What are the causes of acute pancreatitis (AP)?

• Mechanical: gallstones, microlithiasis (biliary sludge), sphincter of Oddi dysfunction, papillary stenosis, duodenal diverticula, pancreas divisum, trauma
• Toxins: alcohol, drugs, scorpion venom
• Infectious: viral, bacterial, parasitic
• Metabolic: hypertriglyceridemia, hypercalcemia
• Ischemic: thromboembolic, vasculitis, hypotension, dehydration
• Genetic: cystic fibrosis, hereditary
• Tumors: ampullary, pancreatic, intraductal papillary mucinous tumors (IPMT)
• Other: idiopathic, postoperative, postendoscopic retrograde cholangiopancreatography (ERCP), pregnancy

What are the most common causes of acute pancreatitis?
Gallstones and alcohol abuse are the most common causes of AP in the United States, each accounting for at least 30-35% of cases. The leading etiology depends on the population studied; for instance, alcoholism may predominate in many inner cities.
Idiopathic AP, in which a source is not identified, ranks as the third leading cause of AP. Recent studies, however, have demonstrated the presence of microlithiasis in up to two thirds of these patients when they undergo further investigation with repeated gallbladder ultrasound or bile crystal analysis. The theory that many cases of idiopathic AP are caused by microlithiasis is supported by a reduction in recurrences of AP in patients who undergo endoscopic sphincterotomy or cholecystectomy when compared with untreated patients (10% vs. 73%, p<.01). Chemical dissolution with ursodeoxycholic acid can also prevent recurrences.

Which drugs have been reported to cause acute pancreatitis?
The list can be remembered by using the mnemonic “NO IDEA”:
N
NSAIDs (sulindac, salicylates)
O
Other (valproate)
I
IBD drugs (sulfasalazine, 5-aminosalicylic acid)
Immunosuppressants (l-asparaginase, azathioprine, 6-mercaptopurine)
D
Diuretics (furosemide, thiazides)
E
Estrogens
A
Antibiotics (metronidazole, sulfonamides, tetracycline, nitrofurantoin, stibogluconate)
AIDS drugs (didanosine, pentamidine)

Drug-induced pancreatitis can occur immediately upon initiation of the drug or be delayed by months.

How is pregnancy associated with acute pancreatitis?
Coexisting cholelithiasis or microlithiasis is present in about 90% of cases. Other causes include hyperlipidemia and medications. Most episodes occur in the third trimester or postpartum period. The overall prognosis is good.

Which infectious agents have been implicated in causing acute pancreatitis? Viruses (i.e., mumps, coxsackievirus, cytomegalovirus, varicella-zoster, herpes simplex, Epstein-Barr, hepatitis A, hepatitis B); bacteria (i.e., Mycoplasma, Legionella, Leptospira, Salmonella, tuberculosis, brucellosis); fungi (i.e., Aspergillus, Candida albicans); and parasites (Toxoplasma, cryptosporidium, ascaris, Clonorchis sinensis)

How do Clonorchis sinensis and ascaris cause acute pancreatitis?
These parasites cause AP by blocking the main pancreatic duct and obstructing drainage of pancreatic secretions.

Is there an increased incidence of acute pancreatitis in patients with acquired immunodeficiency syndrome (AIDS)?
Yes. Up to 10% of patients with AIDS develop AP. The cause is usually multifactorial, with drugs and infections being the most common. Read the rest of this entry »

What is Barrett’s esophagus?
Barrett’s esophagus is a metaplastic change in the lining of the normally squamous-lined esophagus that is recognized at endoscopy. As a result of gastroesophageal reflux disease, the esophagus is lined with intestinal metaplasia, a premalignant epithelium.

How is Barrett’s esophagus diagnosed?
The ultimate criterion for histologic diagnosis is the presence of goblet cells. Currently, two techniques are necessary: endoscopy to recognize abnormal-appearing esophageal epithelium and biopsy to detect intestinal metaplasia.

