Symptomatic and incidental thromboembolism are both associated with mortality in pancreatic cancer.

Pancreatic cancer is known to be associated with VTE, but contemporary rates of incidental and symptomatic VTE events and their association with mortality are incompletely understood. We conducted a retrospective cohort study of consecutive pancreatic adenocarcinoma patients at the University of Rochester from 2006-2009. Data were analysed using a Cox model with time-dependent covariates. A total of 1,151 radiologic exams of 135 patients were included. Forty-seven patients (34.8%) experienced VTE including 12 pulmonary emboli (PE), 28 deep-vein thromboses (DVTs) and 47 visceral vein events. Incidental events comprised 33.3% of PEs, 21.4% of DVTs and 100% of visceral VTE. Median (95% CI) conditional survival beyond three months was 233 (162-322) more days for those without VTE, which was significantly greater than 12 (3-60) days for those with DVT as first event (p<0.0001) and 87 (14-322) days with visceral first events (p=0.022). In multivariate analysis, DVT (HR 25, 95% CI 10-63, p <0.0001), PE (HR 8.9, 95% CI 2.5-31.7, p = 0.007) and incidental visceral events (HR 2.6, 95% CI 1.6-4.2, p =0.0001) were all associated with mortality, though anticoagulants reduced these risks by 70% (26-88%, p = 0.009). In conclusion, VTE occurs in over one-third of contemporary pancreatic cancer patients and, whether symptomatic or incidental, is strongly associated with worsened mortality. The role of anticoagulation in treating incidental or visceral VTE warrants further study.

Rituximab in indolent lymphomas.

Indolent non-Hodgkin lymphoma (NHL) comprises a group of incurable, generally slow-growing lymphomas highly responsive to initial therapy, with a relapsing and progressive course. Rituximab, an anti-CD20 antibody, has had a large impact on the treatment of indolent NHL. Its effectiveness as a single agent and in conjunction with known chemotherapy regimens has made it a standard of care in the treatment of NHL. Analysis of data obtained from NHL clinical trials, as well as data from the National Cancer Institute, indicate that the overall survival (OS) of patients with indolent NHL has improved since the discovery of rituximab. Given its effectiveness and tolerability, rituximab is currently being investigated as a maintenance agent with encouraging results. This review summarizes several landmark trials utilizing rituximab as a single agent and in combination with chemotherapy for treatment of NHL. In addition, a review of the studied rituximab maintenance dosing schedules and its impact on NHL will be presented. Overall, rituximab has changed the landscape for treatment of indolent NHL; however, additional research is necessary to identify the optimal dosing schedule, as well as patients most likely to respond to prolonged rituximab therapy.

Cancer patients and awareness of venous thromboembolism.

Cancer-associated thrombosis leads to morbidity and mortality in cancer patients. We sought to ascertain awareness of venous thromboembolism (VTE) and receptiveness to thromboprophylaxis amongst ambulatory cancer patients. In all 190 patients completed the survey over a three-week period. Of these, 100 patients (53%) reported unawareness of the increased risk of thrombosis with malignancy. Of the examined patients, 161 (86%) were willing to use oral anticoagulant for prophylaxis, and 86 (46%) were willing to perform daily anticoagulant injections. This study reveals an alarming lack of knowledge amongst patients regarding the increased risk of thrombosis. Informed patients are willing to use prophylaxis, if its effectiveness is established.

New insights into cancer-associated thrombosis.

Venous thromboembolism (VTE) is an increasingly frequent complication of anticancer therapy. The underlying mechanisms are not completely understood, but are related in part to oncogene activation and tissue factor (TF) expression. Several risk factors have been identified including site and stage of cancer, patient comorbidities, and specific therapeutic agents. Candidate biomarkers such as blood counts, TF, and P-selectin have recently been identified. A risk model predictive of chemotherapy-associated VTE has been validated. Thromboprophylaxis with low molecular weight heparin (LMWH), unfractionated heparin (UFH), or fondaparinux is recommended for hospitalized medical and surgical cancer patients. Long-term anticoagulation with LMWH is safe and effective in reducing recurrent VTE in cancer. The role of thromboprophylaxis in ambulatory cancer patients receiving chemotherapy is an area of active investigation.

The PXL1 gene of Saccharomyces cerevisiae encodes a paxillin-like protein functioning in polarized cell growth.

The Saccharomyces cerevisiae open reading frame YKR090w encodes a predicted protein displaying similarity in organization to paxillin, a scaffolding protein that organizes signaling and actin cytoskeletal regulating activities in many higher eucaryotic cell types. We found that YKR090w functions in a manner analogous to paxillin as a mediator of polarized cell growth; thus, we have named this gene PXL1 (Paxillin-like protein 1). Analyses of pxl1Delta strains show that PXL1 is required for the selection and maintenance of polarized growth sites during vegetative growth and mating. Genetic analyses of strains lacking both PXL1 and the Rho GAP BEM2 demonstrate that such cells display pronounced growth defects in response to different conditions causing Rho1 pathway activation. PXL1 also displays genetic interactions with the Rho1 effector FKS1. Pxl1p may therefore function as a modulator of Rho-GTPase signaling. A GFP::Pxl1 fusion protein localizes to sites of polarized cell growth. Experiments mapping the localization determinants of Pxl1p demonstrate the existence of localization mechanisms conserved between paxillin and Pxl1p and indicate an evolutionarily ancient and conserved role for LIM domain proteins in acting to modulate cell signaling and cytoskeletal organization during polarized growth.