​Kembara Xtra - Medicine - Barrett Esophagus

​Kembara Xtra - Medicine - Barrett Esophagus 
INTRODUCTION 
Distal esophageal mucosa metaplasia from native stratified squamous epithelium to aberrant columnar (intestinalized) epithelium; presumably a result of long-term GERD
Increases the risk of developing esophageal adenocarcinoma

EPIDEMIOLOGY /STATISTICS : 
Predominant age >50 years; more common in men; estimated to affect 1% to 2% of adults; extremely uncommon in children
Incidence
Esophageal adenocarcinoma (EAC) incidence is increasing in the United States, with a 6-fold increase (to 2.5 cases per 100,000) since the 1970s. The annual incidence of adenocarcinoma in all Barrett patients is estimated to be 0.5% per year. This increase is due to changes in smoking and obesity rather than reclassification or overdiagnosis. 

Prevalence
Unknown, but estimated to be between 1.5 million and 2 million adults in the United States (extrapolated from an incidence of 1.6% in the overall population of Sweden).


Etiology and pathophysiology: Prolonged gastroesophageal reflux causes damage to the mucosa, which results in columnar metaplasia. Gastroesophageal junction (GEJ) cells are likely to undergo differentiation as a result of bile acid reflux.
In the esophagus, columnar cells are more likely to develop into cancer than squamous cells. Carcinogenesis is aided by HER2/neu (ERBB2) oncogene overexpression and CDX2 gene activation.
Barrett esophagus (BE) is related with elevated levels of COX-2, a mediator of inflammation and regulator of epithelial cell development.
Normal epithelium, esophagitis or reflux exposure, metaplasia (BE), dysplasia (low or high-grade), and adenocarcinoma are the stages of the classic progression.
Genetics
Numerous genetic markers that indicate a familial propensity to GERD and BE have been found. Adenocarcinoma is caused by acquired genetic alterations, which are being researched as biomarkers for risk stratification and early identification.
Hiatal hernia, age >50 years, male gender, and white ethnicity—incidence in white males is significantly higher than that in white women and African American men.
Intra-abdominal obesity, smoking history, and at least one first-degree family who has BE or EAC are all risk factors.


PREVENTIVE MEASURES 
Reduced risk of BE and slower progression to esophageal cancer may result from losing weight, quitting smoking, eating a healthy diet rich in fruits and vegetables, and drinking wine in moderation .



CONDITIONS OFTEN Associated with: 
Obesity, GERD, and hiatal hernia


DIAGNOSIS HISTORY 
Determine the underlying risk factors.
Common GERD symptoms include regurgitation and heartburn.
Weight loss, anorexia, dysphagia, odynophagia, hematemesis, or melena are symptoms suggestive of complex GERD or cancer. Atypical symptoms include chest pain, odynophagia, persistent cough, water brash, globus feeling, laryngitis, or wheezing.


ALERT
Up to 50% of EAC and BE patients do not report having GERD, proving that BE is not symptomatic on its own.
MEDICAL ANALYSIS
No particular physical examination results for BE were found.


Results Relating to GERD DIFFERENTIAL DIAGNOSIS
Inflammatory esophagitis and simple GERD
● abdominal hernia



DETECTION & INTERPRETATION OF DIAGNOSIS

To diagnose BE, an endoscopy with many biopsies that show intestinal metaplasia extending 1 cm proximal to the GEJ is necessary.
The pathology of gastric cardia-type epithelium does not clearly indicate malignancy and could be a result of sampling error.
Due to the different definitions of GEJ landmarks, the relevance of specialized intestinal metaplasia at the GEJ is unclear, making it difficult to determine its cancer risk.
WARNING: Endoscopic screening is debatable and hasn't been researched prospectively. Men with frequent or chronic GERD symptoms and two or more risk factors, such as age >50, white ethnicity, central obesity, smoking history, family history of BE or EAC (ACG), or patients with multiple risk factors, should be screened.
 It is not usually advised to screen for BE in people with GERD in the general population (1),(2).[C].
No preliminary tests (lab or imaging).
Testing for Helicobacter pylori is not advised. According to meta-analyses, there is a negative correlation between H. pylori infections and BE, which may be due to a reduction in acid production.
No biomarkers currently available are useful for diagnosis; some are being researched for risk stratification.
Other/Diagnostic Procedures

