to indicate with certainty the presence or the absence of a peptic ulcer.

Observations on the histology of the gastric mucosa in chronic gastric ulcer.

Histologic changes were studied in the gastric mucosa of 18 patients with a chronic, lesser curve, gastric ulcer. Biopsies were taken approximately 2 cm from the ulcer margin, and from the opposite wall of the stomach body. Morphologic appearances noted in the active phase of ulceration were found to persist during the healing process (12 patients) and, on follow-up study, at 6 to 10 weeks (5 patients). The ulcer failed to heal in 6 patients, 5 were treated surgically and another refused operation; all had persisting gastritis. Twelve patients had been treated with carbenoxolone, which did not appear to influence histology. The ability of the ulcer to heal in the presence of continuing gastritis, the persistence of gastritis after the ulcer healed and the lack of difference in the surrounding mucosa between healed and unhealed ulcers indicate that the relationship between the two lesions is uncertain.

How sectioning the sciatic nerve affects the blastomogenic action of strontium-89

The role of sciatic nerve section on the blastomogenic effect of strontium-89 has been studied in albino mice. Three out of fifteen animals developed malignant tumors on the limbs with an intact somatic innervation. But only one animal developed a tumor on the denervated limb, on the place of an unhealing trophic ulcer. The tumor was a benign one, an osteosclerotic osteoma. The results could not be accounted for by any difference in the strontium content of the normal and denervated limbs since the difference was comparatively small.

On repeated surgeries for stomach and duodenal ulcers

Prof. S. S. Girgolav (Journal of Modern Surgery, vol. III, issue, 4.1928), having examined his 54 cases of repeated operations, came to the conclusion that with callosal ulcers of the lesser curvature of the stomach, resection should be done the first time. If after G E there was no light gap and an unhealed ulcer was found during the repeated operation, then, obviously, the anastomosis does not work and resection is necessary. If the anastomosis is functional and the ulcer is in the new or old site, resection is recommended. In case of complaints of upset gastric digestion and the absence of an ulcer during a second operation, the anastomosis should be destroyed.

THE SURGICAL TREATMENT OF GASTRIC AND DUODENAL ULCER AND ITS RESULTS.

The contributions to the literature of ulcer of the stomach and duodenum have become so numerous that it will be impossible in a paper of this character to give credit for the many valuable advances which have been brought out by individual workers. I wish in this connection, however, to express my appreciation of their labors. For more than twenty years the complications of this malady have received attention. Operations for benign stenosis of the pylorus and some acute secondary manifestations have occasionally been performed, but not until the last five years has there been a surgical invasion into the field of unhealed ulcers with a view of giving relief from pain, under-feeding and chronic disability which so frequently accompany the disease. Acute ulcer of the stomach and duodenum properly belong to the domain of internal medicine, and surgery has to do only with the complications such as perforation, hemorrhage