Many faces of angioedema: focus on the diagnosis and management of abdominal manifestations of hereditary angioedema.

Angioedema of the intestinal tract is an infrequent but well-described cause of abdominal pain that can occur because of inherited, acquired, allergic, or drug-induced causes. Hereditary angioedema (HAE) is a genetic disorder that causes recurrent attacks of severe edema of various body parts, including the intestinal tract. Moderate to severe abdominal pain occurs in 43-93% of such attacks due to intestinal edema. Laryngeal edema is a potentially life-threatening manifestation. Failure to recognize and diagnose HAE or other causes of intestinal angioedema can lead to years of delay in diagnosis, and in the case of HAE, often to unnecessary abdominal surgeries. Recognizing the typical history of recurrent attacks of abdominal pain, oropharyngeal/laryngeal angioedema or cutaneous angioedema, family history of similar symptoms, association of attacks with stress or menses, and exacerbation of attacks after administration of estrogens or angiotensin-converting enzyme inhibitors will increase diagnostic accuracy. Interdisciplinary treatment is often necessary after the diagnosis of HAE, first with acute management in the emergency room or the intensive care unit, followed by either drug prophylaxis against future attacks using a C1-esterase inhibitor concentrate or attenuated androgens and discontinuation of medications known to trigger attacks. Newer drugs approved for treatment of acute attacks may have future roles in the prevention of attacks if further studies support their efficacy. Gastroenterologists in particular should maintain a high index of suspicion for the possibility of HAE or other causes of intestinal angioedema in patients with a history of recurrent abdominal pain.

Diagnosis and management of angioedema with abdominal involvement: a gastroenterology perspective.

Abdominal involvement in angioedema is often a challenge to diagnose. Acute onset abdominal pain is its most common presenting symptom, and misdiagnosis may lead to unnecessary surgical intervention. Familiarity with the types and presentations of angioedema can be invaluable to clinicians as they consider the differential diagnoses of a patient presenting with abdominal pain. Detailed personal and family histories, careful physical examination of the patient, combined with knowledge of angioedema types, can help clinicians perform their diagnostic evaluation. An accurate diagnosis is essential in order to provide appropriate treatment to patients with angioedema. Depending upon the diagnosis, treatment may be the avoidance of provoking factors (such as allergens or medications), inhibiting histamine-provoked reactions, or treating C1 esterase inhibitor deficiency.

Octreotide therapy for advanced hepatocellular carcinoma.

Treatment options for advanced hepatocellular carcinoma (HCC) remain limited. Recently, octreotide has been proposed for therapy, although its efficacy remains controversial. Thus, the aim of this open-label pilot study was to evaluate the response of HCC to long-acting octreotide (Sandostatin LAR). Thirty patients were enrolled for this prospective 2-year trial. Initially, patients were given short acting octreotide to ensure drug tolerability. Thereafter, patients received long-acting octreotide 30 mg IM every 4 to 6 weeks. Measurable disease was assessed at 3-month intervals. Five of 30 patients were unable to tolerate the test dose, and 1 patient was reevaluated and underwent hepatic resection. The remaining 24 patients, who received long-acting octreotide, all had advanced stage of disease with multifocal-massive morphology (67%), vascular thrombosis (63%), or extrahepatic spread (17%), but well compensated liver disease. The treatment was well tolerated, except for diarrhea. Median time to tumor progression was 3.6 months, and median survival was 5.1 months. Seven patients (29%) had stable disease (median duration of 8.0 months) with 2 patients demonstrating disease stability for 24 months. In conclusion, although occasional patients appear to have stable disease on long-acting octreotide therapy, overall the beneficial response in terms of time to tumor progression and survival is limited.

Angioedema. Pathogenesis, differential diagnosis, and treatment.

Angioedema is a constellation of syndromes that present a great challenge to the clinician. The term "angioedema" describes the localized, transient, episodic edema of the deeper layers of the skin or of the mucosa of the gastrointestinal tract. Although angioedema may affect any part of the body, the skin and gastrointestinal tract are involved most commonly by far. Episodic abdominal pain arising from angioedema affecting any intra-abdominal organ may occur without skin angioedema; therefore, angioedema must be included in the differential diagnosis of intermittent, unexplained abdominal pain. Angioedema is caused by extravasation of plasma in the affected areas, which at times is accompanied by nonspecific, minimal cellular infiltrate. The most commonly identified causes of angioedema are medications, allergens, and physical agents, but most angioedema is idiopathic. Rare forms of angioedema associated with either hereditary or acquired faulty activation of the complement and kallikrein-kinin systems have been extensively described. Taking a comprehensive personal and family history, performing a physical examination, and compulsively monitoring the response to therapy are the most rewarding and cost-effective diagnostic and treatment tools. Diligent and knowledgeable follow-up by the attending physician spares patients costly and unnecessary tests as well as harmful treatment. The most effective treatment depends on the identification of the causative mechanism and--especially when the mechanism is not identified--on the clinician's knowledge and experience with innovative therapeutic regimens.

COX-2 inhibits Fas-mediated apoptosis in cholangiocarcinoma cells.

Fas expression has been shown to negatively regulate the progression of cholangiocarcinoma cells in xenografts. However, many human cholangiocarcinomas express Fas, suggesting these cancers have developed mechanisms to inhibit Fas-mediated apoptosis. Cyclooxygenase-2 (COX-2), which generates prostanoids, is expressed by many cholangiocarcinomas. Therefore, our aim was to determine whether COX-2 expression inhibits death receptor--mediated apoptosis in KMBC cells, a cholangiocarcinoma cell line. These cells express messenger RNA for the death receptors Fas, tumor necrosis factor receptor 1 (TNF-R1), death receptor 4 (DR4), and DR5. Agonists for these death receptors, CH-11, TNF-alpha, and TRAIL all induced apoptosis. However, COX-2, whether induced by proinflammatory cytokines or transient transfection, only significantly inhibited Fas-mediated apoptosis. The COX-2 inhibitor NS-398 restored Fas-mediated apoptosis in COX-2 transfected cells. Prostaglandin E2 reduced apoptosis and mitochondrial depolarization after treatment with the Fas agonist CH-11. Of a variety of antiapoptotic proteins examined, COX-2/prostaglandin E2 only increased expression of Mcl-1, an antiapoptotic member of the Bcl-2 family. In conclusion, these data suggest that prostanoid generation by COX-2 specifically inhibits Fas-mediated apoptosis, likely by up-regulating Mcl-1 expression. Pharmacologic inhibition of COX-2 may be useful in augmenting Fas-mediated apoptosis of cholangiocarcinoma cells.

Hereditary angioedema as a cause of transient abdominal pain.

Isolated angioedema, without urticaria or itching, occurs as a result of an inherited or acquired defect in C1 esterase inhibitor activity. Most cases of isolated angioedema are caused by one of two types of hereditary angioedema (HAE). We present a case of the much rarer type II HAE with abdominal pain as the sole presenting symptom. Hereditary angioedema should be suspected in young adults with episodic abdominal pain for which common causes have been excluded. A history of HAE or episodic abdominal pain in family members is not necessary for diagnosis.