In the United States about 4.6 million people have active peptic ulcers. 500,000 new cases of peptic ulcers diagnosed each year. Peptic Ulcers are by definition a break in the lining of the stomach or the first portion of the small intestine called the duodenum. 3000 cases of duodenal ulcers and 3000 of gastric ulcers die each year, with four times as many duodenal ulcers than gastric ulcers. 70% of ulcers occur in between ages of 25-64 years old. The annual direct and indirect health care costs of the disease are estimated to be $10 billion dollars a year. H pylori infection accounts for 90% of duodenal ulcers and 70-90% gastric ulcers. Prevalence is equal among males and females. Lifetime prevalence is 11-14% in men and 8-11% in female
Causes of Peptic Ulcers
- Helicobacter pylori infection- Gram -negative spiral rod like organism found in 48 percent of all patients with peptic ulcer disease. H pylori adhere to the gastric mucosa and have an inflammatory protein that increases virulence and ulcer potential. Eradication of H. pylori reduces the incidence of ulcer recurrence from 67% to 6%
- Non-steroidal anti-inflammatory drugs (NSAIDS)- most common cause of ulcers without H.pylori infection. NSAIDS cause mucosal erosions. NSAIDS inhibit the formation of prostaglandins and the protective cyclooxygenase 2 mediated effects which are protective to the stomach lining
- NSAIDS are responsible for approximately one half of all perforated ulcer
- Other drugs commonly cause ulcers- Steroids, Potassium, Chemotherapeutic Agents, Bisphosphonates
- Cancers- Gastric cancer, Lymphomas, Lung Cancers
- Hypersecretory conditions- Rare but secrete large amounts of acids (Zollinger-Ellison Syndrome)
Other infections or diseases responsible for ulcers
- Tuberculosis
- Chron’s Disease
- Cirrhosis
- Cytomegalovirus
- Renal Failure
- Sarcoidosis
- Multiple cancer states
- Stress ulcers following ventilator support or multi-system failure
- Shock leading to lower tissue perfusion
- Smoking- increases the incidence of ulcers and slows or prohibits healing
Clinical Features of Ulcer Disease
- Episodic burning epigastric pain usually occurring on an empty stomach or 2-5 hours after a meal
- Night-time pain
- Stomach pain relieved with food, antacids or anti-secretory agents
- Vomiting
- Loss of appetite
- Chronic heartburn
- Weight loss
- Dark or bloody stools
Abdominal pain is absent in at least 30 percent of older adults with active peptic ulcers. Ulcers are relatively rare in children and most occur between the age of 8-17 years old. Duodenal ulcers more common in this population. Perforation is rare.
In older age groups, they are more likely to have painless ulcers and can present with non-specific complaints such as falls, confusion, restlessness and abdominal distension. These patients can have hemorrhagic complications where transfusions of blood are necessary.
Severe Symptoms
Not all ulcers bleed and not all ulcers cause pain but below are the severe symptoms that need immediate attention
- Severe anemia
- Hematemesis- vomiting up blood
- Melena- dark or bloody stool
- Persistent vomiting indicating obstruction
- Persistent upper abdominal pain radiating to the back
- Persistent pain and weight loss
These patients should be sent for immediate evaluation with Esophagogastroduodenoscopy- This is a test where a lighted flexible tube is used to visually inspect the esophagus and stomach. Under the age of 55 years old without severe symptoms can be sent for evaluation. They should be advised to stop smoking, alcohol and illicit drug use. NSAIDS should be stopped immediately.
Testing for Ulcers
- Esophagogastroduodenoscopy
- Upper GI studies- where EGD is unsuitable , Barium is swallowed and followed by X-ray
- Testing for H. Pylori by blood, breath testing or stool
Treatment of Peptic Ulcers
- H2-Receptor Antagonists- these drugs inhibit the stimulation of the H2 receptor in the gastric parietal cell which then reduces gastric acid secretion Old saying, “No acid, no ulcer.” Examples in this class, Tagamet, Pepsid, Axid and Zantac. Zantax was recently withdrawn from the market due to a contaminant known as N-Nitrosodimethylamine (NDMA) a possible carcinogen
- Proton Pump Inhibitors (PPI)- these drugs inhibit the parietal cell H/K/ATP pump. Thus, decreasing the production of stomach acid. Examples in this class, Prilosec, Prevacid , Aciphex, Nexium, Protonix
- Cytoprotective Agents- these drugs stimulate mucus production and work by forming a coating that protects the lining of the stomach. Examples in this class, Cytotec and Carafate
- Antibiotic Agents- these drugs are used against H.pylori. Examples in this class are; Ampicillin, Clarithromycin, Tetracycline and Metronidazole
- Other Medications include antacids, lidocaine, bismuth, and anti-spasmodics
Surgery
Surgery is indicated in patients who are intolerant to medical regimes and those at high risk of complications. Also ,those with ulcers that fail to heal after multiple trials of medical therapy.
Surgery usually involves partial stomach removal and vagotomy. (Cutting part of the nerve that supplies the stomach).
