Catastrophic Arteriovenous Thromboembolism as Initial Manifestation of Pancreatic Cancer

  Context The association between cancer and thrombosis is well-known. Among gastrointestinal malignancies, pancreatic cancer has perhaps the strongest association with thromboembolic events. However, simultaneous arterial and venous thromboses affecting multiple organs at the time of initial diagnosis is rare, with an incidence of less than 1%. Case report We report herein a case of a 61-year-old woman who presented with digital ischemia, a non-ST elevation myocardial infarction and an ischemic stroke, along with deep vein thromboses and pulmonary embolism. She was subsequently diagnosed with metastatic pancreatic cancer. Discussion This report highlights the intriguing association between pancreatic cancer biology, tumor metastases, and triggering of venous and arterial thromboembolic events. Current evidence points towards early thromboembolic phenomena as a harbinger of poor outcome in pancreatic cancer, and studies attempting to define the role of prophylactic anticoagulation in these patients are ongoing. 

Lasers, stem cells, and COPD

The medical use of low level laser (LLL) irradiation has been occurring for decades, primarily in the area of tissue healing and inflammatory conditions. Despite little mechanistic knowledge, the concept of a non-invasive, non-thermal intervention that has the potential to modulate regenerative processes is worthy of attention when searching for novel methods of augmenting stem cell-based therapies. Here we discuss the use of LLL irradiation as a "photoceutical" for enhancing production of stem cell growth/chemoattractant factors, stimulation of angiogenesis, and directly augmenting proliferation of stem cells. The combination of LLL together with allogeneic and autologous stem cells, as well as post-mobilization directing of stem cells will be discussed

Intravenous ascorbic acid to prevent and treat cancer-associated sepsis?

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis

Generalized cerebral atrophy seen on MRI in a naturally exposed animal model for creutzfeldt-jakob disease

<p>Abstract</p> <p>Background</p> <p>Magnetic resonance imaging has been used in the diagnosis of human prion diseases such as sCJD and vCJD, but patients are scanned only when clinical signs appear, often at the late stage of disease. This study attempts to answer the questions "Could MRI detect prion diseases before clinical symptoms appear?, and if so, with what confidence?"</p> <p>Methods</p> <p>Scrapie, the prion disease of sheep, was chosen for the study because sheep can fit into a human sized MRI scanner (and there were no large animal MRI scanners at the time of this study), and because the USDA had, at the time of the study, a sizeable sample of scrapie exposed sheep, which we were able to use for this purpose. 111 genetically susceptible sheep that were naturally exposed to scrapie were used in this study.</p> <p>Results</p> <p>Our MRI findings revealed no clear, consistent hyperintense or hypointense signal changes in the brain on either clinically affected or asymptomatic positive animals on any sequence. However, in all 37 PrP^Scpositive sheep (28 asymptomatic and 9 symptomatic), there was a greater ventricle to cerebrum area ratio on MRI compared to 74 PrP^Scnegative sheep from the scrapie exposed flock and 6 control sheep from certified scrapie free flocks as defined by immunohistochemistry (IHC).</p> <p>Conclusions</p> <p>Our findings indicate that MRI imaging can detect diffuse cerebral atrophy in asymptomatic and symptomatic sheep infected with scrapie. Nine of these 37 positive sheep, including 2 one-year old animals, were PrP^Scpositive only in lymph tissues but PrP^Scnegative in the brain. This suggests either 1) that the cerebral atrophy/neuronal loss is not directly related to the accumulation of PrP^Scwithin the brain or 2) that the amount of PrP^Scin the brain is below the detectable limits of the utilized immunohistochemistry assay. The significance of these findings remains to be confirmed in human subjects with CJD.</p

Immune alterations in untreated and treated multiple myeloma

The incidence of second malignancies was shown to be increased in patients with multiple myeloma. Although a shared genetic predisposition or common environmental carcinogens may account for the occurrence of both myeloma and additional cancers, multiple immune defects encountered in myeloma might play an important role in this regard. This review explores the impairments in both cellular and humoral mediated immunity in multiple myeloma, linking them with increased susceptibility to infections and additional cancers. In addition, the recent therapeutic advances transformed myeloma into a chronic entity, with multiple relapses and salvage therapies, which may result in cumulative immunosuppression. Although recent reports have suggested an increased rate of second cancers in myeloma patients treated with lenalidomide, the true impact of this agent and other novel anti-myeloma therapies on the incidence of additional malignancies remains to be clarified. </jats:p

Targeting macrophages in classical Hodgkin’s lymphoma may seem rational, but is it safe?

A few reports have linked increased numbers of tissue macrophages with treatment failure and reduced lifespan in classical Hodgkin’s lymphoma (HL) patients. Some investigators even suggested to target the macrophages in HL with biologic therapy, thus eliminating them from the tumor microenvironment. This review explores the risk: benefit equation of such approach as well as what the author believes is the driving force behind the ‘great’ migration of macrophages in HL. This article unravels the inflammatory pathways and immune alterations in classical HL that lead to a complex network consisting of T-cells, numerous cytokines, macrophages, and other cells. Macrophages are thought to play a crucial role in tumor antigen processing and presentation tasks, Reed–Sternberg (RS) cell phagocytosis, and antibody-dependent cellular cytotoxicity, therefore their extinction may be hazardous. The author believes RS cells should be targeted by the biologics, not the macrophages, and links his hopes with the existing investigational anti-CD30 therapies in relapsed/refractory classical HL. </jats:p

Bortezomib: friend or foe of hemolytic anemia?

Over the last decade, bortezomib moved in a stepwise fashion from a benchside promise into a bedside reality and is currently an important tool in the treatment of plasma cell disorders. This review focuses on the relationship between bortezomib and hemolytic anemia. In animal models with lupus-like disease, this agent was shown to deplete the auto-reactive plasma cells and serum autoantibody levels. In humans, two isolated reports advocate the efficacy of bortezomib in autoimmune hemolytic anemia, but important concerns remain with data interpretation and length bias. Conversely, bortezomib may be causative of hemolytic anemia, as reported in a cohort of patients with chronic lymphocytic anemia. Concerted efforts of both basic and clinical researchers are necessary to further explore the safety and efficacy of this agent in nonmalignant disorders, including autoimmune disorders and anemias. </jats:p

Bevacizumab in lung cancer: Lackluster performance and unjustified expense?

A recent retrospective analysis of a large cohort of patients aged 65 and older with advanced non-small cell lung cancer failed to demonstrate any improvement in survival with the addition of bevacizumab to the platinum doublet in the first-line therapy. A few points have to be made: 1) a vast majority of patients with lung cancer are 65 and older; 2) important including fatal toxicity can occur with the use of bevacizumab; and 3) costs of bevacizumab are significant. Integrating the conclusions of this study into clinical practice and further analysis of underlying physical, psychosocial, and economic hurdles of bevacizumab use in lung cancer patients are certainly justified. </jats:p