Cases from Brooke Army Medical Center

Sphincter of Oddi dysfunction, GI stromal tumor, alcoholic hepatitis, and more.


Case 1: Sphincter of Oddi dysfunction

The patient

A 40-year-old man was evaluated for new epigastric discomfort. During the last six months, he reported six episodes of cramping epigastric discomfort with radiation to the right shoulder lasting 1.5 to 4 hours. He noted associated symptoms, including nausea without vomiting, jaundice, and dark urine. He reported no fevers, chills, or weight loss. On presentation, he appeared comfortable and had normal vital signs. Physical examination was notable for scleral icterus and mild abdominal tenderness in all quadrants. There was no evidence of Murphy's sign, ascites, palpable mass, or hepatosplenomegaly. Cardiac and pulmonary examinations were unremarkable.

Review of laboratory values revealed normal blood counts, renal function, and lipase level. Liver tests were remarkable for elevated total bilirubin level of 4.0 g/dL (reference range, 0.1 to 1.2 mg/dL), direct bilirubin level of 2.5 g/dL (reference range, 0 to 0.3 mg/dL), aspartate aminotransferase level of 577 U/L (reference range, <35 U/L), and alanine aminotransferase level of 488 U/L (reference range, <35 U/L). Right upper quadrant ultrasound, hepatobiliary iminodiacetic acid (HIDA) scan, and magnetic resonance cholangiopancreatography revealed a normal gallbladder without evidence of cholelithiasis, normal-caliber common bile duct without stones or obstructive lesion, and normal gallbladder ejection fraction. Given his symptoms, elevated liver chemistries, and lack of obstructing lesion, he was diagnosed with a functional biliary sphincter of Oddi disorder and referred for endoscopic retrograde cholangiopancreatography (ERCP) with sphincterotomy.

The diagnosis

Sphincter of Oddi dysfunction (SOD) is related to stenosis or dyskinesia of the sphincter of Oddi and was previously categorized in three subtypes based on the combination of findings, including typical biliary colic, biliary ductal dilation, and dynamic elevations in liver tests during bouts of pain in the absence of an obstructing biliary lesion. Rome IV criteria have reclassified the phenotypes of SOD. Patients with all three of the above features (who were previously classified as having type I SOD) are considered to have biliary obstruction and should proceed to ERCP with sphincterotomy. Sphincterotomy results in improvement in greater than 90% of these patients. Patients with pain and either biliary dilation or elevated liver tests (previously type II SOD) are now diagnosed with “functional biliary sphincter of Oddi disorder.” Optimal management is controversial, and experts recommend either sphincter of Oddi manometry or empiric sphincterotomy in initial management. Approximately 60% to 70% of these patients improve with sphincterotomy. Patients with pain but no other features (previously type III SOD) are considered to have “functional abdominal pain.” ERCP has been shown to be no better than a sham procedure for treatment of these patients and is not recommended. The timing of testing is important as radiologic and laboratory manifestations can quickly normalize.

Pearls

  • SOD is a potentially curable condition that should be considered in patients with biliary colic and either dynamic liver chemistry elevation or biliary ductal dilation without an obstructing lesion.
  • The timing of laboratory and radiologic assessment is important in evaluating for SOD as abnormalities resolve quickly with resolution of symptoms.

Case 2: Bleeding gastrointestinal stromal tumor

The patient

A 51-year-old woman with a history of hypertension presented with a small amount of melena for several days. She also reported epigastric pain that improved after eating and said that she had had a similar history two to three years prior, associated with taking ibuprofen. On presentation, the patient had normal vital signs. Physical examination was unremarkable with the exception of melena in the rectal vault. Laboratory evaluation was notable for normocytic anemia with hemoglobin level of 6.5 g/dL (female reference range, 12.0 to 15.0 g/dL), a hematocrit of 19.7% (reference range, 36% to 44%), and an international normalized ratio of 1.1.

Endoscopic evaluation identified a 5-cm mass protruding into the gastric cardiac lumen with a small clean-based ulcerated area at the apex of the mass that bled on contact. A CT of the abdomen and pelvis revealed an 8-cm mass at the posterior gastric cardia. Endoscopic ultrasound with fine-needle aspiration was performed, with pathology from biopsies consistent with gastrointestinal stromal tumor. She was treated with neoadjuvant imatinib prior to surgical resection, and her melena resolved.

The diagnosis

Gastrointestinal stromal tumor (GIST) is a relatively rare cause of upper gastrointestinal bleeding. GISTs may be found in the esophagus, small intestine, colon, and rectum but are most commonly found in the stomach. Acute hemorrhage and abdominal pain are possible presenting symptoms. Therapy is typically surgery for all lesions greater than 2 cm. Previously, GISTs were known for very poor response to typical chemotherapy when locally advanced or metastatic, but the tyrosine kinase inhibitors have proven very effective. Whether initial surgery or neoadjuvant imatinib is optimal is still being determined, but National Comprehensive Cancer Network guidelines recommend neoadjuvant therapy if negative margins cannot be safely achieved in surgery, and if there is any unresectable, recurrent, or metastatic disease. High-risk characteristics include size greater than 5 cm, more than five mitoses per 50 high-powered fields, and anatomic location resulting in a potentially morbid resection. The severity of bleeding lesions must also be taken into account, with surgery required for brisk, life-threatening bleeding. Low-grade chronic bleeding is likely to resolve with neoadjuvant imatinib therapy.

