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Disorders of the Stomach and Duodenum Recurrent vomiting should also raise concern for other conditions. ¢ Patients with Barrett esophagus should receive proton The list of possible organic causes of dyspepsia is exten- pump inhibitor therapy; endoscopy-based ablation sive (Table 5); the most common are peptic ulcer disease and therapies are recommended for confirmed dysplasia. gastroesophageal reflux disease (20% of patients with erosive ¢ Dysphagia with solid foods is the most common pre- esophagitis report dyspepsia). If no structural, organic, or senting symptom of esophageal carcinoma. metabolic cause of dyspepsia symptoms is identified after evaluation, the term functional dyspepsia applies. Functional dyspepsia represents a heterogeneous group of Disorders of the Stomach gastrointestinal disorders predominated by one or more upper

Recurrent vomiting should also raise concern for other conditions. ¢ Patients with Barrett esophagus should receive proton The list of possible organic causes of dyspepsia is exten- pump inhibitor therapy; endoscopy-based ablation sive (Table 5); the most common are peptic ulcer disease and therapies are recommended for confirmed dysplasia. gastroesophageal reflux disease (20% of patients with erosive ¢ Dysphagia with solid foods is the most common pre- esophagitis report dyspepsia). If no structural, organic, or senting symptom of esophageal carcinoma. metabolic cause of dyspepsia symptoms is identified after evaluation, the term functional dyspepsia applies. Functional dyspepsia represents a heterogeneous group of Disorders of the Stomach gastrointestinal disorders predominated by one or more upper gastrointestinal symptoms. Diagnostic criteria for functional and Duodenum dyspepsia are shown in Table 6. Functional dyspepsia is fur- ther categorized into postprandial distress syndrome if the Dyspepsia predominant symptoms are meal-induced (Table 7) or epigas- Clinical Features tric pain syndrome if the predominant symptoms are epigas-

gastrointestinal symptoms. Diagnostic criteria for functional and Duodenum dyspepsia are shown in Table 6. Functional dyspepsia is fur- ther categorized into postprandial distress syndrome if the Dyspepsia predominant symptoms are meal-induced (Table 7) or epigas- Clinical Features tric pain syndrome if the predominant symptoms are epigas- Dyspepsia is a term to describe epigastric pain. Associated tric pain and/or burning (Table 8). symptoms can include early satiety, epigastric burning, nausea, and postprandial symptoms (e.g., pain, fullness, bloating, or Evaluation and Management belching). Heartburn may be present but is not a primary Testing for dyspepsia should be based on patient age, symptom symptom; it may indicate coexisting gastroesophageal reflux. severity, and risk for gastric cancer. Upper endoscopy is com- monly performed to exclude upper gastrointestinal neoplasia; TABLE 5. Structural and Other Causes of Dyspepsia however, it is invasive and costly. Given the low incidence of

and postprandial symptoms (e.g., pain, fullness, bloating, or Evaluation and Management belching). Heartburn may be present but is not a primary Testing for dyspepsia should be based on patient age, symptom symptom; it may indicate coexisting gastroesophageal reflux. severity, and risk for gastric cancer. Upper endoscopy is com- monly performed to exclude upper gastrointestinal neoplasia; TABLE 5. Structural and Other Causes of Dyspepsia however, it is invasive and costly. Given the low incidence of Cc ategory malignancy and consideration for cost effectiveness in the Clinical Examples | Gastroesophageal Gastroesophageal reflux disease, peptic ulcer disease, Helicobacter TABLE 6. Rome 4 Diagnostic Criteria for pylori gastritis, gastric cancer/ Functional Dyspepsia lymphoma, gastric amyloidosis, Ménétrier disease, gastroparesis | One or more of the following?: | Small bowel Celiac disease, Crohn disease Bothersome postprandial fullness

Cc ategory malignancy and consideration for cost effectiveness in the Clinical Examples | Gastroesophageal Gastroesophageal reflux disease, peptic ulcer disease, Helicobacter TABLE 6. Rome 4 Diagnostic Criteria for pylori gastritis, gastric cancer/ Functional Dyspepsia lymphoma, gastric amyloidosis, Ménétrier disease, gastroparesis | One or more of the following?: | Small bowel Celiac disease, Crohn disease Bothersome postprandial fullness Pancreatic Pancreatitis, pancreatic cancer Bothersome early satiation } } ' Infectious Giardia lamblia, Strongyloides | Bothersome epigastric pain stercoralis, tuberculosis, syphilis Bothersome epigastric burning Common medications NSAIDs, aspirin, iron, antibiotics No evidence of structural disease (including at upper | (erythromycin, ampicillin), narcotics, endoscopy) that is likely to explain the symptoms estrogens and oral contraceptives, theophylline, levodopa, digitalis *Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis. Other systemic Coronary artery disease, kidney conditions disease, thyroid dysfunction, adrenal | Reproduced with permission from Stanghellini V, Chan FK, Hasler WL, Malagelada JR, | Suzuki H, Tack J, et al. Gastroduodenal disorders. Gastroenterology. 2016;150: insufficiency, hyperparathyroidism, | 1380-92. [PMID: 27147122] doi:10.1053/j.gastro.2016.02.011. Copyright 2016, pregnancy The AGA Institute.

Pancreatic Pancreatitis, pancreatic cancer Bothersome early satiation } } ' Infectious Giardia lamblia, Strongyloides | Bothersome epigastric pain stercoralis, tuberculosis, syphilis Bothersome epigastric burning Common medications NSAIDs, aspirin, iron, antibiotics No evidence of structural disease (including at upper | (erythromycin, ampicillin), narcotics, endoscopy) that is likely to explain the symptoms estrogens and oral contraceptives, theophylline, levodopa, digitalis *Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis. Other systemic Coronary artery disease, kidney conditions disease, thyroid dysfunction, adrenal | Reproduced with permission from Stanghellini V, Chan FK, Hasler WL, Malagelada JR, | Suzuki H, Tack J, et al. Gastroduodenal disorders. Gastroenterology. 2016;150: insufficiency, hyperparathyroidism, | 1380-92. [PMID: 27147122] doi:10.1053/j.gastro.2016.02.011. Copyright 2016, pregnancy The AGA Institute. TABLE 7. Rome 4 Diagnostic Criteria for Postprandial Distress Syndrome

Pancreatic Pancreatitis, pancreatic cancer Bothersome early satiation } } ' Infectious Giardia lamblia, Strongyloides | Bothersome epigastric pain stercoralis, tuberculosis, syphilis Bothersome epigastric burning Common medications NSAIDs, aspirin, iron, antibiotics No evidence of structural disease (including at upper | (erythromycin, ampicillin), narcotics, endoscopy) that is likely to explain the symptoms estrogens and oral contraceptives, theophylline, levodopa, digitalis *Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis. Other systemic Coronary artery disease, kidney conditions disease, thyroid dysfunction, adrenal | Reproduced with permission from Stanghellini V, Chan FK, Hasler WL, Malagelada JR, | Suzuki H, Tack J, et al. Gastroduodenal disorders. Gastroenterology. 2016;150: insufficiency, hyperparathyroidism, | 1380-92. [PMID: 27147122] doi:10.1053/j.gastro.2016.02.011. Copyright 2016, pregnancy The AGA Institute. TABLE 7. Rome 4 Diagnostic Criteria for Postprandial Distress Syndrome Criteria? Supportive Remarks | Must include one or both of the following at least 3 days Postprandial epigastric pain or burning, epigastric bloating, excessive per week: belching, and nausea can also be present Bothersome postprandial fullness (i.e., severe enough Vomiting warrants consideration of another disorder to affect usual activities) Heartburn is not a dyspeptic symptom but may often coexist Bothersome early satiation (i.e., severe enough to prevent finishing a regular-sized meal) Symptoms that are relieved by evacuation of feces or gas should generally not be considered as part of dyspepsia No evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms on routine Other individual digestive symptoms or groups of symptoms, such as from investigations (including upper endoscopy) gastroesophageal reflux disease and irritable bowel syndrome, may coexist |