Why is Barrett’s esophagus important?
It is a premalignant lesion for adenocarcinoma of the esophagus and presumably for a proportion of adenocarcinomas of the gastric cardia. The cancer continuing to have the most rapidly rising incidence in the United States and Western Europe over the past three decades has been adenocarcinoma of the esophagus in white men. Read the rest of this entry »

Who is affected by pill-induced esophageal injury?
Anyone of any age who ingests caustic pills is susceptible to pill-induced injury. Reported cases range from ages 5-89. Women outnumber men by a ratio of 1.5:1. It is not uncommon for pills to stick in a normal esophagus during transit. One study showed that 36 of 49 normal subjects who assumed a supine position after swallowing a round, nonsticky barium tablet with 15 mL of water retained the tablet in the esophagus for 5-45 minutes. A more sticky gelatin tablet remained in the esophagus for more than 10 minutes in over one half of normal subjects who ingested the pill in a supine position. Esophageal dysmotility or structural abnormalities, such as rings or strictures, are clearly not required for pill-induced injury.

What factors contribute to esophageal retention of pills?
Esophageal clearance is determined by several factors, some of which can be modified to decrease the risk of pill-induced injury. Upright posture improves esophageal clearance of pills. The volume of water ingested with pills also affects clearance, although no study has identified the volume required to ensure passage through the esophagus. One study showed that 11 of 18 patients retained a barium pill swallowed with 15 mL of water compared with 3 of 18 who swallowed the pill with 120 mL of water. Other partially modifiable factors include structural abnormalities, such as rings or strictures, which can be dilated as needed. Abnormal esophageal motility is sometimes improved with pharmacologic agents, but motility is usually normal in patients with pill-induced injury. Taking the pill with inadequate fluid and lying down immediately afterward are often the only identifiable risk factors.

What are the risk factors for pill-induced injury?
Anyone who takes a caustic pill is at risk, but some patients are at particular risk for severe pill-induced esophageal injury, including those with structural abnormalities of the esophagus, both pathologic (stricture, tumor, ring) and physiologic (hiatal hernia, narrowing of the esophagus secondary to compression from the left atrium, aortic arch, left mainstem bronchus). Cardiac disease is a risk factor because of esophageal compression by a dilated left atrium and frequent use of inherently caustic medications (e.g., aspirin, potassium chloride, quinidine). Patients who have undergone thoracotomy are at increased risk because they are bedridden and may develop adhesions and fibrosis that trap the esophagus between the aorta and vertebral column, making it more susceptible to compression by an enlarged left atrium and thus decreasing esophageal clearance. Supine positioning during pill ingestion impairs esophageal clearance and places patients at risk. The stickiness of the pill surface, the inherent caustic nature of certain drugs, and the volume of liquid consumed with pills affect risk. Elderly patients and patients with underlying gastroesophageal reflux disease (GERD) are at increased risk. GERD may cause a more acidic environment; because many drugs, including nonsteroidal anti-inflammatory drugs (NSAIDs), are weak acids, their absorption into tissues is increased in an acidic environment.

Describe the typical presentation of patients with pill-induced injury.
The typical patient has no prior history of esophageal disease and presents with the sudden onset of retrosternal pain, which may have awakened the patient from sleep (particularly if pills were ingested with little liquid just before or while lying down) and may be exacerbated by swallowing. The pain may be mild or so severe that swallowing is impossible. The pain increases typically over the first 3-4 days before gradually subsiding. Painless dysphagia is uncommon (20%) and may suggest an alternative diagnosis. Less common symptoms and signs include dehydration, weight loss, fever, and hematemesis. Patients with preexisting esophageal problems, such as GERD, frequently present with worsening symptoms of heartburn, regurgitation, and dysphagia. Read the rest of this entry »

What is the incidence of esophageal cancer in the United States, and is it changing?
Esophageal cancer is relatively infrequent in the United States. The annual incidence is <10 of 100,000 population, whereas in some areas of China the annual incidence is >100 of 100,000. Over the past three decades, the incidence of distal esophageal adenocarcinoma has increased sharply in North America, whereas the incidence of squamous cell carcinoma of the esophagus has fallen. The rise in esophageal adenocarcinoma has been most marked in white men. Recent studies suggest that the incidence of esophageal adenocarcinoma is rising in African-American and Hispanic men. For unknown reasons, the disease remains rare in women. Although the absolute numbers of cases of esophageal cancer remain low, there has been a remarkable rise in the incidence of distal esophageal cancer over the past three decades in most developed countries, making it one of the most rapidly growing cancers in the United States. The decline in distal gastric cancers over the same period has been correlated with a decline in the prevalence of Helicobacter pylori infection in the United States.

