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Gastroenterology and Hepatology

Terms in this set (110)


Liver test elevations in the setting of a recently started medication should raise the suspicion of a possible drug induced liver injury.

This patient has drug-induced liver injury secondary to trimethoprim-sulfamethoxazole therapy. Antibiotics are common causes of drug-induced liver injury, which can cause either an elevation in the aminotransferases or, as in this patient, a cholestatic form of liver injury. Some drugs have their own particular fingerprint of injury. For example, acetaminophen causes a predominant hepatocellular injury, whereas trimethoprim-sulfamethoxazole often produces a cholestatic form characterized by an alkaline phosphatase level more than twice normal. If a mixed pattern injury occurs in combination with an elevated alkaline phosphatase level, the patient is at increased risk of progressive liver injury. Phenytoin is an example of a drug that characteristically produces a mixed pattern. Drug-induced liver injury is often difficult to diagnose because there is no gold standard for diagnosis. Some drugs causing hepatic injury may be associated with the more familiar hypersensitivity syndrome characterized by fever, rash, and peripheral eosinophilia, but many drug reactions are characterized only by hepatic injury. Therefore, it is often a diagnosis of exclusion of other causes of liver injury in the presence of a potential offending agent taken within a recent period of time, usually weeks. Most patients can be monitored conservatively because discontinuation of the offending drug usually leads to eventual recovery, which can, however, take months. It is important to monitor for signs of progressive liver injury by monitoring prothrombin time and clinical status of the patient.

Cholecystectomy is incorrect because the patient has no radiographic evidence to suggest cholecystitis, her gallbladder is normal on imaging, she has no Murphy sign, gallstones, leukocytosis, or anything else to suggest cholecystitis. Endoscopic retrograde cholangiopancreatography (ERCP) is not correct because the patient has no clinical or radiographic suggestion of choledocholithiasis. Proceeding to ERCP in the absence of clinical suspicion is unlikely to be effective and places the patient at up to a 5% risk of post-ERCP pancreatitis. Liver biopsy is incorrect because there is a good clinical suspicion that the patient has drug-induced liver injury. If, however, her condition does not improve or if the diagnosis were less clear, then biopsy may be correct. Another time when liver biopsy might be appropriate is in the patient with hepatocellular injury who may have autoimmune hepatitis, which could respond to corticosteroid therapy.

Patients with ulcerative colitis who become corticosteroid-dependent should be started on therapy with an immunomodulator, such as azathioprine or 6-mercaptopurine with a steroid taper.

5-Aminosalicylates (5-ASA) are the first-line therapy for ulcerative colitis, and remission can often be induced and maintained with a 5-ASA only. When 5-ASA therapy is not effective initially or patients develop a flare while in remission on 5-ASAs, often a short course of corticosteroids is required to induce or re-induce remission. However, corticosteroids are not effective as maintenance therapy and have many potential side effects, including hyperglycemia, osteoporosis, hypertension, mood instability, acne, infection, and osteonecrosis. Although some patients may maintain remission with continued 5-ASA therapy after corticosteroid taper, other patients become corticosteroid-dependent or -resistant, as did this patient, and therapy with an immunomodulator such as 6-mercaptopurine or azathioprine should be started. These agents are nucleotide analogues that interfere with DNA synthesis and induce apoptosis. Therapy with these agents may be required for up to 3 months before providing clinical benefit, and therefore, they are generally started with corticosteroids, which are then tapered.

Because corticosteroids are not effective maintenance therapy, simply increasing the dose of prednisone without adding an immunomodulator would not be appropriate in this patient. The addition of another 5-ASA, such as olsalazine, will not provide any greater benefit. Antibiotic therapy has not been shown to be effective in the treatment of ulcerative colitis, and the patient's stool was negative for Clostridium difficile. Budesonide is a nonsystemic corticosteroid that is useful in the induction of remission in patients with ulcerative colitis disease involving the terminal ileum and right colon, but would not be of added benefit in this patient with pan-ulcerative colitis.

In patients with a high pretest probability of gastroesophageal reflux disease who fail to respond to a therapeutic trial of a proton pump inhibitor, ambulatory esophageal pH monitoring is most useful.

This patient's clinical presentation is highly suggestive of gastroesophageal reflux disease (GERD). The typical symptoms of pyrosis, along with obesity, make the pretest probability of GERD high, although the lack of response to proton pump inhibitor therapy argues against the diagnosis. In patients with a high pretest probability of GERD who fail to respond to a therapeutic trial, ambulatory esophageal pH monitoring is most useful. Ambulatory pH monitoring employs a narrow-gauge cannula placed transnasally into the distal esophagus. Simultaneous pH measurement is made by several detectors. An endoscopically placed ambulatory monitor is becoming more commonly used. Abnormal esophageal acid exposure is determined by the percentage of time that esophageal pH is less than 4.0, esophageal acid exposure time, number of reflux episodes, mean duration and number of reflux episodes, and longest duration of reflux. The patient can record time of meals, episodes of reflux symptoms or pain, supine position, and other parameters to correlate symptoms to actual abnormal esophageal acid exposure.

Barium esophagography is a useful initial test in the evaluation of oropharyngeal reflux and to determine the presence of strictures but is less useful in determining significant episodes of gastroesophageal reflux or their relationship to symptoms. CT scan of the chest is performed in cases of dysphagia to investigate potential masses in the region of the gastric cardia. Esophageal manometry is useful in esophageal motility disorders such as diffuse esophageal spasm, achalasia, and hypotonic motility disorders. Newer techniques of esophageal function include esophageal impedance monitoring, which provides information on esophageal bolus transit as opposed to manometry's ability to detect esophageal contractile activity.

In patients younger than 55 years who have new-onset dyspepsia without alarm symptoms, a "test and treat" approach for Helicobacter pylori is recommended.

This patient has new-onset uninvestigated dyspepsia. In a patient younger than 55 years without alarm features, the recommendation is to "test and treat" for Helicobacter pylori infection. The H. pylori stool antigen test detects active infection and therefore can be used in the initial diagnosis as well as for eradication testing.

An abdominal ultrasonography can be used in the evaluation of presumed biliary colic or chronic mesenteric ischemia (the latter if Doppler evaluation is additionally performed). The likelihood of biliary disease in this patient who is post-cholecystectomy and who has normal serum chemistry tests is low. Chronic mesenteric ischemia is also very unlikely because her pain does not increase with eating, and she has not lost weight, has no known risk factors for atherosclerosis, and has no abdominal bruits. An esophagogastroduodenoscopy is not needed given her age and lack of alarm features, but the procedure could be considered if her symptoms persist after H. pylori treatment. Gastric scintigraphy is used in the evaluation of gastroparesis and should only be performed after mechanical obstruction has been ruled out with upper endoscopy or barium radiography. The patient's predominant symptom is pain and she has not vomited or had early satiety, and therefore, dyspepsia is more likely than gastroparesis. Although this patient has had several abdominal surgeries putting her at risk for a small-bowel obstruction from adhesions, the fact that her pain does not worsen with eating, she has not vomited, has maintained normal bowel movements, and has normal bowel sounds make obstruction unlikely; therefore, a small-bowel radiograph would be unnecessary at this point.

Laboratory findings in patients with autoimmune hepatitis include elevated serum aminotransferase values, hypergammaglobulinemia, mild hyperbilirubinemia, elevated serum alkaline phosphatase values, and the presence of autoantibodies.

This patient has autoimmune hepatitis, a disorder that occurs most commonly in girls and young women. Like this patient with hypothyroidism, many affected patients have other autoimmune disorders and a family history of autoimmunity. These patients usually present with vague symptoms. Fatigue, which occurs in 85% of patients, is the most common presenting symptom, followed by jaundice (46%), anorexia (30%), myalgias (30%), and diarrhea. On physical examination, 78% of patients have an enlarged liver. Others have a normal examination despite the presence of advanced disease. The results of liver chemistry tests can be quite elevated, with aminotransferase concentrations into the thousands, but typically less than 500 IU at presentation, with elevated bilirubin, often with near-normal alkaline phosphatase. Autoimmune serologic tests, specifically antinuclear antibodies, anti-smooth muscle antibodies, and antibody to liver/kidney microsome type 1 (anti-LKM1), may be positive but are not detected in up to 25% of patients. Antibody levels are not prognostic of the disease course.

Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of unknown cause. It is an autoimmune disorder that occurs predominantly in women (80% to 90% of cases) between 40 and 60 years of age. The diagnostic triad associated with primary biliary cirrhosis includes a cholestatic liver profile, positive antimitochondrial antibody titers, and compatible histologic findings on liver biopsy. Serum alkaline phosphatase level is usually elevated ten times or more above normal. The patient's near normal alkaline phosphatase concentration and negative antimitochondrial antibody essentially rule out primary biliary cirrhosis. Although drug-induced liver injury can cause similar liver test abnormalities, the patient has not taken any new medications recently, making this diagnosis unlikely. She has no pain to suggest cholecystitis. Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown cause that is characterized by progressive bile duct destruction and may lead to secondary biliary cirrhosis. Laboratory findings include a cholestatic liver profile, with serum alkaline phosphatase levels three to five times greater than normal and mild hyperbilirubinemia. This patient's alkaline phosphatase level is minimally elevated making primary sclerosing cholangitis unlikely.

Enteral feeding is the preferred route of providing nutrition in patients with severe acute pancreatitis.

This patient has moderate to severe acute pancreatitis and after 5 days remains febrile, continues to be in pain, and cannot take in any oral nutrition. The patient will likely have an extended period before being able to take in oral nutrition. Two routes are available for providing nutrition in patients with severe acute pancreatitis: enteral nutrition and parenteral nutrition. Enteral nutrition is provided through a feeding tube ideally placed past the ligament of Treitz so as not to stimulate the pancreas. Parenteral nutrition is provided through a large peripheral or central intravenous line. Enteral nutrition is preferred over parenteral nutrition because of its lower complication rate, especially a lower infection rate. A meta-analysis of six studies with 263 participants compared enteral nutrition with total parenteral nutrition. Enteral nutrition was associated with a significantly lower incidence of infections, reduced surgical interventions to control complications of pancreatitis, and a reduced length of hospital stay. In another randomized, controlled trial, enteral nutrition showed a trend towards faster attenuation of inflammation, with fewer septic complications, and also was a dominant therapy in terms of cost-effectiveness.

Imipenem therapy is only helpful in acute pancreatitis when there is evidence of pancreatic necrosis. Pancreatic necrosis is diagnosed by a contrast-enhanced CT scan that shows nonenhancing pancreatic tissue. In patients with noninfected pancreatic necrosis, antibiotics may decrease the incidence of sepsis, systemic complications (for example, respiratory failure), and local complications (for example, infected pancreatic necrosis or pancreatic abscess). Randomized, prospective trials have shown no benefit from antibiotic use in acute pancreatitis of mild to moderate severity but may lead to development of nosocomial infections with resistant pathogens. Similarly pancreatic débridement is recommended only in patients with pancreatitis and infected pancreatic necrosis.

In a radiopaque marker study, patients with slow-transit functional constipation have prolonged transit of markers through the proximal colon, whereas patients with dyssynergic functional constipation have normal transit time but impaired rectal expulsion of the markers.

Functional constipation is a common complaint. To make the diagnosis, there should not be any secondary causes such as an underlying metabolic or neurologic disease, mechanical obstruction, or drug effect. The disorder is characterized by the presence of two of the following Rome III criteria for functional constipation (for at least 3 months): straining during ≥25% of defecations; lumpy or hard stools ≥25% of defecations; sensation of incomplete evacuation for ≥25% of defecations; sensation of anorectal obstruction/blockage for ≥25% of defecations; manual maneuvers to facilitate ≥25% of defecations; and less than three defecations per week. Patients should not meet the Rome criteria for irritable bowel syndrome, which consist of recurrent abdominal pain or discomfort at least 3 days a month in past 3 months associated with two or more of the following: improvement with defecation; onset associated with change in frequency of stool; and onset associated with change in form (appearance) of stool. Patients with functional constipation should also not have alternating loose stools and constipation. There are two types of functional constipation: slow-transit (colonic inertia) and dyssynergic. This patient has slow-transit functional constipation. Affected patients have prolonged transit of radiopaque markers through the proximal colon, which is likely the result of an abnormality in the enteric nerve plexus.

In dyssynergic functional constipation or pelvic floor dysfunction (also known as outlet delay), transit time through the colon is normal but rectal expulsion of radiopaque markers is impaired, often resulting from the loss of the coordinated relaxation (or paradoxical contraction) of the puborectalis muscle and external anal sphincter. A radiopaque marker study therefore helps to differentiate these two types of functional constipation. Anorectal manometry can also help distinguish the two types, but a simpler diagnostic maneuver is having the patient mimic a bowel movement and attempt to expel the examiner's inserted finger; if the patient cannot do so, dyssynergia rather than slow transit is present. This patient does not meet criteria for irritable bowel syndrome. There is no underlying disease or radiographic evidence in this patient to support the diagnosis of chronic pseudo-obstruction.

Antibiotics, endoscopic variceal band ligation, and intravenous octreotide are the first-line therapies for acute esophageal variceal bleeding.

The first step in the management of acute variceal hemorrhage is the restoration of the intravascular volume using a large bore peripheral intravenous line or a central line. Packed erythrocytes are used as need to replace blood loss and clotting factors are replaced as needed. Platelet transfusions may be indicated if values fall below 50,000/µL (50 × 109/L). In addition, this patient should undergo urgent esophagogastroduodenoscopy and band ligation of esophageal varices. Clinical studies have shown that sclerotherapy was superior to balloon tamponade alone, vasopressin alone, and a combination of vasopressin and balloon tamponade in controlling active variceal hemorrhage, preventing early rebleeding, and improving survival in patients with esophageal and gastroesophageal varices. Band ligation has been shown to be as effective as sclerotherapy for preventing early rebleeding. Therapy should also be started with intravenous octreotide, which reduces portal venous blood inflow through inhibition of the release of vasodilatory hormones and is more effective for controlling bleeding than placebo; however, its ultimate effect on survival is unknown. Bacterial infections are present in a sizable percentage of hospitalized patients with variceal bleeding and are associated with a high mortality rate. Clinical trials have demonstrated that the use of prophylactic antibiotics in these patients results in a reduction in infectious complications and possibly mortality.

Arteriography is not first-line therapy in patients with a variceal bleed from venous portal hypertension. Arteriography is reserved for patients with a presumed arterial source of bleeding as can be seen in peptic ulcer disease or tumors anywhere along the gastrointestinal tract. In such cases, arteriography can be used to identify and embolize the specific vessel involved. This method is usually reserved for cases in which the patient is actively bleeding and either endoscopic therapy has failed to stop the bleeding or the presence of active bleeding interferes with identification of the bleeding site and the patient is unstable. Mesocaval shunt is a surgical shunt that decompresses the portal system by diverting portal venous flow into the inferior vena cava, thus bypassing the liver. This type of shunt is rarely used for acute variceal bleeding as it carries a high intraoperative risk in an acutely decompensated patient with underlying liver disease and coagulopathy. Intravenous nadolol is not appropriate because this patient is hypotensive and needs endoscopic intervention rather than medical therapy. Lastly, transjugular intrahepatic portosystemic shunting (TIPS) should not be used without first performing an upper endoscopy with esophageal band ligation. Many variceal bleeds can be controlled with endoscopic therapy alone, obviating the need for urgent TIPS which can have significant comorbidities including hepatic decompensation, bleeding complications, or resultant encephalopathy.

Patients with mucosa-associated lymphoid tissue (MALT) lymphoma should be tested for Helicobacter pylori infection.

This patient has a mucosa-associated lymphoid tissue (MALT) lymphoma, a low-grade B-cell lymphoma arising from the mucosal lymphoid tissue of the gastrointestinal tract. Half of MALT lymphomas are indolent, and most are located within the stomach. MALT lymphomas are thought to arise from clonal lymphocyte expansion in patients with chronic active gastritis secondary to Helicobacter pylori infection; eradication therapy for H. pylori infection alone results in lymphoma regression in up to 80% of affected patients; therefore, testing for H. pylori by stool antigen test is indicated in this patient.

Patients with HIV infection are at increased risk for Burkitt lymphoma, which can occur in the gastrointestinal tract; however, these tumors tend to be large and are usually located in the terminal ileum or rectum rather than the stomach and are not associated with chronic active gastritis. Patients with MALT lymphoma who have increased extent of disease as evidenced by ulceration, invasion through the gastric wall, or lymphadenopathy, which were not present in this case, are more likely to require standard chemotherapy for lymphoma. Although intestinal lymphoma is a malignant complication of celiac disease, this form of lymphoma is of T-cell origin (also known as enteropathy-associated T-cell lymphoma), and therefore, measurement of serum tissue transglutaminase antibody is not necessary. Surgical resection would not be required in a patient with early-stage MALToma who may fully respond to H. pylori eradication alone.

Achalasia is a primary motility disorder of the esophagus and requires manometric diagnosis.

The patient's history is typical for achalasia, an uncommon but important primary motility disorder of the esophagus. The barium study and endoscopic appearance described are typical for achalasia, but the diagnosis is confirmed manometrically with esophageal motility studies. The manometric diagnosis of achalasia usually includes an elevated lower esophageal sphincter pressure, failure of the lower esophageal sphincter to relax with swallowing, and diminished or absent peristalsis of the esophageal body.