Criteria? Supportive Remarks | Must include one or both of the following at least 3 days Postprandial epigastric pain or burning, epigastric bloating, excessive per week: belching, and nausea can also be present Bothersome postprandial fullness (i.e., severe enough Vomiting warrants consideration of another disorder to affect usual activities) Heartburn is not a dyspeptic symptom but may often coexist Bothersome early satiation (i.e., severe enough to prevent finishing a regular-sized meal) Symptoms that are relieved by evacuation of feces or gas should generally not be considered as part of dyspepsia No evidence of organic, systemic, or metabolic disease that is likely to explain the symptoms on routine Other individual digestive symptoms or groups of symptoms, such as from investigations (including upper endoscopy) gastroesophageal reflux disease and irritable bowel syndrome, may coexist | *Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis. Reproduced with permission from Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al. Gastroduodenal disorders. Gastroenterology. 2016;150:1380-92. [PMID: 27147122] doi:10.1053/j.gastro.2016.02.011. Copyright 2016, The AGA Institute. 10

Disorders of the Stomach and Duodenum TABLE 8. Rome 4 Diagnostic Criteria for Epigastric Pain Syndrome Criteria? Supportive Remarks Must include the following symptoms at least Pain may be induced by ingestion of a meal, relieved by ingestion of a meal, or may 1 day per week: occur while fasting Bothersome epigastric pain and/or burning Postprandial epigastric bloating, belching, and nausea can also be present (i.e., severe enough to affect usual activities) Persistent vomiting suggests another disorder No evidence of organic, systemic, or metabolic Heartburn is not a dyspeptic symptom but may often coexist disease that is likely to explain the symptoms on routine investigations (including upper The pain does not fulfill biliary pain criteria endoscopy) Symptoms that are relieved by evacuation of feces or gas should generally not be | considered as part of dyspepsia | | Other individual digestive symptoms or groups of symptoms, such as from gastroesophageal reflux disease and irritable bowel syndrome, may coexist ’Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis. Reproduced with permission from Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al. Gastroduodenal disorders. Gastroenterology. 2016; 150:1380-92. [PMID: 27147122] doi:10.1053/j.gastro.2016.02.011. Copyright 2016, The AGA Institute.

’Criteria fulfilled for the last 3 months with symptom onset at least 6 months before diagnosis. Reproduced with permission from Stanghellini V, Chan FK, Hasler WL, Malagelada JR, Suzuki H, Tack J, et al. Gastroduodenal disorders. Gastroenterology. 2016; 150:1380-92. [PMID: 27147122] doi:10.1053/j.gastro.2016.02.011. Copyright 2016, The AGA Institute. evaluation of dyspepsia in younger adults, the American 60 years and older. The ACG/CAG guidelines recommend College of Gastroenterology (ACG) and the Canadian against routine use of upper endoscopy in patients younger Association of Gastroenterology (CAG) have jointly recom- than 60 years with dyspepsia, even in most patients with mended routine use of upper endoscopy only in patients age alarm features (weight loss, anemia, dysphagia, and vomiting) because these features poorly predict structural pathology, such as malignancy, peptic ulcer disease, or esophagitis.

evaluation of dyspepsia in younger adults, the American 60 years and older. The ACG/CAG guidelines recommend College of Gastroenterology (ACG) and the Canadian against routine use of upper endoscopy in patients younger Association of Gastroenterology (CAG) have jointly recom- than 60 years with dyspepsia, even in most patients with mended routine use of upper endoscopy only in patients age alarm features (weight loss, anemia, dysphagia, and vomiting) because these features poorly predict structural pathology, such as malignancy, peptic ulcer disease, or esophagitis. Testing for Helicobacter pylori infection Endoscopy may be considered in younger patients at higher If result is positive, treat with 14 days of eradication therapy risk for malignancy, such as those with multiple or severe alarm features; those who have emigrated from regions with a H. pylori negative or high prevalence of malignancy (Asia, Russia, and South No symptom relief following H. pylori therapy America); or those with a positive family history of gastric malignancy. Proton pump inhibitors For patients younger than 60 years with dyspepsia (if not already tried) symptoms, the ACG/CAG guidelines recommend noninvasive

Testing for Helicobacter pylori infection Endoscopy may be considered in younger patients at higher If result is positive, treat with 14 days of eradication therapy risk for malignancy, such as those with multiple or severe alarm features; those who have emigrated from regions with a H. pylori negative or high prevalence of malignancy (Asia, Russia, and South No symptom relief following H. pylori therapy America); or those with a positive family history of gastric malignancy. Proton pump inhibitors For patients younger than 60 years with dyspepsia (if not already tried) symptoms, the ACG/CAG guidelines recommend noninvasive | No symptom relief testing for Helicobacter pylori. Other testing, such as routine laboratory tests, screening for celiac disease, abdominal

Testing for Helicobacter pylori infection Endoscopy may be considered in younger patients at higher If result is positive, treat with 14 days of eradication therapy risk for malignancy, such as those with multiple or severe alarm features; those who have emigrated from regions with a H. pylori negative or high prevalence of malignancy (Asia, Russia, and South No symptom relief following H. pylori therapy America); or those with a positive family history of gastric malignancy. Proton pump inhibitors For patients younger than 60 years with dyspepsia (if not already tried) symptoms, the ACG/CAG guidelines recommend noninvasive | No symptom relief testing for Helicobacter pylori. Other testing, such as routine laboratory tests, screening for celiac disease, abdominal Antidepressants imaging, or gastric emptying, should be considered on an Tricyclic antidepressants individual basis. Consider mirtazapine if nausea and/or weight loss present Management of dyspepsia is directed at treating the Consider buspirone if early satiety present cause. Patients who test positive for H. pylori should receive

Antidepressants imaging, or gastric emptying, should be considered on an Tricyclic antidepressants individual basis. Consider mirtazapine if nausea and/or weight loss present Management of dyspepsia is directed at treating the Consider buspirone if early satiety present cause. Patients who test positive for H. pylori should receive | No symptom relief eradication therapy. If H. pylori results are negative or H. pylori eradication does not relieve the dyspepsia, an empiric Prokinetic agents trial of a proton pump inhibitor (PPI) should be pursued. Metoclopramide? Patients diagnosed with functional dyspepsia can be treated Domperidone (where available)’ with a variety of interventions (Figure 8). | No symptom relief e For patients with dyspepsia, routine upper endoscopy to HVC Referral to gastroenterologist for consideration of exclude malignancy is reserved for patients age 60 years endoscopy, additional functional testing, and CAM therapies and older.

| No symptom relief e For patients with dyspepsia, routine upper endoscopy to HVC Referral to gastroenterologist for consideration of exclude malignancy is reserved for patients age 60 years endoscopy, additional functional testing, and CAM therapies and older. FIGURE 8. Treatment algorithm for functional dyspepsia. e Upper endoscopy is not necessary in most patients with HVC CAM = complementary and alternative medicine. dyspepsia younger than 60 years, even in the presence 2Avoid metoclopramide treatment longer than 12 weeks because of the increased risk for tardive dyskinesia with of alarm symptoms. longer-term use that is often irreversible. e Patients younger than 60 years with dyspepsia symptoms HVC ‘Increased risk for serious ventricular arrhythmias or sudden cardiac death, particularly with doses greater than should be tested and, if results are positive, treated for 30 mg or when used in patients older than age 60 years. Use the lowest possible dose for the shortest duration necessary. ECGs should be obtained at baseline and periodically thereafter to evaluate the QTc interval. Requires Helicobacter pylori infection. Investigational New Drug Application in the United States. 11

Disorders of the Stomach and Duodenum TABLE 10. Second-Line Treatment for Helicobacter pylori Infection After Failure of Initial Treatment Treatment Regimen Duration of Therapy Clinical Indicators PPI, standard dose twice daily? 14 days Failure of clarithromycin-based or Bismuth subcitrate, 120-300 mg, or subsalicylate, 300 mg four times daily TG aaa AIeGY Tetracycline, 500 mg four times daily Metronidazole, 500 mg three or four times daily PPI, standard dose twice daily 14 days Failure of bismuth-based or Levofloxacin, 500 mg once daily aay Amoxicillin, 1 g twice daily PPI, standard dose twice daily? 10-14 days Failure of bismuth-based therapy Clarithromycin, 500 mg twice daily Amoxicillin, 1 g twice daily Metronidazole or tinidazole, 500 mg twice or three times daily PPI = proton pump inhibitor. *Standard-dose PPls: esomeprazole, 40 mg; lansoprazole, 30 mg; omeprazole, 20 mg; pantoprazole, 40 mg; rabeprazole, 20 mg. Adapted with permission from Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. | 2017 112:212-239. [PMID: 28071659] doi:10.1038/ajg.2016.563.