What are the risk factors for the development of esophageal cancer?
Smoking and alcohol use have been associated with the development of squamous cell carcinoma of the esophagus, but they do not appear to be major risk factors for the development of esophageal adenocarcinoma. Squamous cell carcinoma is much more frequent in African Americans than in whites, whereas adenocarcinoma is much more frequent in whites. Frequent, long-standing heartburn is an important risk factor for the development of esophageal adenocarcinoma. In some studies, obesity has been shown to be an independent risk factor, and obese patients with reflux disease are at particularly high risk for the development of esophageal cancer. Recent studies have drawn an epidemiologic link between the widespread use of drugs that affect the lower esophageal sphincter and the increasing risk of esophageal cancer. A true cause-and-effect relationship has not been established. Diets low in fresh fruits and vegetables have also been associated with esophageal cancer.

What are the current recommendations for screening and surveillance of esophageal cancer in patients at risk?

1. Screening. Currently, there is no acceptable screening method for esophageal cancer in the United States. Some economic models have suggested that a one-time screening endoscopy to identify Barrett’s esophagus may be cost-effective in patients with long-standing reflux esophagitis, but the assumptions for the risk of developing cancer in Barrett’s esophagus in the model may be too high. The American College of Gastroenterology guidelines suggest that patients with chronic GERD are most likely to have Barrett’s esophagus and should undergo endoscopy.
2. Surveillance. Surveillance is recommended in patients with Barrett’s esophagus, and the grade of dysplasia determines the interval for surveillance. In patients with low-grade dysplasia as the highest grade after a 6-month follow-up endoscopy with concentrated biopsies in the area of dysplasia, annual endoscopy is recommended until there is no dysplasia. The finding of high-grade dysplasia requires a repeat endoscopy (after double-dose therapy with proton pump inhibitor). Special attention should be paid to any mucosal irregularity, and endoscopic mucosal resection should be considered. An intensive biopsy protocol should ideally be performed with a therapeutic endoscope and large-capacity biopsy forceps. An expert pathologist should confirm the interpretation of high-grade dysplasia. Focal high-grade dysplasia (less than five crypts) may be followed with a 3-month surveillance. Intervention should be considered in a patient with confirmed multifocal high-grade dysplasia. Surveillance endoscopy intervals are lengthening; when dysplasia is not found on two consecutive surveillance endoscopies, a 3-year interval for surveillance is recommended by the American College of Gastroenterology guidelines.

How is esophageal cancer diagnosed?
Endoscopy and biopsy are necessary for the diagnosis of esophageal cancer. Staging has become important in the management of patients with esophageal cancer. Staging helps determine the choice of treatment and is an important determinant of prognosis. Computed tomography (CT) of the chest and abdomen is the recommended initial test for staging.

Discuss the role of endoscopic ultrasound in the diagnosis and staging of esophageal cancer.
In patients who appear to have limited local disease on CT and no evidence of distant metastases, endoscopic ultrasound may be helpful in regional staging. Esophageal cancer is seen as a hypoechoic interruption of the layers of the esophagus. Endoscopic ultrasound is better than CT at staging the depth of insertion. This factor becomes important in deciding between different methods of curative therapy. For example, patients with cancer localized to the mucosa can be considered for mucosal resection, but deeper levels of invasion make this therapy inappropriate. Endoscopic ultrasound has better results in regional staging than the newest spiral CT scanners. Magnetic resonance imaging (MRI) has not been particularly helpful in imaging the depth of local invasion. Endoscopic ultrasound may also be helpful in the evaluation of mediastinal lymph nodes. Large nodes (>10 mm) that are uniformly hypoechoic are suspicious. Fine-needle aspiration under ultrasound guidance may help to establish lymph node involvement. Read the rest of this entry »

A 47-year-old hypertensive man has been treated with amlodipine 10 mg/day orally, for chronic stable angina pectoris and hypertension. He complains of ankle edema that worsened after her dose of amlodipine was recently increased. Are diuretics indicated?
Ankle edema is a common side effect of dihydropyridine calcium channel blockers, occurring in 7-20% of patients treated. It is a dose-dependent side effect and readily responds to down-titration of the calcium channel blocker dose. Another novel strategy to minimize the occurrence of this ankle edema is to combine calcium channel blockade with ACE inhibition. This combination is more effective than monotherapy with either drug in lowering blood pressure and is associated with lower prevalence of any dose-related side effects, including ankle edema.