Diffuse esophageal spasm typically presents with noncardiac chest pain. The diagnosis of diffuse esophageal spasm is made manometrically by the finding of more than 20% of swallows having simultaneous contractions in the distal esophagus. Peptic stricture would present with dysphagia, but would typically show a longer, non-tapered stricture on barium esophagography. Furthermore, peptic strictures seldom present with megaesophagus, as seen in this patient. Scleroderma esophagus leads to loss of esophageal motility and often severe reflux or distal esophageal strictures, not a dilated esophagus.

Treatment of achalasia is usually pneumatic dilatation of the esophagus or surgical myomectomy, the latter of which can be done laparoscopically. Pneumatic dilatation, even in experienced hands, is associated with a 5% to 10% risk of esophageal perforation. Botulinum toxin injection can afford relief of achalasia in patients who are not considered candidates for endoscopic or surgical interventions.

The inflammation in Crohn disease is transmural and can extend into any adjacent structure, including muscle.

The prevalence of extraintestinal manifestations in patients with inflammatory bowel disease ranges from 21% to 40%. In most large studies, the prevalence is higher in Crohn disease than in ulcerative colitis. The right colon and transverse colon can abut the right psoas muscle, and the transmural inflammation of Crohn disease can lead to extension into the surrounding tissues and abscess formation. In this patient, who has a history of stricturing disease with fistula formation, it is likely that the fever, pain, and limp are complications of penetrating disease.

Peripheral and axial musculoskeletal syndromes occur in approximately 30% of patients with inflammatory bowel disease and are considered part of the seronegative spondyloarthropathies. The course of peripheral arthritis tends to parallel the activity of the bowel disease. Isolated hip involvement would be an unusual extra-colonic manifestation of Crohn disease and it would not explain this patient's physical examination findings.

Patients with inflammatory bowel disease are at increased risk for developing osteoporosis, secondary to the disease process itself and the medications commonly used for treatment (such as corticosteroids). The fracture risk in such patients is 40% greater than that of the general population. All patients with inflammatory bowel disease older than 65 years with a history of corticosteroid use for more than 3 months should undergo bone mineral density scan. Furthermore, both short- and long-term corticosteroid therapy is associated with avascular necrosis of the femoral head. However, this patient has not taken corticosteroids for 25 years, and neither steroid-related avascular necrosis nor osteoporosis is likely and cannot account for her fever and flank pain.

An ascitic fluid absolute polymorphonuclear cell count greater than 250/mL is indicative of spontaneous bacterial peritonitis.

This patient should have a diagnostic paracentesis to confirm the etiology of the ascites and to rule out spontaneous bacterial peritonitis (SBP). All patients who present with ascites should have a diagnostic paracentesis to categorize the ascites as secondary to portal hypertension or to other causes. This patient should have a small amount of fluid sampled for cell count with differential. An absolute polymorphonuclear cell count greater than 250/mL is indicative of SBP. Also total protein should be measured as well as albumin to calculate the serum albumin to ascites gradient (SAAG). An SAAG greater than 1.1 is consistent with portal hypertension; an SAAG less than 1.1 can occur in patients with malignant ascites. Patients do not always have symptoms suggestive of SBP such as fever, abdominal pain, or leukocytosis; therefore, their absence should not preclude a paracentesis to rule out SBP. In addition this patient has an elevated serum creatinine, which poses the possibility of hepatorenal syndrome for which SBP is a significant risk. Therefore, it is important to determine whether she has SBP.

Furosemide and spironolactone therapy is not indicated in the setting of an elevated serum creatinine and possible hepatorenal syndrome, because diuresis can precipitate worsening hemodynamic status or renal failure. Ceftriaxone and albumin are appropriate therapy for spontaneous bacterial peritonitis but are not indicated unless a diagnostic paracentesis can confirm the diagnosis. TIPS is not first-line therapy for new-onset ascites.

Patients whose Crohn disease becomes refractory to immunomodulator therapy should be given anti-tumor necrosis factor-α inhibitor therapy.

The patient's Crohn disease had been well controlled on therapy with the immunomodulator azathioprine but is no longer responding; the small-joint arthritis may also be a complication of azathioprine. The next agent that should be used is the biologic agent infliximab an anti-tumor necrosis factor-α inhibitor. This potent biologic agent can bring the disease into remission quickly while sparing the effects of systemic corticosteroids. However, there is an increased risk of lymphoma and solid tumors associated with infliximab therapy. Recently it has been reported that combined infliximab and azathioprine is associated with an increased risk of hepatosplenic T-cell lymphoma in pediatric patients. Therefore, combination therapy is not preferred in patients who are receiving fixed-interval infliximab (every 8 weeks). Azathioprine dosage should be tapered and therapy with this agent eventually discontinued. Early use of infliximab has been shown to be more effective than conventional management with corticosteroids for induction of remission.

Corticosteroids are not used as maintenance therapy in Crohn disease primarily because of their numerous short- and long-term complications. The patient's disease has now failed to respond to the steroid-sparing immunomodulator, and there is no role for corticosteroids. Calcineurin inhibitors have not been shown to be efficacious in Crohn disease. Mesalamines are not effective in immunomodulator-refractory Crohn disease.
Gastro 20

A 38-year-old man is evaluated for a 3-month history of bloating (blähen) and increased frequency of defecation. He has four to six bowel movements a day, including nocturnal bowel movements several times a week. The stool tends to be loose but there is no blood or melena. He has significant bloating but no abdominal pain. The patient underwent a Roux-en-Y gastric bypass procedure 2 years ago for morbid obesity; he lost 45.5 kg (100 lb) after the procedure. His weight stabilized 1 year ago, but he has lost 2.2 to 4.5 kg (5 to 10 lb) in the past few months. His medical history also includes hypertension, which resolved after the bariatric surgery, and his medications include a daily multivitamin with iron and daily oral calcium, vitamin D, and vitamin B12 supplements. The patient's sister has Crohn disease, and he has twin 15-month-old daughters who attend a daycare center.

On physical examination, the blood pressure is 110/62 mm Hg, and the BMI is 29. He has redundant abdominal skin and healed abdominal incisions. The abdomen is not distended or tender; bowel sounds are normal. There is normal rectal tone and no palpable rectal abnormalities or perianal disease.

Laboratory studies:
Hemoglobin 11.7 g/dL (117 g/L)
Mean corpuscular volume 103 fL
Vitamin B12 185 pg/mL (136.5 pmol/L) (n 150-670pmol/l)
Folate 30 ng/mL (67.9 nmol/L) (n 4-20 nmoll)
C-reactive protein 0.6 mg/dL (6.0 mg/L)
Tissue transglutaminase antibodies
(IgA and IgG) Negative

Stool culture and examination for fecal leukocytes and ova and parasites on three stool specimens are negative. Colonoscopy with terminal ileal examination is grossly normal. Esophagogastroduodenoscopy shows altered anatomy consistent with the bypass procedure; small-bowel biopsy specimens are negative. CT enterography is normal.

Which of the following is the most likely diagnosis?
A Celiac disease
B Crohn disease
C Giardiasis
D Irritable bowel syndrome
E Small intestinal bacterial overgrowth

Small intestinal bacterial overgrowth is a late complication of bariatric surgery and should be considered in patients presenting with diarrhea, bloating, and features of malabsorption after such surgery.

Patients who undergo bariatric surgery are at risk for specific early and late complications of the procedure; small intestinal bacterial overgrowth is a late complication that can manifest with bloating, diarrhea, and features of malabsorption. Having segments of small bowel excluded from the usual stream of gastric acid, bile, and proteolytic enzymes, which all act to decrease excess bacterial growth in the small bowel, is a risk factor for bacterial overgrowth. The diarrhea in bacterial overgrowth can be from deconjugation of bile salts from the intestinal bacteria leading to fat malabsorption as well as from decreased disaccharidase levels leading to carbohydrate malabsorption. Other clues in this patient include the macrocytic anemia, with a low serum vitamin B12 level (bacteria bind and consume vitamin B12 and cleave it from intrinsic factor) and an elevated serum folate level (intestinal bacteria synthesize folate). Even though the patient is taking oral vitamin B12 replacement, his level is still low, suggesting inadequate replacement versus excessive loss. Culture of the small intestine or breath testing can be done to substantiate the diagnosis; alternatively, an empiric trial of antibiotic therapy could be considered.

Although celiac disease should be considered in any patient with diarrhea and features of malabsorption, the negative serologic studies and negative small-bowel biopsy rule out the diagnosis. Irritable bowel syndrome should not cause nocturnal stools, weight loss, and vitamin derangements. Crohn disease is possible given the patient's symptoms and family history of inflammatory bowel disease, but the negative endoscopic, histologic, and radiographic findings make this disorder unlikely. The patient has young children in diapers who attend a daycare center, and, therefore, giardiasis is in the differential diagnosis; however, stool ova and parasite testing on three occasions has been negative, with the yield for repeated testing close to 90%.
Gastro 22

A 44-year-old man with a long history of alcohol abuse is evaluated on the sixth day of hospitalization for acute pancreatitis. On admission to the hospital, he was afebrile, the blood pressure was 150/88 mm Hg, the pulse rate was 90/min, and the respiration rate was 16/min. Abnormal findings were limited to the abdomen, which was flat and tender to palpation without peritoneal signs. Bowel sounds were normal. Plain abdominal and chest radiographs were normal. Abdominal ultrasonography revealed a diffusely enlarged, hypoechoic pancreas without evidence of gallstones or dilated common bile duct. He was treated with aggressive intravenous hydration and opioid analgesia. For the past 2 days, the patient has had repeated febrile episodes, persistent severe abdominal pain, and increasing shortness of breath.

On physical examination, the temperature is 38.6 °C (101.5 °F), the blood pressure is 98/60 mm Hg, the pulse rate is 112/min, and the respiration rate is 22/min; oxygen saturation is 92% with the patient breathing oxygen 3 L/min. Breath sounds are decreased at the base of both lungs. The abdomen is distended and diffusely tender with hypoactive bowel sounds. Laboratory studies reveal leukocyte count of 19,800/µL (19.8 × 109/L), creatinine 1.4 mg/dL (106.8 µmol/L), amylase 388 U/L, and lipase 842 U/L.

Which of the following is the most appropriate next step in the evaluation of this patient?
A CT scan of the abdomen with intravenous contrast
B Endoscopic retrograde cholangiopancreatography
C Endoscopic ultrasonography
D Stool chymotrypsin

Patients with severe alcoholic hepatitis, as defined by a discriminant function score of 32 or more, benefit from corticosteroid therapy.

This patient has severe alcoholic hepatitis. Excessive alcohol intake may cause liver disease directly or may increase the risk of an unfavorable outcome in patients with pre-existing liver disease. This patient with chronic alcohol abuse has a history of recent heavy alcohol use, elevated serum aspartate aminotransferase (AST) and alanine aminotransferase values (usually greater than 300 U/L) and a serum aspartate aminotransferase concentration that is greater than the alanine aminotransferase concentration in roughly a 2 to 1 ratio, elevated alkaline phosphatase concentration, jaundice, coagulopathy, and encephalopathy. Moreover, other causes of acute and chronic liver disease have been excluded. The severity of the presentation and poor prognosis are underscored by the presence of the very high serum bilirubin concentration, coagulopathy, and encephalopathy.

The mortality risk in this setting is calculated by the discriminant function as follows: (4.6 × [prothrombin time − control prothrombin time]) + serum bilirubin. A discriminant function score of greater than 32 identifies patients with a 50% mortality rate within 30 days and has been used to identify patients who have a survival benefit from corticosteroid therapy. In addition, nutrition therapy has been shown to improve survival in severely malnourished hospitalized alcoholic patients.

The presentation of alcoholic hepatitis may resemble infection because of the fever and leukocytosis; however, this patient's chest radiograph and blood and urine cultures were negative. In the absence of active bleeding, fresh frozen plasma is not indicated. Although many patients with alcoholic hepatitis recover with appropriate therapy, it would be inappropriate to offer liver transplantation to an alcoholic patient who is not involved in rehabilitation counseling. Some transplant programs require abstinence of at least 6 months. This not only confirms a commitment to abstaining from alcohol but also allows time for improvement of the alcoholic hepatitis to the point that transplantation may not be needed. Antibiotic therapy has no role in alcoholic hepatitis. Fresh frozen plasma is not a priority in a patient with alcoholic hepatitis and a coagulopathy unless active bleeding is present.
Gastro 24

A 64-year-old woman is evaluated in the emergency department for her second episode of painless bloody stool. Four weeks ago, she was evaluated in the hospital for maroon stool; the hemoglobin at that time was 2 g/dL (20 g/L) lower than previous complete blood counts; esophagogastroduodenoscopy was normal; colonoscopy showed some old blood but no active bleeding. The patient was observed for 2 days and discharged with instructions for outpatient follow-up. Her current episode consisted of two maroon stools, one this morning and one 2 hours ago. Nasogastric lavage yields coffee grounds that clear with 1 L of saline. The patient had a colonoscopy 2 years ago at which time a single adenomatous polyp was detected and removed. She has no personal or family history of bleeding or gastrointestinal malignancy and is otherwise healthy; she has no upper gastrointestinal symptoms, does not use alcohol, and her only medication is a multivitamin.

On physical examination, the temperature is 37.1 °C (98.7 °F), the blood pressure is 98/62 mm Hg, the pulse rate is 94/min, and the respiration rate is 14/min; the BMI is 23.5. There is no scleral icterus; examinations of the heart and lungs are normal. The abdomen is soft with increased bowel sounds but no hepatosplenomegaly. Rectal examination reveals the presence of maroon and red blood but no palpable masses or hemorrhoids. Laboratory studies reveal hemoglobin of 9.4 g/dL (94 g/L) with a mean corpuscular volume of 86 fL; leukocyte count with differential and platelet count are normal. Prothrombin time, activated partial thromboplastin time, and INR are normal, as are liver chemistry tests. Serum blood urea nitrogen is 34 mg/dL (12.1 mmol/L), and creatinine is normal.

Which of the following is the most appropriate next step in the evaluation of this patient?
A Colonoscopy
B Double-balloon enteroscopy
C Esophagogastroduodenoscopy
D Technetium red blood cell scan
E Wireless capsule endoscopy

Repeat upper endoscopy in a patient with obscure upper gastrointestinal bleeding will identify a bleeding source in a significant proportion of patients.

This patient presents with obscure overt bleeding in that blood loss is clinically apparent because of the maroon stool, but the source is not identified despite endoscopic investigation. The most appropriate next test would be to repeat upper endoscopy. Studies have shown that between one third and two thirds of sources of obscure upper gastrointestinal bleeding are found within the reach of the upper endoscope on repeat endoscopy. The missed lesions are most often bleeding erosions associated with hiatus hernia, gastroduodenal angiodysplasia, Dieulafoy lesions, gastric antral vascular ectasias, and peptic ulcers. Moreover, endoscopy offers therapeutic options if a lesion is found in addition to establishing a diagnosis.

A colonoscopy is less likely to be helpful because the blood detected on nasogastric lavage suggests an upper gastrointestinal source. Wireless capsule endoscopy may be helpful if a repeat upper endoscopy is normal to assess the remainder of the small bowel; however, in contrast to endoscopy, capsule endoscopy does not offer therapeutic options. A radiolabeled red blood cell scan would not be the next test of choice; the results are nonspecific and would delay diagnosis and therapy that could be delivered more rapidly with endoscopy. In double-balloon enteroscopy, deep intubation of the small bowel is achieved by using a two-balloon technique to anchor the endoscope and assist in advancement. The procedure is lengthy and requires prolonged sedation, although it offers diagnostic and therapeutic capabilities. This test is reserved until a more proximal source of bleeding has been excluded and wireless capsule endoscopy has been performed. The capsule would direct whether the double-balloon enteroscope is to be introduced via the mouth (for jejunal abnormalities) or anus (ileal abnormalities).

Botulinum toxin injection can afford relief of achalasia in patients who because of age or comorbidities are not candidates for endoscopic or surgical intervention.

This patient's history is typical for achalasia, an uncommon but important primary motility disorder of the esophagus. Although endoscopic evaluation is required to investigate the possibility of a mass lesion leading to partial esophageal obstruction, the diagnosis of achalasia is made manometrically using esophageal motility studies. The manometric diagnosis usually includes an elevated lower esophageal sphincter resting pressure, failure of the lower esophageal sphincter to relax with swallowing, and diminished or absent peristalsis of the esophageal body. Radiologic findings of note in achalasia include a "bird's beak" abnormality of the distal esophagus, widening of the esophagus, and less commonly, megaesophagus with an air/fluid level. CT of the chest can be employed to differentiate achalasia from pseudoachalasia, the latter mimicking the true motility disorder but caused by a mass lesion at the distal esophagus or gastric cardia.

Treatment of achalasia is usually pneumatic dilatation of the esophagus or surgical myomectomy, the latter of which can be done laparoscopically. Pneumatic dilatation, even in experienced hands, is associated with a 5% to 10% risk of esophageal perforation. Botulinum toxin injection can afford relief of achalasia in patients like this one who because of age or comorbidities are not candidates for endoscopic or surgical intervention. Botulinum toxin inhibits the release of acetylcholine from nerve endings and has been used successfully for decades to treat certain spastic disorders of skeletal muscle such as blepharospasm and torticollis. Anticholinergic therapy is not indicated for achalasia.

Proton pump inhibitors are the drugs of choice in NSAID-induced gastric injury whether or not NSAID therapy is discontinued.