Pearls

  • GISTs may cause acute gastrointestinal bleeding from any site in the GI tract.
  • Low-grade chronic bleeding from GISTs may be successfully controlled with neoadjuvant imatinib therapy.

Case 3: Alcoholic hepatitis

The patient

A 49-year-old man with a medical history of alcohol abuse, gastroesophageal reflux disease, chronic back pain, and hypertension was admitted to the hospital after reporting jaundice, decreased appetite, and dark stools for four to five days. He had been treating back pain with ibuprofen and increased alcohol intake. On presentation he was noted to be afebrile with a blood pressure of 102/68 mm Hg, a heart rate of 83 beats/min, a respiratory rate of 25 breaths/min, and an oxygen saturation of 97%.

Laboratory evaluation was notable for a total bilirubin level of 47.1 mg/dL (reference range, 0.1 to 1.2 mg/dL), direct bilirubin level greater than 20 mg/dL (reference range, 0 to 0.3 mg/dL), alkaline phosphatase level of 168 U/L (reference range, 33 to 131 U/L), aspartate aminotransferase level of 131 U/L (reference range, <35 U/L), alanine aminotransferase level of 56 U/L (reference range, <35 U/L), international normalized ratio of 1.6, platelet count of 101,000 cells/µL with a normal white blood cell count, and mild anemia. Serologic evaluation for alternative causes of chronic liver disease showed no significant abnormalities. A right upper quadrant ultrasound was negative for cholelithiasis or biliary ductal dilation.

The patient was diagnosed with severe alcoholic hepatitis, with a calculated Maddrey discriminant function (MDF) of 64. He was started on therapy with prednisolone, 40 mg daily for seven days, after which response to therapy was assessed with a repeat total bilirubin level that was found to be 43.6 mg/dL and a Lille score that was calculated to be 0.925. Prednisolone therapy was discontinued, and the patient eventually died of his illness.

The diagnosis

Alcoholic hepatitis is the most acute manifestation of alcoholic liver disease and has an increasing burden on the health care system. Short-term mortality is variable in alcoholic hepatitis and can be predicted with the MDF, Model for End-stage Liver Disease (MELD) score, and/or the Glasgow alcoholic hepatitis score. Patients with severe alcoholic hepatitis (defined by MDF >32) have high short-term mortality rates and may benefit from pharmacologic therapy with glucocorticoids in addition to general supportive management and alcohol abstinence. Glucocorticoid therapy typically consists of prednisolone, 40 mg daily for 28 days, followed by a two- to four-week taper. Prednisone requires activation in the liver, which can be variable in patients with chronic liver disease, making prednisolone the preferred agent.

The prolonged duration of prednisolone therapy required for alcoholic hepatitis carries risks of infection, gastrointestinal bleeding, and glucose intolerance, and so the drug should be withdrawn if not effective after a week of therapy. The Lille score is a method to determine clinical response that can be calculated after seven days of therapy. This score is determined by change in total bilirubin level in addition to age, renal insufficiency, albumin level, and prothrombin time. A Lille score greater than 0.45 indicates poor response and should result in discontinuation of glucocorticoid therapy.

Pearls

  • Response to glucocorticoid therapy in severe alcoholic hepatitis is variable and should be monitored given the risks associated with the prolonged therapy required.
  • A Lille score above 0.45 indicates a poor response to glucocorticoids and supports discontinuation of therapy.

Case 4: Chronic mesenteric ischemia

The patient

A 75-year-old man with a history of coronary artery disease, atrial fibrillation, and tobacco use presented with three months of intermittent lower abdominal pain. His pain began within 30 to 120 minutes of a meal and lasted approximately one to two hours. The pain was associated with diarrhea and improved with bowel movements or antacids. The patient also reported sitophobia (“food fear”) secondary to abdominal pain, which resulted in a 30-pound weight loss. His abdominal examination showed no distension, tenderness to palpation, rebound, or guarding. His white blood cell count and lipase level were within normal limits. Stool cultures, stool antigen for Entamoeba histolytica, and testing for ova and parasites were negative.

Figure 1 Coronal view from abdominal CT showing significant atherosclerosis in the abdominal aorta and the right and left common iliac arteries
Figure 1. Coronal view from abdominal CT showing significant atherosclerosis in the abdominal aorta and the right and left common iliac arteries.
Figure 2 Magnetic resonance angiography reconstruction showing high-grade stenosis of the proximal celiac artery (arrowhead) and occlusion of the superior mesenteric artery (arrow)
Figure 2. Magnetic resonance angiography reconstruction showing high-grade stenosis of the proximal celiac artery (arrowhead) and occlusion of the superior mesenteric artery (arrow).

