Diseases of the Esophagus

Gastroesophageal reflux disease (GERD)

General

Gastroesophageal reflux disease (GERD) occurs when stomach acid frequently flows back into the esophagus. This backwash, known as acid reflux, irritates or damages the esophageal lining. Some reflux is normal in the general population, however, GERD patients report weekly significant discomfort or other related symptoms/complications. Humans typically have an acid pocket ‘floating’ in the gastric cardia that is not buffered by food ingestion; this is a primary source of the reflux content. In many cases, GERD patients have dysfunction of the lower esophageal sphincter (LES). With normal digestion, as the LES empties into the stomach, it closes to prevent food and stomach acid from refluxing up into the esophagus. GERD occurs when the LES fails to tighten appropriately.

Epidemiology

GERD occurs in roughly 10-20% of the western population and risk increases in ages above 40.

Symptoms

Patients typically experience a burning chest pain after meals, despite the pH buffering effect of food. Symptoms occur between 30-60 minutes postprandial and worsens when reclining. The pain has been described to radiate from behind the chest bone to the neck and throat. A sour taste, globus sensation, cough, and hoarseness in one’s voice may also be present. The severity of symptoms is not correlated with the degree of damage to the mucosal lining.

Risk factors

Known risk factors that decrease LES strength are scleroderma and pregnancy. Obesity, which causes intragastric pressure, may also advance its development.

Cause

GERD may be provoked by a number of physiological disorders, as listed above. It is primarily the result of reduced tone of the LES, resulting in transient relaxation which allows for food and stomach acid to reflux into the esophagus. The caustic effect of the stomach acid is sometimes accompanied by bile or alkaline pancreatic secretions.

Pregnancy, obesity, and scleroderma are known to negatively affect the strength of the LES. Patients with hiatal hernias also experience GERD, although the correlative mechanism is debated.

[Unfinished Figure 1: The image shows an esophagus afflicted with GERD.]

Diagnostics

Diagnostic studies are not needed for patients with mild GERD symptoms indicative of uncomplicated reflux disease. In severe or chronic cases, GERD can be diagnosed by esophageal manometry or 24-hour esophageal pH recording. Positive results are defined by a pH reading below 4. A barium swallow test can be used to find reflux or look for hiatal hernia. Biopsies to rule out Barrett’s esophagus or adenocarcinoma can be performed in patients unresponsive to lifestyle therapies.

Treatment

Treatments initially involve lifestyle modifications, such as weight loss, smaller and more frequent meals, eliminating late night snacks, light exercise. Avoidance of acidic foods, including fatty foods, alcohol, spearmint, peppermint, coffee/tea, citrus fruits, or tomato-based foods, is often recommended. If lifestyle modifications fail to relieve symptoms, antacids to neutralize stomach acid may be given to patients with mild symptoms. In patients with more severe and chronic symptoms, H2 receptor antagonists (cimetidine or ranitidine) or PPIs (omeprazole, lansoprazole) may be administered. Nissen fundoplication may be used as a surgical intervention to relieve aggressive disease.

Prognosis

Early treatment is recommended to avoid the development of aggressive symptoms.

Caution

Further investigation is required when symptoms persist despite empiric acid inhibitory therapy. Particularly, the presence of alarm symptoms, such as troublesome dysphagia, odynophagia, weight loss and iron deficiency anemia, mandate deeper investigation to rule out complications (such as Barrett esophagus or peptic stricture) or other diseases (such as coronary artery disease).

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Barrett esophagus

General

Barrett’s esophagus is a columnar metaplasia typically found in people with long-term gastroesophageal reflux disease (GERD). It arises when the squamous mucosa of the distal esophagus changes to resemble the tissue lining the intestine. While it does not induce specific symptoms, patients often experience the effects of GERD and are at a heightened risk for developing esophageal adenocarcinoma.

Epidemiology

It occurs in approximately 10-15% of patients with advanced GERD. Roughly 0.2-0.5% of patients with Barrett esophagus each year develop adenocarcinoma from the dysplastic epithelium. About half of all Barrett patients do not have reflux symptoms.

Symptoms

While Barrett’s esophagus does not inherently cause symptoms, patients experience discomfort due to symptoms of advanced GERD such as heartburn, chest pain, difficulty swallowing and regurgitation.

Risk factors

Patients suffering from chronic reflux are at risk. Incidence is also heightened in patients with truncal obesity independent of GERD. Male gender, smoking and old age are also correlated.

Cause

The exact cause for Barrett’s esophagus is unknown, but it is a result of severe esophageal injury. Barrett esophagus patients are known to present with hiatal hernia and show low pH during testing as well as increased acid and bile exposure of the esophagus. It is still unknown why the columnar metaplasia occurs or why some severe GERD patients never develop Barrett’s.

Diagnostics

An upper endoscopy (EGD) is used to diagnose, showing irregular salmon colored mucosa at a proximally displaced gastroesophageal junction. An EGD screening is encouraged for patients with chronic and advanced GERD. Biopsies obtained at endoscopy confirm the diagnosis.

Treatment

Patients often require surveillance endoscopy aimed at discovering dysplasia in an early stage. Proton pump inhibitors reliably relieve symptoms and reverse esophagitis, but do not adequately reverse the histological changes. Endoscopic resection or ablation therapy can be used to eliminate the affected tissue. Due to the risk of complications such as bleeding and perforation, these invasive treatments may not be recommended for patients with nondysplastic Barrett esophagus with a low risk of developing esophageal cancer.

Caution

Barrett’s esophagus increases one’s predisposition to esophageal adenocarcinoma. Thus, in patients with high dysplasia, endoscopy should be considered to monitor for signs of esophageal cancer. Untreated or unresponsive GERD can develop into Barrett esophagus.

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Infectious esophagitis (fungal candida, viral CMV)

General

Candida albicans, herpes simplex, and cytomegalovirus (CMV) are the most common pathogens of infectious esophagitis. Incidence of fungal, candida, and viral CMV infectious esophagitis have increased due to an increased use of immunosuppression therapies for organ transplantation, chronic inflammatory diseases and chemotherapy. Risk for infectious esophagitis rises in HIV patients as CD4 count decreases.

Candida esophagitis, most commonly caused by C. albicans, initially presents in the throat and causes esophagitis as it becomes pathogenic. The presence of oral thrush may be indicative of a co-infection.

Viral esophagitis may be inflicted by the herpes simplex 1 or 2 virus or the varicella-zoster virus in children with chickenpox or adults with zoster.

Similarly, CMV esophagitis pervades commonly among patients who have undergone transplantation, long-term dialysis or long-term steroid therapy, or had an HIV-infection.

Epidemiology

Only 75% of patients with candida esophagitis and 25–50% of patients with viral esophagitis exhibit oral thrush. Thus, it is not a proper diagnostic for the etiology of esophageal infection.

Symptoms

Odynophagia is a common symptom in all 3 etiologies, accompanied by chest pain, dysphagia, and hemorrhage. Candida esophagitis also presents with characteristic white plaques, that may complicate to bleeding, perforation, stricture, or systemic infection in rare cases.

Risk factors

Patients with preexisting inflammatory conditions, chemotherapy, or those that have received an organ transplant and require immunosuppression therapies are at heightened risk for development.

Cause

Candida esophagitis is caused by C. albicans infection. Viral esophagitis can be caused by herpes simplex 1 or 2 or the varicella-zoster virus.

Diagnostics

An endoscopy with biopsy is standard to diagnose all forms of infectious esophagitis. Sores on the nose or lips can elude to herpetic esophagitis etiology, while a biopsy of the ulcer margins can confirm the diagnosis. If endoscopy is performed for viral esophagitis, endoscopic findings typically show vesicles and small, punched-out ulcerations. CMV lesions present as serpiginous ulcers permeating otherwise healthy mucosa, and are most prevalent in the distal esophagus. For preemptive diagnoses, monoclonal antibodies to CMV and in situ hybridization tests can also be used to confirm.