Complications of Peptic Ulcer Disease
About 25% of patients who have peptic ulcer disease have a serious complication:
- Hemorrhage
- Perforation
- Obstruction
Perforation:
Free peritoneal perforation is a sudden medical emergency. Initial volume resuscitation and broad -spectrum antibiotics are instituted followed by surgical intervention. The surgical intervention may be done laparoscopically with a patch or open surgery with partial removal of the stomach area
Gastric Outlet Obstruction:
5-8% of patients with peptic ulcer disease can obstruct due to inflammation, spasm, edema scarring and fibrosis. The site of the obstruction dictates the treatment. Malignancy is a common cause of obstruction. Surgery is usually needed for all causes in this category.
Bleeding or Hemorrhage:
Upper Gastrointestional bleeding occurs in 15-20% of all patients with peptic ulcer disease. It is the most common cause of death and the most common indication for surgery. Again, it should be noted, 20 percent of bleeding is from asymptomatic ulcers commonly seen in the elderly population. If the patient is hemodynamically stable, the procedure of choice is EGD
Several modalities of endoscopic therapy are currently available to manage the active bleeding ulcer;
- Injection therapy
- Hemostatic clips
- Argon plasma coagulator
- Combination of the above
Injection therapy is performed endoscopically with epinephrine in a 1:10000 dilution injected into the ulcer area. Hemoclips have been used successfully to treat actively bleeding ulcer by approximating two folds and clipping them together. Coagulation is performed via EGD with a heater probe applied to the bleeding site. It should also be noted, transcatheter embolization may also be useful in cases where endoscopic therapy has failed.
Platelet-Rich-Plasma
Platelet Rich Plasma is an autologous blood derived product that provides supra- physiologic concentrations of clotting factors, growth factors and cytokines that facilitate tissue repair in the body. In review of the literature, PRP in being used in the treatment of active bleeding ulcers and post treatment to enhance hemostasis and repair of damaged tissues.
Studies Using Platelet-Rich-Plasma in the Treatment of Peptic Ulcer Disease:
- The Additive Effect of Platelet-Rich-Plasma in the Treatment of Actively Bleeding Peptic Ulcer Clin Endosc 2021 Nov; 54(6) 864-871. PMID 34030430
Background- Peptic ulcer bleeding is the most common cause of upper gastrointestinal bleeding. Platelet-Rich-Plasma enhances tissue repair , and is therefore used in various medical treatments. A combination of mechanical or electrothermal hemostasis has been recommended for upper gastrointestional tract bleeding treatment. This study evaluated the additive efficacy of PRP in bleeding peptic ulcer hemostasis and recovery.
Methods- 80 patients with peptic ulcer bleeding were initially treated by hemoclipping and were randomly chosen for either additional PRP or additional epinephrine injections. Both groups were then compared with regard to hemostasis and the frequency of complications
Results- Blood count was substantially increased in the PRP treated group with full recovery occurring in 60.5% compared to 31.3% of patients in the epinephrine group. There was no recurrent bleeding in the PRP group but 12.5% patients in the epinephrine group exhibited rebleeding
Conclusion- PRP showed additional benefit in reducing peptic ulcer bleeding with no significant complications
- Effectiveness of Autologous Platelet-Rich-Plasma for the Healing of Ulcers after Endoscopic Submucosal Dissection Clin Endosc 2019 Sep; 52(5) 472-478 PMID 31096727
Aims- The aim of this study was to evaluate the clinical efficacy and safety of local PRP injections after endoscopic submucosal dissection
Methods- two groups one received a proton pump inhibitor only and the second group received a proton pump inhibitor and PRP injections
Results- The rate of ulcer reduction was greater in the PRP group after 28 days, 59% to 52%
Conclusion- The local injection of Platelet Rich Plasma is a safe and effective procedure for ulcer healing
- Platelets Accelerate Gastric Ulcer Healing Through Presentation of Vascular Endothelial Growth Factor Br J Pharmacol 2006 Jun:148(3): 274-278. PMID 16565732
Studies have shown that circulating platelets contribute significantly to gastric ulcer healing, acting as a delivery system for growth factors to the site of injury. The studies indicate that VEGF released from platelets accounts for the accelerated healing of gastric ulcers. The study also indicated that intact platelets were required at the site of injury and appears crucial for enhancement of the healing process.
- Combination Of Cells Technologies and Mini-invasive Surgery in The Treatment of Chronic Gastric Ulcers Klin Khir 2015 Oct;(10): 25-28 PMID 26946654
The results of experimental and clinical use of stimulants of local reparative processes (PRP) in the treatment of chronic gastric ulcer were analyzed. In the experimental part of the study the benefits of using platelet-rich-plasma as donator growth factors were proven. The ability to stimulate the activity of fibroblasts and vessel formation in the young connective tissue with improving of oxygenation in ulcers and enhancing of cell proliferation, differentiation and connective tissue maturation and healing of gastric ulcers were demonstrated. In clinical studies, the advantages of combination of standard antiulcer therapy and local endoscopic injection of platelet-rich-plasma compared to only conservative therapy were shown.
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