This patient has gastric erosions and ulcerations consistent with NSAID-induced gastropathy, which would account for her iron-deficiency anemia. In most patients with NSAID-induced gastric injury, discontinuation of the NSAID in addition to starting proton pump inhibitor therapy, would be reasonable, but in certain patients (like this one who requires NSAID therapy for her rheumatoid arthritis), the best option is to start proton pump inhibitor therapy, which has been found to heal peptic ulcerations whether or not NSAID therapy is ongoing. In such patients, reducing the dose of the NSAID versus switching to either a selective COX-2 inhibitor, such as celecoxib, or an NSAID with a safer side effect profile, such as nabumetone, etodolac, or meloxicam, should be considered. This patient did not receive sufficient pain relief with celecoxib and she is already taking nabumetone; therefore, simply adding a proton pump inhibitor is indicated.

Although high-dose H2-receptor antagonists such as famotidine are thought to be helpful in preventing ulcers, these agents have not been first-line therapy since the advent of proton pump inhibitors because they are not as effective. Misoprostol can reduce NSAID-related ulcers, but it has a dose-related side effect of diarrhea and would therefore not be indicated in this patient with diarrhea-predominant irritable bowel syndrome. Sucralfate has been used for ulcer prophylaxis, but there is no good evidence for its use in patients with long-term NSAID use and current ulcers.

Hepatic abscess is usually managed with percutaneous drainage of the lesion and intravenous antibiotics.

This patient requires percutaneous drainage of the hepatic lesion, which is likely an abscess. He has a history of recurrent diverticulitis, which does not appear to have been adequately treated in the past. He now has fever, right upper quadrant pain, and a large fluid-filled lesion in his liver. The clinical manifestations of pyogenic liver abscess usually include fever and right upper quadrant abdominal pain. Most pyogenic liver abscesses are due to biliary tract infection. Intra-abdominal infection may result in liver abscesses from seeding via the portal vein, whereas systemic bacteremia may cause abscesses from seeding via the hepatic artery. Abscesses resulting from an intra-abdominal infection are frequently due to anaerobic organisms, and many liver abscesses are polymicrobial. Percutaneous aspiration is recommended for diagnosis and subsequent treatment of a suspected pyogenic liver abscess. Antibiotics may be started even before aspiration and should not interfere with culture results. Parenteral antibiotic therapy to cover enteric gram-negative bacilli, anaerobes, and enterococci is recommended until culture results are available. Antibiotics specific for the causative organisms are then started and are continued for 4 to 6 weeks. Oral agents can be instituted after the abscess is drained and the patient is afebrile.

Lobectomy is not required in this patient because in most cases, a hepatic abscess can be managed with the combination of antibiotics and percutaneous drainage. Endoscopic retrograde cholangiopancreatography (ERCP) would not be appropriate because there is no evidence that this patient has cholangitis or obstructive jaundice. Although he has abnormal liver chemistry tests, these can be explained by the presence of the large abscess rather than biliary disease, especially because the CT scan does not show any evidence of ductal dilatation to suggest obstructive jaundice or cholangitis, which might require ERCP. MRI with gadolinium is not appropriate because the diagnosis can be made on the information provided, and no further confirmatory imaging is needed. The patient needs to be treated, and antibiotics and percutaneous drainage are required at this time.

In patients with gallstone pancreatitis and evidence of biliary obstruction, endoscopic retrograde cholangiopancreatography and stone removal reduces morbidity and mortality by reducing the risk of biliary sepsis.

This patient has a classic presentation of acute pancreatitis with the acute onset of epigastric abdominal pain, nausea, and vomiting associated with markedly elevated pancreatic enzymes. The presence of stones in the gallbladder, a dilated bile duct, and elevated aminotransferase levels highly suggest gallstones as the cause of pancreatitis. The scleral icterus, jaundice, and elevated bilirubin level suggest continuing bile duct obstruction. Abdominal ultrasonography has a sensitivity of only 50% to 7lllll5% for choledocholithiasis, and a common duct stone should be suspected in the correct clinical situation even when ultrasonography does not show a stone.

Endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy and stone removal is the most appropriate procedure in patients with acute gallstone pancreatitis and with imaging and biochemical evidence of biliary obstruction from a common duct stone. The procedure can document the diagnosis of choledocholithiasis and remove the gallstones, which lessens the morbidity and mortality due to biliary sepsis.

CT scan will likely show evidence of acute pancreatitis and magnetic resonance cholangiopancreatography (MRCP) will show pancreatitis and the presence of a common duct stone, with sensitivities for CT being approximately 75% for stones and MRCP having sensitivities ranging from 80% to 100% as compared with ERCP for the diagnosis of choledocholithiasis. Biliary scintigraphy may show obstruction of the cystic or common bile duct but will not determine the cause. However, CT, biliary scintigraphy, and MRCP will not be therapeutic for bile duct stones.

CT angiography is the most sensitive diagnostic test for acute mesenteric ischemia.

This patient most likely has acute mesenteric ischemia, a potentially fatal condition that typically affects elderly patients. The disorder may result from embolic or thrombotic occlusions of the splanchnic vessels or may be nonocclusive. Superior mesenteric artery embolism is the most common cause, accounting for approximately 50% of cases and usually developing from ventricular or left atrial thrombi in patients with atrial fibrillation. This patient's age, recent myocardial infarction, atrial fibrillation, history of discontinuing anticoagulation, and hypotension are all significant risk factors for this condition. His low-grade fever, hypotension, sudden onset of severe abdominal pain out-of-proportion to physical examination findings, as well as his elevated leukocyte count all support the diagnosis. CT arteriography is a sensitive test for acute mesenteric ischemia; the procedure can evaluate the mesenteric vessels and also assess for signs of bowel ischemia and rule out other potential causes of acute onset abdominal pain, such as perforation or obstruction. Surgical consultation should be done simultaneously because if the results of CT arteriography support the diagnosis of acute mesenteric ischemia, the patient may need emergent surgery. Traditional angiography is the gold standard for diagnosis of acute mesenteric ischemia and can also offer therapeutic options such as the use of vasodilators as well as balloon dilation and stent placement. Surgery is required for patients with peritoneal signs and/or evidence of bowel necrosis on imaging. Surgical interventions include peritoneal lavage, resection of necrotic and perforated bowel, thrombolectomy, patch angioplasty, endarterectomy, and bypass procedures. Successful thrombolytic therapy in stable patients without peritoneal signs has been reported.

Colonoscopy would not be appropriate for this patient, because it does not evaluate the mesenteric vessels or the small intestine, only the mucosa of the colon. Intravenous famotidine therapy for possible dyspepsia would also not be appropriate in this patient with a potentially life-threatening condition. Likewise, although the patient may be somewhat constipated, giving him lactulose only is not correct.

Interferon therapy can precipitate autoimmune hepatitis, and therapy should be discontinued in affected patients.

This patient is experiencing a flare of autoimmune hepatitis precipitated by interferon therapy. Such a flare can occur in patients with quiescent autoimmune hepatitis or as new-onset disease induced by interferon therapy. Other autoimmune diseases can develop or be exacerbated during interferon therapy, including rheumatoid arthritis, sarcoidosis, dermatitis, and type 1 diabetes mellitus. Accordingly, interferon therapy should be used cautiously in patients with autoimmune disease and is contraindicated in patients with pre-existing autoimmune hepatitis. This patient has worsening liver disease as well as established hypothyroidism; therefore, the interferon and ribavirin therapy should be discontinued and the patient monitored closely. If the autoimmune hepatitis does not stabilize, treatment for this disorder will have to be considered. This patient should not be rechallenged with hepatitis C therapy because it is likely to cause worsening liver disease.

Decreasing the dosage of the interferon and ribavirin is not an option, because the autoimmune response is not dose-related. Although some patients receiving therapy for hepatitis C experience a flare of hepatitis before clearing the virus, this patient has persistent viral replication, and given the newly positive antinuclear antibody and anti-smooth muscle antibody test results suggestive of autoimmune hepatitis and personal and family history of autoimmune disorders, therapy should be discontinued to avoid worsening hepatic decompensation.

Irritable bowel syndrome is a diagnosis of exclusion but in the absence of alarm symptoms, invasive work up is not necessary

This patient presents with symptoms that meet the Rome III criteria for irritable bowel syndrome (IBS). The Rome criteria were developed to establish consensus guidelines for diagnosis of functional bowel disorders. Criteria for IBS are symptoms of recurrent abdominal pain or discomfort and a marked change in bowel habit for at least 6 months, with symptoms experienced on at least 3 days a month for at least 3 months. Two or more of the following must also apply: (1) pain is relieved by a bowel movement; (2) onset of pain is related to a change in frequency of stool; and/or (3) onset of pain is related to a change in the appearance of stool. IBS is the most common gastrointestinal condition diagnosed in the United States. It is characterized by chronic abdominal pain and altered bowel habits in the absence of any organic cause.

In this otherwise healthy young woman, reassurance that she has a chronic but not a life-threatening disease with recommendation of a high-fiber diet should be the initial therapy. CT enteroscopy or colonoscopy would be premature at this point given the absence of alarm symptoms: fever, weight loss, blood in stool, abnormal physical examination, family history of inflammatory bowel disease or colon cancer, or pain or diarrhea that awakens/interferes with sleep.

This patient does not have evidence of malabsorption, anemia, or weight loss to suggest a diagnosis of celiac disease; therefore, an empiric gluten-free diet would be inappropriate.
Gastro 35

A 37-year-old woman is evaluated for diffuse musculoskeletal pain at her 1-year follow-up after a Roux-en-Y gastric bypass for medically complicated obesity. Before surgery she had type 2 diabetes mellitus for which she required insulin therapy; after surgery the diabetes was manageable with diet modification alone. She also had hyperlipidemia, for which she took a statin, but after surgery her hyperlipidemia resolved and she discontinued statin therapy 6 months ago. She has lost 36.4 kg (80 lb) since surgery but she thinks that her weight has stabilized over the past few months. She has two to three bowel movements of well-formed stool a day. She has some diffuse musculoskeletal pain but otherwise feels well. Her medical history includes the gastric bypass, a cholecystectomy, diet-controlled type 2 diabetes mellitus, and hypothyroidism. Her medications include levothyroxine, a multivitamin containing iron, vitamin B12 by injection, and over-the-counter calcium and vitamin D.

On physical examination, vital signs are normal; the BMI is 29. There is redundant skin over the arms and trunk and mild thyromegaly. There is no jaundice or scleral icterus. Abdominal examination reveals no tenderness or hepatomegaly; there is normal muscle strength with no focal muscle tenderness. Laboratory studies show a serum alkaline phosphatase of 314 U/L; all other tests, including complete blood count, aminotransferases, bilirubin, γ-glutamyltranspeptidase, serum thyroid-stimulating hormone, free thyroxine, and calcium, are normal.

Which of the following is the most appropriate next step in the evaluation of this patient?
A Anti-smooth muscle antibody test
B Measurement of 25-hydroxyvitamin D
C Measurement of serum creatine kinase
D Measurement of triiodothyronine
E Ultrasonography of the liver

Nutritional deficiencies are common after bariatric surgery, and patients typically need ongoing supplementation with iron, vitamin B12, calcium, and vitamin D.

Patients who have bariatric surgery are at risk for various vitamin deficiencies. After such surgery, most patients require ongoing therapy with a multivitamin containing iron, along with vitamin B12, calcium, and vitamin D. Other requirements include folic acid and vitamin A, which are often adequately replaced through the use of a multivitamin, although additional supplementation may be required. In addition, thiamine should be given for the first 6 postoperative months. This patient is taking calcium and vitamin D supplementation, but over-the-counter vitamin D supplementation may not be of sufficient quantity to sustain the requirements in this patient. Her diffuse musculoskeletal discomfort and elevated serum alkaline phosphatase are likely the result of vitamin D deficiency, with resultant osteomalacia, and, therefore, serum 25-hydroxyvitamin D should be measured.

Anti-smooth muscle antibody is a serologic marker of autoimmune hepatitis; although this disorder may produce abnormal liver chemistry studies, it usually is considered a hepatitic condition with predominant elevation of the aminotransferases rather than cholestasis. Serum creatine kinase may be a reasonable test in a patient who has myalgias while taking a statin, but this patient's musculoskeletal pain began months after she stopped taking the drug. Although thyroid dysregulation can cause both myalgias and abnormal liver chemistry results, the patient's thyroid-stimulating hormone and thyroxine levels are within normal limits while she is taking thyroid hormone replacement; therefore, further thyroid function testing is unnecessary. Ultrasonography of the liver would be the next best step in a patient who has serum chemistry results indicative of cholestasis, but with alkaline phosphatase being the only test elevated and without clinical features of biliary disease, nonhepatic causes of an elevated alkaline phosphatase need to be considered.

Initial genetic testing for colon cancer syndromes is most effective in a patient with cancer rather than in an unaffected family member.

This patient has a family history that meets the Amsterdam criteria for hereditary nonpolyposis colorectal cancer (HNPCC). He should be referred to a genetic counselor to review the family history and be able to address the many issues that surround genetic testing and the implications for both the patient and his family members.

The best approach to test for HNPCC in this case and confirm the diagnosis would be to obtain tumor tissue from the patient's mother and test it for microsatellite instability. If the test is positive, a blood test can be done in the patient's mother in an attempt to find a germline mutation in the mismatch repair genes, and if identified, the patient may be tested to determine whether he is a carrier of that mutation. A negative blood test in the mother does not exclude the diagnosis of HNPCC. Screening for colon cancer in HNPCC should be initiated between age 20 and 25 years and requires a complete colonoscopy because cancers frequently occur in the ascending colon.

Genetic testing for colon cancer syndromes should be performed under the guidance of a genetic counselor. The counselor is skilled at appropriate data collection, pedigree analysis, and pre- and posttest counseling. Flexible sigmoidoscopy may identify polyposis for patients with familial adenomatous polyposis; however, it is inadequate screening for other hereditary colorectal cancer syndromes, such as attenuated familial adenomatous polyposis and HNPCC.

Irritable bowel syndrome is a clinical diagnosis that can be made confidently when patients meet the Rome III criteria and do not have alarm indicators.

This patient has irritable bowel syndrome. As a young woman, she fits the demographic profile, and she also meets the Rome III criteria, with abdominal pain relieved by defecation and a change in bowel habits. The most recent formal criteria are the Rome II criteria, which require the presence of at least two of three symptoms occurring for 3 months (not necessarily consecutive) during a 12-month period. These symptoms include pain relieved with defecation, onset associated with change in stool frequency, or onset associated with change in the consistency of the stool. In clinical practice, these criteria have a positive predictive value of 98%. Importantly, she has no alarm indicators, including older age, male sex, nocturnal awakening, rectal bleeding, weight loss, or family history of colon cancer. In the absence of alarm symptoms, additional tests have a diagnostic yield of 2% or less. Furthermore, laboratory studies indicate no anemia or thyroid deficiency. Irritable bowel syndrome is a clinical diagnosis, and there are no laboratory, radiographic, or endoscopic findings that aid in diagnosis. Additional evaluation is not only unnecessary and expensive but also potentially harmful, especially when invasive procedures are ordered; additionally, confidence in the diagnosis is undermined when serial testing is ordered. The patient should be reassured that although this problem is annoying and inconvenient, it is not life-threatening. The patient has constipation-predominant irritable bowel syndrome, and her symptoms will likely be alleviated if she has more frequent and satisfying bowel movements. Because fiber supplementation has not been helpful, a nonabsorbed osmotic laxative such as polyethylene glycol will likely provide her significant relief.

There is no indication for the patient to undergo a CT scan or colonoscopy. Oral contraceptives are not typically associated with the syndrome, and she began taking the medication after the onset of her symptoms.

In patients with dysphagia, immediate onset of symptoms with initiation of a swallow, difficulty swallowing liquids, and cough associated with the swallowing difficulty are characteristic of oropharyngeal rather than esophagealdysphagia.

The diagnosis and management of swallowing difficulties depend initially on determining whether the patient's symptoms are characteristic of either oropharyngeal dysphagia or esophageal dysphagia. The cornerstone of this determination is the medical history. In this patient, the immediate onset of symptoms with the initiation of a swallow, the difficulty swallowing liquids, and the cough associated with the swallowing difficulty make oropharyngeal, or transfer, dysphagia more likely than esophageal dysphagia. Videofluoroscopy, which allows real-time radiographic analysis of swallowing function, is the most sensitive test for oropharyngeal dysphagia. The procedure can show abnormal movement of a bolus, such as aspiration, pooling in pharyngeal recesses, movement of anatomic structures, muscle activities throughout the area, and oral and pharyngeal transit times. Common causes of oropharyngeal dysphagia are stroke, Parkinson disease, amyotrophic lateral sclerosis, myasthenia gravis, and muscular dystrophy.

Ambulatory esophageal pH monitoring is the most accurate technique to diagnose gastroesophageal reflux disease but is not the study of choice for evaluation of oropharyngeal dysphagia. CT scan of chest and abdomen can be an important adjunct to the evaluation of patients with esophageal dysphagia, because extraluminal causes of obstruction can be detected by cross-sectional imaging. Esophageal manometry is used in the diagnostic evaluation of patients with motility disorders of the esophagus. Although patients with such disorders may present with dysphagia of both solids and liquids, the immediate onset of symptoms with swallowing makes oropharyngeal dysphagia more likely.

The two noninvasive tests for determining Helicobacter pylori eradication are the stool antigen test and the urea breath test; the sensitivity of breath testing is adversely (nachteilig) affected by recent therapy with a proton pump inhibitor or antibiotic.