Treatment

Candida esophagitis can be treated with oral fluconazol or amphotericin B deoxycholate. Patients who do not respond to the oral treatment can receive intravenous echinocandin. Viral herpetic esophagitis can be eliminated with acyclovir, famiciclovir, or valacyclovir. Ganciclovir and valganciclovir have also been shown to be effective in treating CMV infection. Therapy is carried out until complete recovery, which may last for 3–6 weeks.

Prognosis

Recovery depends on the extent of the infection and level of immune competence. In some patients maintenance therapy may be required to evade a relapse.

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Eosinophilic esophagitis

General

Eosinophilic esophagitis is caused by the accumulation of eosinophils in the esophagus, which inflames the surrounding tissues in response to food or environmental sensitivities. Diet plays a large role in the pathogenesis and treatment.

Epidemiology

The USA has identified 4-6 cases per 10,000 the majority of which were white males between 30-40. The rise in recent disease has been theorized to be due to both increasing incidence and increasing clinical recognition.

Symptoms

Preadolescents present with chest or abdominal pain, nausea, vomiting, and food aversion. Adults often present with similar symptoms, as well as atypical chest pain and heartburn frequently resistant to PPI therapy.

Risk factors

Patients often have a personal and/or family history of other allergic disorders. Family members are at a heightened risk. Eosinophilic esophagitis typically afflicts white males between ages 30-40.

Cause

The precise cause is known but it is believed to be aggravated by an immune response to foods or environmental allergens.

Diagnostics

The diagnosis can be reached by empirical esophageal symptoms and mucosal biopsies obtained from upper endoscopy presenting squamous epithelial eosinophil inflammation. The condition is commonly confused with GERD, drug hypersensitivity, connective tissue disorders, hypereosinophilic syndrome, Crohn’s disease, and infection. To diagnose, patients may be tested via serum IgE, skin prick testing, and/or atopy patch testing for a variety of foods and/or aeroallergens. If positive, the allergens are removed from the diet. Likewise, empirical diet management may be performed, in which main allergen foods are removed from the diet (soy, nuts, gluten, eggs, seafood), and reintroduced one by one to find the trigger.

Treatment

Treatment with PPI‘s show clinical and histologic improvement in up to half of all patients. Topical glucocorticoids (fluticasone, budesonide) can be used if elimination treatments are ineffective, or one month of systemic steroids using prednisone. Esophageal dilation can relieve related dysphagia in those with fibrostenosis, although it should be practiced cautiously to limit risks for esophageal laceration or perforation of the rigid esophagus—a common consequence of the disease.

Prognosis

The disease is typically chronic, thus symptoms may be managed but not fully eliminated.

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Esophageal varices

General

Esophageal varices is a very common source of upper gastrointestinal bleeding. Varices are most often formed when blood flow to the liver is blocked, escalating blood pressure within the portal vein (portal hypertension). Portal hypertension accelerates blood through smaller vessels, such as veins of the lower esophagus, not designed to carry large supplies of blood. The smaller vessels balloon as blood passes through at high rates, occasionally rupturing and bleeding. Portal hypertension may be indicated by the appearance of thrombocytopenia, sudden development of ascites, encephalopathy, or bleeding/nonbleeding esophageal varices.

Epidemiology

An estimated 5-15% of cirrhotic patients develop esophageal varices annually. Approximately 30% will suffer from acute variceal bleeding within their lifetime. With such high risk for cirrhotic patients, routine endoscopies are commonplace to search for varices.

Symptoms

Only bleeding varices exhibit symptoms. Patients may experience vomiting blood, black or bloody stools, or lightheadedness. Signs of liver disease, which increase risk for esophageal varices, include jaundice, easy bleeding or bruising, and ascites.

Risk factors

Varices may rupture as blood pressure escalates. Portal hypertension should thus be monitored carefully to lower the risk of bleeding. Red marks on the varices, found endoscopically, or enlarged varices show higher rates of bleeding. Patients with severe liver cirrhosis or failure are at a greater risk for developing disease.

Cause

The direct cause is portal hypertension. Esophageal varices may indirectly arise as a consequence of liver cirrhosis or thrombosis in the portal vein.

Diagnostics

Endoscopy should be performed immediately if esophageal varices are suspected in any patient; variceal bleeding is typically severe and may quickly result in hypovolemia or shock. Bleeding from esophageal varices most commonly occurs in the distal 5 cm of the esophagus.

Treatment

Variceal hemorrhage is lethal; hence the need for rapid assessment and resuscitation with fluids or blood products. Over-transfusion may lead to increased central and portal venous pressures, increasing the risk of re-bleeding. Furthermore, cirrhotic patients often have coagulopathy, which complicates efforts to stop the bleeding.

Endoscopic ligation and IV vasoactive medication (octreotide, somatostatin, vapreotide, terlipressin) are used to seal bleeding varices. Long term treatment adopts the usage of nonselective beta blockers with endoscopic ligation; the combination of the two has been found to be more effective to reduce relapses of bleeding. A transjugular intrahepatic portosystemic shunt (TIPS) should be used for patients who do not respond to endoscopic and medical interventions.

Prognosis

The prognosis depends on the underlying condition. Untreated or unresponsive bleeding varices can be fatal, with a mortality rate of 60-80% within 1-4 years of diagnosis.

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Achalasia

General

Achalasia impedes the relaxation of the lower sphincter of the esophagus, ceasing peristalsis, and preventing food from passing from the esophagus into the stomach. It presents with the degeneration of esophageal muscles and nerves, provoked by the loss of ganglion cells within the myenteric plexus.

Epidemiology

Incidence is rare, with 1-10 cases per 100,000 and typically onsets between age 25 and 60.

[Unfinished figure 6: note the bird beak appearance and tapering of the lower esophagus]

Symptoms

More progressed cases of achalasia exhibit increasing dilatation and sigmoid deformity of the esophagus, as well as with hypertrophy of the lower esophageal sphincter (LES). Generally, symptoms include dysphagia, regurgitation, chest pain, and weight loss.  Chest pain has been described as a squeezing, pressure-like retrosternal pain, that can extend to the neck, arms, jaw, and back.

Cause

The exact cause of achalasia is unknown. Ultimately, the disease affects the excitatory (cholinergic) and inhibitory (nitric oxide) ganglionic neurons of the esophagus. Without proper innervation, peristaltic movements and LES relaxation are impeded. The LES remains contracted the end of the esophagus, forming a barrier that blocks the passage of food into the stomach.

The condition may be hereditary or due to a preexisting autoimmune disease. Recent evidence suggests a connection with latent human herpes simplex 1 infection.

Risk Factors

Weight loss occurs commonly in patients with more advanced denervation. Regurgitation, a common symptom in which food or fluids become stuck in the dilated esophagus, elevates one’s risk for secondary infections, such as bronchitis, pneumonia, or lung abscess from aspiration of foods.

Diagnostics

A barium swallow x-ray will reveal a dilated esophagus, poor emptying, absence of air in the stomach, and tapering at the LES giving it a bird’s beak-like appearance [see figure]. In advanced cases, the esophagus may show a sigmoid configuration.

Endoscopy usually follows to exclude a distal stricture or a submucosal infiltrating carcinoma.

The diagnosis is confirmed by esophageal manometry. Esophageal manometry measures the changes in pressure within the esophagus by inserting a thin tube through the nose or mouth that is lined with pressure sensors. Achalasia is diagnosed with manometry by the failure for LES to relax when at rest and an absence of peristaltic contractions. It can be used to find incidence of early disease before the onset of esophageal dilation and food retention, making it a more sensitive diagnostic test than the barium swallow x-ray.

Treatment

Unfortunately, there is no known cure or prevention method. Therapies exist that target the reduction of LES pressure through pharmacologic intervention, pneumatic balloon dilation, and/or surgical myotomy. Reducing LES pressure allows for esophageal pressurization and gravity to continue emptying. Once lost, peristalsis cannot be fully recovered.