Endoscopy: It is common practice for diagnosis and monitoring to visually identify columnar epithelium (reddish, velvety texture) replacing squamous epithelium (pale, glossy appearance) in the distal esophagus.
In order to confirm the diagnosis, biopsies are required.
Sort illness extent into long segments (more than 3 cm) and short segments (less than 3 cm).
The Prague grading system used GEJ and the squamocolumnar junction to describe BE. The columnar modifications' circumferential extent is indicated by the letter "C". The letter "M" denotes the columnar mucosa's greatest proximal extension.
Advanced imaging methods including confocal laser endomicroscopy and narrow band imaging (NBI) may be used to detect dysplasia.
 Wide-area transepithelial sample combined with brush cytology may help detect dysplasia.
Systematic endoscopic biopsy results support the diagnosis:
- Seattle protocol: four-quadrant biopsies taken at predetermined intervals in conjunction with biopsies of any obvious mucosal anomalies; takes more time but yields a higher level of information than random biopsies.
- The sensitivity of capsule endoscopy is lower than that of traditional endoscopy.


Interpretation of Tests
Diagnostic is specialized intestinal metaplasia, also known as specialized columnar epithelium.
Before starting treatment, the diagnosis of dysplasia (and grade) should be validated by two gastrointestinal pathologists.
One pathologist report is required to determine whether BE is benign .
The International Consensus Group advises defining BE by the presence of columnar mucosa in the esophagus (noting whether intestinal metaplasia is present). Cardia-type columnar epithelium may predispose to cancer (unclear risk).
If a screening endoscopy identifies erosive esophagitis, a second endoscopy should be performed after 8 to 12 weeks of proton pump inhibitor (PPI) therapy to rule out underlying BE. Biopsies should be postponed until healing has taken place.


TREATMENT 
MEDICATION
The purpose of medical treatment is to manage GERD and lessen esophagitis.
Neither the use of high-dose PPIs to reduce stomach acid production nor the use of antireflux surgery to lessen esophageal acid exposure results in the regression of BE. However, these treatments may lessen the chance of progression or cancer.


Initial Line
All patients with BE should get daily PPI treatment, as opposed to the progressive care of GERD without evidence of BE.
PPIs should be taken 30 to 60 minutes before a meal, ideally the morning meal.
Patients should continue receiving PPI therapy forever. PPI dosage needs to be raised if GERD symptoms were initially present until they are under control (2)[A].
PPI medication should be titrated according to symptoms; frequent pH monitoring is not advised. Manage patients whose symptoms are uncontrolled by PPI in accordance with the most recent guidelines for the treatment of uncontrolled GERD.


REASONS FOR ADMISSION AND FURTHER REFERENCE 
All patients with high-grade dysplasia or intramucosal carcinoma and the majority of individuals with low-grade dysplasia (apart from those who do not want treatments) should be referred for endoscopic removal of their Barrett.
Prior to endoscopy, start PPI medication to lessen reactive esophagitis/atypia (2)[C].
Refer patients who are considering esophagectomy (rare) to a facility with a high patient volume.


ADVANCED THERAPIES
Aspirin and high-dose, twice-daily PPI may slow the development of dysplasia, though this is not yet generally advised.
Barrett dysplasia to adenocarcinoma progression was not observed to be affected by the COX-2 selective inhibitor celecoxib.
- Patients with BE and risk factors for cardiovascular disease should think about using low-dose aspirin.
Statins may be useful in chemoprevention alone or in combination with aspirin or NSAIDs, but they are not currently generally advised.
Lack of dysplasia Assuming good overall patient health, there is typically no need for additional therapy; carry on with routine surveillance.
In order to treat dysplasia,
High grade dysplasia: Refer for endoscopic mucosal resection and/or endoscopic therapy to prevent progression to adenocarcinoma unless the patient is unable to tolerate the procedure. Low grade dysplasia: Refer for consideration of endoscopic therapy (typically radiofrequency ablation or cryotherapy) to reduce the risk of progression to adenocarcinoma.
- Intramucosal carcinoma: if possible, endoscopic resection, followed by ablation of any remaining Barrett, with surgery as a backup.
- More advanced carcinoma: Discuss resection with oncology and surgery.
– Reevaluation with biopsies and increased PPI dosage is recommended in cases of indeterminate grade dysplasia.
- More than 90% of patients have success with endoscopic eradication, but it frequently necessitates many sessions and can be accompanied by problems (3).
– Patients who have undergone previous ablation require continuing monitoring for recurrence.