Prehypertension
Data from the Framingham cohort indicate that blood pressure bears a linear relationship with cardiovascular risk down to a systolic blood pressure of 115 mm Hg; based on these data, it is recommended that individuals with blood pressures in the gray area of 120–139/80–89 mm Hg be categorized as having prehypertension. This demonstrates a trend away from defining hypertension as a simple numerical threshold and toward a more subtle appreciation of blood pressure as a component of overall cardiovascular risk. This trend gains support from increasing evidence for a relationship between blood pressure and disruption of cardiovascular function at levels below the hypertensive threshold. Because prehypertension often develops into hypertension (50% of people within 4 years), even low-risk prehypertensive patients should be monitored annually. Circumspection about labeling patients as hypertensive is warranted since there is evidence that simply telling someone that he or she has hypertension has unintended consequences, transforming a perception of general health into one of general ill-health.

How do you classify or stage HTN severity? Is this classification practically useful in your approach to antihypertensive drug therapy?
HTN is now classified into two stages, depending on whether BP is > 160/100 mmHg. Patients with stage 2 HTN (BP >1 60/100 mmHg) are rarely controlled to a goal BP of < 140/90 mmHg on a single BP-lowering drug. In fact, the ALLHAT trial as well as several other trials have shown that at least two or more drugs are needed in two thirds of hypertensives; in one third of hypertensive patients, three BP-lowering drugs may be needed to get BP to goal.

What are current guidelines for treatment of HTN?
To maximize BP control, the current guidelines recommend routine initiation of two BP-lowering drugs in patients with stage 2 HTN. This combination can include any of the following classes of antihypertensive drugs: thiazide diuretics, beta blockers, ACE inhibitors, or calcium channel blockers. Since thiazide diuretics are readily available, inexpensive, and as effective as calcium channel blockers or beta blockers in reducing cardiovascular complications of hypertension, they are generally recommended as an important part of any antihypertensive drug regimen. However, the selection of a specific antihypertensive drug class should take into consideration comorbid conditions associated with HTN, such as diabetes mellitus, heart failure, CAD, or renal failure as well as the patient’s tolerance of specific drug classes. Read the rest of this entry »

Define achalasia.
The term achalasia (Greek = lack of relaxation) describes the pathophysiologic hallmark of the disease: failure of the lower esophageal sphincter (LES) to relax. This term has replaced the previous designation cardiospasm, which implies an exaggerated state of contraction. The second cardinal feature is aperistalsis of the body of the esophagus. However, LES dysfunction is more important because gravity appears to be able to compensate for the lack of pumping ability in the body of the esophagus, in most cases.  

How common is achalasia?
Achalasia is a relatively uncommon disorder, with prevalence estimated at about 8 cases per 10,000 and an incidence rate approximately 0.5 new cases per year per 100,000. The incidence is increased with age, particularly after the seventh decade but equal between men and women.

Define vigorous achalasia.
The term vigorous is applied to cases of achalasia in which prominent contractions can be noticed in the body of the esophagus, either on radiography or by manometry. These contractions are simultaneous and therefore fulfill the manometric definition of aperistalsis required for the diagnosis of achalasia. They should be distinguished from isobaric waves, which can be seen in patients with achalasia and represent bolus-induced passive fluctuations in pressure within the common cavity of the dilated esophagus. Vigorous achalasia may represent an early stage of the disease.

What is the relationship between diffuse esophageal spasm (DES) and achalasia?
DES may be regarded as a “cousin” of achalasia. The primary manometric distinction between DES and vigorous achalasia is the presence of at least some normal peristalsis in the former. LES dysfunction is seen often in DES but to a lesser degree than in achalasia. Some evidence suggests that in a small subset (about 5% or less) of patients, DES may evolve into classic achalasia.

What is the major pathologic lesion in achalasia? How does it produce the disease?
Although other lesions have been described, including degeneration of the vagus nerve and changes in its dorsal motor nucleus, the myenteric plexus appears to be the major site of the disease. The characteristic finding is loss of ganglion cells, which appears to be selective for inhibitory neurons (those producing nitric oxide and/or vasoactive intestinal peptide [VIP]) with relative sparing of the cholinergic (stimulatory) nerves. Thus, the normal balance of excitatory and inhibitory neural input to smooth muscle is upset. The loss of inhibition, coupled with a relative preservation of the excitatory stimulus, may be responsible for the LES abnormalities. An inflammatory infiltrate, characteristically mononuclear, is also seen commonly in the myenteric plexus. It is speculated that unchecked inflammation at this site leads to neuronal destruction and, eventually, to the clinical manifestations of achalasia. Read the rest of this entry »