Pharmacologic interventions often yield poor recovery. Nitrates or calcium channel blockers can be administered before eating, and Botulinum toxin injections into the LES can be used to inhibit the release of acetylcholine from nerve endings, showing a dysphagia improvement in 65-85% of cases. After 6-9 months, 50% of patients experienced relapses, but 75% of patients improved with repeated injections. Because of higher efficacy in pneumatic dilation therapy and surgery, Botulinum toxin is most appropriate for patients who do not qualify for more invasive procedures.

Pneumatic dilation and Heller myotomy are the most effective and durable therapies. It involves using an endoscope to inflate a cylindrical balloon across the LES and has shown to relieve dysphagia in up to 95% of patients. Only 35% experienced relapses within a 10 year period, but improved with repeated dilation. Perforation occurred in 0.5–5% of cases. Dilation is less effective in patients under 45 years for whom Laparoscopic Heller myotomy may be preferred.

Laparoscopic Heller myotomy is performed most often, normally in conjunction with an antireflux procedure (partial fundoplication) and PPI therapy, with positive improvements in over 90% of patients.

Prognosis

If left untreated or poorly treated, achalasia can develop into stasis esophagitis, which can later develop into esophageal squamous cell cancer.

Caution

Caution should be exercised in the differential diagnosis of achalasia. Small cell lung cancers can lead to paraneoplastic syndrome which mimics the symptoms of achalasia. Likewise, Chagas disease also presents with the same esophageal dysfunction, making it indistinguishable from idiopathic achalasia. It should be heavily considered with patients from Central and South America.

Pseudoachalasia, caused by primary or metastatic tumors that invade the gastroesophageal junction, presents with similar symptoms. Endoscopic ultrasonography and chest CT to probe the distal esophagus may be necessary to rule out the diagnosis.

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Hernia diaphragmatica

General

Diaphragmatic hernias, also known as hiatal hernias, form when the upper part of the stomach herniates through the mediastinum and the esophageal hiatus of the diaphragm. While smaller hernias are virtually undetectable and asymptomatic, larger hiatal hernias may obstruct the pathway of food in the esophagus. Hiatal Hernias are categorized into Type I-Type IV. Type I, known as sliding hiatal hernia, comprises almost all cases and occurs when the gastroesophageal junction and gastric cardia move upwards as the phrenoesophageal ligament weakens and the hernia dilates. Type II, III, and IV are all paraesophageal and involve different areas of the stomach. In type II, the gastric fundus herniates, while the gastroesophageal junction is attached to the hiatus. In type III, the gastric fundus and gastroesophageal junction herniate. In both types, if the hernia is large enough, the stomach can invert during herniation, leading to gastric volvulus or strangulation. In type IV, other viscera, aside from the stomach, will herniate through the mediastinum–often the colon.

Epidemiology

25% of patients with minor GERD, 75% of severe erosive esophagitis cases, and over 90% of patients with Barrett esophagus also present with hiatal hernias.

Symptoms

Hiatal hernias, if small, may present asymptomatically. Some hernia patients present with GERD; these patients are associated with elevated acid reflux or delayed clearance. Patients may experience transient LES relaxations and straining from the reflux of acid caused by the herniated sac. Heartburn, dysphagia, chest or abdominal pain, shortness of breath, or regurgitation of foods are also common.

Risk Factors

Risk increases for elderly and obese populations.

Cause

Sliding hernias are caused by heightened intra-abdominal pressure. This can be provoked by obesity or pregnancy, as well as hereditary predispositions.

Diagnostics

X-rays, upper endoscopy, or esophageal manometry may be performed to confirm the diagnosis.

Treatment

Surgery may be necessary to repair large or symptomatic hernias. Medication can be taken for symptoms of GERD.

Prognosis

Small hiatal hernias are asymptomatic and do not require treatment. In larger hernias, prognosis is determined by surgery outcome. Nissen fundoplication is effective in 90-95% of cases to relieve symptoms of GERD.

Caution

Delayed esophageal acid clearance can cause esophagitis and Barrett’s esophagus.

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Zenker’s diverticulum

General

Zenker’s diverticulum is a bulge or pouch protruding above the upper esophageal sphincter (UES), in an area known as the Killian’s Triangle.

Epidemiology

It predominantly appears in elderly male populations. Incidence is higher in northern Europe, USA, and Canada. It rarely presents in patients under the age of 40 years.

Symptoms

When small, Zenker’s Diverticula do not trap food and thus do not cause symptoms. Patients with large diverticula experience dysphagia, regurgitation of food debris, aspiration, protrusion in the neck, and halitosis. A cricopharyngeus bar may be present radiographically, however can be asymptomatic or secondary to other neuromuscular etiologies. It is thus important to rule out other possible esophageal disorders before executing treatments.

Risk Factors

Risk for developing Zenker’s Diverticulum increases with age.

Cause

It is thought to arise from a reduction in elasticity of the upper esophageal sphincter. The inelasticity of the UES elevates hypopharyngeal pressure, which forces food against and distorts the posterior wall of the hypopharynx during swallowing, creating the Zenker’s Diverticulum pouch. After thousands of swallows, food continues to push deeper against the hypopharynx and increases the size of the diverticulum.

Diagnostics

A barium swallow test to locate the position and size is standard for diagnosis. Endoscopic evaluation is also an option, simultaneously excluding any malignant causes.

Treatment

Symptomatic Zenker’s Diverticulum is treated with surgery (an upper esophageal myotomy or a marsupialization procedure) to sever the constricted cricopharyngeus muscle and decompress the pouch. Less invasive approaches may include flexible endoscopy or endoscopic diverticulotomy.

Prognosis

Obstruction of the esophagus, and the potential complications, such as aspiration pneumonia, are dangerous and mandate proper treatment. Although observed in only 0.5% of cases, squamous cell carcinoma can develop rarely. Following surgical intervention, 90% of patients show symptomatic improvement.

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Esophageal carcinoma

General

Esophageal cancers are most prominently caused by squamous cell carcinomas or adenocarcinomas. Adenocarcinomas emerge from dysplastic columnar epithelium tissue in the distal esophagus and are often accompanied with chronic gastric reflux and/or Barrett’s esophagus. Aneuploidy and p53 mutations are normally present in the dysplastic epithelium, where 15% overproduce the HER2/neu gene. Patients that present with advanced dysphagia exemplify late stages of the disease, as issues with swallowing only become apparent when more than 60% of the circumference of the esophagus has been engulfed by cancer. The cancer advances to lymph nodes, liver, lungs, pleura, and bone. In upper and mid-esophageal disease, tracheoesophageal fistulas can develop. Development of squamous cell carcinomas is associated with drinking and smoking habits. Patients may suffer from hypercalcemia if bone metastases are not present

Epidemiology

Incidence of squamous cell carcinomas is closely associated to location. Most cases present in Northern China, Iran, central Asia, Afghanistan, Siberia, and Mongolia. It is believed to have a familial tie, although precise genes have not been identified. High endemic regions of the disease have been found in Finland, Iceland, Curaçao, southeastern Africa, and northwestern France. It is predominantly associated among black males and within individuals of lower socioeconomic statuses, in which it often afflicts after age 50.

Incidence of adenocarcinomas has increased 7-fold in the US over the last 40 years; most cases are found within white male populations.

Symptoms

Patients initially present with rapid weight loss and progressive dysphagia, beginning with a difficulty to process hard solids and worsens to difficulties with semi-solids and liquids. Odynophagia, pain extending to the chest and back, regurgitation or vomiting, and aspiration pneumonia are also experienced in etiologies.

Risk Factors

The development of squamous cell esophageal cancers is associated with excessive alcohol consumption and tobacco use. Consuming whiskey excessively is correlated to higher incidence of disease than wine or beer. Intake of nitrates, smoked opiates, and fungal toxins in pickled vegetables, as well as mucosal damage from overly hot tea, lye, radiation-induced strictures, and chronic achalasia are also linked. Esophageal webs secondary to glossitis and iron deficiency and congenital hyperkeratosis and pitting of the palms and soles have both been correlated to squamous cell esophageal cancer as well as deficiencies of molybdenum, zinc, selenium, and vitamin A. Pre-existing head and neck cancer can also elevate risk for development.

