Carl Freter

Insight into Sweet's syndrome and associated-malignancy: A review of the current literature

Sweets syndrome (acute febrile neutrophilic dermatosis) is an infrequent skin disease characterized by sudden onset of fever, leucocytosis and erythematous plaques or nodules infiltrated by neutrophils. There are three main clinical settings in which Sweets syndrome has been described: classical or idiopathic Sweets syndrome, malignancy-associated Sweets syndrome and drug-induced Sweets syndrome. Classical Sweets is often preceded by an upper respiratory tract infection and may be associated with inflammatory bowel disease and pregnancy. Approximately 21% of patients have an associated malignancy, most commonly hematological disease. The syndrome may occur as a paraneoplastic accompaniment to established cancer or may be a first sign of malignancy or its recurrence. The incidence is said to be increasing in recent years due to the frequent use of growth factors in cancer patients. Several anticancer agents including all-trans-retinoic acid proteosome inhibitors, hypomethylating agents, tyrosine kinase inhibitors and lenalidomide are potential harbingers of Sweets syndrome. Unfortunately, little is known about the pathophysiology of Sweets syndrome and there are no established guidelines for treatment of malignancy-associated Sweets syndrome. Systemic corticosteroids are the mainstay of treatment. Sweets syndrome caused by anticancer agents sometimes involves withdrawal or temporary discontinuation of anticancer agents, use of systemic corticosteroids and/or rechallenge with either with the same anticancer agents or different agents. This report provides insights into the pathophysiology, clinical presentation, diagnostic work, differential diagnosis and management of malignancy-associated Sweets syndrome published in reported cases.

Lung cancer screening: from imaging to biomarker

Despite several decades of intensive effort to improve the imaging techniques for lung cancer diagnosis and treatment, primary lung cancer is still the number one cause of cancer death in the United States and worldwide. The major causes of this high mortality rate are distant metastasis evident at diagnosis and ineffective treatment for locally advanced disease. Indeed, approximately forty percent of newly diagnosed lung cancer patients have distant metastasis. Currently, the only potential curative therapy is surgical resection of early stage lung cancer. Therefore, early detection of lung cancer could potentially increase the chance of cure by surgery and underlines the importance of screening and detection of lung cancer. In the past fifty years, screening of lung cancer by chest X-Ray (CXR), sputum cytology, computed tomography (CT), fluorescence endoscopy and low-dose spiral CT (LDCT) has not improved survival except for the recent report in 2010 by the National Lung Screening Trial (NLST), which showed a 20 percent mortality reduction in high risk participants screened with LDCT compared to those screened with CXRs. Furthermore, serum biomarkers for detection of lung cancer using free circulating DNA and RNA, exosomal microRNA, circulating tumor cells and various lung cancer specific antigens have been studied extensively and novel screening methods are being developed with encouraging results. The history of lung cancer screening trials using CXR, sputum cytology and LDCT, as well as results of trials involving various serum biomarkers, are reviewed herein.

Iron deficiency anemia related to hereditary hemorrhagic telangiectasia: response to treatment with bevacizumab.

Hereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant condition associated with arteriovenous malformations (AVMs) or telangiectasias of the pulmonary, gastrointestinal or hepatic circulations. The authors present a case of a 52-year-old woman with a known diagnosis of HHT who presented for evaluation of anemia. She had an extensive history of iron sucrose infusions, frequent blood transfusions and hospitalizations for anemia related to gastrointestinal bleeding and epistaxis. The patient was treated with bevacizumab at a dose of 5 mg/kg infusion every 2 weeks for 4 cycles. In the next 4 months, her hemoglobin improved to 13.7 g/dL and she did not require iron or packed red blood cell transfusions for the next 8 months. Abnormal angiogenesis primarily due to mutations in the transforming growth factor β receptor endoglin and the activin receptor-like kinases is a central contributor to the formation of AVMs in HHT. Bevacizumab is a monoclonal antibody against vascular endothelial growth factor and therefore may be a useful treatment against AVM formation in patients with HHT. The authors do caution that therapy has to be individualized as there are no randomized trials regarding its usage in patients with HHT.

Thromboprophylaxis and Incidence of Venous Thromboembolism in Patients With Hemophilia A or B Who Underwent High-Risk Orthopedic Surgeries.

