Causes and Management of Gastric and Duodenal Ulcer in Adolescents

Many etiological hypotheses have been suggested to explain the development of peptic ulcers during the last 300 years (including gastric ulcer and duodenal ulcer). In the last two decades, significant progress has been made in understanding the pathophysiology of peptic ulcer disease, particularly with regard to the involvement of Helicobacter pylori and nonsteroidal anti-inflammatory medications (NSAIDs). This study will attempt to review literature on etiology and management of gastric and duodenal ulcers among adolescents.


INTRODUCTION
Many individuals have ulceration of the gastric or duodenal mucosa. Both gastric and duodenal ulcers are included in the term peptic ulcer disease (PUC). Reduced efficiency of the stomach mucosal barriers, excessive acid output,

Review Article
and infection with Helicobacter pylori bacteria are some of the factors that may lead to ulcer development. PUD is a prevalent condition that affects millions of people each year in the United States. Peptic ulcer illness has a significant financial impact on our health-care system, accounting for about 10% of all medical costs associated with digestive disorders [1]. In the last two decades, significant progress has been made in understanding the pathophysiology of peptic ulcer disease, particularly with regard to the involvement of Helicobacter pylori and nonsteroidal anti-inflammatory medications (NSAIDs). This has resulted in significant modifications in diagnostic and treatment techniques, with the potential to improve clinical outcomes while also lowering health-care expenditures [2].
The geographic distribution of a disease may provide important information about its cause. Similarly, any historical changes in prevalence linked to changes in lifestyle may provide further information. The frequency of ulcers varies throughout the globe, with duodenal ulcers predominating in Western cultures and stomach ulcers being more common in Asia, particularly Japan [3].
A systematic review of the literature regarding the epidemiology of PUD reveals a few key facts. First, it demonstrates that PUD is still a very frequent disorder over the world, with annual incidences ranging from 0.10% to 0.19% for physician-diagnosed PUD and from 0.03% to 0.17% for PUD identified after hospitalisation. Physician-diagnosed PUD had a 1-year frequency of 0.12-1.%, while PUD diagnosed during hospitalizations had a 1-year prevalence of 0.10-0.19% [4]. Their results demonstrate that the prevalence of PUD has reduced in many nations in recent decades, most likely due to a reduction in H. pylori infection, especially in Western populations [4].
However, it is possible that the status in Asian countries is different; a recent study in Korea found that the prevalence of H. pylori infection in people with GU was growing with time, whereas H. Pylori infection in people with DU was declining [5].
The most trustworthy study of physiciandiagnosed prevalence came from Sweden, and it used cross-sectional data from the general population to include both symptomatic and asymptomatic PUD [6]. A systematic review reported the total prevalence of PUD was 4.1%, with 19.5% of all PUD cases being asymptomatic [4]. When compared to the lower rates found in other studies of physician-diagnosed PUD in primary care, it appears that a proportion of people with PUD go undetected. Severe consequences, such as gastrointestinal bleeding, may be the initial signs of PUD in people who are asymptomatic. Haemorrhage is linked to a 10% mortality rate and a high rate of recurrence [7].
Over the last few decades, management of H. pylori-associated PUD has vastly improved, culminating in the common use of proton pump inhibitor (PPI)-based triple therapy for H. pylori eradication [8]. However, over this time period, prescriptions for medicines implicated in the aetiology of PUD, such as aspirin and NSAIDs, have also increased, and adherence to gastroprotection for the prevention of NSAIDinduced PUD remains far from optimum [9].

Helicobacter Pylori Infection
Helicobacter pylori infection is a prevalent cause of peptic ulcers in adolescents [10]. H. Pylori is linked to both gastric and duodenal ulcer disorders. In the first decade after the discovery of H. pylori, roughly 95 percent of duodenal ulcers and 85%of stomach ulcers were found in the presence of H. pylori infection, according to data from throughout the world [11]. Several cohort studies found that H. pylori-positive participants have a 3 to 10 times higher lifetime risk of ulcer disease than H. pylori-negative individuals, and that 10 to 15% of H. pyloripositive individuals develop ulcer disease throughout long-term follow-up [12]. These findings are based on research conducted in industrialised countries. It's unclear whether H. pylori-positive people in developing nations are at risk for the same diseases. H. pylori eradication regimens concluded the evidence for a causal relationship between H. pylori and ulcer disease by demonstrating that eradication of this bacterium significantly lowered the likelihood of recurrent ulcer illness [13].
A combination of host and bacterial variables promote ulcer formation in the presence of H. pylori. Ulcers are most common where mucosal inflammation is the most severe. This is frequently the gastric transitional zone between corpus and antrum in people with low acid output, which leads to gastric ulcer disease. If acid output is normal to high, juxta-pyloric and duodenal ulcer disease develops in the distal stomach and proximal duodenum [14].
The rate ratio of antral gastritis for children with H. pylori infection (relative to uninfected individuals) varied from 1.9 to 71.0 in a pooled study of early data (1983)(1984)(1985)(1986)(1987)(1988)(1989)(1990)(1991)(1992)(1993)(1994), (median, 4.6) [15]. Thus, there was significant evidence for a link between H. pylori infection and antral gastritis and duodenal ulcer in children, but only limited evidence for a link between H. pylori infection and stomach ulcer in adults. Nonetheless, a subsequent retrospective study from Japan (1995-2001) stated that the prevalence of H. pylori was very high in antral (nodular) gastritis and duodenal ulcer (98.5% and 83%, respectively), but it also demonstrated that H. pylori was a definable risk factor for the development of gastric ulcer, despite the fact that infection prevalence did not reach 50%. In the age range of 10-16 years, H. pylori was substantially related to duodenal and stomach ulcers, but not in the age group of 9 years [16].