Risk factors for adenocarcinomas include: white males, 50 years or older, truncal obesity, history of smoking, family history of Barrett esophagus or esophageal adenocarcinoma.

Cause

Adenocarcinomas arise from damaged esophageal tissues. Most patients initially present with Barrett’s esophagus or advanced GERD, in which the dysplastic epithelium develops into cancerous tissue.

Squamous cell carcinomas, as stated above, are correlated to excessive alcohol and tobacco use.

Diagnostics

Both cancers are identical radiographically and endoscopically, thus further examination is required to conclude the etiology. Esophagoscopy is performed to identify and confirm tumors. For heavy smokers or drinkers suspected of squamous cell carcinoma, endoscopic evaluation of the larynx, trachea, bronchi, and fundus of the stomach should also be conducted to investigate other at risk areas. CTs of the mediastinum and para-aortoc lymph nodes show local tumor spread, while PET scanning shows distant metastases, such as spread to mediastinal lymph nodes. Both scans provide invaluable information to craft the borders for radiation therapy and assessments on how to proceed with treatments.

Treatment

Surgery is necessary for tumor elimination. Less invasive transthoracic esophagectomies are preferred, while new research is investigating the efficacy of endoscopic resections of superficial squamous cell cancers or adenocarcinomas but have not yielded enough evidence to show that conventional surgical procedures have better or worse outcomes. Likewise, efficacy of the treatment of Barrett’s esophagus using endoscopic ablation of dysplastic tissues is unknown.

Prognosis

Life expectancy after diagnosis is poor; 5-year survival rates are around 10% after initial diagnosis.

Surgical excision of the tumor is a common practice. However, total removal only occurs in 45% of patients, often leaving behind tumor cells in the resection margins. In these surgeries, there is a mortality rate of approximately 5% arising from postoperative fistulas, subphrenic abscesses, and cardiopulmonary complications.

Caution

Adenocarcinoma can arise as a complication of advanced GERD or from the dysplastic epithelium of advanced Barrett’s esophagus.  An estimated 0.2-0.5% of patients with Barrett’s esophagus develop esophageal adenocarcinoma per year.

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Mallory-weiss syndrome

General

Mallory-weiss syndrome refers to a laceration of the mucosa in gastroesophageal junction. If the tear happens upon an artery, it can cause upper gastrointestinal hemorrhaging.

Epidemiology

Roughly 5-15% of upper gastrointestinal bleeding is derived from Mallory-weiss tears. It occurs more frequently in patients with alcoholism, males, and within ages 40-60.

Symptoms

Hematemesis, upper abdominal pain, and melena are common symptoms. Patients often report sudden hematemesis after a period of non-bloody vomiting. Half of cases also present with a history of retching and/or straining. There are no physical signs unique to Mallory-Weiss syndrome; the signs are similar to any other hemorrhagic conditions or shock. Examination for signs of severe bleeding and shock, including tachycardia, thready pulse, hypotension, dehydration, reduced skin turgor, and capillary filling time must be performed to rule out deep lacerations, followed by immediate intervention if necessary.

Risk Factors

Alcoholism increases one’s predisposition to developing a tear, as well as violent vomiting, retching, hiccups, or coughing. Patients who have experienced blunt trauma to the abdomen or chest, or have a sudden increase in intragastric pressure are at an elevated risk for development. Patients with a confirmed tear and latent portal hypertension are more susceptible to continued or repeated bleeding.

Cause

The tears can emerge from a sudden increase in intra-abdominal pressure, as what occurs when lifting heavy items and during severe retching or vomiting. When pressure elevates suddenly, the gastric contents are pushed against the esophagus, causing longitudinal mucosal tears. The tears may extend into the submucosal blood vessels, resulting in upper GI bleeding.

Diagnosis

An upper endoscopic evaluation of the mucosal membrane is standard for the diagnosis. Tears of a few centimeters are normally found at the gastroesophageal junction or below the junction in the mucosa. Endoscopy may also reveal other causes for hemorrhage; such as esophageal varices, peptic ulcers, and erosive gastritis.

Treatment

Patients are treated initially with fluid replacements and blood transfusions to compensate the losses. The bleeding, in many cases, stops without intervention within 48 hours. For lacerations that do not spontaneously coagulate, endoscopic hemostatic therapy is recommended. Epinephrine injections, cauterization, or mechanical compression of the artery are sufficient in almost all cases. Unresponsive patients mandate embolization or surgery.

Prognosis

Prognosis depends on underlying disease and treatment. Complications can arise depending on the blood loss, such as hypovolemic shock, metabolic disturbance, and myocardial infarction.  Death is possible if the bleeding is not controlled.

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Caustic burns

General

The intake of acid and/or liquid or crystalline alkali will induce caustic esophageal burns. Aspiration of the substances can induce further injury to the larynx, trachea, or bronchi. Severe burning, chest pain, retching, dysphagia, and drooling may be experienced immediately after.

Epidemiology

Ingestion of toxic fluids is often accidental in children. Caustic ingestion in adults occurs more often in those with an underlying mental illness.

Symptoms

In advanced cases, major symptoms can include severe burning with varying extents of chest pain, gagging, dysphagia or odynophagia, drooling, and dyspnea. Patients without the major symptoms above and no oropharyngeal damage are unlikely to have advanced caustic injury.

Risk Factors

Purposeful ingestion of toxins may have resulted from an underlying mental illness and/or intent to commit suicide.

Cause

Caustic esophageal burns are caused by the intake of strong alkali, such as the sodium or potassium hydroxide found in drain cleaners, or acids, such as hydrochloric, sulfuric, and phosphoric acid.

Diagnosis

Following ingestion, initial ICU hospitalization is recommended. A laryngoscopy should be performed immediately to evaluate damage to the airway and oropharyngeal mucosa, as well as an examination of circulation. In patients with respiratory distress, a laryngoscopy can determine if tracheostomy is needed. Radiographs of the chest and abdomen should be performed to find any evidence of pneumonitis or perforation.

Treatment

Intravenous fluids, intravenous PPI to deter gastric stress ulceration, and analgesics should be given as an immediate therapy. Patients without esophageal or gastric mucosal lesions do not require further treatment and can be discharged.

Those with severe damage and acute complications are required to fast. A nasoenteric feeding tube should be inserted after 24 hours and liquids can be administered after 2-3 days if the injury permits secretions. The patient should be monitored closely in case of the need for emergency surgery, in which esophagectomy and colonic or jejunal interposition can be performed.

Prognosis

Recovery time for those with mild damage, such as edema, erythema, exudates or superficial ulcers is quick. Risk for stricture development in these groups is low and these patients may start a liquid or regular diet after 24–48 hours. Up to 65% of those with deep or circumferential ulcers or necrosis suffer from complications. Common acute complications may include perforation with mediastinitis or peritonitis, bleeding, stricture, or esophagealtracheal fistulas. Esophageal stricture develops in 70% of the cases in weeks to months after the caustic injury, and need repeated dilation.

As severe burns damage the esophageal tissue, there is a 2-3% risk of developing esophageal squamous carcinoma. Endoscopic monitoring to track potential development should be executed for 15–20 years following the injury.

Caution

Nasogastric lavage and oral antidotes may worsen injury and should not be used for treatment. Patients with severe burns should also not be given corticosteroids or antibiotics.

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Diffuse esophageal spasm (DES)

General

Poor consensus exists on the exact pathophysiology and history of DES. It presents with episodes of dysphagia, chest pain, and abnormal esophageal contractions, however is difficult to differentiate from achalasia radiographically.

Epidemiology

Incidence is estimated to be around 1 case in 100,000 yearly. Women are more commonly afflicted than men and incidence is higher among caucasian populations than other ethnicities. Occurrence is linked with increasing age, as DES is rarely found among children.

Symptoms

DES manifests with dysphagia of liquids and solids and abnormal chest pain, similar to angina. Esophageal chest pain is non-cardiac. The pain is prolonged, disrupts sleep, and accompanies meals. Unlike cardiac pain, it is alleviated by antacids, and often presents with heartburn, dysphagia, or occasional regurgitation. Complaint of a globus hystericus, a sensation of an object in the throat, is common. Patients also experience reflux, anxiety and/or depression.