Total hip replacement (THR) and total knee arthroplasty (TKA) carry a high risk of postoperative venous thromboembolism (VTE); therefore, anticoagulation prophylaxis is recommended in these patients. Unfortunately, there are no guidelines about VTE prophylaxis in patients with hemophilia who underwent these high-risk surgeries. To determine whether these patients have high risk of VTE, we conducted a retrospective study on patients with hemophilia who underwent elective THR/TKA at our institute from 2004 to 2012. Postoperatively, we collected information on duration and method of factor VIII/IX infusion, VTE-prophylaxis, and complications. There were 23 patients with hemophilia, 18 (78%) with hemophilia A and 5 (22%) with hemophilia B, who underwent high-risk surgeries (39% THR and 61% TKA). The VTE prophylaxis included sequential compression device, 12 (52%), and prophylactic enoxaparin, 1 (4%). Ten (43%) patients did not receive VTE prophylaxis. At 1-year follow-up, we did not find any evidence of clinical VTE in our patients. Better risk stratification is needed to identify patients who would benefit from pharmacological prophylaxis.

Targeting cholesterol synthesis increases chemoimmuno-sensitivity in chronic lymphocytic leukemia cells.

BackgroundCholesterol plays an important role in cancer development, drug resistance and chemoimmuno-sensitivity. Statins, cholesterol lowering drugs, can induce apoptosis, but also negatively interfere with CD-20 and rituximab-mediated activity. Our goal is to identify the alternative targets that could reduce cholesterol levels but do not interfere with CD-20 in chemo immunotherapy of chronic lymphocytic leukemia (CLL).MethodsMEC-2 cells, a CLL cell line, and the peripheral blood mononuclear cells (PBMCs) from CLL patients were treated with cholesterol lowering agents, and analyzed the effect of these agents on cholesterol levels, CD-20 expression and distribution, and cell viability in the presence or absence of fludarabine, rituximab or their combinations.ResultsWe found that MEC-2 cells treated with cholesterol lowering agents (BIBB-515, YM-53601 or TAK-475) reduced 20% of total cellular cholesterol levels, but also significantly promoted CD-20 surface expression. Furthermore, treatment of cells with fludarabine, rituximab or their combinations in the presence of BIBB-515, YM-53601 or TAK-475 enhanced MEC-2 cell chemoimmuno-sensitivity measured by cell viability. More importantly, these cholesterol lowering agents also significantly enhanced chemoimmuno-sensitivity of the PBMCs from CLL patients.ConclusionOur data demonstrate that BIBB-515, YM53601 and TAK-475 render chemoimmuno-therapy resistant MEC-2 cells sensitive to chemoimmuno-therapy and enhance CLL cell chemoimmuno-sensitivity without CD-20 epitope presentation or its downstream signaling. These results provide a novel strategy which could be applied to CLL treatment.

Postoperative bleeding in an elderly patient from acquired factor V inhibitor: rapid response to immunosuppressive therapy.

Acquired factor V inhibitor is a rare but potentially life-threatening hemorrhagic disorder caused by the development of autoantibodies directed against coagulation factor V. The management of acute bleeding and inhibitor eradication is the mainstay of the treatment. The authors report a case of a 79-year-old man who underwent right hip arthroplasty and postoperatively, when on Coumadin for deep venous thrombosis prophylaxis, developed bleeding from the surgical site with a hematoma and abnormal coagulation parameters. Further workup revealed an acquired factor V inhibitor. The approach to treat this rare and challenging disorder is discussed. The patient responded rapidly with disappearance of factor V inhibitor titers after initiation of treatment with rituximab, prednisone and cyclophosphamide.

Gemcitabine and cisplatin-induced tumor lysis syndrome in a patient with gallbladder carcinoma: A case report

We report a case of tumor lysis syndrome (TLS) in a patient with gallbladder carcinoma. TLS has not been reported in association with this type of tumor. TLS typically occurs in cases of highly proliferative hematological malignancies and small cell carcinoma. Two factors that may have contributed to TLS in this case include multifactorial mild acute renal failure shortly before the administration of chemotherapy and the aggressive morphology of the gallbladder carcinoma, which was a poorly differentiated sarcomatoid variant. This case raises concern for the development of TLS in certain types of patients with solid tumors.