ALERT
For the majority of BE without dysplasia, endoscopic eradication is not advised; instead, treatment should be customized.
Keep these patients under observation.


SURGICAL PROCEDURES
Although antireflux surgery, such as fundoplication, may manage GERD symptoms, it has not been demonstrated to reverse BE, lower the risk of cancer, or be more effective than conventional medical treatment.
ALERT 
Esophageal cancer risk does not appear to be reduced with antireflux surgery.
Esophagectomy is conclusive, but it should only be taken into account in cases of high-grade dysplasia when minimally invasive endoscopic eradication therapy has failed.
Compared to endoscopic therapy, morbidity and mortality are higher.
- Preferred for patients with submucosal invasion (stage T1SM2 or higher) or T1a patients with poor differentiation, lymphovascular invasion, or incomplete endoscopic mucosal resection - Added benefit of lymph node removal - Mortality rate: 5% in patients with high-grade dysplasia who are otherwise healthy - Serious postoperative complications: 30-50% - Should ideally be carried out by a skilled surgeon in a high-volume center.


ALTERNATIVE & COMPLEMENTARY MEDICINE
A prospective study of 339 BE patients found those taking vitamin C, vitamin E, or a multivitamin once a day had a lower risk of developing EAC.


Aspects of Geriatrics

In patients who are poor surgical candidates, surveillance or no treatment may be preferable to endoscopic eradication therapy or esophagectomy. When a patient is not a therapy candidate, stop monitoring them.


CONTINUING CARE AFTERCARE RECOMMENDATIONS
Although it is debatable, surveillance (to detect high-grade dysplasia or early cancer) is advised in patients with histologically proven BE, particularly for those in high-risk categories.
The duration of surveillance depends on the degree of dysplasia (1) [C].
Patients who are initially diagnosed with BE do not need an endoscopy within a year.
No dysplasia: Examine every three to five years.
- Stop monitoring if the life expectancy is less than five years (4)[C].
Survey every 6 to 12 months for low-grade dysplasia without ablation plans.
- Routine surveillance if a patient's absence of low-grade dysplasia is established following two successive endoscopies.
If dysplasia persists after 3 to 6 months of enhanced acid suppression, repeat the survey; if not, conduct it every 12 months.
Survey every three months for high-grade dysplasia without eradication therapy. Survey every 3 months for 4 months, twice every 6 months, then once every 12 months while eradication therapy is being used.


ALERT
Following suggested surveillance measures could increase the likelihood of finding dysplasia and malignancy.
Even if the patient has undergone esophagectomy, antireflux surgery, or endoscopic ablation therapy, surveillance should continue.


NUTRITIONAL INTAKE 
Steer clear of items that cause reflux, including coffee, alcohol, chocolate, peppermint, carbonated beverages, garlic, onions, spicy food, fatty food, citrus, and tomato-based goods.


PATIENT EDUCATION 
Lifestyle changes, such as quitting smoking, losing weight, standing up straight after meals, avoiding wearing tight clothing, and elevating the head of the bed
There is insufficient proof that treating GERD prevents or necessarily reverses BE or esophageal cancer.


PROGNOSIS
Esophageal cancer is estimated to occur in people with BE between 0.12 and 0.6% of the time each year:
Low-grade dysplasia: cancer risk is 0.7-8% each year, however it may be temporary .
The use of biomarkers for risk stratification, chemoprevention of neoplastic progression, capsule endoscopy for screening, and the use of vitamins and antioxidants for prevention and treatment are promising areas for investigation. High-grade dysplasia: cancer risk 5-9% each year (2), (3).


COMPLICATIONS
Similar to GERD: ulceration, bleeding, and stricture

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