Risk Factors

Chest pain may be confused with cardiac pain. Proper avenues should be taken to rule out cardiac disease.

Cause

The cause of DES remains elusive. Recent evidence suggests that development of DES is related to a nitric oxide (NO) deficiency.

Diagnosis

A barium swallow x-ray can be performed to evaluate the structure of the esophagus. A diseased esophagus is normally shaped like a “corkscrew,” thus it is simple to distinguish radiographically. However, a 24-hour manometry test should be done to confirm the diagnosis, as the curling corkscrew structure can also be found in patients of achalasia. A 24-hour manometry is performed to evaluate abnormal contractions. Characteristically, DES contractions are uncoordinated or spastic in the distal esophagus. Contractions occur spontaneously and with a high-amplitude.

Treatment

Due to the difficulties in diagnosing the disease and the large symptom overlap with other etiologies, it has been difficult to conduct large controlled clinical trials. Known treatments using short or long term nitrates, calcium-channel blockers, anti- cholinergic agents, 5-phosphodiesterase inhibitors, visceral analgesics (tricyclic agents or SSRI) have shown to be effective. In patients nonresponsive to first-line treatments, endoscopic botulinum toxin injections into the distal esophagus and esophageal dilation have also shown positive outcomes in symptom reduction.

Acid suppression combined with PPI can be used for patients exhibiting symptoms of GERD.

Prognosis

Prognosis may be contingent on the management of other gastrointestinal diseases, such as GERD or achalasia. Mortality due to DES is low. It can significantly decrease the quality of life in a patient and lead to later morbidity from a decreased capacity to eat without pain or engage in normal activities, which can challenge the patient emotionally and physiologically.

Caution

DES is associated with a high incidence of GERD or other neuromuscular diseases.

As abnormal chest pain or angina is commonly experienced, patients should be evaluated for heart disease. Many of the symptoms also overlap with peptic or infectious esophagitis. Therefore, other etiologies must be ruled out before proceeding with treatment.

After treatments are carried out, before restarting oral feeding, the patient should receive a contrast-swallowing test to eliminate risk of possible leakage.

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Diseases of the stomach

Gastritis (acute, chronic, typea/b, other)

General

Gastritis refers to the inflammation of the gastric mucosa and is categorized predominately by either duration of disease, as well as histologic characteristics, or by mechanism for infection. Due to the wide range of causal mechanisms, there is no specific clinical presentation of the disease.

Acute gastritis is most commonly caused by a minor H. pylori infection. The H. pylori infection typically occurs during childhood or infancy and lasts a lifetime unless eradicated with antibiotics. The mode of transmission is unknown. Inflammation is mediated by neutrophils causing edema and hyperemia. If poorly treated, the majority of acute gastritis patients advance to chronic disease – mostly asymptomatic and without sequelae.

In primitive stages of chronic gastritis, the inflammation may appear spatially patchy and affect superficial and glandular areas of mucosa. With time, the disease may advance deeper into the tissues, causing glandular destruction, atrophy and/or intestinal metaplasia. In cases of advanced infection, metaplasia of gastric glands can transform the composition from gastric tissue to intestinal tissue containing goblet cells. This morphological transformation can predispose an individual to gastric cancer.

Chronic gastritis can be classified according to disease progression. Superficial gastritis is the first stage of chronic disease, in which inflammation is consolidated to the lamina propria of the surface mucosa, and edema and cellular infiltrates begin to attack gastric glands. The inflammation typically does not progress beyond this phase. In a minority of the population, atrophic gastritis follows, defined by inflammation infiltrating deeper into the gastric mucosa and the destruction of gastric glands. Gastric atrophy, the final stage, is characterized by complete loss of glandular structure and a mucosa so thin that the blood vessels underneath may become visible.

It can further be divided by the area of the stomach: antral-predominant, corpus pre-dominant, or pangastritis. Chronic gastritis is then classified on phenotype (affected gastric anatomy): type A or type B. Type A gastritis is characterized by autoimmune involvement, in which antibodies against the parietal cells circulate and attack the fundus and body.

Type B Gastritis, caused by H pylori infection, occurs more commonly and afflicts the antral region of the stomach. Although Type B is described as “antral predominant” cases have been recorded of inflammation radiating to the fundus and body, causing pangastritis. Pangastritis normally occurs 15-20 years after the first infection. The degree of inflammation is directly correlated to the amount of H. pylori organisms found. The term AB Gastritis may be used to describe mixed disease.

Other forms of gastritis are lymphocytic, arioliform, eosinophilic, granulomatous, and Russell body.  Lymphocytic gastritis occurs when mature T cells and plasmacytes attack the body of the stomach. The causal origin is unknown and there are no specific symptoms unique to the disease. A subset of these patients is also found to have thickened folds capped by nodules with a central depression. This type of presentation is called varioliform gastritis. In both forms of disease, H. pylori does not have a significant effect in development. Glucocorticoids or sodium cromoglycate therapy has not yielded clear results for treatments.

The attack of eosinophils on the layers of the stomach is known as Eosinophilic Gastritis. Infiltration causes systemic allergy and can extend to diffuse eosinophilic gastroenteritis. Eosinophils predominately overtake the antral region of the stomach. Endoscopically, edema is present within the folds of the stomach, which can obstruct outlets. Major symptoms include epigastric discomfort, nausea, and vomiting.  Glucocorticoids are an effective treatment.

Granulomatous gastritis is associated with Crohn’s disease, and can be characterized by granulomas, ulcers, or stricture development. Histoplasmosis, candidiasis, syphilis, tuberculosis can also cause granulomatous gastritis, although occurrence is much less common. Even more rare, cases of granulomatous gastritis mediated by sarcoidosis, idiopathic granulomatous gastritis, and eosinophilic gastric granulomas have also been observed. Identification of the underlying cause may require multiple endoscopies with biopsy and cytology or a full-thickness biopsy of the stomach to rule out malignant tissues.

Russell body gastritis (RBG) is a lesion in the mucosa. Endoscopically, it appears tumor-like, although the lesion is benign and its origin is unknown. Etiology is unknown, however it is observed by the existence of plasma cells with Russell bodies (RBs) expressing kappa and lambda light chains. With only 10 known cases, 7 have been identified with H. pylori infection.

Epidemiology

Chronic H. pylori gastritis (of the antrum) is present in 30-50% of the Western population. The percentage increases with age. Developing countries see percentages around 80%. Recent decades have shown a decrease of infection in children in Western countries. The H. pylori-mediated antrumgastritis is also present in 75% of peptic ulcer patients. NSAID gastritis in expected in 25-50% of chronic (>4 weeks)  users.

In acute gastritis, females are usually more affected than men. In H. pylori infection associated gastritis, males are more commonly affected than females. The incidence rates of H. pylori infection are high in Japan, Columbia, Costa Rica and China, and comparatively low in the United States. H. pylori infection is common in Southern and Eastern Europe, Mexico, South America, Africa, most Asian countries, and aboriginal people in North America.

Symptoms

Patients with acute gastritis mediated by a H. pylori infection experience rapid onset of epigastric pain, nausea, and vomiting. Without proper medical attention, the acute gastritis can transform into chronic.

Type A gastritis is associated with pernicious anemia. Antibodies, which attack parietal cells and impair intrinsic factor (IF), indirectly prevent proper absorption of vitamin B12. Deficiencies of B12 can then lead to secondary megaloblastic anemia and neurologic dysfunction. Damaged parietal cells are also unable to produce hydrochloric acid, causing hypo- or achlorhydria (low or no production of hydrochloric acid), which can last up to 1 year after initial infection. As a result, gastrin levels are characteristically heightened in those with pernicious anemia, as the combination of achlorhydria and the healthy antral mucosa (the site of G cell production) drives hypergastrinemia. Dietary metabolism and absorption of micronutrients, like iron, calcium, magnesium and zinc, or absorption of some medicines (e.g., dipyridamol, some iron formulations and anti-fungal medicines like fluconazole or itraconazole, thyroxin and atazanovir) are impaired in an acid-free stomach. The acid-free stomach is ultimately colonized with microbes from the mouth.