*Standard-dose PPls: esomeprazole, 40 mg; lansoprazole, 30 mg; omeprazole, 20 mg; pantoprazole, 40 mg; rabeprazole, 20 mg. Adapted with permission from Chey WD, Leontiadis GI, Howden CW, Moss SF. ACG clinical guideline: treatment of Helicobacter pylori infection. Am J Gastroenterol. | 2017 112:212-239. [PMID: 28071659] doi:10.1038/ajg.2016.563. minimum of 14 days, ideally with antibiotics different from portal hypertension are additional causes. Although erosive those used for initial treatment (Table 10). gastropathy may result in gastrointestinal bleeding, it rarely causes clinically significant bleeding. Eradication Testing No sooner than 4 weeks after completion of eradication ther- Atrophic Gastritis apy and cessation of PPI therapy (if possible), eradication of Chronic atrophic gastritis can present as environmental meta- H. pylori should be tested by using a C-urea breath test, fecal plastic atrophic gastritis, also called multifocal atrophic gastritis, antigen test, or gastric biopsy performed during upper endos- or as autoimmune atrophic gastritis. Environmental metaplastic copy. Serologic testing is not used to confirm H. pylorieradica- atrophic gastritis is the result of H. pylori infection and typically tion because results can remain positive following H. pylori lessens after H. pylori eradication. Autoimmune atrophic gastri- eradication. tis is caused by formation of autoantibody to parietal cell anti- gens and is commonly associated with pernicious anemia. The achlorhydria from chronic atrophic gastritis can lead to iron e Gastric biopsies during upper endoscopy or noninvasive deficiency, small intestinal bacterial overgrowth, and enteric testing methods, including *C-urea breath and stool infections. The hypergastrinemia associated with autoimmune antigen tests, can confirm active H. pylori infection; atrophic gastritis can promote development of gastric neuroen- negative serologic results can exclude infection, but a docrine tumors. Goals of therapy for autoimmune atrophic positive serologic result may require confirmation. gastritis include prevention of pernicious anemia and iron defi- ¢ Treatment regimens for H. pylori consist of a minimum ciency with vitamin B,, supplementation and iron replacement of three agents, including two antimicrobial agents and along with surveillance for gastric neoplasm. See MKSAP 19 one antisecretory agent; treatment duration is 14 days in Hematology for further discussion of pernicious anemia in the most cases. setting of autoimmune gastritis. Screening upper endoscopy e Eradication of H. pylori is tested with a %C-urea breath with gastric biopsy is recommended for patients with pernicious test, fecal antigen test, or gastric biopsy performed during anemia. Otherwise, there are no universally accepted surveil- upper endoscopy no sooner than 4 weeks after comple- lance protocols for gastric neoplasm in chronic atrophic gastritis, tion of eradication therapy and cessation of PPI therapy and endoscopic surveillance should be considered on an indi- (if possible). vidual basis. Annual endoscopy is generally not necessary.

minimum of 14 days, ideally with antibiotics different from portal hypertension are additional causes. Although erosive those used for initial treatment (Table 10). gastropathy may result in gastrointestinal bleeding, it rarely causes clinically significant bleeding. Eradication Testing No sooner than 4 weeks after completion of eradication ther- Atrophic Gastritis apy and cessation of PPI therapy (if possible), eradication of Chronic atrophic gastritis can present as environmental meta- H. pylori should be tested by using a C-urea breath test, fecal plastic atrophic gastritis, also called multifocal atrophic gastritis, antigen test, or gastric biopsy performed during upper endos- or as autoimmune atrophic gastritis. Environmental metaplastic copy. Serologic testing is not used to confirm H. pylorieradica- atrophic gastritis is the result of H. pylori infection and typically tion because results can remain positive following H. pylori lessens after H. pylori eradication. Autoimmune atrophic gastri- eradication. tis is caused by formation of autoantibody to parietal cell anti- gens and is commonly associated with pernicious anemia. The achlorhydria from chronic atrophic gastritis can lead to iron e Gastric biopsies during upper endoscopy or noninvasive deficiency, small intestinal bacterial overgrowth, and enteric testing methods, including *C-urea breath and stool infections. The hypergastrinemia associated with autoimmune antigen tests, can confirm active H. pylori infection; atrophic gastritis can promote development of gastric neuroen- negative serologic results can exclude infection, but a docrine tumors. Goals of therapy for autoimmune atrophic positive serologic result may require confirmation. gastritis include prevention of pernicious anemia and iron defi- ¢ Treatment regimens for H. pylori consist of a minimum ciency with vitamin B,, supplementation and iron replacement of three agents, including two antimicrobial agents and along with surveillance for gastric neoplasm. See MKSAP 19 one antisecretory agent; treatment duration is 14 days in Hematology for further discussion of pernicious anemia in the most cases. setting of autoimmune gastritis. Screening upper endoscopy e Eradication of H. pylori is tested with a %C-urea breath with gastric biopsy is recommended for patients with pernicious test, fecal antigen test, or gastric biopsy performed during anemia. Otherwise, there are no universally accepted surveil- upper endoscopy no sooner than 4 weeks after comple- lance protocols for gastric neoplasm in chronic atrophic gastritis, tion of eradication therapy and cessation of PPI therapy and endoscopic surveillance should be considered on an indi- (if possible). vidual basis. Annual endoscopy is generally not necessary. Gastric Intestinal Metaplasia Miscellaneous Gastropathy Gastric intestinal metaplasia is a preneoplastic gastropathy Erosive Gastropathy frequently arising from chronic inflammation associated with Erosive gastropathy can result from exposure to medications H. pylori infection. As such, patients with gastric intestinal and toxins, including NSAIDs, iron, and alcohol. Ischemia and metaplasia should be tested for H. pylori and then treated if

Gastric Intestinal Metaplasia Miscellaneous Gastropathy Gastric intestinal metaplasia is a preneoplastic gastropathy Erosive Gastropathy frequently arising from chronic inflammation associated with Erosive gastropathy can result from exposure to medications H. pylori infection. As such, patients with gastric intestinal and toxins, including NSAIDs, iron, and alcohol. Ischemia and metaplasia should be tested for H. pylori and then treated if 14

Disorders of the Stomach and Duodenum the infection is identified. Other causes of chronic inflamma- TABLE 11. Risk Factors for NSAID-Related Upper tion, including other gastric infections, chemical agents, and Gastrointestinal Complications autoimmune disease, may also promote progression to gastric | History of upper gastrointestinal bleeding intestinal metaplasia. No conclusive evidence shows that long- History of peptic ulcer disease term PPI use promotes development of intestinal metaplasia. Helicobacter pylori infection Gastric intestinal metaplasia is believed to be an intermediary | Age >65 years stage in the multistage progression from chronic atrophic gas- tritis to gastric adenocarcinoma. If metaplasia is secondary to Hemodialysis or peritoneal dialysis