NONSTEROIDAL ANTIINFLAMMA-TORY DRUG-INDUCED GASTRO-DUODENAL INJURY
The two most major independent variables in peptic ulcer disease are nonsteroidal antiinflammatory drugs (NSAIDs) and H. pylori infection [17]. Their prevalence as a cause of peptic ulcer varies and is linked to the usage of NSAIDs and the prevalence of H. pylori infection in a community [18]. In the senior population, NSAID usage and H. pylori infection are both prevalent.
The use of NSAIDs is becoming a more significant risk factor for PUD. The use of NSAIDs and low-dose aspirin has been linked to an increase in hospitalizations among the elderly owing to peptic ulcer bleeding and perforation. . In one Finnish study, 12% of people aged 60 to 74 used prescription NSAIDs on a daily basis, while 9 percent of the same group used both prescribed and over-the-counter (OTC) NSAIDs at the same time [21]. The risk of peptic ulcer bleeding (PUB) among non-aspirin NSAID users is affected by the type of NSAID taken. When compared to ketorolac (Relative Risk (RR) 14.4; 95%CI 5.2-39.9), the risk was found to be lowest when using aceclofenac (2.6; 1.5-4.6), diclofenac (3.1; 2.3-4.2), or ibuprofen , Chung and Shelat [28] all found that using NSAIDs increases the risk of ulcer perforation. Celecoxib, a selective inhibitor of the cyclo-oxygenase-2 (COX-2) enzyme, was first brought to the market in 1999. The COX-2 selective inhibitors have no effect on the cyclooxygenase-1 (COX-1) enzyme, which is involved in GI mucosal protection and platelet function, but they do prevent inflammation and discomfort caused by prostaglandin production, which is reliant on the COX-2 enzyme. The use of any coxib was not related with PUB (RR 1.5; 95 percent CI 0.9-2.4) in a case-control study conducted in Spain between 2001 and 2004, while the use of rofecoxib marginally raised the risk of PUB (2.1; 1.1-4.0) (Lanas et al. 2006

OTHER DRUGS
In a Danish population-based case-control research, the use of selective serotonin reuptake inhibitors (SSRIs) was linked to a slightly higher incidence of PUB (or hemorrhagic gastritis). The precise mechanism by which an SSRI affects the risk of bleeding is unclear, although its capacity to suppress platelet aggregation and increase stomach acid production are two possibilities [33].

OTHER RISK FACTORS
PUD and associated consequences are more common as people become older [26]. A prior history of PUD is a strong predictor of recurrence [25]. In Spain, female gender was associated with a lower incidence of PUB (Lanas et al. 2006), whereas in Korea, male gender was associated with a higher risk of PUB [35]. PUD is made more likely by smoking (Aro et al. 2006, Lanas et al. 2006) [25]. In Finland, smoking was a dose-dependent risk factor for PUB, while alcohol use was not [36]. In Asia, findings contradicting those of the Finnish research have been published, with alcohol consumption linked to PUB but no link identified between smoking and PUB [35,37]. It has also been shown that smoking is a risk factor for ulcer perforation [26]. In a Swedish population-based research, obesity was linked to an increased incidence of simple stomach ulcer (Aro et al. 2006). Psychological stress and abrupt changes in living circumstances, such as witnessing a lifethreatening earthquake or being housed in a refugee shelter, have been linked to the development of PUD in recent research [38,39,40]. Until recently, the use of gastroprotective agents, such as PPIs, as stress ulcer prophylaxis in all critically ill patients in intensive care units was standard practice, despite concerns about its necessity for all patients and potential side effects (nosocomial pneumonia, Clostridium difficile infection, or cardiovascular events) [41].