Risk Factors

Acute gastritis infection is more commonly found among the elderly and people from developing countries. Common risk factors include excessive use of alcohol, NSAIDs, or cocaine, HIV/AIDS and bacterial infections such as Helicobacter pylori. Less common risk factors may include food poisoning (bacterial gastroenteritis), autoimmune gastritis predisposing to vitamin B12 deficiency and other autoimmune disorders such as Hashimoto’s disease and type 1 diabetes, stress as a result of major surgery or trauma or other illness, traumatic injury, burns or severe infections, bile reflux, low fiber diet, pernicious anemia and viral and parasitic infections.

Diagnosis

H. pylori causing acute gastritis can be identified using mucosa attained through gastric biopsies, as well as in blood, stool, or breath tests. Upper endoscopy or barium swallow x-ray may provide additional information.

Chronic gastritis is distinguished histologically from acute by lymphocytic and plasma cell activity. Superficial atrophic changes and gastric atrophic changes suggest severity and risks for gastric cancer. The levels of severity are defined by endoscopic and serologic markers. In addition, the clinical advantage of measuring serum biomarkers such as pepsinogen I and II levels, gastrin-17, and anti-H. pylori is also under review.

Treatment

Treatment depends on the type, cause, and severity of gastritis. Medications known to cause gastritis, such as NSAIDs (aspirin, naproxen, ibuprofen), should be discontinued. Smoking cessation and abstinence from alcohol use is also recommended.

Acute H. pylori gastritis is treated by a course of antibiotics to eradicate H. pylori. In the first instance, a combination of three drugs is usually used to treat H. pylori infection. This treatment normally includes a proton pump inhibitor (PPI), as well as two antibiotics. This is known as a triple therapy and the course of treatment runs between 10 and 14 days. It remains unclear whether a symptomless incidental finding of H. pylori gastritis requires treatment. The eradication treatment may lead to allergic reactions or pseudomembranous colitis, and chronic gastritis may decrease GERD symptoms through hypochlorhydria. Presence of peptic ulcers would require treatment in any case.

For the treatment of symptomatic chronic gastritis, H. pylori should be eliminated in all cases. Eradication of H pylori is successful in over 85% of patients and cures chronic gastritis, given that the bacteria was the instigator. Pernicious anemic patients are given parenteral vitamin B12 supplementation indefinitely. Some patients may need lifestyle and dietary changes.

Prognosis

Prognosis depends on the treatment and extent of the disease. Management of clinically relevant chronic gastritis is mostly aimed at reducing symptoms and managing the underlying cause to slow down or halt the process.

Caution

Phlegmonous gastritis can be fatal when inflammation diffuses through the entire gastric wall, in some instances causing complete tissue death. It some cases, it can be mediated by treatment interventions, such as polypectomy and injection of the mucosa with India ink. Immunocompromised patients may also be susceptible to infectious herpetic or CMV gastritis.

Type B gastritis with atrophy and metaplasia may advance to gastric adenocarcinoma and gastric MALT lymphoma, in which the chronic T cell creation – as an attempt to destroy the infection – subsequently induces overproduction of cytokines, which aid the development of the B cell tumor.

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Functional dyspepsia

General

Functional dyspepsia, known as non-ulcer dyspepsia or indigestion, refers to general discomfort or pain of unknown origin within the gastrointestinal tract. Patients often present with normal results on upper gastrointestinal endoscopy, yet complain of stomach pain, nausea, bloating, or belching.

Epidemiology

Indigestion is found in 7% of adults. Typically 3% of general doctor’s visits are due to dyspepsia.

Symptoms

Patients typically exhibit epigastric pain, heartburn, nausea, fullness, or vomiting. If heartburn is the chief complaint, it may be associated with GERD.

Risk Factors

Elderly populations have higher risk of development. Consuming alcohol or caffeine excessively, high-fatty foods, overeating, or psychiatric disorders are also linked to development.

Cause

Functional causes typically involve a motility component, where either the motility or relaxation has decreased in the proximal gastrointestinal tract. Dyspepsia may be induced by overeating or quick ingestion of foods, eating foods with high fat content, stress-induced eating, and/or overindulgence in alcohol or coffee. Many classes of medication have also been found to provoke dyspepsia.

Diagnosis

A patient’s history should be taken to specify the frequency and duration, location and type of pain, and the onset following meals. Dysmotility-like dyspepsia typically features complaints of nausea and quick postprandial satiety, whereas ulcer-like dyspepsia typically features epigastric pain as the main complaint. Patients without H. pylori or other gastrointestinal disease are presumed to have functional dyspepsia or abnormally presenting GERD.

If the patient experiences drastic weight loss, recurrent vomiting, chronic or intense pain, worsening dysphagia, hematemesis, or melena, an endoscopy or CT of the abdomen should be performed to rule out more serious disease.

Noninvasive methods should be initially conducted for patients under the age of 60, in which incidence of gastric cancer is rare.  A noninvasive test for H. pylori (urea breath test, fecal antigen test) is standard and is 95% accurate. Serological tests do not yield much information in low-prevalence populations, thus the test for H. pylori should suffice. Peptic ulcer disease for patients with negative H. Pylori tests that are not using NSAID can be ruled out. Initial workups for patients above the age of 60 should include laboratory work for blood count, electrolytes, liver enzymes, calcium, and thyroid function analysis. An upper endoscopy should be conducted in patients above the age of 60, and younger patients that present with more serious symptoms or symptoms unresponsive to therapy. However, in patients that originate from areas with high endemic incidence of gastric cancers, including, central or South America, China and Southeast Asia, or Africa, a cautionary endoscopy can be performed after the age of 45 years.

Treatment

If functional dyspepsia is found to be provoked by a medication or alcohol consumption, use should be terminated immediately. There are several treatment options dependent on symptomatology. PPI’s or gastroprokinetics (domperidone) may be tried, as well as ‘triple therapy’ to eradicate any influence of H. pylori if previous options have failed.

About 30% of patients feel better with placebo therapies. Those with underlying psychological disorders experience relief from low dosages of antidepressants. Psychotherapy or hypnotherapy, as well as herbal remedies, may also improve symptoms in some subsets of patients.

Prognosis

Patients may be symptom free with intermittent use of medication, or recover following eradication of H. Pylori and resulting therapies. Symptoms may be relieved by lifestyle modifications, such as alcohol or caffeine reduction, or consumption of smaller low fat-meals.

Caution

Due to the vague nature of the symptoms and the vast overlap with other more serious conditions, it is integral that it is differentiated from more fatal diseases. More than 50% of primary care physicians misdiagnose patients with peptic ulcers or GERD, instead of functional dyspepsia. Chronic and severe stomach pain may also be instigated by pancreatic carcinoma and chronic pancreatitis. In this case, epigastric pain can extend to the back, and normally provokes anorexia, rapid weight loss, steatorrhea, or jaundice. Similarly, the epigastric pain of dyspepsia should be distinguished from cholelithiasis or choledocholithiasis, which also presents with epigastric and/or right upper quadrant pain.

Diabetes mellitus, thyroid disease, chronic kidney disease, myocardial ischemia, intra-abdominal malignancy, gastric volvulus or paraesophageal hernia, chronic gastric or intestinal ischemia, and pregnancy are all associated with similar epigastric pain.

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Peptic ulcer

General

Peptic ulcers are lesions that perforate the muscularis mucosae of the gastric or duodenal mucosa and extend over 5mm in diameter.

Epidemiology

The United States has approximately 500,000 peptic ulcer cases each year, 4 million of which relapse after primary treatments. One in ten adults in the US live with ulcers for their lifetime. Duodenal ulcers are more common than gastric ulcers. The duodenal ulcers are more common in men, the gastric ulcers are equally prevalent in both genders. Sixty percent of gastric ulcers arise within the antrum, while 25% of arise in the lesser curvature of the body.