the infection is identified. Other causes of chronic inflamma- TABLE 11. Risk Factors for NSAID-Related Upper tion, including other gastric infections, chemical agents, and Gastrointestinal Complications autoimmune disease, may also promote progression to gastric | History of upper gastrointestinal bleeding intestinal metaplasia. No conclusive evidence shows that long- History of peptic ulcer disease term PPI use promotes development of intestinal metaplasia. Helicobacter pylori infection Gastric intestinal metaplasia is believed to be an intermediary | Age >65 years stage in the multistage progression from chronic atrophic gas- tritis to gastric adenocarcinoma. If metaplasia is secondary to Hemodialysis or peritoneal dialysis H. pyloriinfection, eradication therapy may decrease progres- Use of high-dose or multiple NSAIDs sion to gastric adenocarcinoma. Given the rarity of gastric Concomitant use of aspirin (even low-dose), nonaspirin adenocarcinoma in the United States, current guidelines rec- antiplatelet agents, anticoagulants, oral glucocorticoids, or selective serotonin reuptake inhibitors ommend against the routine use of surveillance endoscopy in gastric intestinal metaplasia. Surveillance endoscopy can be considered in patients at increased risk (such as those with complete or extensive gastric intestinal metaplasia on endos- Gastrointestinal Complications copy; those with a family history of gastric cancer; persons of NSAIDs from racial/ethnic minority groups; or those who have emi- Epidemiology and Risk Factors grated from East Asia, Russia, or South America). Upper gastrointestinal complications can occur with short- or long-term NSAID use and are dose dependent, with a linear Eosinophilic Gastritis increase in incidence over time. Nearly 1% to 2% of patients Eosinophilic gastritis is a rare gastropathy characterized by taking long-term NSAID therapy experience a clinically infiltration of eosinophils in the gastric mucosa. Secondary significant upper gastrointestinal event (bleeding ulcer, perfo- causes of eosinophilia should first be excluded, including ration, or obstruction) annually. The rate of upper gastrointes- parasitic and bacterial infections of the stomach, inflamma- tinal adverse events rises to 14% for elderly NSAID users. The tory bowel disease, hypereosinophilic syndrome, myeloprolif- greatest risk factor for NSAID-related upper gastrointestinal erative disorders, polyarteritis nodosa, allergic vasculitis, complication is a history of gastrointestinal bleeding. Risk fac- scleroderma, drug injury, and drug hypersensitivity. The cause tors are listed in Table 11. of primary eosinophilic gastritis is unknown but is believed to Use of low-dose aspirin for cardioprophylaxis is associ- be an allergic process. Symptoms vary widely based on depth ated with a twofold to fourfold increase in risk for upper of eosinophilia and other gastrointestinal tract involvement. gastrointestinal complications, including bleeding ulcer, per- Treatment includes avoidance of food allergens, elemental foration, and obstruction. Use of enteric-coated aspirin does diets, and/or glucocorticoids. not lower this risk, and an increase in aspirin dosage is associ- ated with an increased risk for upper gastrointestinal compli- Lymphocytic Gastritis cations. See MKSAP 19 General Internal Medicine 2 for Lymphocytic gastritis is a rare gastropathy typically presenting discussion of indications for primary and secondary preven- with nonspecific dyspeptic symptoms and a normal-appearing tion of cardiovascular disease with aspirin. stomach on endoscopy. On occasion, the stomach may have thick- ened folds covered by small nodules and aphthous ulceration. Prevention of NSAID-Induced Injury Celiac disease is the most common cause of lymphocytic gastritis. Prevention of NSAID-related upper gastrointestinal adverse Other causes include HIV infection, Crohn disease, common vari- events includes avoiding NSAIDs; addressing modifiable risk able immunodeficiency, and, rarely, H. pylori infection. factors; coadministering gastroprotective agents, such as PPIs, misoprostol, or H,-blockers; or using a selective cyclooxyge- ¢ Autoimmune atrophic gastritis is associated with perni- nase (COX)-2 inhibitor. PPIs are the preferred gastroprotective cious anemia, iron deficiency, small intestinal bacterial agent for the treatment and prophylaxis of NSAID-related overgrowth, and gastric carcinoid. (including aspirin-related) upper gastrointestinal complica- tions and are superior to H,-blockers for preventing PUD and ¢ Management of autoimmune atrophic gastritis includes bleeding related to low-dose aspirin use. Misoprostol may be prevention of pernicious anemia and iron deficiency used instead of PPIs in patients intolerant of or unwilling to with vitamin B,. supplementation and iron replacement along with surveillance for gastric neoplasm. take PPIs. However, side effects of misoprostol, such as diar- rhea, abdominal discomfort, and nausea, can be limiting, and ¢ Helicobacter pylori is associated with upper gastrointesti- the drug is contraindicated in pregnancy. nal conditions other than peptic ulcer disease, including Selective COX-2 inhibitors are associated with decreased environmental metaplastic atrophic gastritis, gastric risk for gastrointestinal toxicity compared with NSAIDs, intestinal metaplasia, and, rarely, lymphocytic gastritis. although the risk is still elevated. When coadministered with

H. pyloriinfection, eradication therapy may decrease progres- Use of high-dose or multiple NSAIDs sion to gastric adenocarcinoma. Given the rarity of gastric Concomitant use of aspirin (even low-dose), nonaspirin adenocarcinoma in the United States, current guidelines rec- antiplatelet agents, anticoagulants, oral glucocorticoids, or selective serotonin reuptake inhibitors ommend against the routine use of surveillance endoscopy in gastric intestinal metaplasia. Surveillance endoscopy can be considered in patients at increased risk (such as those with complete or extensive gastric intestinal metaplasia on endos- Gastrointestinal Complications copy; those with a family history of gastric cancer; persons of NSAIDs from racial/ethnic minority groups; or those who have emi- Epidemiology and Risk Factors grated from East Asia, Russia, or South America). Upper gastrointestinal complications can occur with short- or long-term NSAID use and are dose dependent, with a linear Eosinophilic Gastritis increase in incidence over time. Nearly 1% to 2% of patients Eosinophilic gastritis is a rare gastropathy characterized by taking long-term NSAID therapy experience a clinically infiltration of eosinophils in the gastric mucosa. Secondary significant upper gastrointestinal event (bleeding ulcer, perfo- causes of eosinophilia should first be excluded, including ration, or obstruction) annually. The rate of upper gastrointes- parasitic and bacterial infections of the stomach, inflamma- tinal adverse events rises to 14% for elderly NSAID users. The tory bowel disease, hypereosinophilic syndrome, myeloprolif- greatest risk factor for NSAID-related upper gastrointestinal erative disorders, polyarteritis nodosa, allergic vasculitis, complication is a history of gastrointestinal bleeding. Risk fac- scleroderma, drug injury, and drug hypersensitivity. The cause tors are listed in Table 11. of primary eosinophilic gastritis is unknown but is believed to Use of low-dose aspirin for cardioprophylaxis is associ- be an allergic process. Symptoms vary widely based on depth ated with a twofold to fourfold increase in risk for upper of eosinophilia and other gastrointestinal tract involvement. gastrointestinal complications, including bleeding ulcer, per- Treatment includes avoidance of food allergens, elemental foration, and obstruction. Use of enteric-coated aspirin does diets, and/or glucocorticoids. not lower this risk, and an increase in aspirin dosage is associ- ated with an increased risk for upper gastrointestinal compli- Lymphocytic Gastritis cations. See MKSAP 19 General Internal Medicine 2 for Lymphocytic gastritis is a rare gastropathy typically presenting discussion of indications for primary and secondary preven- with nonspecific dyspeptic symptoms and a normal-appearing tion of cardiovascular disease with aspirin. stomach on endoscopy. On occasion, the stomach may have thick- ened folds covered by small nodules and aphthous ulceration. Prevention of NSAID-Induced Injury Celiac disease is the most common cause of lymphocytic gastritis. Prevention of NSAID-related upper gastrointestinal adverse Other causes include HIV infection, Crohn disease, common vari- events includes avoiding NSAIDs; addressing modifiable risk able immunodeficiency, and, rarely, H. pylori infection. factors; coadministering gastroprotective agents, such as PPIs, misoprostol, or H,-blockers; or using a selective cyclooxyge- ¢ Autoimmune atrophic gastritis is associated with perni- nase (COX)-2 inhibitor. PPIs are the preferred gastroprotective cious anemia, iron deficiency, small intestinal bacterial agent for the treatment and prophylaxis of NSAID-related overgrowth, and gastric carcinoid. (including aspirin-related) upper gastrointestinal complica- tions and are superior to H,-blockers for preventing PUD and ¢ Management of autoimmune atrophic gastritis includes bleeding related to low-dose aspirin use. Misoprostol may be prevention of pernicious anemia and iron deficiency used instead of PPIs in patients intolerant of or unwilling to with vitamin B,. supplementation and iron replacement along with surveillance for gastric neoplasm. take PPIs. However, side effects of misoprostol, such as diar- rhea, abdominal discomfort, and nausea, can be limiting, and ¢ Helicobacter pylori is associated with upper gastrointesti- the drug is contraindicated in pregnancy. nal conditions other than peptic ulcer disease, including Selective COX-2 inhibitors are associated with decreased environmental metaplastic atrophic gastritis, gastric risk for gastrointestinal toxicity compared with NSAIDs, intestinal metaplasia, and, rarely, lymphocytic gastritis. although the risk is still elevated. When coadministered with 15

