In the outpatient clinic, you will encounter patients who have failed to heal their gastric or duodenal ulcers even after more than 1-2 years of treatment after the first visit. Therefore, in this article, we mainly discuss what are the reasons for the delay in healing ulcers. 1, persistent Helicobacter pylori infection – Guangdong infection rate of 40%, up to 60% in the north, some areas such as Gansu infection rate of up to 80%. For active duodenal ulcer patients hp infection rate of up to 80-90%. Successful cure of H. pylori infection predicts accelerated healing of most refractory (and non-specific) ulcers. How to get rid of the bacteria program is discussed in a separate article written by myself. Even in patients with ulcers refractory to acid suppression therapy, eradication of H. pylori improves ulcer healing. Persistent H. pylori infection may be the cause of refractory peptic ulcers, either because H. pylori was not tested for in the first place or was left untreated because of false-negative test results, or because antibiotic therapy given did not eradicate such bacteria. The latter occurs most likely because of the choice of an inappropriate treatment regimen, antibiotic resistance (especially to metronidazole or clarithromycin), or poor patient compliance. Although the urea whistle test and fecal antigen test are the noninvasive tests of choice for demonstrating H. pylori eradication, their sensitivity is only about 90%, but the test has a 10% failure rate. In refractory or complicated cases, endoscopy is highly recommended to confirm that the ulcer has healed and to definitively rule out persistent H. pylori infection. 2. Non-steroidal anti-inflammatory drugs (NASIDs) – Continued use of NASIDs is a critical factor in a significant number of refractory ulcers. Large ulcers – The rate of healing of gastric ulcers is approximately 3mm per week; therefore, large ulcers take longer to heal. The size of the ulcer also affects the healing rate of DU. For example, one study showed that the 3 risk factors associated with non-healing of duodenal ulcers after 4 weeks of treatment were: history of previous ulcers, ulcer size and smoking. Ulcers greater than or equal to 10 mm in diameter were less likely to heal compared with smaller ulcers (62% vs 76%). Large ulcers often form a dense scar. 4. Smoking – Smoking, especially heavy smoking, may lead to poor ulcer healing. 5. Poor healing – Contributing factors to poor healing include an intense inflammatory response, dense scarring, or reduced mucosal blood flow, which can impair angiogenesis and tissue repair. The same factors that lead to poor initial ulcer healing can also cause rapid ulcer recurrence. 6. Hypersecretory state of gastric acid – A small percentage of refractory duodenal ulcer ( DU ) cases are caused by gastrinomas. In a subset of refractory DU patients without gastrinomas, increased levels of basal, nocturnal, and maximal gastric acid secretion may be a contributing factor. Blood gastrin levels can be tested at our institution. In addition, the healing rate of DU is strongly correlated with the degree of suppression of gastric acid secretion, and to a lesser extent gastric ulcers. Atrophic gastritis predicts better ulcer healing, presumably due to lower levels of gastric acid secretion. 7, Impaired efficacy of acid-suppressing drugs – Cytochrome P450 fast metabolizing phenotype may account for the poor response to PPI therapy in some patients. Co-existing Diseases – Co-existing diseases such as uremia, whooping failure, cirrhosis, and slow catabolic states due to a variety of disorders can promote ulcer formation and complications and poor healing. Synchronized use of certain drugs (e.g., corticosteroids, cytotoxic drugs, and cocaine) is also a contributing factor to ulcer formation. 8, emotional stress – some evidence suggests that psychological factors and poor tolerance of stress in particular can increase the occurrence of peptic ulcer disease. 9. Uncommon causes of refractory ulcers – If refractory ulcers are present and Helicobacter pylori infection and NSAID use have been ruled out, uncommon causes of peptic ulcers should be considered, ranging from gastrinomas to rare infections or inflammatory diseases. Inflammatory diseases include eosinophilic gastroenteritis, which can occur at any age and is seen without a significant increase in eosinophils, and sclerosing, IgG4-positive inflammatory diseases associated with refractory gastric ulcers and autoimmune pancreatitis. With the increasing use of endoscopic submucosal dissection and endoscopic mucosal resection for the treatment of early gastric cancer, medical ulcers have arisen and are difficult to manage.