Although testing for eradication of Helicobacter pylori is not cost-effective or practical in most cases, in this patient with a history of significant gastrointestinal bleeding from H. pylori infection requiring hospitalization and transfusion, eradication testing would be important to prevent future complications. In addition to patients with H. pylori-associated ulcers, eradication testing should be considered in patients with previous early-stage gastric cancer, H. pylori-related MALT lymphoma, or persistent dyspepsia after a test-and-treat approach. The father's history of gastric cancer would be another compelling reason to evaluate for eradication of the organism in this patient. Urea breath testing is a noninvasive test for evaluation of H. pylori eradication, but the sensitivity of the test can be markedly reduced in patients taking a proton pump inhibitor or recent antibiotics, and therefore, waiting to perform this test in 4 to 8 weeks after recent discontinuation of omeprazole would be recommended rather than testing now, which may lead to false negative results.

Although serum antibody testing is widely available and has good negative predictive value, it is not recommended after therapy because sustained antibody titers cannot easily distinguish between active and treated infection. Because this patient had a duodenal rather than gastric ulcer, a follow-up esophagogastroduodenoscopy to assess for healing and rule out malignancy is not required; in addition, repeating the procedure to evaluate for H. pylori eradication would not be a cost-effective testing method and would only be recommended if additional histopathologic evaluation were needed, for example, if dysplasia had been found initially. To do no further testing would not be recommended in this patient with a significant H. pylori-associated ulcer bleed.

Patients with chronic pancreatitis present with abdominal pain and in more severe cases with malabsorption and endocrine insufficiency.

This patient has chronic pancreatitis secondary to alcohol abuse, which has resulted in malabsorption. The three classic findings in chronic pancreatitis are abdominal pain that is usually mid-epigastric, postprandial diarrhea, and diabetes mellitus secondary to pancreatic endocrine insufficiency. Malabsorption occurs in patients with chronic pancreatitis when approximately 80% of the pancreas is destroyed. Malabsorption presents with diarrhea and steatorrhea, weight loss, and deficiencies of fat-soluble vitamins because the damaged pancreatic gland is no longer producing the pancreatic exocrine enzymes to absorb food. Patients with a typical presentation may not need additional testing. However, most patients with chronic pancreatitis have only nonspecific abdominal pain and require diagnostic radiographic imaging studies. The presence of pancreatic calcifications on radiographs confirms the diagnosis. Plain films of the abdomen will show pancreatic calcifications in approximately 30% of patients. Most patients, however, require abdominal CT scans, which are able to detect pancreatic calcification in up to 90% of patients. CT scanning can also exclude other causes of pain. Radiographic evidence of pancreatic ductal dilation, pseudocysts, or mass lesions may also help identify the cause of pain and determine the type of therapy.

Antiendomysial antibodies are a marker for celiac disease, which is unlikely in this patient with an evident history of pancreatic malabsorption. Although colonoscopy is indicated as a screening tool for average risk asymptomatic patients beginning at the age of 50 years and for patients with a change in bowel habits and weight loss, this patient's history suggests pancreatic malabsorption and colonoscopy is less likely than abdominal CT scan to confirm the diagnosis. Stool studies are appropriate for determining the cause of an acute infectious diarrhea, but this patient has had diarrhea for 8 months and infectious diarrhea is not usually associated with such a degree of weight loss.

About 5% patients with acute hepatitis B virus infection develop acute progressive hepatitis B with fulminant hepatic decompensation and need urgent liver transplantation.

The markedly elevated aminotransferase levels, positive hepatitis B surface antigen, and IgM antibody to hepatitis B core antigen establish the diagnosis of acute hepatitis B. Patients at greatest risk for exposure to hepatitis B virus (HBV) infection are those with a history of multiple sexual partners and injection drug users. The course of HBV infection depends mainly on the age at which a patient is exposed. Most patients who are first exposed as adults develop flu-like symptoms with malaise, nausea, vomiting, and diarrhea with associated jaundice. Children on the other hand most often do not develop symptoms after exposure to HBV. Despite the presentation of an acute infection, most adult patients will clear their infection after a few months. Therefore, most patients can be monitored as outpatients and treated for symptoms only. However, about 5% patients develop acute progressive hepatitis B with hepatic decompensation and need urgent liver transplantation. These patients tend to have an elevated INR and a rising bilirubin level and may develop encephalopathy, a marker of fulminant hepatic failure. This subgroup of patients needs to be recognized, admitted to the hospital, and started on antiviral therapy. Telbivudine, lamivudine, adefovir, and entecavir are acceptable options. Transplantation evaluation should be pursued. Transplantation should be performed when a poor outcome is anticipated but before the patient develops uncontrolled sepsis or prolonged periods of increased intracranial pressure that would preclude recovery even if a functioning liver is transplanted. In the United States, patients with fulminant hepatic failure are given highest priority for transplantation and often receive a transplanted liver within 1 week of evaluation.

Interferon should be avoided in patients with acute hepatitis B and particularly in fulminant hepatic failure due to hepatitis B because of the increased risk of hepatic necroinflammation. The patient has no evidence of ductal dilatation on ultrasonography, and therefore, there is a low yield and high risk to proceed with endoscopic retrograde cholangiopancreatography. Corticosteroids have been studied as a treatment for fulminant hepatic failure and have been found to be not effective. In addition, corticosteroid use is associated with an increased risk for infectious complications.

Variceal hemorrhage occurs in 25% to 40% of patients with cirrhosis; upper endoscopy is indicated in patients with newly diagnosed cirrhosis.

This patient presented with asymptomatic elevation of hepatic biochemical tests; further testing demonstrated the presence of hepatitis C virus infection and signs of cirrhosis (splenomegaly, nodular liver contour, thrombocytopenia). Variceal hemorrhage occurs in 25% to 40% of patients with cirrhosis, and since mortality from variceal bleeding is high, screening for varices is a high priority task in all patients with newly discovered cirrhosis. Esophagogastroduodenoscopy is the next best management option to exclude the presence of esophageal varices. Depending on the size and appearance of the varices and the patient's Child-Pugh grade, prophylactic treatment may be indicated.

Patients with hepatitis C may be candidates for treatment with pegylated interferon and ribavirin; however, in this patient, cirrhosis and its potential complications must be assessed before therapy is begun. Moreover, treatment efficacy is lower in patients with cirrhosis than in patients without cirrhosis. Liver transplantation is the treatment of choice for suitable candidates with end-stage liver disease, fulminant hepatic failure, and certain metabolic disorders. Although the patient appears to have cirrhosis, there is no ascites, jaundice, or hepatic dysfunction that is severe enough to warrant consideration of transplantation. Treatment is recommended for all patients with chronic hepatitis B who have abnormal serum alanine aminotransferase values, HBV DNA levels >105 copies/mL, and liver biopsy findings of active disease. The oral agents lamivudine, adefovir, and entecavir are safe and well tolerated and may improve liver function in patients with decompensated hepatitis B. However, there is no indication that this patient has hepatitis B and therapy with lamivudine is not indicated.

Measurement of serum anti-tissue transglutaminase antibodies has a sensitivity and specificity of approximately 90% for celiac disease.

Celiac disease is a small-bowel disorder characterized by mucosal inflammation, villous atrophy, and crypt hyperplasia, which occur on exposure to gluten. The disease is rather common, affecting nearly 1% (1/133 persons) of the population. Although many affected patients have diarrhea and steatorrhea, as well as bloating, abdominal pain, and malabsorption of vitamins and minerals, other patients are asymptomatic at diagnosis. Such patients may be found to have anemia or osteoporosis as part of routine health maintenance testing. Still others present with neurologic symptoms, dermatitis herpetiformis, or elevated concentrations of liver enzymes. The elevated alanine aminotransferase in this patient should normalize with a gluten-free diet if he has celiac disease. The patient's elevated alkaline phosphatase concentration is likely the result of increased bone turnover as a result of vitamin D and calcium malabsorption. Celiac disease is one of the most common causes of osteoporosis in men. Measurement of serum anti-tissue transglutaminase antibodies has a sensitivity and specificity of approximately 90% for celiac disease.

α1-Antitrypsin deficiency affects approximately 1 in 1600 persons, and although measurement of α1-antitrypsin is an appropriate test in the work-up of abnormal liver function tests, it is not the next best test because of the low prevalence of the disease compared to celiac disease, and it cannot explain the patient's anemia. The patient admits to social use of alcohol, and this is to be strictly avoided in the setting of liver disease. Unless the patient was actively drinking alcohol around the time of the testing, measuring the blood alcohol would not be helpful. Furthermore, in alcoholic liver disease, the aspartate aminotransferase concentration is usually greater than the alanine aminotransferase. Liver biopsy would be an extreme measure to take as a result of a mildly abnormal set of liver chemistry tests and is not indicated as an initial step.
Gastro 47

A 45-year-old man is brought to the emergency department by fire rescue after his wife found him in bed lethargic and disoriented. The previous 2 days, the patient had been agitated and irritable and his speech was slurred. The patient has a history of cirrhosis complicated by esophageal variceal bleeding, ascites, and lower extremity edema, and his medications are furosemide, spironolactone, propranolol, and lactulose. He has a long history of alcohol dependence but has been sober for 1 year.

On physical examination, the patient is somnolent but arousable although not responsive to commands; he is afebrile. The blood pressure is 100/78 mm Hg, the pulse rate is 65/min, and the respiration rate is 12/min; the BMI is 26. There are no focal neurologic deficits; the pupils are equal and reactive to light. There is shifting abdominal dullness and 2+ lower extremity edema. The stool is negative for occult blood.

Laboratory studies:
Leukocyte count 5600/µL with normal differential (5.6 × 109/L)
Glucose (random) 112 mg/dL (6.21 mmol/L)
Sodium 135 meq/L (135 mmol/L)
Potassium 3.5 meq/L (3.5 mmol/L)
Chloride 100 meq/L (100 mmol/L)
Bicarbonate 28 meq/L (28 mmol/L)
Bilirubin (total) 4.0 mg/dL (68.4 µmol/L)
Bilirubin (direct) 2.3 mg/dL (39.3 µmol/L)
Aspartate aminotransferase 78 U/L
Alanine aminotransferase 45 U/L
Alkaline phosphatase 167 U/L
Albumin 2.7 g/dL (27 g/L)
Ammonia 230 µg/dL (135 µmol/L)
Blood alcohol Negative

Urinalysis is negative. Dipstick is positive for 3+ leukocyte esterase and nitrites. CT scan of the head is normal. A diagnostic peritoneal fluid tap excludes spontaneous bacterial peritonitis. Empiric antibiotic therapy is started.

Which of the following is the most appropriate management for this patient?
A Corticosteroids
B Increase lactulose therapy
C Intravenous albumin
D Transjugular intrahepatic portosystemic shunt (TIPS)

First-line therapy for hepatic encephalopathy is lactulose.

This patient has severe encephalopathy manifested by worsening somnolence. The patient began manifesting signs of increasing encephalopathy days prior to the admission, when his wife noticed that he was becoming more agitated and slurring his speech. Encephalopathy progresses from subtle findings, such as reversal of the sleep-wake cycle or mild mental status changes, to irritability, confusion, slurred speech, and ultimately coma if not recognized and treated. There can be multiple inciting causes of encephalopathy in patients with cirrhosis, including dehydration, infection (especially spontaneous bacterial peritonitis), diet indiscretions, gastrointestinal bleeding, and medications. This patient likely became worse with the development of the urinary tract infection.

The best course of management is to treat the infection and to discontinue the diuretics and increase the lactulose to respond to the encephalopathy. The dose of lactulose should be titrated to achieve two to three soft stools per day with a pH below 6.0. Approximately 70% to 80% of patients with hepatic encephalopathy improve on lactulose therapy, and treatment is usually well tolerated.

Corticosteroids have no role in the reversal of hepatic encephalopathy. Although albumin therapy is often instituted in patients hospitalized with infections, especially spontaneous bacterial peritonitis and associated dehydration, it is not a primary treatment of encephalopathy. Transjugular intrahepatic portosystemic shunt (TIPS) is also not appropriate because placement of TIPS is likely to precipitate worsening hepatic encephalopathy as more blood is bypassed through the shunt rather than processed by the liver.
Gastro 49

A 73-year-old woman who has been hospitalized for 3 weeks for urosepsis requiring parenteral nutrition is evaluated for 2 days of pain in the right upper quadrant of the abdomen and new-onset fever. The patient required mechanical ventilation but was recently weaned from the ventilator. Her medications include intravenous imipenem, furosemide, and omeprazole.

On physical examination, the temperature is 38.7 °C (101.7 °F), the blood pressure is 140/80 mm Hg, the pulse rate is 98/min, and the respiration rate is 18/min; the BMI is 35. The abdomen is diffusely tender with increased discomfort in the right upper quadrant with guarding and rebound. Bowel sounds are hypoactive and there is no ascites.

Laboratory studies:
Leukocyte count 17,000/µL (17 × 109/L) with 15% band forms
INR 1.3
Bilirubin (total) 2.4 mg/dL (41.0 µmol/L)
Bilirubin (direct) 1.7 mg/dL (29.0 µmol/L)
Aspartate aminotransferase 44 U/L
Alanine aminotransferase 35 U/L
Alkaline phosphatase 150 U/L
Albumin 3.8 g/dL (38 g/L)
Urinalysis Negative

Ultrasonography of the abdomen shows a distended gallbladder with an edematous wall and pericholecystic fluid, pancreatic edema unchanged from previous imaging, and increased liver echotexture consistent with fatty infiltration; there is no cholelithiasis or sludge or dilatation of biliary duct.

Which of the following is the most appropriate next step in the management of this patient?
A Addition of an antifungal agent
B Endoscopic retrograde cholangiopancreatography
C Observation on current therapy
D Percutaneous cholecystostomy

Definitive therapy for acalculous cholecystitis is cholecystectomy; percutaneous cholecystostomy may be necessary in critically ill patients who cannot undergo cholecystectomy.

This patient has evidence of cholecystitis on imaging, with gallbladder wall edema and the presence of pericholecystic fluid. However, she does not have any evidence of either cholelithiasis or choledocholithiasis. Therefore, the patient has acalculous cholecystitis. The clinical presentation of acalculous cholecystitis is variable. In critically ill patients, the only clues may be fever, leukocytosis, or nonspecific abdominal pain. In other patients, it may present similarly to calculous cholecystitis with right upper quadrant pain, fever, and right upper quadrant tenderness and a positive Murphy sign. Patients at risk for acalculous cholecystitis are those who are ill in the hospital with comorbidities, requiring long-term parenteral nutrition. These patients may be too ill for cholecystectomy and, therefore, require percutaneous drainage of the gallbladder until they are stable enough to undergo definitive therapy with surgery.

Without intervention acalculous cholecystitis has a mortality rate of 10% to 50%, and, therefore, this patient cannot continue to be observed with ongoing antibiotic therapy. The patient does not have any evidence of choledocholithiasis as the cause of her pain or cholecystitis, and, therefore, endoscopic retrograde cholangiopancreatography will not be therapeutic and places the patient at increased risk of complications or worsening pancreatitis. Although antifungal therapy should be considered in patients with necrotizing pancreatitis whose condition deteriorates clinically on antibiotic therapy, this patient's pancreatitis is stable and not the cause of the current change in her status.

Patients with pseudoachalasia tend to be older than patients with achalasia, have a shorter duration of symptoms, and have greater weight loss.

This patient presents with classic symptoms of achalasia: relatively short history of dysphagia, dilated esophagus, "bird's beak" abnormality on barium study, and typical manometric criteria for the diagnosis. However, in the presence of a mass lesion of the distal esophagus, the diagnosis of pseudoachalasia must be considered. Pseudoachalasia, also known as secondary achalasia, is not a primary motility disorder of the esophagus; rather it is a result of obstruction or neuronal infiltration at the gastroesophageal junction. The lesion is often neoplastic. Differentiation of pseudoachalasia from true achalasia can be problematic. Patients with pseudoachalasia tend to be older than patients with achalasia, have a shorter duration of symptoms, and have greater weight loss. Neither barium esophagography nor esophageal manometry can distinguish between primary and secondary achalasia. In this case, a history of lymphoma and the presence of a submusosal lesion require further evaluation. Endoscopic ultrasonography will allow delineation of the depth and invasiveness of the lesion, as well as permit transluminal needle biopsy of the mass.

Repeat mucosal biopsy is unlikely to be of sufficient depth to make a tissue diagnosis. Surgical exploration is not necessary to retrieve an adequate histologic sample of the lesion. Pneumatic dilatation and botulinum toxin injection are reserved for patients with primary achalasia, not pseudoachalasia, which frequently responds to treatment of the underlying disorder.

Management of hereditary nonpolyposis colorectal cancer (HNPCC) requires regular testing for colon cancer and HNPCC-associated cancers starting at an early age.

This patient's family history meets the Amsterdam II clinical criteria for hereditary nonpolyposis colorectal cancer (HNPCC), which use the 3-2-1 rule: three relatives with an HNPCC-associated cancer, two generations affected, one person diagnosed before age 50 years. She should therefore be considered to be at risk for cancers associated with the disorder despite the negative genetic tests. The patient was tested negative for germline mutations MLH1 and MSH2, but because there is no information whether a mutation had been identified in an affected member (her father, sister, or uncle), it is not clear whether the test represents a true negative in which case she is not at risk for HNPCC or if the test is uninformative. A genetic test for HNPCC must be interpreted along with consideration for the clinical and genetic data within the kindred. The strong family history of HNPCC-associated cancers suggests that the patient remains at risk for HNPCC, and she should be treated as if she is affected. Recommendations included colonoscopy every 1 to 2 years from age 20 to 25 years and surveillance for gynecologic malignancy every 1 to 2 years from age 30 years. Abdominal CT scan is not part of the consensus screening guideline for HNPCC.