Disorders of the Stomach and Duodenum aspirin, however, a selective COX-2 inhibitor provides no TABLE 12. Causes of Gastroparesis advantage over an NSAID in preventing an upper gastrointes- | Common Causes | tinal adverse event. Given the increased risk for PUD with | Diabetes mellitus (40% in long-standing type 1 diabetes concomitant use of an NSAID or selective COX-2 inhibitor | mellitus, 20% in type 2 diabetes mellitus) with low-dose aspirin, at-risk individuals should receive gas- | Postsurgical (e.g., Nissen fundoplication, bariatric surgery, troprotective therapy. Compared to an NSAID plus a PPI in pancreatic surgery) patients at high risk, a selective COX-2 inhibitor plus a PPI Idiopathic (e.g., postviral) offers a lower risk for perforation, obstruction, and bleeding as well as for NSAID and COX-2 withdrawal due to gastrointesti- Infrequent Causes nal adverse events. Connective tissue disease (e.g., systemic sclerosis) After an NSAID-induced bleeding peptic ulcer, the safest Neurologic disease (e.g., Parkinson disease) strategy is avoidance of future NSAID use. Ifan NSAID must be Eating disorders used, the combination of a selective COX-2 inhibitor plus a | Hypothyroidism PPI provides the best gastrointestinal protection to prevent Amyloidosis rebleeding. Paraneoplastic syndromes (e.g., small cell lung cancer)

nal adverse events. Connective tissue disease (e.g., systemic sclerosis) After an NSAID-induced bleeding peptic ulcer, the safest Neurologic disease (e.g., Parkinson disease) strategy is avoidance of future NSAID use. Ifan NSAID must be Eating disorders used, the combination of a selective COX-2 inhibitor plus a | Hypothyroidism PPI provides the best gastrointestinal protection to prevent Amyloidosis rebleeding. Paraneoplastic syndromes (e.g., small cell lung cancer) Mesenteric ischemia e Upper gastrointestinal complications, such as bleeding, | Medications (e.g., opiates, anticholinergic agents) are common with use of NSAIDs (both short- and long- term) and low-dose aspirin. e Proton pump inhibitors are the preferred agent for pre- test using C-labeled Spirulina platensis (Table 13). Gastric venting and treating NSAID-related (including aspirin- scintigraphy is the most commonly used, but the optimal

Mesenteric ischemia e Upper gastrointestinal complications, such as bleeding, | Medications (e.g., opiates, anticholinergic agents) are common with use of NSAIDs (both short- and long- term) and low-dose aspirin. e Proton pump inhibitors are the preferred agent for pre- test using C-labeled Spirulina platensis (Table 13). Gastric venting and treating NSAID-related (including aspirin- scintigraphy is the most commonly used, but the optimal related) upper gastrointestinal complications. duration of this study is 4 hours. Narcotic and anticholinergic agents must be stopped at least 72 hours before a gastric emp- e In individuals with high risk for gastrointestinal com- tying study. Once delayed emptying is objectively confirmed, plications, including those with previous NSAID-induced additional testing may be required to determine the cause of gastrointestinal bleeding, the combination of a selective the gastroparesis. cyclooxygenase-2 inhibitor plus a proton pump inhibitor provides the best gastrointestinal protection if avoidance Management of NSAIDs is not possible. Symptom severity does not correlate with severity of delayed gastric emptying, particularly with regard to abdominal bloat-

related) upper gastrointestinal complications. duration of this study is 4 hours. Narcotic and anticholinergic agents must be stopped at least 72 hours before a gastric emp- e In individuals with high risk for gastrointestinal com- tying study. Once delayed emptying is objectively confirmed, plications, including those with previous NSAID-induced additional testing may be required to determine the cause of gastrointestinal bleeding, the combination of a selective the gastroparesis. cyclooxygenase-2 inhibitor plus a proton pump inhibitor provides the best gastrointestinal protection if avoidance Management of NSAIDs is not possible. Symptom severity does not correlate with severity of delayed gastric emptying, particularly with regard to abdominal bloat- Gastroparesis ing and epigastric pain. This suggests that gastroparesis is not simply a motility disorder but also a disorder of altered sensa- Presentation tion. Initial management includes correcting dehydration and Gastroparesis is a heterogeneous clinical syndrome character- electrolyte abnormalities along with nutritional support if ized by the presence of specific symptoms, absence of mechan- needed. Initial dietary intervention should consist of small, ical outlet obstruction, and objective evidence of delay in frequent meals that are low in fat and soluble fiber. Referral to a gastric emptying into the duodenum. The most common dietitian may be beneficial. In diabetic gastroparesis, poor gly- symptoms, in order of prevalence, are nausea (90%), vomiting cemic control (blood glucose level >200 mg/dL [11.1 mmol/L]) (84%), upper abdominal pain (72%), and early satiety (60%). can worsen symptoms as well as gastric emptying, and tight Other symptoms may include abdominal fullness and bloat- glycemic control is the most important element of treatment. ing. Symptoms may be chronic or persistent or may occur Pharmacologic therapy is used to improve gastric emp- intermittently. More severe cases may involve weight loss and tying and treat symptoms. Metoclopramide is the only proki- evidence of malnutrition and/or dehydration. A viral pro- netic approved in the United States for treatment of drome, such as gastroenteritis or respiratory infection before gastroparesis. To minimize the significant risk for neurologic symptom onset, may suggest postviral gastroparesis, a condi- side effects (dystonia, parkinsonian movements, tardive dys- tion that can resolve over time. Gastroparesis has a variety of kinesia), the lowest effective dose should be used. Therapy causes (Table 12). must be stopped immediately if neurologic side effects develop. Diagnostic Testing Erythromycin improves gastric emptying, but use should The first study to evaluate suspected gastroparesis is upper be limited to treatment of flares or short-term use (2 to endoscopy to exclude gastric outlet obstruction. Once a struc- 3 weeks) because of risk for tachyphylaxis. tural cause for symptoms has been excluded, an objective test Antiemetics and centrally acting modulators, including to assess gastric emptying is performed: gastric scintigraphy, tricyclic antidepressants and mirtazapine, can also relieve wireless motility capsule, or gastric emptying carbon breath symptoms but have no beneficial effect on gastric emptying.

Gastroparesis ing and epigastric pain. This suggests that gastroparesis is not simply a motility disorder but also a disorder of altered sensa- Presentation tion. Initial management includes correcting dehydration and Gastroparesis is a heterogeneous clinical syndrome character- electrolyte abnormalities along with nutritional support if ized by the presence of specific symptoms, absence of mechan- needed. Initial dietary intervention should consist of small, ical outlet obstruction, and objective evidence of delay in frequent meals that are low in fat and soluble fiber. Referral to a gastric emptying into the duodenum. The most common dietitian may be beneficial. In diabetic gastroparesis, poor gly- symptoms, in order of prevalence, are nausea (90%), vomiting cemic control (blood glucose level >200 mg/dL [11.1 mmol/L]) (84%), upper abdominal pain (72%), and early satiety (60%). can worsen symptoms as well as gastric emptying, and tight Other symptoms may include abdominal fullness and bloat- glycemic control is the most important element of treatment. ing. Symptoms may be chronic or persistent or may occur Pharmacologic therapy is used to improve gastric emp- intermittently. More severe cases may involve weight loss and tying and treat symptoms. Metoclopramide is the only proki- evidence of malnutrition and/or dehydration. A viral pro- netic approved in the United States for treatment of drome, such as gastroenteritis or respiratory infection before gastroparesis. To minimize the significant risk for neurologic symptom onset, may suggest postviral gastroparesis, a condi- side effects (dystonia, parkinsonian movements, tardive dys- tion that can resolve over time. Gastroparesis has a variety of kinesia), the lowest effective dose should be used. Therapy causes (Table 12). must be stopped immediately if neurologic side effects develop. Diagnostic Testing Erythromycin improves gastric emptying, but use should The first study to evaluate suspected gastroparesis is upper be limited to treatment of flares or short-term use (2 to endoscopy to exclude gastric outlet obstruction. Once a struc- 3 weeks) because of risk for tachyphylaxis. tural cause for symptoms has been excluded, an objective test Antiemetics and centrally acting modulators, including to assess gastric emptying is performed: gastric scintigraphy, tricyclic antidepressants and mirtazapine, can also relieve wireless motility capsule, or gastric emptying carbon breath symptoms but have no beneficial effect on gastric emptying. 16