MANAGEMENT OF GASTRIC AND DUODENAL ULCERS
Patients with acute peptic ulcer bleeding or perforation should be evaluated as soon as possible and resuscitated before receiving final treatment. A rigorous strategy for blood transfusions is recommended by international standards, with a hemoglobin goal level of 70 g/l [42]. When all the patients hospitalized with severe acute upper GIB in Spain were analyzed, there was a tendency toward improved survival among PUB patients with restricted strategies, but it was not statistically significant [43].
A difficult clinical issue is coagulopathy and acute bleeding. The precise goal level for the International Normalized Ratio (INR) of coagulation has not been established, and it should be determined based on the particular patient's cause for anticoagulation or the presence of disease-causing coagulopathy [44]. It is strongly advised that risk stratification scores be used [42]. When predicting rebleeding or death in PUB patients, the pre-and postendoscopic Rockall scores, the Glasgow Blatcford score, or a newer AIMS65 score are useful for separating patients into low-and highrisk groups [45,46].
In the treatment of PUD patients, gastroprotective agents (GPAs) and endoscopic therapies are critical, while surgery is required in instances of refractory bleeding or perforation. Interventional radiology is increasingly being used in PUB, particularly in patients who are too frail to undergo surgery.

GASTROPROTECTIVE AGENTS (GPAs)
The use of GPAs, particularly proton pump inhibitors (PPIs), has risen in recent decades [47,48]. The PPIs are used to maintain a neutral stomach pH, which is favouring clot formation. GPAs such as H2-receptor antagonists, antacids, misoprostol, sucralfate, and alginic acids are currently used in small amounts compared to PPIs [49]. PPI usage is linked to a lower risk of bleeding as a complication of PUD [RR 0. European trial [34], monotherapy use of GPA was linked with a modestly higher risk of acute upper. The use of GPA is ineffective for preventing bleeding in individuals who have a number of recognized risk factors. Patients with high-risk stigmata of ulcer bleeding should get continuous intravenous PPI therapy for the next 72 hours after the index endoscopy, according to worldwide recommendations [42,50].

TREATMENT OF H. pylori
To eliminate H. pylori infection, a one-week combination treatment of two antimicrobials (amoxicillin, clarithromycin, tetracycline, or metronidazole) plus a PPI is generally suggested [51]. At least 80% of patients should respond to the first-line eradication treatment [52]. In vitro metronidazole resistance, on the other hand, does not necessarily imply therapeutic failure. Because of the rising frequency of antibiotic resistance throughout the globe, a prolonged 10day or two-week treatment is now advised [53,52]. Susceptibility testing may be useful in the treatment of H.pylori infection when first-line eradication medication has failed.

ENDOSCOPIC INTERVENTION
For ulcers with active bleeding, a non-bleeding visible artery, or an adhering clot (Forrest Ia-IIb), endoscopic treatment is indicated to reduce the risk of recurrent bleeding. Some studies recommend removing an adherent clot (IIb) in the search for an artery, and endoscopic treatment should only be used if one is found [44]. Endoscopic treatment is not required in patients with haematin on the ulcer base (IIc) or a clean base ulcer (III). Dual treatment with epinephrine injection is suggested by worldwide recommendations to reduce the risk of rebleeding, surgery, and death [42,50]. Injection, heat, and mechanical techniques of endoscopic therapy have historically been used. Endoscopic topical hemostatic powders have recently been available on the market [54]. However, several national audits have shown that the percentage of patients getting dual treatment for significant stigmata of hemorrhages is as low as 34% in Canada, 35% in Italy, and 38% in the United Kingdom [55], (Barkun et al. 2004).

SURGICAL TREATMENT
Because of effective conservative therapies, the necessity for elective surgery has reduced significantly [56]. However, perforated ulcers and refractory rebleedings still need emergency surgery. As observed in Western nations, the necessity for emergency surgery due to PUB in Sweden dropped substantially between 1987 and 2004, while the use of endoscopic therapies rose [57,44]. Only 1.3% of PUB patients required surgery, according to a new research from the Netherlands [58]. In acute PPU patients, the superiority of open versus laparoscopic surgery is debatable. There was no statistically significant difference in complications or death between the open and laparoscopic techniques in a Cochrane systematic review of three randomised clinical trials on PPU patients with repair using an omentum patch or fibrin sealant [59].

TAE
TAE is an option for individuals with severe and recurring bleeding who do not respond to endoscopic treatment. There are no prospective randomized controlled trials comparing surgery with TAE. When compared to surgery, TAE is linked with greater rebleeding rates with no significant difference in mortality, although patients admitted to TAE were considerably older and may not have been surgical candidates owing to comorbidities [60]. Patients underwent TAE had fewer postoperative complications, but no difference in rebleeding rate or mortality [61], while TAE use among endoscopy-refractory PUB patients in Denmark was linked to a lower 30-day mortality rate than surgical haemostasis [61,62].

CONCLUSION
Persistent H. pylori infection, prolonged use of NSAIDs, severe comorbidities that impede ulcer healing, or other diseases such as gastrinoma or stomach cancer are also frequent causes. Patients may be candidates for surgical therapy if the ulcer persists after addressing the aforementioned risk factors. Vagotomy or partial gastrectomy are two surgical alternatives.

CONSENT
It is not applicable.

ETHICAL APPROVAL
It is not applicable.

COMPETING INTERESTS
Authors have declared that no competing interests exist.