An abdominal CT showed significant atherosclerotic disease (Figure 1), but the gallbladder, common bile duct, and pancreas were unremarkable. Abdominal magnetic resonance angiography (MRA) showed high-grade stenosis of the proximal celiac artery and occlusion of the proximal superior mesenteric artery (SMA) (Figure 2). Abdominal ultrasound with duplex confirmed celiac axis and SMA stenoses. The celiac and SMA velocities were 503 and 478 cm/s, respectively. The patient was treated with endovascular stenting of the SMA by vascular surgery, and his symptoms resolved.

The diagnosis

Chronic mesenteric ischemia was first described as “intestinal angina” by G.H. Goodman in 1918. Typical symptoms include postprandial abdominal pain, weight loss (80% of patients), sitophobia, nausea, vomiting, and diarrhea. Abdominal pain usually starts within 15 to 30 minutes after eating and can last up to two hours. Both a mismatch between splanchnic blood flow and intestinal metabolic demand and increased blood flow to the stomach in the postprandial period have been proposed as possible mechanisms. This condition has been associated with arterial dissection, vasculitis, fibromuscular dysplasia, radiation, and cocaine abuse. Approximately 50% of patients also have a history of coronary artery or peripheral vascular disease.

The diagnosis of chronic mesenteric ischemia can be supported by duplex ultrasonography, CT angiogram, magnetic resonance imaging/MRA, and traditional angiography. During duplex ultrasonography, peak systolic velocities of 200 cm/s or greater in the celiac artery or 275 cm/s or greater in the SMA (or inferior mesenteric artery) have a sensitivity of 92% and a specificity of 96% for a 70% or greater stenosis. Revascularization is indicated in symptomatic patients with documented splanchnic artery stenosis. These patients can be treated with percutaneous stenting or with open surgical revascularization.

Pearls

  • Chronic mesenteric ischemia is characterized by postprandial abdominal pain, weight loss, sitophobia, nausea, vomiting, and diarrhea.
  • In symptomatic patients with a documented splanchnic artery stenosis, surgical or percutaneous revascularization is indicated.

Case 5: Esophageal cancer in an immunocompromised patient

The patient

A 53-year-old man with HIV/AIDS (CD4&plus; cell count 92 cells/mm3, history of Kaposi's sarcoma, Mycobacterium avium complex infection) was admitted to the hospital for the evaluation of a six-month history of progressive dysphagia, odynophagia, and 40-pound weight loss. He initially experienced dysphagia with solid foods only, but it progressed to both solids and liquids. He became concerned when he could no longer swallow his antiretroviral drugs. He reported no other gastrointestinal symptoms. Of note, the patient reported a history of Candida esophagitis approximately two years prior but was noted to have oral thrush at that time. His social history was significant for a 57 pack-year history of smoking and occasional alcohol use.

Figure 3 Lumen of the circumferential esophageal stricture, as seen through a neonatal endoscope given inability to traverse the stricture with a regular adult endoscope
Figure 3. Lumen of the circumferential esophageal stricture, as seen through a neonatal endoscope given inability to traverse the stricture with a regular adult endoscope.

Vital signs were normal. On physical examination, he was in no acute distress. There was no evidence of oral thrush, and his cardiovascular and lung examinations were unremarkable. He had no lymphadenopathy. He was evaluated by esophagogastroduodenoscopy (EGD) and found to have a circumferential stricture in his mid-esophagus, measuring approximately 9 cm in length (Figure 3). Multiple biopsies were obtained, which revealed invasive squamous-cell carcinoma.

The diagnosis

The two main types of esophageal malignancy are squamous-cell carcinoma (SCC) and adenocarcinoma. Current data indicate that the incidence of SCC has been decreasing in the United States, while the incidence of adenocarcinoma has increased. These changes have been postulated to be due to decreased alcohol and tobacco use and increases in body mass index and reflux disease, respectively. There is a possible association between HIV infection and an increased risk of non-AIDS cancers, especially those associated with infections and smoking. HIV infection has been found to be an independent risk factor for esophageal human papillomavirus infection. However, no evidence yet directly links HIV infection with an increased risk for SCC. SCC is more commonly located in the mid-esophagus (as in this patient), while adenocarcinomas are typically located in the distal esophagus near the gastroesophageal junction. Esophageal malignancies commonly present with “red flag” symptoms including progressive solid-food dysphagia and weight loss.

Immunosuppressed patients presenting with odynophagia and oral thrush can be empirically treated for Candida esophagitis. Endoscopic evaluation should be considered in patients who do not respond to Candida treatment within 72 hours, and in patients with “red flag” symptoms. Esophageal cancer, both in the immunocompetent and the immunocompromised patient, can be treated with various combinations of surgery, chemotherapy, and radiation. The specific therapeutic approach will vary, depending on tumor-node-metastasis staging. Unfortunately, the mortality associated with this disease remains high.

Pearls

  • Esophageal dysphagia is considered a “red flag” symptom, and this condition should be promptly evaluated by EGD in patients with risk factors for esophageal cancer.
  • Patients with HIV/AIDS presenting with odynophagia and oral thrush can be empirically treated for Candida esophagitis; endoscopic evaluation should be considered in patients who do not respond within 72 hours.