Disorders of the Stomach and Duodenum TABLE 13. Diagnostic Tests Assessing Gastric Emptying | Test Advantages Disadvantages Clinical Pearls | | Gastric scintigraphy Considered the gold Radiation exposure (technetium Study lasting 4 hours is most accurate | standard radiolabeled meal) : er e s | Assesses solid emptying (liquid emptying | | Requires specially trained personnel __is less accurate) | | Cost Blood glucose should be <275 mg/dL | (15.3 mmol/L) | Wireless motility Can also assess small Cost Consider in patient suspected of having | Seawe ans cola Can’t be used with pacemaker or : eal) suet ili riy pciebeay bl g implantable cardioverter- Stop antisecretory agents because study | | No radiation defibrillator relies on measurement of pH | Ambulatory study Risk for capsule retention

| Test Advantages Disadvantages Clinical Pearls | | Gastric scintigraphy Considered the gold Radiation exposure (technetium Study lasting 4 hours is most accurate | standard radiolabeled meal) : er e s | Assesses solid emptying (liquid emptying | | Requires specially trained personnel __is less accurate) | | Cost Blood glucose should be <275 mg/dL | (15.3 mmol/L) | Wireless motility Can also assess small Cost Consider in patient suspected of having | Seawe ans cola Can’t be used with pacemaker or : eal) suet ili riy pciebeay bl g implantable cardioverter- Stop antisecretory agents because study | | No radiation defibrillator relies on measurement of pH | Ambulatory study Risk for capsule retention | Gastric emptying No radiation Avoid in setting of Spirulina Accuracy adversely affected by conditions | | carbon breath test supplementation or egg, milk, or altering endogenous CO; production | wheat hypersensitivity Avoid physical activity during testing

| Gastric emptying No radiation Avoid in setting of Spirulina Accuracy adversely affected by conditions | | carbon breath test supplementation or egg, milk, or altering endogenous CO; production | wheat hypersensitivity Avoid physical activity during testing Avoid in patients with small-bowel malabsorption, pancreatic insufficiency, COPD, chronic heart failure, or advanced liver disease Interventional therapy, such as enteral feeding via jeju- Hyperplastic polyps of the stomach are thought to have nostomy, gastric stimulator placement, gastric peroral endo- malignant potential, with 5% to 19% harboring dysplasia or scopic myotomy, pyloroplasty, and subtotal or total gastrectomy, malignancy. Risk factors for malignant potential of hyperplas- can be considered in patients who do not respond to dietary tic polyps include size greater than 1 cm and pedunculated and pharmacologic therapy. morphology. All hyperplastic polyps greater than 0.5 to 1.0 cm should be resected. Adenomas in the stomach can be sporadic or associated e After gastric outlet obstruction is excluded by upper with hereditary syndromes, including familial adenomatous endoscopy, patients suspected of gastroparesis should polyposis and Lynch syndrome. Those in the stomach should undergo an objective test of gastric emptying, typically be resected and endoscopic surveillance should be per-

e After gastric outlet obstruction is excluded by upper with hereditary syndromes, including familial adenomatous endoscopy, patients suspected of gastroparesis should polyposis and Lynch syndrome. Those in the stomach should undergo an objective test of gastric emptying, typically be resected and endoscopic surveillance should be per- gastric scintigraphy. formed 1 year after resection and then every 3 to 5 years thereafter. e Initial management of gastroparesis includes correcting dehydration and electrolyte abnormalities; nutritional Gastric Subepithelial Lesions support; small, frequent meals that are low in fat and Gastrointestinal Stromal Tumors soluble fiber; and, in patients with diabetes mellitus, Gastrointestinal stromal tumors (GISTs) are the most common improved glycemic control. mesenchymal tumors of the stomach. GISTs may present with ¢ Metoclopramide is a prokinetic drug that improves gastric symptoms, such as bleeding or abdominal pain, but are also emptying but is associated with dystonia, tardive dyski- found incidentally. Endoscopic ultrasonography is the best nesia, and parkinsonism. diagnostic modality for evaluation of a GIST. High-risk features on endoscopic ultrasonography include size greater than 2 cm, lobulated or irregular borders, invasion into adjacent struc-

gastric scintigraphy. formed 1 year after resection and then every 3 to 5 years thereafter. e Initial management of gastroparesis includes correcting dehydration and electrolyte abnormalities; nutritional Gastric Subepithelial Lesions support; small, frequent meals that are low in fat and Gastrointestinal Stromal Tumors soluble fiber; and, in patients with diabetes mellitus, Gastrointestinal stromal tumors (GISTs) are the most common improved glycemic control. mesenchymal tumors of the stomach. GISTs may present with ¢ Metoclopramide is a prokinetic drug that improves gastric symptoms, such as bleeding or abdominal pain, but are also emptying but is associated with dystonia, tardive dyski- found incidentally. Endoscopic ultrasonography is the best nesia, and parkinsonism. diagnostic modality for evaluation of a GIST. High-risk features on endoscopic ultrasonography include size greater than 2 cm, lobulated or irregular borders, invasion into adjacent struc- Gastric Polyps and tures, and heterogeneity. A GIST can be biopsied, but the high- risk endoscopic features are better predictors of malignant Subepithelial Lesions potential. Treatment consists of surgical or endoscopic exci- Gastric Polyps sion if the GIST is symptomatic or high-risk features are pre- Polyps in the stomach include fundic gland polyps, hyper- sent. For GISTs without high-risk features, yearly endoscopic plastic polyps, and adenomas. All gastric polyps should be surveillance is indicated. See MKSAP 19 Oncology for staging biopsied to determine polyp histology. Fundic gland polyps and treatment of GISTs. and hyperplastic polyps account for 70% to 90% of stomach polyps. Fundic gland polyps have no potential for malig- Gastrointestinal Neuroendocrine Tumors nancy and are common with PPI use. Multiple fundic gland Neuroendocrine tumors (NETs; formerly called carcinoid polyps are also found in patients with familial adenomatous tumors) are well-differentiated lesions originating in the diges- polyposis. tive tract, lungs, or, rarely, kidneys or ovaries. NETs can be

Gastric Polyps and tures, and heterogeneity. A GIST can be biopsied, but the high- risk endoscopic features are better predictors of malignant Subepithelial Lesions potential. Treatment consists of surgical or endoscopic exci- Gastric Polyps sion if the GIST is symptomatic or high-risk features are pre- Polyps in the stomach include fundic gland polyps, hyper- sent. For GISTs without high-risk features, yearly endoscopic plastic polyps, and adenomas. All gastric polyps should be surveillance is indicated. See MKSAP 19 Oncology for staging biopsied to determine polyp histology. Fundic gland polyps and treatment of GISTs. and hyperplastic polyps account for 70% to 90% of stomach polyps. Fundic gland polyps have no potential for malig- Gastrointestinal Neuroendocrine Tumors nancy and are common with PPI use. Multiple fundic gland Neuroendocrine tumors (NETs; formerly called carcinoid polyps are also found in patients with familial adenomatous tumors) are well-differentiated lesions originating in the diges- polyposis. tive tract, lungs, or, rarely, kidneys or ovaries. NETs can be 17

Disorders of the Stomach and Duodenum encountered throughout the gastrointestinal tract, including metaplasia with high-grade dysplasia should be resected the stomach. They may present symptomatically or may be because 25% of cases progress to adenocarcinoma. Screening found incidentally. These tumors are usually sporadic but can be and surveillance are indicated for patients with familial ade- seen in the setting of Zollinger-Ellison syndrome; atrophic gas- nomatous polyposis and Lynch syndrome. tritis; and rare syndromes, such as multiple endocrine neoplasia type 1 and neurofibromatosis type 1. NETs are classified by size, Clinical Manifestations and Diagnosis number, and anatomic distribution. Management of gastroin- Symptoms of gastric adenocarcinoma may be vague. They testinal NETs includes endoscopic surveillance for lesions include poor appetite, weight loss, abdominal pain, early sati- smaller than 1 cm, especially when multiple lesions are present. ety, nausea, and vomiting. Signs of gastric adenocarcinoma Endoscopic or surgical excision is indicated for gastrointestinal include iron deficiency anemia. Diagnosis is typically made by NETs with high-risk features, such as solitary lesions not found upper endoscopy with biopsy. in the setting of atrophic gastritis or Zollinger-Ellison syndrome. For treatment of gastric cancer, see MKSAP 19 Oncology. See MKSAP 19 Oncology for treatment of gastrointestinal NETs.