Breast cancer is not associated with HNPCC. False-negative germline testing is very rare and repeating the blood testing is not indicated.

The hepatorenal syndrome resolves with liver transplantation.

This patient has the hepatorenal syndrome. The diagnosis is made in the absence of other causes of renal disease in the setting of advanced liver disease. Other causes of renal failure should be excluded by performing a careful history and physical examination, obtaining basic laboratory tests, and ruling out an infectious process (especially spontaneous bacterial peritonitis). Failure to improve following withdrawal of diuretics and administration of 1-1.5 L of normal saline is indicative of the hepatorenal syndrome. Renal replacement therapy is indicated for patients with clinically significant volume overload or severe electrolyte abnormalities. There are two basic forms of the syndrome: type 1, which is what this patient has, is rapidly progressive over a course of 1 to 2 weeks; type 2 more commonly occurs in the outpatient setting in patients who also have diuretic-resistant ascites. Type 1, however, leads to rapidly progressive renal dysfunction and oliguria ultimately necessitating the initiation of supportive dialysis.

The hepatorenal syndrome is purely a reflection of advanced liver disease caused by severe renal vascular vasoconstriction in the setting of profound splanchnic vasodilation. The syndrome is not due to intrinsic renal disease and reverses with liver transplantation. Therefore, this patient should proceed with liver transplant alone, and the kidney function will return after liver function is restored.

A peritoneovenous shunt drains peritoneal fluid from the peritoneum into the internal jugular vein and has been used both for the treatment of refractory ascites and the hepatorenal syndrome. Insertion of a peritoneovenous shunt has been shown to modestly improve the creatinine concentration but not survival. Furthermore, shunting is associated with the risk of complications and cannot be recommended for this patient. Angiotensin-converting enzyme (ACE) inhibitors such as lisinopril have been used in the treatment of hepatorenal syndrome without success. In addition, this class of drugs can induce hypotension and reduce the glomerular filtration rate. Angiotensin-converting enzyme inhibitors cannot be recommended for the treatment of hepatorenal syndrome.

Ileus is a functional obstruction of the bowel that commonly complicates the postoperative period; treatment is generally supportive, including the discontinuation of medications that slow gut motility and correction of electrolyte abnormalities.

This patient has a postoperative ileus. An ileus is a functional, as opposed to mechanical, gut obstruction that occurs when the normal bowel motility is inhibited. Metabolic derangements, medications such as narcotic analgesics and anticholinergic agents, and infection may exacerbate or contribute to the development of an ileus. The pathogenesis of a postoperative ileus likely relates to impaired gut electrical, neurologic, and hormonal activity; inflammatory mediators; and a dysmotility effect from anesthesia. Patients have difficulty tolerating oral intake and may complain of bloating, abdominal pain, and lack of flatus and stool passage; abdominal distention, normal or decreased bowel sounds, and diffuse mild tenderness may be observed on physical examination. An abdominal plain film generally shows air throughout the intestine but may be confused with mechanical small-bowel obstruction because air-fluid levels and minimal colonic gas may also be seen; therefore, CT and barium studies may help distinguish these entities. Management of an ileus is generally supportive, including the discontinuation of any medications such as narcotics and calcium channel blockers that may further slow gut motility and correction of electrolyte and other metabolic abnormalities.

Although nasogastric tubes may be appropriate for a small-bowel obstruction, they are generally not efficacious in managing an ileus except to provide symptomatic relief from emesis. Rectal tubes are used to decompress the colon but would not be helpful in treating an ileus. Studies of metoclopramide therapy in this setting have not shown accelerated postoperative gastrointestinal recovery.

Four-hour gastric scintigraphy of a solid meal is the test of choice for establishing the diagnosis of gastroparesis.

This patient has the typical clinical features of delayed gastric emptying after an episode of infectious gastroenteritis. The abrupt onset of this syndrome makes postviral gastroparesis likely, especially because mechanical obstruction has been excluded. The test of choice to substantiate the diagnosis of gastroparesis is a 4-hour gastric scintigraphy of a solid meal.

In the absence of abdominal pain and with normal liver chemistry studies, the utility of biliary ultrasonography would be low in the evaluation of her symptoms. Although central nervous system lesions should always be considered in a patient with nausea and vomiting of unknown cause, the presence of her early satiety, bloating, and retained gastric contents makes central nervous system pathology unlikely, and, therefore, MRI of the head would not be indicated. Patients with cyclical vomiting syndrome or bulimia may benefit from biofeedback training, but neither condition is likely in this patient. Patients with cyclical vomiting tend to have discrete periods of intense vomiting, often feeling well between episodes, whereas patients with bulimia are unlikely to present for an evaluation of vomiting and do not have an abrupt onset as in this patient. Even though this patient likely has postviral gastroparesis, stool cultures for a viral infection would not be helpful because the acute viral infection has resolved.

Ursodeoxycholic acid therapy is indicated for early-stage primary biliary cirrhosis and may reduce the rate of liver transplantation and prolong survival in affected patients.

This patient has early-stage primary biliary cirrhosis, and the most appropriate therapy is ursodeoxycholic acid. Primary biliary cirrhosis is a chronic progressive cholestatic liver disease of unknown cause. This disorder is overwhelmingly a disease of women (>90%) older than 30 years. The most common symptom is persistent fatigue, which occurs in as many as 80% of patients. Either localized or general pruritus frequently develops. The pruritus often begins in the perineal area or on the palmar and plantar surfaces and is typically worse at night or in a warm environment. Jaundice and abdominal pain may also develop. However, many patients may be asymptomatic at presentation. An antimitochondrial antibody titer of ≥1:40 is the serologic hallmark for the presence of primary biliary cirrhosis and occurs in 90% to 95% of patients. However, the titer does not appear to correlate with the severity or progression of the clinical disease. Treatment with ursodeoxycholic acid improves the biochemical profile, reduces pruritus, decreases progression to cirrhosis, and delays the need for liver transplantation if begun at an early stage of disease. The data are more conflicting for later stages of disease. Therapy is usually continued indefinitely.

Alendronate may be appropriate for patients with primary biliary cirrhosis and osteoporosis, but this patient has normal bone mineral density and is taking adequate calcium and vitamin D replacement. Hormone replacement therapy is no longer regarded as the mainstay of therapy for osteoporosis. In the Women's Health Initiative, the use of conjugated estrogens and medroxyprogesterone in postmenopausal women increased the risk of cardiovascular disease, invasive breast cancer, stroke, deep venous thrombosis, and pulmonary embolism. The patient reports no menopausal symptoms that might be an indication for short term use of estrogen replacement therapy. The patient has no indications of liver failure, and therefore liver transplantation is not indicated.

Patients with acute hepatitis have a marked elevation of aminotransferases, whereas patients with primary sclerosing cholangitis have a cholestatic pattern.

This patient likely has primary sclerosing cholangitis, a chronic cholestatic liver disease associated with inflammatory bowel disease and characterized by fibrosis, inflammation, and stricturing of the biliary tree. Up to 85% of affected patients have underlying inflammatory bowel disease, but <5% of patients with inflammatory bowel disease have primary sclerosing cholangitis. The disorder is more common in patients with ulcerative colitis than with Crohn disease. Most patients are diagnosed while asymptomatic with abnormal results on liver biochemistry tests, but jaundice and pruritus can occur in patients with advanced disease. The diagnosis is usually made by endoscopic retrograde cholangiopancreatography, which is especially useful in advanced disease where histologic samples can be taken to rule out cholangiocarcinoma and stents can be placed if there is a dominant stricture. Magnetic resonance cholangiopancreatography can also be used.

Autoimmune hepatitis, which is more common in women than in men, may have a cholestatic picture as in this patient, but it is often associated with other autoimmune disorders, such as hemolytic anemia, idiopathic thrombocytopenic purpura, type 1 diabetes mellitus, thyroiditis, and celiac disease. Laboratory findings in patients with autoimmune hepatitis include elevated serum aminotransferase values, hypergammaglobulinemia, mild hyperbilirubinemia, elevated serum alkaline phosphatase values, and the presence of autoantibodies. Serum gamma globulin values ≥1.5 times the upper limit of normal are common. This patient's gamma globulin level is not elevated (estimated by subtracting the albumin concentration from the total protein), making autoimmune hepatitis unlikely.

Patients with acute hepatitis C are usually asymptomatic and therefore rarely present clinically, but 60% to 85% of persons who acquire acute hepatitis C develop chronic infection. The cholestatic picture in the absence of other signs of advanced liver disease is inconsistent with hepatitis C cirrhosis. Hepatitis A can present acutely with fulminant liver failure, but the concentrations of the aminotransferases would be much higher, usually greater than 500 U/L.

Screening for colorectal cancer in the average-risk population should be started at age 50 years.

This patient is at average risk for colorectal cancer; this population includes persons with no personal or family history of colon adenoma or cancer and who do not have a condition that predisposes them to cancer, such as inflammatory bowel disease. Screening for colorectal cancer is cost effective and well tolerated; it also saves lives. Screening is feasible because the 10 to 15 years needed for a polyp to develop into cancer are sufficient time to detect and remove an adenoma. Screening in the average-risk population should be started at age 50 years; there are various effective screening strategies in average-risk patients, with surveillance intervals depending upon chosen strategy. Endoscopic screening of the distal colon with flexible sigmoidoscopy decreases colon cancer diagnoses in the screened colonic segment and decreases colorectal cancer-related mortality by 45%. Colonoscopy reduces the incidence of colorectal cancer by 76% to 90% when compared with control populations. Advanced adenomas (≥1 cm in diameter, villous histology, high-grade dysplasia or cancer) are detected three times more often by sigmoidoscopy than by fecal occult blood testing.

Annual fecal occult blood testing is an option but requires that two samples be collected from each of three spontaneously passed stools. Digital examination to retrieve a sample is not an acceptable substitute. Flexible sigmoidoscopy in combination with fecal occult blood testing in 5-year intervals would be an option as well. Double-contrast barium enema is no longer considered to be a primary method of colorectal cancer screening by the U.S. Preventive Services Task Force. If double-contrast barium enema must be used for technical or anatomical reasons, the correct screening interval is 5 to 10 years.
Gastro 60

A 74-year-old man is evaluated for a 2-month history of recurrent melena. He has had recurrent 2 - or 3-day periods of black, tarry stool followed by normal stool for the next week. His most recent black stool was yesterday. During this time, he has developed anemia and required transfusions of a total of eight units of blood. He has not had chest pain, abdominal pain, nausea or vomiting, or bleeding. The patient's medical history includes hypertension and mild chronic obstructive pulmonary disease; his medications are enalapril, albuterol by metered-dose inhaler, and aspirin.

On physical examination, the temperature is 37.0 °C (98.6 °F), the blood pressure is 132/74 mm Hg, the pulse rate is 84/min, and the respiration rate is 12/min; the BMI is 26.5. There is no scleral icterus and no abdominal distention or tenderness; bowel sounds are normal and there is no organomegaly. Rectal examination reveals black, tarry stool that is positive for occult blood. Laboratory studies reveal hemoglobin of 8.6 g/dL (86 g/L) with a mean corpuscular volume of 80 fL; leukocyte count, platelet count, prothrombin time, activated partial thromboplastin time, and INR are normal. Esophagogastroduodenoscopy on two occasions and a colonoscopy fail to identify a bleeding source.

Which of the following is the most appropriate next step in the evaluation of this patient?
A CT angiography
B Double-balloon enteroscopy
C Intraoperative endoscopy
D Small-bowel barium examination
E Wireless capsule endoscopy

Fundic gland polyps convey no defined cancer risk and require no follow-up.

Fundic gland polyps, the most common form of gastric polyps, are small (1 to 5 mm in diameter), multiple (often <10), located in the body and fundus of the stomach, and convey no known cancer risk. The endoscopic description of this patient's polyps is classic for fundic gland polyps, with histologic confirmation of the diagnosis. In this setting, no further testing is recommended.

Fundic gland polyps may occur more frequently in patients with familial adenomatous polyposis syndrome, in which case fundic gland polyps are often found in greater numbers, with higher risk of dysplasia, yet low cancer risk. Unless this patient had a known family history of familial adenomatous polyposis or had an unusually high number of polyps with or without dysplasia, colonoscopy would not be recommended simply because of the presence of the polyps. Gastric hyperplastic polyps often occur in the setting of chronic active gastritis and may regress with eradication of Helicobacter pylori; however, fundic gland polyps are not related to H. pylori infection and testing for the organism is not recommended in this setting. Testing for H. pylori is also not indicated in this patient because his symptoms are controlled with omeprazole. Although only one of the polyps was sampled, repeating the endoscopy to remove other polyps is not necessary because of the uniformity of the polyps on visual inspection and the fact that they convey no defined cancer risk. Endoscopic ultrasonography is similarly not required because these lesions have no defined risk for invasiveness.

Evaluation of abnormal liver test results after liver transplantation often requires a liver biopsy especially to differentiate between recurrent hepatitis C virus infection and rejection.

This patient has abnormal liver chemistry tests after receiving a liver transplant for hepatitis C virus (HCV)-related cirrhosis, and a liver biopsy is indicated to distinguish between rejection and recurrent HCV infection. HCV is known to recur in the transplanted liver almost immediately after surgery if the patient was viremic at the time of transplant. As a result, some degree of inflammation is to be expected and in some patients early histologic injury as the HCV establishes itself in the new liver. In a small percentage of patients, the HCV can recur very quickly and aggressively a few months after liver transplantation, a condition termed rapidly recurring cholestatic hepatitis C, which carries a poor prognosis. Fortunately, most patients have a much more benign course, with approximately 30% still developing recurrent cirrhosis within 5 to 10 years after transplantation. Identifying those patients who show histologic injury in the liver graft and initiating therapy in these patients is important. Therefore, this patient should undergo a liver biopsy to assess histology and also to rule out other causes of post-transplantation abnormal liver chemistry tests, such as acute cellular rejection, which would clearly be managed quite differently from recurrent HCV infection. Pegylated interferon and ribavirin are effective in clearing the virus in about 30% to 40% of patients with post-transplant hepatitis C and are indicated for patients with progressive histologic changes. Prophylactic treatment has not yet been shown to be effective.

Because liver chemistry tests after transplantation are expected to be normal, conservative management with observation is not appropriate, and since this patient may have either recurrent HCV or rejection as a cause of his liver test abnormalities, it is incorrect to simply discontinue mycophenolate or start anti-HCV therapy with pegylated interferon and ribavirin without a histologic diagnosis.

Diverticular bleeding is one of the most common sources of lower gastrointestinal bleeding, but diagnosis and therapy via colonoscopy are secondary to volume resuscitation and achieving hemodynamic stability.

The likely source of gastrointestinal bleeding in this patient is lower, with diverticulosis and vascular ectasia being most likely. Although a brisk upper gastrointestinal bleeding source is possible, generally an elevated blood urea nitrogen level and symptoms referable to the upper gastrointestinal tract would be seen. The patient's recent colonoscopy and lack of other symptoms and large-volume bleeding make a neoplasm unlikely. Colonic ischemia generally presents with abdominal pain and only a small amount of bleeding. Regardless of the source of bleeding at this point in the emergency department, however, the first rule of management is to achieve hemodynamic stability. This patient is volume-depleted and not hemodynamically stable. Therefore, the most appropriate next step is to ensure proper intravenous access, generally via two large-bore peripheral catheters or a central line for volume repletion with crystalloid fluids and blood products as necessary.

A nasogastric tube may be considered after volume resuscitation if an upper gastrointestinal bleeding source were suspected, but given his lack of upper gastrointestinal symptoms and normal blood urea nitrogen concentration, this is unlikely. Further, if an upper gastrointestinal source were highly suspected, an esophagogastroduodenoscopy should be performed regardless of the lavage results, which have a high false-negative rate. Although a colonoscopy is the diagnostic test of choice to evaluate for diverticular bleeding, vascular ectasias, neoplasms, internal hemorrhoids, and other possible sources of lower gastrointestinal bleeding, again this should not occur before volume resuscitation. A bleeding scan would be indicated only if endoscopic evaluation is not revealing and the patient continues to bleed. Up to 90% of diverticular bleeding resolves spontaneously. If a bleeding diverticulum is detected on colonoscopy, it can be treated with epinephrine injection and/or thermal coagulation.
Gastro 66

A 25-year-old woman is brought to the emergency department by her husband for yellowing of the eyes and increasing confusion and somnolence. The patient is 30 weeks' pregnant and just returned from visiting her parents in Africa. She has been previously healthy and takes only prenatal vitamins. Previously a social drinker, she stopped consuming alcohol entirely at the onset of her pregnancy.

On physical examination, the temperature is 37.2 °C (99.0 °F), the blood pressure is 90/40 mm Hg, the pulse rate is 100/min, and the respiration rate is 12/min; the BMI is 20. Examination reveals a gravid uterus and asterixis.