Ulcers can appear at any age, but patients between the ages 30-55 have much higher incidence of development. While the elimination of H. Pylori has dramatically reduced duodenal ulcer disease, the incidence of gastric ulcers has risen due to the use of NSAIDs and aspirin.

Symptoms

Discrimination between gastric and duodenal ulcers is difficult based on symptoms alone. Non-symptomatic ulcers are found regularly.

Nausea and retching are common, especially with gastric ulcers. Mild dyspepsia is a trademark symptom of the disease, with around 80-90% of patients experiencing it. It is centralized to the epigastrium and has been defined as dull, aching, gnawing, or persistent hunger pains.  Postprandial pain is more associated with gastric ulcers. A majority of people experience discomfort in intervals, with pain-free periods and painful periods. Changes of periodicity of pain from occasional discomfort to persistent or radiating pain may be indicative of a perforation.

The clinician should ask if they are having any black tarry stools, hematemesis, coffee ground emesis, or bright red blood per rectum. Physical examination may show epigastric pain or tenderness.

These symptoms may continue for weeks or months before patients seek medical help. Patients may present with an upper GI bleeding. Excessive vomiting or weight loss are abnormal with uncomplicated ulcer disease and may be indicative of a cancer or gastric outlet obstruction.

Risk Factors

Heightened incidence occurs in patient populations between the ages 30-55 and excessive use of NSAIDs or aspirin. While stress and spicy foods do not induce peptic ulcers, they can worsen symptoms. Smoking is a significant risk factor as well.

Cause

H. pylori infection and excessive NSAID use account for 80-95% of cases of ulcer disease.  A major causative factor (60% of gastric and 90% of duodenal ulcers) is chronic inflammation due to Helicobacter pylori that colonize the antral mucosa. The immune system is unable to clear the infection, despite the appearance of antibodies. Thus, the bacterium can cause a chronic active gastritis (type B gastritis), resulting in a defect in the regulation of gastrin production. Excess gastrin stimulates the production of gastric acid by parietal cells. The acid erodes the mucosa and causes the ulcer. Another major cause of PUD is the use of NSAIDs. The gastric mucosa protects itself from gastric acid with a layer of mucus, the secretion of which is stimulated by certain prostaglandins. NSAIDs block the activity of cyclooxygenase 1 (cox-1), which is essential for the production of these prostaglandins.

Factors such as diet, alcohol, and stress have not been shown to precipitate ulcers. Roughly 5-10% of gastric or duodenal ulcers are caused by other gastrointestinal disease, including Zollinger-Ellison syndrome, CMV, Crohn disease, lymphoma, certain agitative medications, or cirrhosis or chronic kidney disease. Some incidences may be idiopathic as well.

Diagnosis

While dyspepsia is the most common complaint of ulcerative disease, it is not specific enough to confirm empirically.

If a peptic ulcer perforates, air will leak from the inside of the gastrointestinal tract (which always contains some air) to the peritoneal cavity (which normally never contains air). This leads to “free gas” within the peritoneal cavity. If the patient stands erect, as when having a chest X-ray, the gas will float to a position underneath the diaphragm. Therefore, gas in the peritoneal cavity, shown on an erect chest X-ray or supine lateral abdominal X-ray, is an omen of perforated peptic ulcer disease.

An esophagogastroduodenoscopy (EGD), a form of endoscopy, also known as a gastroscopy, is carried out on patients in whom a peptic ulcer is suspected and is considered the golden standard. By direct visual identification, the location and severity of an ulcer can be described. Moreover, if no ulcer is present, EGD can often provide an alternative diagnosis. Endoscopic biopsies should be performed in the ulcer margins of gastric ulcers to exclude ulcering carcinomas. Biopsy is not needed for ulcers of the duodenum, as they are rarely malignant.

Anemia may indicate a bleeding ulcer. Leukocytosis or severe gastric pain may hint to ulcer penetration or perforation. CT scanning may be used for visualization of perforation, penetration, or obstruction.

Treatment

Treatment with PPI therapy is preferred. H2-receptor antagonists and agents that build mucosal defenses have also been shown to be effective. In ulcerative disease caused by H. pylori, eradication via antibiotics and PPI (triple therapy) or bismuth therapy is the preferred treatment option.

Patients with ulcers due to NSAIDs, that are unable to terminate usage, should also undergo short-term PPI therapy.

If the biopsy proves that a gastric ulcer is benign and there is no evidence of dysplasia or atypia, the patient does not require any further treatment. However, a subsequent biopsy should be conducted 12 weeks after the initiation of therapy if one of these conditions is present. The healing process should be tracked, as non-healing ulcers may be malignant.

Surgery for peptic ulcer is indicated for bleeding and perforated peptic ulcer. Bleeding ulcers are usually treated first with endoscopic therapy but if they bleed after endoscopic therapy, surgery is done to control bleeding. Perforated peptic ulcer is an emergency, immediate laparoscopic closure of ulcer is done.

All patients are required to quit smoking and use NSAIDs only on doctor’s orders.

Prognosis

If H. pylori eradication therapy is unsuccessful, ulcers may return. Prognosis is good if the eradication therapy of Helicobacter pylori is taken. The recurrence rate of patients with peptic ulcer disease is less than 20%. There is a small subgroup of patients that require long-term PPI therapy to prevent recurrence. If NSAIDs use is stopped, often ulcers will regress.

Caution

A barium swallow x-ray is not sensitive nor accurate enough to visualize ulcers. Instead, an endoscopy should always be performed. Following PPI therapy, urea breath tests and fecal antigen tests should not be conducted. The therapy can report false-negatives for up to 2 weeks after. Serologic testing is also significantly less sensitive and specific than fecal antigen or urea breath testing. Thus, if available, both should be prioritized above serological testing.

While PPI therapy is effective in short-term usage, long-term PPI therapy has been shown to cause a decline in vitamin B12, iron, magnesium, and calcium absorption.

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Stomach carcinoma

General

Gastric cancer is the fifth most frequently diagnosed cancer and the third leading cause of cancer deaths worldwide. The vast majority of stomach cancers are adenocarcinomas. Lymphomas, intestinal stromal tumors, and leiomyosarcomas occur more infrequently. Gastric adenocarcinomas are divided into two distinct types: intestinal (well-differentiated) and diffuse (undifferentiated). Both categories of gastric adenocarcinoma have distinct morphologies, pathogenesis, and genetic profiles. The only curative treatment is surgical resection with adequate lymphadenectomy. Patients with an unresectable, locally advanced, or metastatic disease can only be provided with life-prolonging palliative therapy.

Epidemiology

Gastric cancer has been declining rapidly worldwide. Incidence is higher in developing countries, due to lack of refrigeration, quality sanitation, limited diets, and water quality. Incidence is more common in men than women, and more frequent in black men than in white men. Lower occurrence is associated to westernized societies with higher socioeconomic status.

Diffuse carcinomas are found more commonly in younger patients and yield a worse prognosis than the intestinal type.

Symptoms

Early stages of gastric cancer do not cause noticeable symptoms.  As the cancer advances into late stages of the disease, patients experience non-specific weight loss, persistent abdominal pain, dysphagia, hematemesis, anorexia, nausea, early satiety, and dyspepsia. Patients with locally-advanced or metastatic disease normally have more severe abdominal pain, ascites, and fatigue in addition to the general symptoms. Visceral metastasis are visible on imaging and often a gastric-outlet obstruction is present.

A palpable abdominal mass hints to late stages of the disease. The patient may also show signs of metastatic lymphatic spread distribution and/or direct metastasis to peritoneum, which can present as an ovarian mass, Sister Mary Joseph node, Blumer’s shelf (cul-de-sac mass), ascites (peritoneal carcinomatosis), and hepatomegaly. Ascites may spread throughout the cavity as well.

