Thalidomide for the Management of Gastrointestinal Bleeding in a Palliative Care Setting.

BACKGROUND: Palliative care patients frequently present with clinically significant gastrointestinal bleeding. Due to the existence of confounding comorbidities and a remarkably reduced state of general health in many cases, the management of gastrointestinal bleeding in this population is often challenging. SUMMARY: This review summarizes and discusses the role of thalidomide in gastrointestinal bleeding with a special focus on palliative care patients. In addition, an illustrative case report is presented. Thalidomide may be beneficial in gastrointestinal bleeding by exerting antiangiogenic effects. The drug has an acceptable safety profile. Side effects like neurotoxicity may limit its use but can be monitored safely. Due to thalidomide's thrombin generation potential, patients managed with thalidomide-containing regimes should be closely monitored for deep venous thrombosis. Given its teratogenicity, thalidomide should not be administered to women of childbearing potential who are not using adequate contraception. KEY MESSAGE: Physicians caring for patients in a palliative care setting should be aware of thalidomide as an effective therapeutic option when endoscopy fails to find a bleeding source or for those patients who cannot or refuse to undergo endoscopy but present with recurrent or obscure gastrointestinal bleeding.

Expression of CD98hc in Pancreatic Cancer and Its Role in Cancer Cell Behavior.

Background: Cluster of differentiation 98 heavy chain (CD98hc) is a transmembrane protein, which functions both as a coreceptor of ß-integrins, enhancing intracellular integrin-dependent downstream signaling, and as a transporter of branched-chain and aromatic amino acids. As such, it is pivotal in cell cycle regulation and protection of oxidative, nutritional and DNA replication stress. Overexpression of CD98hc occurs widely in cancer cells and is associated with poor clinical prognosis. The role of CD98hc in pancreatic cancer remains to be elucidated. The aim of this study was to determine the expression of CD98hc in pancreatic ductal adenocarcinoma and to define its potential functional role in cancer cell biology. Methods: Immunohistochemical staining for CD98hc was performed on 222 tissue samples of patients with pancreatic ductal adenocarcinoma. The pancreatic cancer cell lines PANC-1 and BxPC-3 were used to determine the effect of CD98hc expression on cancer cell behavior using cell adhesion, cell trans-migration and cell spreading assays. Flow cytometry was performed to study the rate of apoptosis after detachment or serum starvation. shRNA-lentiviral constructs were used to knock down or reconstitute full length or mutated CD98hc. Results: Up to 20% of pancreatic ductal adenocarcinomas express CD98hc in the acinar cells (13%) and islet cells (20%) embedded in tumor tissue. Although expression of CD98hc in tumor tissue was not associated with a particular tumor stage or grade, our data show a trend towards longer overall survival of pancreatic cancer patients without CD98hc expression as compared to those with immunohistochemical positivity. In vitro downregulation of CD98hc in the pancreatic cancer cell lines PANC-1 and BxPC-3 significantly inhibits cell proliferation (p<0.05), self-renewal (p<0.05) and anchorage-independent growth (p<0.05). Conclusion: CD98hc is expressed in a remarkable percentage of pancreatic ductal adenocarcinomas. Due to its important role in cell behavior and malignant cell transformation, it may be a promising molecular target for potential new therapeutic approaches in pancreatic cancer in the future.

Pseudoachalasia as First Manifestation of a Malignancy.

Pseudoachalasia is a condition in which symptoms, radiologic, endoscopic, and manometric findings mimick idiopathic achalasia. About 4% of patients with a typical constellation for idiopathic achalasia will turn out to have pseudoachalasia, posing a major diagnostic challenge. A large spectrum of underlying causes of pseudoachalasia has been described. However, in about 70% of affected patients, this condition is caused by a malignancy (mostly adenocarcinoma of the esophagogastric junction or cardia). We describe a 16-year-old high school student referred for management of achalasia who turned out to have pseudoachalasia due to adenocarcinoma of the cardia. He was cured with preoperative chemotherapy followed by radical surgery. Therapy of pseudoachalasia secondary to neoplasia is directed against the tumor or may be palliative to keep the lumen open. Other causes of pseudoachalasia include esophageal motility disturbances as a paraneoplastic phenomenon (e.g., with small cell lung cancer), post fundoplication or post bariatric surgery, in association with a thoracic aortic aneurysm, or with sarcoidosis or amyloidosis. Therapy is directed accordingly to eliminate or correct the underlying cause.

D-lactic acidosis - case report and review of the literature.

D-lactic acidosis is a rare complication that occurs mainly in patients with malabsorption due to a surgically altered gastrointestinal tract anatomy, namely in short bowel syndrome or after bariatric surgery. It is characterized by rapid development of neurological symptoms and severe metabolic acidosis, often with a high serum anion gap. Malabsorbed carbohydrates can be fermented by colonic microbiota capable of producing D-lactic acid. Routine clinical assessment of serum lactate covers only L-lactic acid; when clinical suspicion for D-lactic acidosis is high, special assays for D-lactic acid are called for. A serum level of more than 3 mmol/L of D-lactate confirms the diagnosis. Management includes correction of metabolic acidosis by intravenous bicarbonate, restriction of carbohydrates or fasting, and antibiotics to eliminate intestinal bacteria that produce D-lactic acid. We report a case of D-lactic acidosis in a patient with short bowel syndrome and review the pathophysiology of D-lactic acidosis with its biochemical and clinical features. D-lactic acidosis should be considered when patients with short bowel syndrome or other malabsorption syndromes due to an altered gastrointestinal tract anatomy present with metabolic acidosis and neurological symptoms that cannot be attributed to other causes. With the growing popularity of bariatric surgery, this metabolic derangement may be seen more frequently in the future.