Laboratory studies:
Hemoglobin 14 g/dL (140 g/L)
Leukocyte count 15,000/µL (15 × 109/L)
Platelet count 450,000/µL (450 × 109/L)
INR 4.7
Bilirubin (total) 12.0 mg/dL (205.2 µmol/L)
Bilirubin (direct) 9.0 mg/dL (153.9 µmol/L)
Aspartate aminotransferase 3000 U/L
Alanine aminotransferase 2870 U/L
Alkaline phosphatase 400 U/L
Albumin 2.3 g/dL (23 g/L)
Ammonia 120 µg/dL (70.4 µmol/L)
Hepatitis A virus (IgM) Negative
Hepatitis B surface antigen (IgG and IgM) Negative
Hepatitis B virus DNA (PCR) Negative
Hepatitis C virus antibody Negative
Antinuclear antibody Negative
Anti-smooth muscle antibody Negative
Antimitochondrial antibody Negative
Alcohol screen Negative
Herpes simplex virus (PCR) Negative

The peripheral blood smear is normal. Ultrasonography of the abdomen shows a small liver, no ductal dilatation, and no varices.

Which of the following is the most likely cause of this patient's fulminant hepatic failure?
A Acute autoimmune hepatitis
B Acute alcoholic hepatitis
C HELLP syndrome
D Hepatitis E virus infection

Pregnant patients and those with chronic advanced liver disease who become infected with hepatitis E virus are at risk for fulminant hepatic failure.

This young pregnant woman has clinical and biochemical evidence of fulminant hepatic failure, which is the rapid development of severe acute liver injury with impaired synthetic function and encephalopathy in a previously normal person or a patient with well-compensated liver disease. She is encephalopathic and has profound coagulopathy with an INR greater than 4.0. Her elevated ammonia level is also a poor prognostic indicator.

Her recent travel to Africa and the fact that she is pregnant should raise suspicion for acquisition of acute hepatitis E virus infection. Hepatitis E virus causes large outbreaks of acute hepatitis in underdeveloped countries. Clinically, hepatitis E is similar to hepatitis A. Hepatitis E is usually self-limited, and chronic infection does not occur. However, patients exposed to this virus especially in the pregnant state or in the presence of chronic advanced liver disease are at risk for developing fulminant hepatic failure. Unfortunately, there is no direct therapy and treatment is supportive care; in this patient management would include delivery of fetus and evaluation for liver transplantation if possible.

Although autoimmune hepatitis and the HELLP syndrome (hemolysis, elevated liver enzymes, low platelets) can both lead to acute liver failure, the patient's platelet count is elevated and she does not have evidence of hemolytic anemia and has a normal peripheral blood smear and therefore, does not meet the criteria for HELLP syndrome. In addition, she does not have associated clinical evidence of pre-eclampsia (hypertension and proteinuria after 20 weeks of gestation) or eclampsia (preeclampsia and seizures (Krämpfe)) often seen with the HELLP syndrome. Although autoimmune hepatitis is a possibility, she has no history of previous liver disease or abnormal liver chemistry tests, and it would be unlikely to see a flare of autoimmune hepatitis in the pregnant state when the immune system is often suppressed by pregnancy. The clinical presentation of patients with alcoholic hepatitis ranges from being asymptomatic to developing jaundice, fever, and findings consistent with portal hypertension. Serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) values are less than 300 U/L, and the AST:ALT ratio is usually greater than 2. Mild to moderate serum alkaline phosphatase elevations are common. The lack of alcohol intake and the marked elevations of the aminotransferase levels with an AST:ALT ratio that is less than 2 excludes alcoholic hepatitis as the cause of her fulminant hepatic failure.

Early dumping syndrome is associated with nausea, bloating, diarrhea, and tachycardia that often occur within 30 minutes after a meal.

This patient has recently undergone a distal gastrectomy and now has classic features of early dumping syndrome. Patients with early dumping syndrome often have diarrhea, nausea, bloating, and tachycardia that occur within 30 minutes of eating as a result of hyperosmolar substances being rapidly emptied into the small bowel in the absence of the pylorus; therefore, carbohydrates and liquid nutrient drinks are often poorly tolerated as this case demonstrates. Late dumping syndrome occurs 1 to 3 hours after a meal and is characterized by neuroglycopenic symptoms.

Although carcinoid syndrome can be associated with diarrhea, flushing, and tachycardia, the diarrhea is often secretory in nature and continuous, including nocturnal episodes, unlike the features in this patient, which seem to be osmotically driven. Patients with chronic mesenteric ischemia also tend to have postprandial symptoms, but abdominal pain is often the predominant feature associated with weight loss secondary to fear of eating (sitophobia), neither of which was present in this patient. A gastrinoma should be considered in a patient with recurrent or complicated peptic ulcer disease that cannot be explained by NSAID use (as in this patient) or Helicobacter pylori infection. Patients with a gastrinoma usually have diarrhea secondary to fat malabsorption because the low pH from excess acid production inactivates pancreatic lipase. This patient notes his symptoms are actually better on a higher-fat diet, which would be more compatible with dumping syndrome because the food will have a longer phase of gastric digestion given that ingested fat can slow gastric emptying. Although irritable bowel syndrome is common in the general population, other diagnoses need to be considered first in this middle-aged man with new-onset symptoms following a surgical procedure.

Microscopic colitis is characterized by chronic watery diarrhea without bleeding; the diagnosis must be made by histologic examination of colonoscopic biopsy specimens.

This patient most likely has microscopic colitis, which is characterized by chronic watery diarrhea without bleeding. There are two types of microscopic colitis: collagenous colitis and lymphocytic colitis. The average age of onset for collagenous colitis is in the sixth decade of life and it tends to affect more women than men. The average age of onset for lymphocytic colitis is in the seventh decade of life, and women seem to be affected slightly more often than men. The cause of microscopic colitis is unknown. One theory is that the use of NSAIDs may contribute to the development of the disorder. Another theory is that it is caused by an autoimmune response. Colonoscopy in affected patients is grossly normal; to make a diagnosis, several biopsies must be taken from the colon. In collagenous colitis, biopsy specimens show more than normal amounts of collagen beneath the lining of the colon. In lymphocytic colitis, the specimen may also show an increased number of lymphocytes. Loperamide, diphenoxylate, and bismuth subsalicylate, either alone or in combination, are effective and well-tolerated when used as initial therapy.

Ulcerative colitis is characterized by bloody diarrhea associated with rectal discomfort, which the patient does not have. Fever, weight loss, tachycardia, dehydration, and significant abdominal tenderness or rebound indicate more severe disease. The patient has not taken any antibiotics and does not have other established risk factors for Clostridium difficile colitis, including recent hospitalization, advanced age, and severe illness. She has not traveled out of the country recently, and therefore, is not at risk for tropical sprue.

In possible acute hepatitis C virus infection in seronegative patients, the most sensitive diagnostic test is measurement of hepatitis C viral RNA.

The patient has signs of an acute hepatitis, including elevated liver test results with concurrent fatigue, malaise, and jaundice, and a recent exposure putting her at risk for viral hepatitis (injection drug use). Acute hepatitis C virus (HCV) infection may occur as a result of injection drug use, and although most infected persons do not develop a clinically apparent acute hepatitis, approximately 20% develop an acute infectious episode. Infected patients may remain seronegative for longer than 8 weeks, and therefore, in this clinical setting with a possibility of recent HCV infection, the most appropriate test would be measurement of HCV RNA. HCV RNA can be measured by PCR-based methods or signal amplification technologies. Hepatitis B virus (HBV) DNA should be measured only if the patient is positive for hepatitis B surface antigen (HBsAg).

HBsAg appears in serum 1 to 10 weeks after an acute exposure to hepatitis B virus and is present in the blood prior to the onset of symptoms or liver aminotransferase elevation. IgM anti-HBc can be the only serologic evidence of HBV infection during the period between the disappearance of HBsAg and the appearance of anti-HBs. Since the serologic tests for HBV are negative in this symptomatic person with elevated liver chemistry tests, there is no value in measuring HBV DNA. Acute hepatitis C is associated with characteristic histopathologic features including steatosis, lymphoid aggregates, and bile duct damage. However, these findings are not specific for HCV and similar findings are associated with acute HBV infection. Liver biopsy in this setting will not lead to a specific diagnosis without complementary serologic testing. MRI of the liver will detail hepatic morphology but will not contribute any more to the diagnosis than the ultrasonography.

An ulcer with a visible vessel as a cause of upper gastrointestinal bleeding has an approximately 50% risk of rebleeding if not treated endoscopically.

Upper endoscopy should be performed at the time of an upper gastrointestinal bleed after appropriate volume resuscitation to provide a diagnosis as to the cause of bleeding, provide a prognosis, and perform endoscopic guided therapy if required. An ulcer with a visible vessel has an approximately 50% risk of rebleeding if not treated endoscopically. These ulcers can be effectively treated with injection therapy, thermal coagulation via endoscopic probes, or mechanical modalities such as endoclips. Clean-based ulcers rebleed in less than 5% of cases and do not require endoscopic therapy.

Prospective trials have shown a 5% to 10% rebleeding rate for endoscopic hemostasis. In these patients, endoscopic therapy may be repeated if the patient remains hemodynamically stable and if the endoscopist thinks that the bleeding lesion is amenable to endoscopic therapy. If repeat endoscopy is unsuccessful or the bleeding vessel is inaccessible or too large, surgical consultation should be obtained. However, in this case endoscopic intervention is the first management choice for an accessible and small visible vessel.

Intravenous omeprazole has been shown to reduce the risk of recurrent upper gastrointestinal bleeding in peptic ulcers after endoscopic hemostasis. Oral omeprazole also may decrease rebleeding. A meta-analysis showed that adjuvant high-dose proton pump inhibitor therapy following endoscopic hemostasis for ulcers at high risk of rebleeding reduces rebleeding, surgery, and mortality. Octreotide may have a marginal benefit by decreasing the rate of nonvariceal bleeding but is inferior to intravenous proton pump inhibitors. Ranitidine is inferior to proton pump inhibitors as an adjunct to endoscopic therapy.

This patient has cholestasis of pregnancy, the most common and most benign pregnancy-related liver disorder. It often presents in the second or third trimester of pregnancy and is associated with pruritus and mild elevation of the bilirubin level with or without a mild elevation of the aminotransferase levels. The total bilirubin rarely exceeds 10 mg/dL (171 µmol/L). The absence of other potentially dangerous pregnancy-related liver diseases needs to be confirmed. Treatment consists of ursodeoxycholic acid, which usually controls the symptoms. Although considered benign, this disorder can be associated with increased risk of fetal distress and preterm delivery; therefore, management should involve an experienced obstetrician.

Acute fatty liver of pregnancy usually occurs during the third trimester of pregnancy; it can be associated with high aminotransferase levels, increased bilirubin level, and evidence of fat on liver ultrasonography. Fetal mortality is high in the absence of delivery. The patient does not have evidence of acute hepatitis A, which often presents with very high aminotransferase levels (usually greater than 500 U/L) in a patient with likely exposure to the virus. The presence of the positive total hepatitis A virus antibody signifies a resolved infection. The HELLP syndrome is incorrect because the diagnostic criteria of this disorder—hemolytic anemia, significantly elevated aminotransferase levels, and thrombocytopenia—are not present. HELLP, a serious pregnancy-related disease also occurs during the third trimester and up to 48 hours postpartum. It is part of the spectrum of eclampsia or pre-eclampsia and should be considered in a pregnant patient who presents with hypertension, proteinuria, and acute liver disease. There is no treatment; therefore, prompt recognition along with urgent delivery of the fetus is the best therapy and often curative. If the disorder is not recognized and treated, the morbidity and the mortality rate of fetus and mother are significant.

Endoscopic retrograde cholangiopancreatography is the most sensitive imaging test for chronic pancreatitis.

Establishing the diagnosis of chronic pancreatitis in a patient with early disease can be difficult. No blood or stool tests are currently available for the accurate diagnosis of early chronic pancreatitis. This patient's pain is most likely secondary to chronic pancreatitis with minimally elevated pancreatic enzymes and a history of harmful drinking. The patient has no evidence of exocrine or endocrine insufficiency and thus likely has early chronic pancreatitis. Normal liver enzymes, normal upper endoscopy, and a normal abdominal ultrasonography and CT scan of the abdomen make biliary causes and peptic ulcer disease less likely the cause of pain.

Endoscopic retrograde cholangiopancreatography (ERCP) has a sensitivity of nearly 95% for chronic pancreatitis and can show ductal dilation, strictures, and irregularity in both the main duct and its side branches. CT scan of the abdomen has a sensitivity of up to 90% for diagnosing chronic pancreatitis and should be ordered with thin cuts of the pancreas to improve sensitivity. Endoscopic ultrasonography may also be used to diagnose chronic pancreatitis with sensitivities equal to ERCP for moderate and advanced chronic pancreatitis but with lower sensitivity and specificity for mild and early chronic pancreatitis. Magnetic resonance cholangiopancreatography does not have sensitivities or specificities that match ERCP in the diagnosis of chronic pancreatitis at this time and cannot be routinely recommended. Biliary scintigraphy is used to diagnose acute cholecystitis and does not have a role in diagnosing chronic pancreatitis. Stool elastase can be abnormal in patients with more advanced chronic pancreatitis, particularly those who have malabsorption. However, stool elastase has poor sensitivity in patients with early chronic pancreatitis. Colonoscopy has a low yield in patients with upper abdominal pain.

The classic findings of acute cholecystitis on ultrasonography are pericholecystic fluid and a thickened gallbladder wall of 3 to 4 mm, and ultrasonographic Murphy sign further confirms the diagnosis.

The patient likely has acute cholecystitis; she has a history of biliary colic, including pain that radiates to the right shoulder, a Murphy sign elicited on examination, fever, leukocytosis, mild bilirubin and aminotransferase elevation, gallstones and pericholecystic fluid, and thickening of the gallbladder wall on ultrasonography. When ultrasonography reveals gallstones and a positive ultrasonographic Murphy sign, the positive predictive value for acute cholecystitis is 92%. When the patient has the additional findings of gallstones and gallbladder wall thickening (≥3 mm), the positive predictive value is 95% for acute cholecystitis. Ultrasonography can be less sensitive in patients with ascites, hypoalbuminemia, hepatitis, obesity, and heart failure. Surgical cholecystectomy is advisable once gallstones lead to such complications as acute cholecystitis. Early cholecystectomy is associated with a shorter recovery period and fewer complications, such as gangrene and empyema of the gallbladder. While definitive evidence regarding the use of antibiotics in acute cholecystitis is lacking, it would seem prudent to consider using antibiotics in toxic-appearing patients.

Endoscopic retrograde cholangiopancreatography would be indicated if there were evidence of bile duct obstruction, which is not present on ultrasonography in this case. Abdominal CT scan would not be useful in this case; it can be useful when complications of acute cholecystitis (such as emphysematous cholecystitis or gallbladder perforation) are suspected. The presence of a sepsis would suggest the diagnosis of gallbladder gangrene and perforation usually occurs after the development of gangrene. MRCP could confirm bile duct obstruction, if it were suspected on ultrasonography.

Chronic intestinal pseudo-obstruction is characterized by chronic or recurrent episodes of abdominal pain, distention, nausea, vomiting and obstipation; the disorder may be due to myopathic causes (such as scleroderma) or neuropathic causes (such as amyloidosis, diabetes mellitus, and paraneoplastic syndromes).

This patient has chronic intestinal pseudo-obstruction (CIPO), which is characterized by chronic or recurrent episodes of abdominal pain, distention, nausea, vomiting, and obstipation; also, in this patient abdominal imaging showing distended (aufgebläht) loops of small bowel supports the diagnosis. Systemic sclerosis, a connective tissue disorder, has been associated with CIPO. Other causes include neuropathic disorders such as amyloidosis, diabetes mellitus, and paraneoplastic syndromes. A hereditary cause is recognized as well. Gastrointestinal manometry may be used to confirm the diagnosis, but this test is available only at academic institutions with motility centers; full-thickness small-bowel biopsy can demonstrate neuronal loss and degenerative features as well as inflammatory enteric neuropathies, histologic features that may be seen in CIPO. Treatment of CIPO is generally supportive, with initial decompression of bowel via nasogastric tube and bowel rest. Medications that decrease intestinal motility (for example, narcotics, calcium channel blockers) should be reduced to the minimum necessary. In this patient's case, nitroglycerin paste might be substituted for nifedipine to manage the Raynaud phenomenon. An oral diet should be adhered to as tolerated; if gastroparesis coexists, medications that increase gastric motility such as metoclopramide may be used. Low-dose octreotide may improve motor activity of the small bowel, and antibiotics may be used when concomitant bacterial overgrowth is present. Laxatives may be used in cases with associated constipation.

Colonic inertia often occurs concomitantly with CIPO, but in this patient, dilated loops of small bowel, rather than colon, are present. Although gastroparesis can also present with similar symptoms and/or coexist with CIPO, it is generally not an acute presentation, nor would patients stop having bowel movements or have distended loops of small bowel on radiography, although gastric distention may occur. Mechanical obstruction needs to be excluded as signs and symptoms are often very similar, and plain abdominal films can appear similar in these two diagnoses. In this patient, imaging studies did not show any obstructive lesion or mass.
Gastro 81

A 63-year-old man is evaluated for a 3-month history of a 9-kg (20-lb) weight loss and 1 month of painless jaundice and decreased appetite. The patient was diagnosed with ulcerative colitis at age 21 years and underwent a colectomy with ileostomy. He was diagnosed with primary sclerosing cholangitis 2 years ago.

On physical examination, the patient is thin and cachectic; he is afebrile. The blood pressure is 130/75 mm Hg, the pulse rate is 80/min, and the respiration rate is 14/min; the BMI is 22. Examination reveals scleral icterus, but no ascites or right upper quadrant tenderness on deep palpation; Murphy sign was not elicited.