encountered throughout the gastrointestinal tract, including metaplasia with high-grade dysplasia should be resected the stomach. They may present symptomatically or may be because 25% of cases progress to adenocarcinoma. Screening found incidentally. These tumors are usually sporadic but can be and surveillance are indicated for patients with familial ade- seen in the setting of Zollinger-Ellison syndrome; atrophic gas- nomatous polyposis and Lynch syndrome. tritis; and rare syndromes, such as multiple endocrine neoplasia type 1 and neurofibromatosis type 1. NETs are classified by size, Clinical Manifestations and Diagnosis number, and anatomic distribution. Management of gastroin- Symptoms of gastric adenocarcinoma may be vague. They testinal NETs includes endoscopic surveillance for lesions include poor appetite, weight loss, abdominal pain, early sati- smaller than 1 cm, especially when multiple lesions are present. ety, nausea, and vomiting. Signs of gastric adenocarcinoma Endoscopic or surgical excision is indicated for gastrointestinal include iron deficiency anemia. Diagnosis is typically made by NETs with high-risk features, such as solitary lesions not found upper endoscopy with biopsy. in the setting of atrophic gastritis or Zollinger-Ellison syndrome. For treatment of gastric cancer, see MKSAP 19 Oncology. See MKSAP 19 Oncology for treatment of gastrointestinal NETs. e The primary nongenetic risk factor for gastric cancer is ¢ Polyps in the stomach include fundic gland polyps, which Helicobacter pylori infection. have no malignant potential; polyps with malignant e In countries with a low incidence of gastric cancer, such HVC potential, including hyperplastic polyps, and adenomas as the United States, screening for gastric cancer should should be resected. be reserved for patients with genetic cancer syndromes. ¢ Gastrointestinal stromal tumors should be evaluated with ¢ Upper endoscopy with biopsy is the diagnostic test of endoscopic ultrasonography and excised if symptoms or choice for gastric cancer. high-risk features are present.

e The primary nongenetic risk factor for gastric cancer is ¢ Polyps in the stomach include fundic gland polyps, which Helicobacter pylori infection. have no malignant potential; polyps with malignant e In countries with a low incidence of gastric cancer, such HVC potential, including hyperplastic polyps, and adenomas as the United States, screening for gastric cancer should should be resected. be reserved for patients with genetic cancer syndromes. ¢ Gastrointestinal stromal tumors should be evaluated with ¢ Upper endoscopy with biopsy is the diagnostic test of endoscopic ultrasonography and excised if symptoms or choice for gastric cancer. high-risk features are present. ¢ Neuroendocrine tumors are usually sporadic but can be seen in the setting of Zollinger-Ellison syndrome; atrophic Gastric Surgery Complications gastritis; and rare syndromes, such as multiple endocrine For complications of bariatric surgery, see MKSAP 19 General neoplasia type 1 and neurofibromatosis type 1. Internal Medicine 2. Partial or complete gastric resections are performed for benign and malignant disease. The extent of resection, type of Gastric Adenocarcinoma reconstruction, and nature of the disease affect postoperative Epidemiology and Risk Factors morbidity and mortality. Partial resection allows preservation Stomach adenocarcinoma has an incidence of 6.6 in 100,000 of some function of the stomach, but patients with malignancy persons and a mortality of 3.1 per 100,000 persons in the require lifelong surveillance of the remaining stomach for United States. Rates have steadily decreased since the 1990s. recurrence. Patients who undergo partial gastrectomy for The two types of gastric cancer are intestinal-type, which is benign disease also have an increased risk for cancer in the more common, and diffuse-type. H. pylori is a recognized risk gastric remnant 15 to 20 years after surgery, with reported factor for both types and is the primary nongenetic risk factor frequency ranging from 0.8% to 8.9%. for gastric cancer. Other risk factors primarily associated with Dumping syndrome, which results from rapid gastric intestinal-type gastric adenocarcinoma include male sex; eth- emptying after gastric surgery, can cause significant postpran- nicity (incidence is highest in persons of Asian and Pacific dial gastrointestinal and vasomotor symptoms. Clinical fea- Island descent, and mortality is highest in non-Hispanic white tures of early dumping syndrome occur within 30 minutes of persons); geography (the highest rates worldwide occur in Asia, eating due to gastrointestinal hormone hypersecretion, auto- Eastern Europe, and Central and South America); a diet high in nomic dysregulation, and bowel distention. Symptoms include smoked, salted, and pickled foods as well as nitrates and palpitations, flushing or pallor, diaphoresis, light-headedness, nitrites; smoking; and obesity. Additional risk factors include hypotension, and fatigue, followed by diarrhea, nausea, previous stomach surgery; chronic atrophic gastritis; and abdominal bloating, cramping, and borborygmus. Symptoms hereditary syndromes, such as hereditary diffuse gastric cancer of late dumping syndrome occur 1 to 3 hours after meals (associated with the diffuse type), Lynch syndrome, and famil- because of reactive hypoglycemia and can include decreased ial adenomatous polyposis. Gastric intestinal metaplasia and concentration, faintness, and altered consciousness. In severe dysplasia are also risk factors for gastric adenocarcinoma. cases, protein-wasting malnutrition can occur. Roughly 25% to 50% of all patients who have undergone Screening and Surveillance gastric surgery experience some symptoms of dumping syn- There is no recommendation for population-based screen- drome, but severe, persistent symptoms occur in only about

¢ Neuroendocrine tumors are usually sporadic but can be seen in the setting of Zollinger-Ellison syndrome; atrophic Gastric Surgery Complications gastritis; and rare syndromes, such as multiple endocrine For complications of bariatric surgery, see MKSAP 19 General neoplasia type 1 and neurofibromatosis type 1. Internal Medicine 2. Partial or complete gastric resections are performed for benign and malignant disease. The extent of resection, type of Gastric Adenocarcinoma reconstruction, and nature of the disease affect postoperative Epidemiology and Risk Factors morbidity and mortality. Partial resection allows preservation Stomach adenocarcinoma has an incidence of 6.6 in 100,000 of some function of the stomach, but patients with malignancy persons and a mortality of 3.1 per 100,000 persons in the require lifelong surveillance of the remaining stomach for United States. Rates have steadily decreased since the 1990s. recurrence. Patients who undergo partial gastrectomy for The two types of gastric cancer are intestinal-type, which is benign disease also have an increased risk for cancer in the more common, and diffuse-type. H. pylori is a recognized risk gastric remnant 15 to 20 years after surgery, with reported factor for both types and is the primary nongenetic risk factor frequency ranging from 0.8% to 8.9%. for gastric cancer. Other risk factors primarily associated with Dumping syndrome, which results from rapid gastric intestinal-type gastric adenocarcinoma include male sex; eth- emptying after gastric surgery, can cause significant postpran- nicity (incidence is highest in persons of Asian and Pacific dial gastrointestinal and vasomotor symptoms. Clinical fea- Island descent, and mortality is highest in non-Hispanic white tures of early dumping syndrome occur within 30 minutes of persons); geography (the highest rates worldwide occur in Asia, eating due to gastrointestinal hormone hypersecretion, auto- Eastern Europe, and Central and South America); a diet high in nomic dysregulation, and bowel distention. Symptoms include smoked, salted, and pickled foods as well as nitrates and palpitations, flushing or pallor, diaphoresis, light-headedness, nitrites; smoking; and obesity. Additional risk factors include hypotension, and fatigue, followed by diarrhea, nausea, previous stomach surgery; chronic atrophic gastritis; and abdominal bloating, cramping, and borborygmus. Symptoms hereditary syndromes, such as hereditary diffuse gastric cancer of late dumping syndrome occur 1 to 3 hours after meals (associated with the diffuse type), Lynch syndrome, and famil- because of reactive hypoglycemia and can include decreased ial adenomatous polyposis. Gastric intestinal metaplasia and concentration, faintness, and altered consciousness. In severe dysplasia are also risk factors for gastric adenocarcinoma. cases, protein-wasting malnutrition can occur. Roughly 25% to 50% of all patients who have undergone Screening and Surveillance gastric surgery experience some symptoms of dumping syn- There is no recommendation for population-based screen- drome, but severe, persistent symptoms occur in only about ing for gastric adenocarcinoma in countries with a low inci- 10%. Oral glucose challenge testing helps make the diagnosis, dence of gastric cancer, such as the United States. Intestinal with a sensitivity of nearly 100% and a specificity of 94%.