Risk Factors

Consumption of foods with high-salt, nitrates, such as those found smoked or cured foods, as well as maintaining a diet void of vitamin A and C elevates risk for carcinoma development. Limited access to refrigerated foods and contaminated drinking water also raises one’s susceptibility. Recall how atrophic gastritis due to H. pylori may progress into cancer. High body mass index (BMI), gastroesophageal reflux, and smoking are associated with an increased risk of adenocarcinomas of the distal esophagus, proximal stomach, and junction. Occupational exposure to rubber manufacturing, tin mining, metal processing, and coal also increases the risk.

Asymptomatic carriers of E-cadherin gene (CDH1) are at heightened risk for diffuse type carcinomas. Carriers often have what appears to be a normal mucosa on endoscopy but possess tumor foci that are invaginated deeper in the gastric wall. Higher risk for lobular breast cancer has also been linked to individuals with the mutation.

Cause

There are two main histologic variants of gastric adenocarcinoma: intestinal type and diffuse-type.
Intestinal type presents due to abnormal cell cohesion, in which the cells arrange in gland-like tubular structures. The resulting lesions often transform into ulcers and are more commonly found along the antrum or lesser curvature of the stomach. Intestinal type carcinomas typically originate from an initial case of chronic gastritis provoked by H. pylori, pernicious anemia, or high-salt diets causing parietal cells death and progress to atrophic gastritis, as a consequence of the reduction in acid production. The atrophic gastritis leads to hypergastrinemia, which provokes chronic inflammation. Inflammation induces intestinal metaplasia, dysplasia, and eventually, adenocarcinoma.

Diffuse-type is characterized by a lack of intercellular adhesions, which inhibits the formation of glandular structures. As a result, cells thicken the stomach wall, without creating a defined tumor. This decreases the ability of the gastric wall to expand, known as linitis plastica. Patients with congenital diffuse-type gastric cancer possess a germ-line mutation (HDGC) in the cell adhesion protein E-cadherin (CDH1), which deters intercellular adhesion.

Tumor invasion and lymph node metastasis is also associated with gene amplification and over-expression of the human epidermal growth factor receptor 2 (HER2).

Diagnosis

An upper endoscopy is standard to obtain direct biopsy of esophageal, gastric or duodenal lesions. Chest and abdominal CTs or PET scans should be performed to further visualize metastasis and determine surgical resectability. Serum markers have limited utility and may be elevated by other sources.

Biopsied tissue should be checked for levels of HER2 genes. High protein levels merit treatment with monoclonal antibodies. Tissues should also be tested for H. pylori.

Treatment

Although about 60% of tumors can be resected, most procedures are non-curative. While surgery is the only cure that currently exists, full resection of the tumor and near lymph nodes is the only possible way to eliminate the cancer and is only permissible in a small subset of cases. Endoscopic resection is offered to patients with early gastric cancer who do not have metastases in the lymph nodes.  Patients in more advanced stages of the disease are referred for gastrectomy with regional lymph node resection. Tumors invaginated in fragile areas, such as around central arteries or veins, are incurable. However, to reduce the pain and pressure that the lesion causes, partial resection to reduce the tumor bulk is recommended.

Gastric adenocarcinomas do not respond to radiotherapy, but it can be used in palliative care to extend patient’s longevity.

Infection with H. pylori has been associated with metachronous gastric lesions; eradication is advised. Surveillance after endoscopic resection is required.

Because carriers of CDH1 have a higher risk for diffuse type gastric cancers, a prophylactic gastrectomy is recommended.

Prognosis

Successful endoscopic resection may offer a 5-year overall survival of 84% to 96% depending on the depth of the tumor compared to gastrectomy survival rates up to 98%. Curative (sub)total gastric resection results  roughly in a 30-50% 5-year survival rate. A palpable tumor with hepatomegaly and ascites usually has a poor prognosis. Palliative care can be offered to patients with unresectable tumors.

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Zollinger-Ellison syndrome

General

Zollinger-Ellison syndrome (ZES) is defined by the growth of gastrinomas, which are neuroendocrine tumors that overproduce the hormone gastrin (hypergastrinemia). Usually, gastric acid secretion is controlled by negative feedback mechanisms by somatostatin released by gastric D cells to maintain gastric acid homeostasis / pH. Excess levels of gastrin lead to a large overproduction of gastric acid (acid hypersecretion), which stimulates heavy growth of gastric mucosa and over-expression of parietal cells. This subsequently causes duodenal ulcers, even distally of the duodenal bulbus.
Primary tumors can be found in the pancreas, the duodenal wall, or within the lymph nodes. Most tumors originate from an area known as the gastrinoma triangle. While duodenal ulcers may be solitary, lone gastric ulcers are not characteristic of Zollinger-Ellison syndrome.

Epidemiology

Females typically have a higher prevalence than males, and exists more predominantly between ages 30-50. While the majority of gastrinomas are solitary or have resectable nodules, more than half are malignant and over one-third have already metastasized to the liver when symptoms emerge.

Symptoms

Due to the overproduction of gastrin, nearly all patients present with peptic ulcers, identical to those of peptic ulcer disease. Acid hypersecretion can also damage the mucosa of the intestine or inactivate the enzymes of the pancreas, leading to diarrhea, steatorrhea, and weight loss. Patients often experience GERD.
Common physical examination findings of Zollinger-Ellison syndrome include epigastric tenderness, pallor, and jaundice.

Risk Factors

Women have higher risk. Incidence has been correlated to MEN1 gene.

Cause

Development of Zollinger-Ellison syndrome is associated with the autosomal dominant syndrome Multiple Endocrine Neoplasia type 1 (MEN 1). Tumors resulting from MEN 1 are harder to resect.

Diagnosis

Heightened serum gastrin levels are integral to the diagnosis. Because peptic ulcer disease is indistinguishable from ulcers of Zollinger-Ellison syndrome, patients should be tested for H pylori. Patients taking NSAIDs or those negative for H. pylori, should then receive fasting gastrin level screenings. This also goes for patients with general peptic ulcers that are unresponsive to treatments or recur, as well as patients with ulcers larger than 2 cm or located distally to the duodenal bulb. Likewise, patients with hypercalcemia or a family history of development, which could indicate MEN1, mandate screening.

Imaging can be used to find metastases; CT or MRI functions well for the location of large tumors, but cannot identify small lesions.

Somatostatin receptor scintigraphy (SRS) is known to be more sensitive than conventional imaging studies. SRS is also called octreoscan and involves using indium-labeled octreotide that has a strong affinity for type 2 somatostatin receptors which are expressed on cells of gastrinoma. Positron emission tomography is used to assess metastasis to other body organs. Invasive modalities include an endoscopic ultrasound to evaluate pancreas more closely and an esophagogastroduodenoscopy (EGD) to visually assess any abnormalities.

Treatment

Short term PPI therapy is effective in reducing symptoms in most patients but is no solution for the slowly growing tumor(s). For a minority of patients who cannot tolerate PPIs, an H2-receptor antagonist is an option.
Surgical exploration is an option in patients with sporadic gastrinomas because of a high propensity for the tumor to metastasize to the liver, lymph nodes, and distant organs. Tumor resection is not always successful when gastrinomas occur in the pancreas.

Hyperparathyroidism from MEN1 causes hypercalcemia which can worsen the symptoms since hypercalcemia increases gastrin levels. Therefore, subtotal parathyroidectomy should precede the resection of the primary tumor which can result in better symptom control and may normalize abnormal gastrin levels.

Prognosis

Prognosis is generally good, and the 5 and 10-year survival rate of patients with Zollinger-Ellison syndrome is approximately 94% and 75%, respectively. Prognosis foremost depends on the stage of cancer. More than half of gastrinomas metastasize to the lymph nodes, liver, or distant organs. Metastasis to the liver has a direct effect on survival as pancreatic gastrinomas have lower long-term survival rates than duodenal gastrinomas. The patients with liver metastases have a 15% 10-year survival after the surgery, but those without liver metastases have a 95% 20-year survival.

Caution

The complication rate is higher than in regular ulcer disease. Complications from acid secretion can cause bleeding and perforation of GI tracts including esophagus, stomach, and duodenum. Other significant risks include death from surgery when resecting gastrinoma or other cancers from MEN1.