Laboratory studies:
Hemoglobin 14.5 g/dL (145 g/L)
Leukocyte count 3400/µL (3.4 × 109/L) with normal differential
Platelet count 225,000/µL (225 × 109/L)
Bilirubin (total) 8.0 mg/dL (136.8 µmol/L)
Bilirubin (direct) 3.6 mg/dL (61.56 µmol/L)
Aspartate aminotransferase 120 U/L
Alanine aminotransferase 145 U/L
Alkaline phosphatase 456 U/L
CA 19-9 1200 U/mL (1200 kU/L)
α-Fetoprotein 9.0 ng/mL (9.0 µ/L)

Magnetic resonance cholangiopancreatography shows dilated intrahepatic bile ducts with new irregular strictures at the common hepatic duct with a periductal irregular mass surrounding the stricture; the pancreatic duct has a normal caliber. The gallbladder appears normal without edema or wall thickening.

Which of the following is the most likely diagnosis?
A Acute cholecystitis
B Cholangiocarcinoma
C Choledocholithiasis
D Progressive primary sclerosing cholangitis

Patients with primary sclerosing cholangitis are at risk for developing cholangiocarcinoma (lifetime prevalence of 10% to 30%).

Primary sclerosing cholangitis is a chronic cholestatic liver disease of unknown cause that is characterized by progressive bile duct destruction and may lead to secondary biliary cirrhosis. Up to 80% of patients with primary sclerosing cholangitis have an inflammatory bowel disease (most often ulcerative colitis), although less than 5% develop primary sclerosing cholangitis. Patients with primary sclerosing cholangitis are at risk for developing cholangiocarcinoma (lifetime prevalence of 10% to 30%). Patients with advanced primary sclerosing cholangitis and cirrhosis are also at risk for developing hepatocellular carcinoma. This patient has a history of primary sclerosing cholangitis and now presents with onset of painless jaundice and weight loss, which should raise the suspicion for cholangiocarcinoma. The detection of an irregular stricture in the hepatic duct further raises concern that a malignancy has developed. Additional pertinent findings are the elevated CA 19-9 level, which although not specific to cholangiocarcinoma, in the correct clinical setting is helpful in raising the likelihood of the diagnosis.

The patient has no findings suggesting acute cholecystitis on physical examination, the leukocyte count is normal, and on imaging the gallbladder appears normal without any wall thickening or edema, which would be expected findings in a patient with acute cholecystitis. Furthermore, biliary ductal dilatation would be uncommon in cholecystitis. Choledocholithiasis usually presents with biliary colic in the absence of weight loss. The lack of cholelithiasis, which does not entirely exclude this diagnosis, in the presence of the other clinical findings makes it less likely. Furthermore, a filling defect in the ducts would be expected rather than an irregular stricture, which makes malignancy more likely. Progressive primary sclerosing cholangitis, although possible given the patient's disease, should not exclude the more likely diagnosis of cholangiocarcinoma in this patient who now presents with painless jaundice, weight loss, an irregular new stricture, and a very elevated CA 19-9.

Alarm features associated with dyspepsia include age greater than 55 years with new-onset symptoms, family history of gastric cancer, weight loss, gastrointestinal bleeding, dysphagia, odynophagia, iron-deficiency anemia, vomiting, and abnormal examination findings.

This patient has new-onset dyspepsia, and although she does not have any worrisome clinical features, the new onset of symptoms at her age and her mother's history of gastric cancer constitute alarm features, and therefore, further evaluation with esophagogastroduodenoscopy is warranted. Alarm features associated with dyspepsia include the following: age greater than 55 years with new-onset symptoms, family history of gastric cancer, weight loss, gastrointestinal bleeding, dysphagia, odynophagia, iron-deficiency anemia, vomiting, or abnormal examination findings.

Although pancreatic disease, such as adenocarcinoma of the pancreas, may present with similar clinical symptoms, evaluation with endoscopic retrograde cholangiopancreatography would not precede upper endoscopy or cross-sectional imaging, especially because of the increased invasiveness of this test. If the patient had not had any alarm features, testing for Helicobacter pylori and treating if positive would be recommended. In this patient with dyspepsia and alarm features, it would be inappropriate to simply diagnose functional dyspepsia or treat her with a neuromodulating agent before a fuller evaluation. An empiric trial with a proton pump inhibitor would be reasonable in a patient with features suggestive of gastroesophageal reflux, but should not replace further evaluation in this elderly patient with new symptoms.

The most common cause of acute pancreatitis in the United States is gallstones, which are diagnosed with abdominal ultrasonography.

The diagnosis of pancreatitis relies heavily on the serum amylase and lipase, which are elevated in 75% to 90% of patients. Serum lipase is more specific and stays elevated longer than amylase. The two most common causes of acute pancreatitis in the United States are alcohol and gallstones. In this patient who does not consume alcohol, gallstones are the most likely cause of acute pancreatitis as shown by the pattern of liver enzymes. Abdominal ultrasonography is the most sensitive test for detecting the presence of gallstones and ductal dilation, which can provide indirect evidence for the presence of a retained common duct stone. Ultrasonography has no risk, is widely available, and is relatively inexpensive.

CT scan is less sensitive than ultrasonography for the detection of cholelithiasis. CT with contrast is indicated in patients with moderate or severe pancreatitis or those who do not improve clinically within 48 to 72 hours, to confirm the diagnosis, to exclude other intra-abdominal processes, to grade the severity of pancreatitis, and to diagnose local complications such as pancreatic necrosis, pseudocyst, or abscess. Magnetic resonance cholangiopancreatography is used if there is a contraindication to intravenous radiocontrast. Endoscopic retrograde cholangiopancreatography (ERCP) is the most sensitive test for choledocholithiasis and can provide direct treatment by removing common duct stones. ERCP is indicated in patients with persisting pancreatitis, persistent elevation of aminotransferase levels, or dilated bile ducts suggesting the presence of retained bile duct stones. Stone extraction with biliary sphincterotomy improves the outcome, prevents further attacks of acute biliary pancreatitis, and reduces pancreatitis-related complications. However, in this patient there is not enough evidence yet that a common duct stone is still present to perform this more invasive test before ultrasonography. Upper endoscopy will not aid in determining the cause of acute pancreatitis.

Patients who have abnormal liver chemistry tests and an abnormal transferrin saturation should be screened for hereditary hemochromatosis.

Although the classic description of hereditary hemochromatosis includes the findings of cirrhosis, type 1 diabetes mellitus, and skin hyperpigmentation ("bronze diabetes"), it is now uncommon for patients to present with this triad because of earlier detection of the disease. The most common presenting symptoms today are fatigue, impotence, and destructive arthropathy, characteristically of the second and third metacarpophalangeal joints. However, many patients are asymptomatic and are diagnosed after abnormal results are noted during routine laboratory testing. Patients who have abnormal liver chemistry tests and an abnormal transferrin saturation should be screened for hereditary hemochromatosis, an autosomal recessive disorder in which mutations in the HFE gene cause increased intestinal absorption of iron; the disorder is a common genetic disorder especially in the white population. The genetic mutation is located on chromosome 6 and is most commonly associated with the C282Y homozygous state or the compound heterozygote C282Y/H63D. This patient not only has elevated transferrin saturation but a serum ferritin greater than 1000 ng/mL (1000 mg/L) which has been shown to be predictive of advanced liver fibrosis in patients with hereditary hemochromatosis. Furthermore, he has diabetes mellitus and arthritis. In addition, his family history is also suggestive of the diagnosis.

Generally, a transferrin saturation of greater than 55% in a man and greater than 50% in a woman should raise suspicion for the disorder. Identifying an affected patient is also important for family members who then should be screened for the disorder as well, generally starting with a simple transferrin saturation and evaluating further those in whom an elevated saturation is found. Identifying patients before they develop disease is important because it can generally be managed with therapeutic phlebotomy until iron stores are depleted.

Therapy with deferoxamine, an iron chelator, is indicated only for patients who cannot tolerate phlebotomy, such as those with significant anemia. Iron chelation therapy is significantly less effective at removing iron than is phlebotomy and must be administered by subcutaneous or intravenous infusion. MRI is not diagnostic for hemochromatosis.
Gastro 89

A 42-year-old woman is evaluated in the emergency department for lower chest pain and dyspnea that awoke her suddenly from sleep. The pain is moderately severe and does not radiate. The patient had laparoscopic Roux-en-Y gastric bypass for morbid obesity 10 days ago and was discharged from the hospital 5 days ago. She has had mild nausea and an average of five bowel movements a day since surgery. She also has a history of reflux esophagitis and hypertension; her medications include a multivitamin with iron, calcium, vitamin D, thiamine, vitamin B12, pantoprazole, metoprolol, and prochlorperazine.

On physical examination, the patient appears to be in mild distress; she is afebrile, the blood pressure is 105/70 mm Hg, the pulse rate is 110/min, and the respiration rate is 22/min. The oxygen saturation is 88% with the patient breathing ambient air, and the BMI is 48. Cardiac examination shows regular tachycardia. The lungs are clear bilaterally. Abdominal examination shows several small, mildly tender surgical incisions with no surrounding erythema; there is no guarding or rebound, and bowel sounds are normal. Laboratory studies reveal a normal complete blood count, normal cardiac enzymes, and normal serum lactate. Electrocardiography shows sinus tachycardia without ST changes. Chest radiograph shows linear atelectasis at the lung bases. Abdominal radiograph shows a small amount of intraperitoneal air, which is unchanged from postoperative radiographs, and a normal bowel gas pattern.

Which of the following is the most likely diagnosis?
A Bowel obstruction
B Gastrojejunostomy leak
C Gastroesophageal reflux
D Myocardial infarction
E Pulmonary embolism

Pulmonary embolism is an infrequent early complication after bariatric surgery, but it accounts for 50% of deaths in these patients.

Pulmonary embolism is a potential early complication (within the first 30 days) of bariatric surgery, and although infrequent, it accounts for 50% of all deaths in such patients. In this patient who recently underwent bariatric surgery and who presents emergently with chest pain, dyspnea, tachycardia, tachypnea, and hypoxemia, pulmonary embolism is the most likely cause, and immediate evaluation and management are important.

A postoperative bowel obstruction may occur secondary to internal hernias or adhesions, and patients with obstruction often present with nausea, pain, and abdominal distention. This patient has had stable nausea since surgery but has normal bowel sounds, is having bowel movements, and has normal abdominal imaging, making obstruction less likely. A patient with an anastomotic leak may also present with tachycardia and pain, but it is often associated with fever and leukocytosis, neither of which this patient has. Some intraperitoneal air would not be uncommon after a recent surgery, but comparison with past films, as in this case, should always be considered. Gastroesophageal reflux is a common cause of noncardiac chest pain, but would not explain the patient's tachycardia, tachypnea, and hypoxemia. Although myocardial infarction needs to be considered in any patient presenting with chest pain, the normal cardiac enzymes and lack of ischemic changes on electrocardiography make myocardial infarction unlikely.

Chronic carriers of hepatitis B are susceptible to superinfection with hepatitis delta virus, which is a defective virus that requires the presence of hepatitis B virus to exist.

This patient likely has a superimposed hepatitis delta virus (HDV) infection, which is most common among injection drug users. HDV is a defective virus that requires the presence of hepatitis B virus (HBV) to exist. The outer lipoprotein envelope of the hepatitis D virus is made of the surface antigen of the HBV (HBsAg). Therefore, detectable hepatitis B surface antigen is necessary for the diagnosis of HDV infection. Two major patterns of serologic response may be seen depending upon the type of infection. In acute HBV/HDV D coinfection, the presence of IgM antibody to hepatitis B core antigen (anti-HBc IgM) is present. This simultaneous infection is clinically indistinguishable from acute HBV infection, although it may be more severe and is associated with a higher prevalence of acute liver failure. In acute HDV superinfection, the IgM antibody to hepatitis B core antigen is negative but the IgG antibody is positive. This type of infection may present clinically as either an apparent worsening of a previously established chronic HBV infection or an acute infection of viral hepatitis in a person with previously unrecognized chronic HBV infection. In this situation, the superimposed HDV infection suppresses hepatitis B replication and the HBV DNA level becomes undetectable. The reason for the suppression of HBV virus replication is unknown. Patients with HDV superinfection may be at greater risk for progression to cirrhosis. This patient's clinical presentation of an acute worsening of a chronic hepatitis B infection is most compatible with a superinfection with HDV. It is possible to diagnose HDV infection by using total anti-HDV antibodies, which would be the next diagnostic step for this patient; IgM and IgG can be detected by enzyme immunoassay or radioimmunoassay.

Acute alcoholic hepatitis is unlikely given the lack of a history of alcohol ingestion and the degree of elevation and pattern of the aminotransferases. In alcohol injury, the aspartate aminotransferase concentration tends to be higher than the alanine aminotransferase but rarely greater than 300 U/L. Ultrasonography did not show a space-occupying liver lesion, and therefore, hepatocellular carcinoma is unlikely. Furthermore, hepatocellular carcinoma is associated with cirrhosis, which is not present in this patient. Reactivation of hepatitis B can occur, but in this case the anti-HB core IgM and DNA should be positive.
Gastro 91

A 57-year-old woman with cirrhosis is evaluated for worsening ascites and abdominal discomfort. The patient has hepatitis C virus infection, which failed to respond to antiviral therapy. She has been followed with regular cross-sectional imaging. Her medications are furosemide, spironolactone, nadolol, lactulose, and acetaminophen.

On physical examination, the patient is afebrile; the blood pressure is 90/50 mm Hg, the pulse rate is 80/min, and the respiration rate is 14/min. The BMI is 26. Examination reveals scleral icterus, a firm palpable liver edge, bulging flanks with shifting dullness, spider angiomata, caput medusae, and 2+ lower extremity edema. Palpation does not elicit Murphy sign, and there is no guarding, rebound, or peritoneal signs.

Laboratory studies
Hemoglobin 16.4 g/dL (164 g/L)
Platelet count 45,000/µL (45 × 109/L)
INR 1.7
Creatinine 1.4 mg/dL (123.76 µmol/L)
Bilirubin (total) 1.8 mg/dL (30.78 µmol/L)
Bilirubin (direct) 0.9 mg/dL (15.39 µmol/L)
Aspartate aminotransferase 67 U/L
Alanine aminotransferase 45 U/L
Alkaline phosphatase 120 U/L
Albumin 2.6 g/dL (26 g/L)
α-Fetoprotein 200 ng/mL (200 µg/L) (n = bis 10 ng/ml)
Amylase 75 U/L
Lipase 58 U/L

MRI of the abdomen shows patent hepatic vessels, cirrhosis, and a new 4.2-cm enhancing mass in the right hepatic lobe. There is no tumor thrombus, and CT scan of the chest shows no pulmonary nodules.

Which of the following is the most appropriate management for this patient?
A Biopsy of the liver mass
B Evaluation for liver transplantation
C Resection of the liver mass
D Systemic chemotherapy

Liver transplantation has become the primary treatment of choice for many patients with cirrhosis and hepatocellular carcinoma.

This patient has radiographic evidence of cirrhosis with recent worsening hepatic decompensation manifested by worsening of ascites. Patients who develop hepatocellular carcinoma can, like this patient, present with new hepatic decompensation. The hemoglobin concentration is also elevated, a finding that can be a paraneoplastic manifestation of hepatocellular carcinoma. Furthermore, the findings on MRI are consistent with hepatocellular carcinoma in a patient with underlying cirrhosis. The patient has a single hepatocellular carcinoma in the absence of vascular involvement or extrahepatic spread; the stage of the tumor (T2) is within the Milan criteria for transplantation. Therefore, the next best management option is evaluation for liver transplantation.

When the imaging suggests hepatocellular carcinoma and there is either an elevation of the serum α-fetoprotein concentration or another image finding suggestive of hepatocellular carcinoma, diagnostic biopsy is not necessary, and there is a small but real risk for tumor seeding with biopsy of this lesion. Hepatic resection is reserved for a select group of patients with hepatocellular carcinoma. Such patients need to have stable disease with good hepatic reserve. Thus hepatic resection is often limited either to patients without underlying cirrhosis or patients who have stable cirrhosis but no evidence of portal hypertension or hepatic dysfunction, which would lead to hepatic decompensation and increased patient morbidity after resection. Although systemic chemotherapy may be considered for patients who have extensive tumors who do not meet the Milan criteria, the preferred therapy in this patient is transplantation rather than systemic chemotherapy.

Magnetic resonance arteriography is a highly sensitive test to diagnose chronic mesenteric ischemia.

This patient has classic signs and symptoms of chronic mesenteric ischemia: postprandial abdominal pain associated with sitophobia (fear of eating) and weight loss in the setting of vascular disease and a history of smoking. The clinical history is an essential part of the diagnosis of the disorder. Other possible causes of her abdominal pain have been evaluated, including biliary disease, peptic ulcer disease, pancreatitis, and malignancy, by the ultrasonography, upper endoscopy, CT scan, and laboratory tests. Although the gold standard for evaluating stenoses of the mesenteric vessels is traditional angiography, CT or magnetic resonance angiography both have high sensitivity in the diagnosis of chronic mesenteric ischemia. Two vessels are involved in 90% of affected patients, and 50% have significant stenosis of all three vessels (celiac artery, superior mesenteric artery, inferior mesenteric artery). Doppler ultrasonography may also be useful in evaluating these vessels.