¢ Neuroendocrine tumors are usually sporadic but can be seen in the setting of Zollinger-Ellison syndrome; atrophic Gastric Surgery Complications gastritis; and rare syndromes, such as multiple endocrine For complications of bariatric surgery, see MKSAP 19 General neoplasia type 1 and neurofibromatosis type 1. Internal Medicine 2. Partial or complete gastric resections are performed for benign and malignant disease. The extent of resection, type of Gastric Adenocarcinoma reconstruction, and nature of the disease affect postoperative Epidemiology and Risk Factors morbidity and mortality. Partial resection allows preservation Stomach adenocarcinoma has an incidence of 6.6 in 100,000 of some function of the stomach, but patients with malignancy persons and a mortality of 3.1 per 100,000 persons in the require lifelong surveillance of the remaining stomach for United States. Rates have steadily decreased since the 1990s. recurrence. Patients who undergo partial gastrectomy for The two types of gastric cancer are intestinal-type, which is benign disease also have an increased risk for cancer in the more common, and diffuse-type. H. pylori is a recognized risk gastric remnant 15 to 20 years after surgery, with reported factor for both types and is the primary nongenetic risk factor frequency ranging from 0.8% to 8.9%. for gastric cancer. Other risk factors primarily associated with Dumping syndrome, which results from rapid gastric intestinal-type gastric adenocarcinoma include male sex; eth- emptying after gastric surgery, can cause significant postpran- nicity (incidence is highest in persons of Asian and Pacific dial gastrointestinal and vasomotor symptoms. Clinical fea- Island descent, and mortality is highest in non-Hispanic white tures of early dumping syndrome occur within 30 minutes of persons); geography (the highest rates worldwide occur in Asia, eating due to gastrointestinal hormone hypersecretion, auto- Eastern Europe, and Central and South America); a diet high in nomic dysregulation, and bowel distention. Symptoms include smoked, salted, and pickled foods as well as nitrates and palpitations, flushing or pallor, diaphoresis, light-headedness, nitrites; smoking; and obesity. Additional risk factors include hypotension, and fatigue, followed by diarrhea, nausea, previous stomach surgery; chronic atrophic gastritis; and abdominal bloating, cramping, and borborygmus. Symptoms hereditary syndromes, such as hereditary diffuse gastric cancer of late dumping syndrome occur 1 to 3 hours after meals (associated with the diffuse type), Lynch syndrome, and famil- because of reactive hypoglycemia and can include decreased ial adenomatous polyposis. Gastric intestinal metaplasia and concentration, faintness, and altered consciousness. In severe dysplasia are also risk factors for gastric adenocarcinoma. cases, protein-wasting malnutrition can occur. Roughly 25% to 50% of all patients who have undergone Screening and Surveillance gastric surgery experience some symptoms of dumping syn- There is no recommendation for population-based screen- drome, but severe, persistent symptoms occur in only about ing for gastric adenocarcinoma in countries with a low inci- 10%. Oral glucose challenge testing helps make the diagnosis, dence of gastric cancer, such as the United States. Intestinal with a sensitivity of nearly 100% and a specificity of 94%. 18

Disorders of the Pancreas First-line treatment for dumping syndrome is dietary, TABLE 14. Causes of Acute Pancreatitis with smaller, more frequent meals and ingestion of liquids Common after meals. Decreasing carbohydrate intake, especially simple Biliary disease carbohydrates, and increasing protein and fiber intake may also alleviate symptoms. Gallstones Acarbose, an o:-glycosidase hydrolase inhibitor that inter- Biliary sludge feres with digestion of polysaccharides to monosaccharides, Microlithiasis (1- to 2-mm stones that are not detected by can be used for late symptoms of dumping syndrome. Other imaging studies) pharmacologic therapies include anticholinergics to slow gas- Alcohol use tric emptying and antispasmodics. Severe cases of dumping Postendoscopic retrograde cholangiopancreatography rarely require octreotide. If a trial of subcutaneous injections Occasional is effective, monthly intramuscular injections of long-acting octreotide can be used. Medications? Furosemide Didanosine e Patients who undergo partial gastrectomy for malignancy Asparaginase require lifelong surveillance for cancer recurrence; patients who have undergone partial gastrectomy for Mesalamine benign disease also have an increased risk for gastric Thiazides cancer. 6-Mercaptopurine/azathioprine e Dumping syndrome results from rapid gastric emptying Sulfasalazine after gastric surgery; first-line treatment is smaller, more Simvastatin frequent meals with liquids taken following meals. Hypertriglyceridemia Hypercalcemia

e Dumping syndrome results from rapid gastric emptying Sulfasalazine after gastric surgery; first-line treatment is smaller, more Simvastatin frequent meals with liquids taken following meals. Hypertriglyceridemia Hypercalcemia Type V choledochocele Disorders of the Pancreas | Rare Acute Pancreatitis Autoimmune Infectious Acute pancreatitis is an inflammatory process involving the pancreas and extrapancreatic organs and is the most common Viral (mumps, coxsackie B virus, cytomegalovirus, hepatitis B virus, varicella-zoster virus, herpes simplex virus, HIV) gastrointestinal cause of hospitalization in the United States. Parasitic (Toxoplasma species, Ascaris lumbricoides, Biliary disease, including gallstones, biliary sludge, and biliary Cryptosporidium species) crystals (microlithiasis), is the most common cause of acute Bacterial (Legionella, Leptospira, Mycoplasma, and pancreatitis (Table 14). Premature activation of digestive Salmonella species) enzymes and release of cytokines cause autodigestion of | Fungal (Aspergillus species) the pancreas and inflammation, which may involve surround- ing tissues and distant organs. Ischemia

Infectious Acute pancreatitis is an inflammatory process involving the pancreas and extrapancreatic organs and is the most common Viral (mumps, coxsackie B virus, cytomegalovirus, hepatitis B virus, varicella-zoster virus, herpes simplex virus, HIV) gastrointestinal cause of hospitalization in the United States. Parasitic (Toxoplasma species, Ascaris lumbricoides, Biliary disease, including gallstones, biliary sludge, and biliary Cryptosporidium species) crystals (microlithiasis), is the most common cause of acute Bacterial (Legionella, Leptospira, Mycoplasma, and pancreatitis (Table 14). Premature activation of digestive Salmonella species) enzymes and release of cytokines cause autodigestion of | Fungal (Aspergillus species) the pancreas and inflammation, which may involve surround- ing tissues and distant organs. Ischemia Acute pancreatitis is classified as mild, moderately severe, Trauma or severe. Mild acute pancreatitis does not involve organ failure Neoplasia or other complications, usually resolves within 1 week, and | Celiac disease has a low mortality rate. Twenty percent of patients with acute |

Acute pancreatitis is classified as mild, moderately severe, Trauma or severe. Mild acute pancreatitis does not involve organ failure Neoplasia or other complications, usually resolves within 1 week, and | Celiac disease has a low mortality rate. Twenty percent of patients with acute | Genetic (only if attacks recur) pancreatitis develop moderately severe or severe disease. Moderately severe acute pancreatitis involves local or systemic @Multiple medications have been linked to acute pancreatitis. A partial list of other suspect medications includes metronidazole, pentamidine, stibogluconate, complications, such as necrosis or organ failure lasting less | tetracycline, sulfasalazine, L-asparaginase, valproic acid, sulindac, salicylates, | | estrogen, and calcium. | than 48 hours. Severe acute pancreatitis involves systemic |

Genetic (only if attacks recur) pancreatitis develop moderately severe or severe disease. Moderately severe acute pancreatitis involves local or systemic @Multiple medications have been linked to acute pancreatitis. A partial list of other suspect medications includes metronidazole, pentamidine, stibogluconate, complications, such as necrosis or organ failure lasting less | tetracycline, sulfasalazine, L-asparaginase, valproic acid, sulindac, salicylates, | | estrogen, and calcium. | than 48 hours. Severe acute pancreatitis involves systemic | inflammatory response syndrome (SIRS), persistent organ failure (usually kidney or respiratory failure), duration longer in location, often radiating to the back); (2) serum lipase or than 48 hours, and one or more local complications. The mor- amylase levels elevated at least three times the upper limit of tality rate is as high as 50%. normal; and (3) characteristic imaging findings (Figure 9). High fever and leukocytosis are part of the cytokine cascade and do Clinical Presentation and Diagnosis not necessarily indicate infection. The diagnosis of acute pancreatitis requires two of the following Patients with acute pancreatitis should undergo transab- three criteria: (1) acute-onset abdominal pain characteristic of dominal ultrasonography to assess for gallstones and biliary pancreatitis (severe, persistent for hours to days, and epigastric duct dilation. Transabdominal ultrasonography is preferred 19