Although colonoscopy would be indicated in this patient to screen for colon cancer if she had not had one within the last 10 years, this test should not be prioritized at this time. Colonoscopy is normal in chronic mesenteric ischemia as it does not involve the colon. A small bowel series would not be helpful in this setting because it evaluates only the lumen and not the vasculature of the small intestine. A gastric emptying study measures the half-time for the stomach to empty its contents and can be helpful in diagnosing gastroparesis; although the symptoms of gastroparesis and chronic mesenteric ischemia overlap, given the patient's history of vascular disease and extreme weight loss as well as the importance of timely diagnosis to avoid a superimposed life-threatening acute ischemic event, a gastric emptying study would not be the most appropriate next test.

Endoscopic treatment of pain in chronic pancreatitis is performed by removing pancreatic duct stones and placing stents in pancreatic duct strictures to decrease pancreatic duct pressure.

Patients with chronic pancreatitis must avoid alcohol. Patients who continue to drink alcohol have an increase in painful attacks and mortality. Pain in chronic pancreatitis results from chronic inflammation, chronic noxious stimulation of the nerves to the pancreas, and increased pancreatic intraductal pressure secondary to pancreatic duct stones, calcifications, or strictures. Large stones in the pancreatic duct can be crushed with extracorporeal shock wave lithotripsy; endoscopic retrograde cholangiopancreatography can then remove the stones and place stents in pancreatic duct strictures to decrease pancreatic duct pressure. Studies have documented symptom improvement in 11% to 75% of patients and resolution of stricture in 10% to 50%.

A surgical pancreatoduodenectomy (Whipple procedure) can be performed to relieve pain but is effective only in patients who have disease limited to the head of the pancreas and who have failed to respond to medical and endoscopic therapy. A surgical procedure to divert the pancreatic duct into the small intestine has been used widely in the treatment of patients with a chronic pancreatitis and a dilated pancreatic duct and is effective in many patients. The procedure involves removing pancreatic tissue that overlies the ductal system in the head of the pancreas. A less invasive procedure is preferred to surgical intervention as the next management step.

Celiac nerve block has been used to treat chronic pancreatitis pain but is considered by many experts to be an unproved therapy. Even in patients who respond, pain returns in 2 to 6 months and significant procedural complications have been reported. Furthermore, it would not be the first procedure of choice in a patient with a pancreatic ductal stone and evidence of obstruction. Pancreatic enzyme supplements are not consistently effective for pain control in chronic pancreatitis.

Topical therapy with corticosteroids or mesalamine is appropriate for distal ulcerative colitis.

Ulcerative colitis can be classified by both extent and severity of disease, and treatment is guided by both factors. This patient has mild to moderate ulcerative proctitis, with disease limited to the distal rectum. Therefore, the best treatment would be local therapy with suppositories or enemas. Options include cortisone foam and mesalamine or corticosteroid suppositories for proctitis and hydrocortisone or mesalamine enemas for left-sided colitis. Topical mesalamine is more effective than topical corticosteroids, and almost half of the dose of topical corticosteroids may be absorbed systemically, leading to adverse long-term side effects. Maintenance of remission can be achieved with topical mesalamine.

Oral 5-aminosalicylates, including sulfasalazine, mesalamine, balsalazide, and olsalazine, are appropriate for distal disease that does not respond to topical therapy or for mild to moderate pancolitis. Oral prednisone is used when symptoms do not respond to 5-aminosalicylates. Because prednisone and other corticosteroids have many acute and chronic toxic effects that are dose- and duration-dependent, the lowest effective dose should be given for the shortest time. Azathioprine or 6-mercaptopurine (6-MP) may be used for patients who have incomplete disease remission while on corticosteroids. However, because both agents have delayed onset of action, concomitant administration of either azathioprine or 6-MP together with a 3- to 4-month course of prednisone is often necessary. The patient's mild and limited disease makes oral immunosuppressive therapy such as prednisone or azathioprine inappropriate.

Controlled trials have not demonstrated a consistent benefit of antibiotic therapy in the treatment of ulcerative colitis. There is probably a role for antibiotics in the treatment of fulminant colitis to treat or prevent a life-threatening infection but not in this patient with mild to moderate disease.

Diuretic-resistant ascites is a common and important indication for referral for liver transplantation.

The patient has diuretic-resistant ascites, which portends a poor survival. Diuretic-resistant ascites is a common indication for liver transplantation and constitutes a reason to refer the patient for transplant evaluation. True refractory ascites is uncommon and can be managed with serial large-volume paracentesis or transjugular intrahepatic portosystemic shunt (TIPS). Randomized trials suggest that both therapeutic procedures are effective in controlling refractory ascites, although TIPS may be associated with a higher complication rate and increased risk for encephalopathy, and patients with poorly compensated liver disease may experience further decompensation after the procedure. The Practice Guidelines Committee of the American Association for the Study of Liver Diseases state that although TIPS will decrease the need for repeated large-volume paracentesis in patients with refractory ascites associated with cirrhosis, it should be used only in those patients who are intolerant of repeated large-volume paracentesis. Patients undergoing paracentesis of more than 5 L of ascitic fluid should be given intravenous albumin at the time of fluid removal in order to prevent post-paracentesis circulatory dysfunction.

Peritoneovenous shunt is rarely used because of an appreciable rate of complications and the lack of evidence that it prolongs patient survival, which may be several years in patients with normal or near normal hepatic and renal function tests but less than 6 weeks in patients with the hepatorenal syndrome. Although diuretic-resistant ascites is present, the patient has a stable serum creatinine, electrolytes are normal, he is not anuric and therefore, dialysis is not indicated.
Gastro 97

A 32-year-old woman is evaluated in the hospital. She was hospitalized 2 days ago because of nausea, vomiting, and dehydration as a result of documented gastroparesis secondary to long-standing, difficult-to-control type 1 diabetes mellitus. Her symptoms had been controlled with oral erythromycin therapy, but the therapy became ineffective with time. She recently began taking metoclopramide, which controlled the nausea and vomiting but caused tardive dyskinesia, and the therapy was stopped. Oral antiemetic therapy has not prevented vomiting, and modifying her diet by eating multiple, small-volume, low-residue meals or limiting her diet to liquid supplements only has not been effective. Over the past 3 months, she has lost 5.8 kg (15 lb) and been hospitalized four times. In addition to type 1 diabetes mellitus, her medical history includes erosive esophagitis, and her medications include insulin glargine and insulin lispro and pantoprazole.

On admission she was given intravenous fluids, and her volume status improved over 2 days. On physical examination, she is afebrile, the blood pressure is 105/68 mm Hg with no orthostatic changes, and the pulse rate is 88/min; the BMI is 21. The patient has intermittent dystonic movements of the mouth; the mucous membranes are moist, skin turgor is intact, and abdominal examination is normal. Laboratory studies reveal a plasma glucose of 160 mg/dL (8.88 mmol/L); all other studies, including complete blood count, serum creatinine, liver chemistry tests, thyroid-stimulating hormone, calcium, tissue transglutaminase, and cortisol, and spot urine for microalbumin, are normal.

Which of the following is the most appropriate next step in the management of this patient?
A Metoclopramide at a reduced dose
B Nasojejunal feeding trial
C Percutaneous gastrostomy tube placement
D Total parenteral nutrition

Patients with metabolic syndrome and persistently elevated liver enzyme concentrations, despite adequate treatment of its components, should undergo liver biopsy.

Nonalcoholic fatty liver disease includes nonalcoholic steatohepatitis (NASH) and steatosis (fatty degeneration). Liver biopsy would differentiate between the two disorders. NASH, the most likely finding in this patient, generally occurs in obese patients with dyslipidemia and diabetes mellitus or glucose intolerance. This patient has the metabolic syndrome with persistently elevated liver chemistry tests despite adequate management of the diabetes and lipid disorder that are components of the syndrome. However, he remains obese. The patient's evaluation excludes viral hepatitis, space-occupying lesions, and hemochromatosis, and the remaining possibilities include NASH and drug-induced liver injury. The liver biopsy specimen would likely show features of NASH, which include macrovesicular steatosis, ballooning degeneration, and lobular inflammation. Also, the presence of fibrosis would further identify this patient as being potentially at risk for progressive fibrosis attributable to NASH. Treatment of NASH depends on the cause. Drugs known to be associated with NASH should be discontinued. If this is not possible, the dose should be reduced. Weight loss is the cornerstone of treatment for patients with obesity, diabetes mellitus, and dyslipidemia.

The patient's metabolic syndrome is adequately controlled, and therefore, therapy with insulin or a fibric acid derivative is not necessary and has not been shown to affect NASH. Because the only abnormality shown on ultrasonography is fatty infiltration, MRI would add little to the patient's evaluation.

In patients with peptic ulcers, nonprescription medications should be reviewed to determine whether NSAIDs are being inadvertently used.

The two most common causes of peptic ulcer disease are NSAIDs and Helicobacter pylori infection, which account for more than 90% of cases. This patient has a history of arthritis for which she takes an over-the-counter analgesic, and therefore, inadvertent use of NSAIDs, which are widely available without a prescription and are often used in arthritis as analgesics, needs to be considered; many patients who take such nonprescription medications are unaware that they are taking NSAIDs.

H. pylori infection has been ruled out in this patient by the negative histology for the organism as well as negative serum antibody testing; therefore, no further testing for H. pylori is needed. Measuring serum gastrin should be considered in a patient in whom there is a suspicion of an acid hypersecretion state, such as a gastrinoma (Zollinger-Ellison syndrome), clinical features of which include multiple peptic ulcers, ulcers in unusual locations, severe esophagitis, or fat malabsorption, none of which this patient has.

Malignancy always needs to be considered in a patient with a gastric ulcer; therefore, biopsies of the ulcer and follow-up endoscopy to ensure ulcer healing would be recommended. However, this patient has a duodenal ulcer, which is much less likely to represent a malignancy, and biopsy of the ulcer or follow-up endoscopy to assess for healing is not needed. Alendronate therapy for osteoporosis has been associated with esophagitis and rare cases of gastric or duodenal ulcers; however stopping alendronate without considering the more common causes of peptic ulcer disease would not be appropriate at this time.

Diabetic autonomic dysmotility may manifest as constipation or diarrhea and is usually seen in the setting of other end-organ disease; treatment is generally supportive.

This patient has chronic diarrhea in the setting of suboptimally-controlled type 1 diabetes mellitus with end-organ disease and likely has autonomic dysfunction that affects her gastrointestinal motility. Dysmotility associated with diabetes can manifest with either diarrhea or constipation; the diarrhea may be painless, nocturnal, and quite severe. In general, treatment should be supportive. Therefore, in addition to repairing fluid, electrolyte, and nutritional deficiencies and attempting to achieve tight glycemic control, diphenoxylate/atropine therapy is the most appropriate therapy for this patient. The patient has already been tested for small-intestine bacterial overgrowth, which may be superimposed upon dysmotility syndromes, but given that the breath test was negative, antibiotic therapy is unnecessary.

Although celiac disease, an immune-mediated sensitivity to gluten and other related proteins in wheat, rye, and barley, is commonly associated with other autoimmune disease such as diabetes mellitus and autoimmune thyroiditis, the patient has already been screened for this condition with serologic testing (anti-tissue transglutaminase and antiendomysial antibodies) and small-bowel biopsy. Therefore, having the patient start a gluten-free diet would not be appropriate. Octreotide, a somatostatin analogue, has been used to treat diarrhea related to diabetic-associated autonomic dysmotility, but the evidence of its efficacy is equivocal and treatment may be complicated by recurrent episodes of hypoglycemia that may be related to reduced secretion of counterregulatory hormones; therefore, octreotide would not be first-line therapy.

Ischemic colitis presents most commonly in elderly patients with atherosclerotic vascular disease with crampy abdominal pain and bloody stool, and in most cases is self-limited.

This patient likely has ischemic colitis, the most frequent form of ischemia of the gastrointestinal tract. This type of ischemia usually affects the elderly with atherosclerotic disease, and in most cases is transient and resolves with conservative management. Patients with acute colonic ischemia usually present with rapid onset of abdominal pain and tenderness over the affected bowel. Rectal bleeding or bloody diarrhea usually develops within 24 hours of the onset of abdominal pain. The typical finding on CT scan is thickening of the bowel wall in a segmental pattern, which is not specific for ischemia and can be seen in infectious colitis and Crohn disease. The finding of patchy segmental ulcerations on colonoscopy in a patient with a compatible history establishes the diagnosis. Colonic ischemia is usually the result of a sudden and usually temporary reduction in blood flow that is insufficient to meet the metabolic demands of discrete regions of the colon but usually develops insidiously without a specific cause being identified. Colonic strictures are a rare complication.

The patient's acute onset of symptoms with bloody diarrhea is not consistent with Crohn disease. Patients with Crohn disease commonly present with a chronic history of abdominal pain, diarrhea, and weight loss. Disease involving the small intestine often causes nonbloody diarrhea, whereas hematochezia is more likely when the colon is involved. Cytomegalovirus colitis usually occurs in immunosuppressed patients, and peptic ulcer disease could present with bright red blood but only in the setting of a large and rapid bleed and could not explain the findings on the CT scan. Irritable bowel syndrome is a diagnosis of exclusion and does not present with rectal bleeding and the changes noted on the CT scan. Segmental thickening suggests a regional disorder rather than a systemic disorder.

Esophagectomy is the procedure with the highest likelihood of long-term cancer-free survival in patients with Barrett esophagus and high-grade-dysplasia.

The rationale for surveillance in patients with Barrett esophagus is that removal of premalignant lesions or in situ malignancies results in superior outcome to treatment of more advanced lesions. Esophagectomy is the procedure of choice to remove all diseased tissue, despite the rigors of the procedure. Resections performed for confirmed high-grade dysplasia have been shown to contain adenocarcinoma in up to 50% of cases. Less invasive approaches, such as ablative therapies and endoscopic mucosal resection, have shown promise, but esophagectomy is still considered the optimal procedure for long-term, disease-free survival.

Endoscopic mucosal resection used in selected patients with mass lesions and without radiographic evidence of lymphatic spread has been associated with excellent 5-year survival rates, but when such lesions arise in the setting of high-grade dysplasia, ablative therapies must accompany the treatment strategy. Photodynamic therapy is an ablative technique that showed early promise in the endoscopic treatment of high-grade dysplasia, but the procedure is associated with an unacceptable incidence of esophageal strictures and has largely been abandoned. Radiofrequency ablation of dysplastic tissue allows therapy of the mucosa with a shallower zone of tissue injury and results in a lower incidence of esophageal stricture. Long-term results for this approach are not yet available. Combined chemotherapy and radiation therapy is a palliative approach used only in patients with unresectable disease. Repeat endoscopy with biopsy is insufficiently aggressive in this patient with confirmed high-grade dysplasia arising in Barrett esophagus.

Uncomplicated diverticulitis is treated with antibiotics to cover gram-negative and anaerobic bacteria, such as a fluoroquinolone and metronidazole.

This patient has uncomplicated diverticulitis; her left lower quadrant pain, fever, and leukocytosis all suggest the diagnosis, and the CT findings confirm it. Uncomplicated mild diverticulitis can be treated in the outpatient setting using broad-spectrum antibiotics such as ciprofloxacin and metronidazole for 7 to 10 days and a soft diet. Patients who are unable to maintain oral intake require hospitalization. As symptoms improve, a full diet can be resumed. The role of diet in preventing recurrence is not well documented, although patients are often asked to follow a high-fiber diet. Four to eight weeks after resolution, patients should undergo evaluation of the colon to exclude other disorders that may mimic diverticulitis, such as a malignancy.

A first-generation cephalosporin, such as cephalexin, is not appropriate because it has poor coverage of many gram-negative aerobic and anaerobic bacteria. A flexible sigmoidoscopy would not provide any additional useful information and may actually be harmful as perforation risk is likely higher in the setting of acute inflammation.

This patient has mild nausea with no vomiting and is able to eat and maintain oral hydration. If she should deteriorate and not tolerate oral feedings, the patient should be given intravenous fluids and parenteral pain control as needed, as well as intravenous antibiotics. Surgical consultation for sigmoid resection would not be appropriate at this time but may be indicated if she develops recurrent episodes of diverticulitis or a complication such as fistula, obstruction, or abscess.

Fatigue, pruritus, an elevated alkaline phosphatase concentration, and the presence of antimitochondrial antibodies strongly suggest the diagnosis of primary biliary cirrhosis and are unusual in other liver disorders.

This patient likely has primary biliary cirrhosis, and measurement of antimitochondrial antibody is a highly sensitive and specific test for the disorder; more than 95% of patients with primary biliary cirrhosis have antimitochondrial antibodies and the false positive rate is approximately 2%. Fatigue, pruritus, an elevated alkaline phosphatase concentration, and the presence of these antibodies strongly suggest this diagnosis and are unusual in other liver disorders, such as acute and chronic hepatitis and alcoholic liver disease. Although fatigue and pruritus used to be the most common presenting symptoms of primary biliary cirrhosis, the disease is now more widely recognized and many patients are diagnosed at earlier stages when they are asymptomatic. Imaging tests should be obtained in patients with chronic cholestasis to exclude extrahepatic bile duct obstruction or other biliary tree abnormalities (i.e., sclerosing cholangitis) in patients with a history of colitis.

If the antimitochondrial antibody is positive, liver biopsy is useful to provide evidence that would stage the disease and rule out drug toxicity or other liver disorders that may cause cholestasis similar to that associated with primary biliary cirrhosis. α1-Antitrypsin deficiency would present with abnormal aminotransferase concentrations, not with a cholestatic picture. A serum protein electrophoresis may demonstrate elevation in serum IgM, but would not be diagnostic of primary biliary cirrhosis.