Adoption of single agent anticancer therapy for advanced hepatocellular carcinoma and impact of facility type, insurance status, and income on survival: Analysis of the national cancer database 2004-2014.

BACKGROUND: This study analyzes the pattern of use of single agent anticancer therapy (SAACT) in the treatment and survival of advanced hepatocellular carcinoma (aHCC) before and after sorafenib was FDA approved in 2007. METHODS: Adult patients diagnosed with HCC and treated with only ACT from 2004 - 2014 were identified in NCDB database. Patients were analyzed during three time frames: 2004-2006 (pre-sorafenib (PS)), 2007-2010 (early sorafenib (ES)) and 2011-2014 (late sorafenib (LS)). Cox proportional hazards models and Kaplan-Meier method were used for analyses. RESULTS: The NCDB contained 31,107 patients with HCC diagnosed from 2004-2014 and treated with ACT alone. Patients were generally men (78.0%), >50 years of age (92.5%). A significant increase in the rate of adaption of SAACT was observed over time: 6.2% PS, 15.2% ES, and 22.2% LS (p < 0.0001). During this later period, the highest proportion of SAACT is among academic and integrated network facilities (23.3%) as compared to community facilities (17.0%, p < 0.0001). The median overall survival of patients with aHCC treated only with SAACT improved significantly over time from 8.0 months (m) (95% CI: 7.4-8.8) to 10.7 m (10.4-11.2) to 15.6 m (15.2-16.0, p < 0.001). Multivariate analysis indicates worse outcomes for patients treated at community cancer programs (HR 1.28, (5% CI: 1.23-1.32), patients without insurance (HR 1.11, 1.06-1.16) and estimated household income of <$63,000 (HR 1.09, 1.05-1.13). CONCLUSION: aHCC patients treated only with ACT have experienced an overall improvement in survival, but significant differences exist between facility type, insurance status, and income.

Monitoring DOACs with a Novel Dielectric Microsensor: A Clinical Study.

BACKGROUND: There are acute settings where assessing the anticoagulant effect of direct oral anticoagulants (DOACs) can be useful. Due to variability among routine coagulation tests, there is an unmet need for an assay that detects DOAC effects within minutes in the laboratory or at the point of care. METHODS: We developed a novel dielectric microsensor, termed ClotChip, and previously showed that the time to reach peak permittivity (T peak) is a sensitive parameter of coagulation function. We conducted a prospective, single-center, pilot study to determine its clinical utility at detecting DOAC anticoagulant effects in whole blood. RESULTS: We accrued 154 individuals: 50 healthy volunteers, 49 rivaroxaban patients, 47 apixaban, and 8 dabigatran patients. Blood samples underwent ClotChip measurements and plasma coagulation tests. Control mean T peak was 428 seconds (95% confidence interval [CI]: 401-455 seconds). For rivaroxaban, mean T peak was 592 seconds (95% CI: 550-634 seconds). A receiver operating characteristic curve showed that the area under the curve (AUC) predicting rivaroxaban using T peak was 0.83 (95% CI: 0.75-0.91, p < 0.01). For apixaban, mean T peak was 594 seconds (95% CI: 548-639 seconds); AUC was 0.82 (95% CI: 0.73-0.91, p < 0.01). For dabigatran, mean T peak was 894 seconds (95% CI: 701-1,086 seconds); AUC was 1 (p < 0.01). Specificity for all DOACs was 88%; sensitivity ranged from 72 to 100%. CONCLUSION: This diagnostic study using samples from "real-world" DOAC patients supports that ClotChip exhibits high sensitivity at detecting DOAC anticoagulant effects in a disposable portable platform, using a miniscule amount of whole blood (<10 µL).

Contribution of platelets, the coagulation and fibrinolytic systems to cutaneous wound healing.

Wound healing is a complex process that consists of multiple phases, each of which are indispensable for adequate repair. Timely initiation and resolution of each of these phases namely, hemostasis, inflammation, proliferation and tissue remodeling, is critical for promoting healing and avoiding excess scar formation. While platelets have long been known to influence the healing process, other components of blood particularly coagulation factors and the fibrinolytic system also contribute to efficient wound repair. This review aims to summarize our current understanding of the role of platelets, the coagulation and fibrinolytic systems in cutaneous wound healing, with a focus on how these components communicate with immune and non-immune cells in the wound microenvironment. We also outline current and potential therapeutic strategies to improve the management of chronic, non-healing wounds.

The role of neutrophils in thrombosis.

Despite significant evidence implicating an important role for neutrophils in thrombosis, their impact on the thrombotic process has remained a matter of controversy. Until 2010, platelets, coagulation factors, fibrinogen and monocytes were implicated in the thrombotic process. Several studies conducted over the last decade now support the growing notion that neutrophils indeed do contribute significantly to this process. Neutrophils can contribute to pathologic venous and arterial thrombosis or 'immunothrombosis' by the release of neutrophil extracellular traps (NETs) and NET release is emerging as a major contributor to thrombogenesis in pathologic situations such as sepsis and malignancy. Further, blood-cell derived microparticles, including those from neutrophils, have been implicated in thrombus formation. Finally, inflammasome activation in the neutrophil identifies another important mechanism that may be operative in neutrophil-driven risk for thrombosis. The knowledge of these roles of neutrophils in thrombosis may pave the road for novel anti-thrombotic agents in the future that do not affect hemostasis.

Patterns of Long-term Cancer Survivorship Care in a National Cancer Institute-Designated Comprehensive Cancer Center.

PURPOSE: The majority of the cancer survivors in the United States are 5 or more years beyond their diagnosis. The follow-up care of these individuals remains a major concern for survivors and for the cancer care system. The purpose of this study was to characterize long-term cancer survivors' visits at a National Cancer Institute-designated comprehensive cancer center. MATERIALS AND METHODS: We abstracted electronic medical record data for 18,882 unique patients' visits during 2010 to determine the distribution of the number of years of survival after the initial cancer diagnosis. We then reviewed 374 patient visits during a randomly selected week in April 2010 to determine whether patients were seen for treatment of a new diagnosis of cancer, a residual or recurrent cancer, for a second or secondary cancer, or for cancer survivorship care while not actively receiving treatment (other than adjuvant hormonal therapy). RESULTS: In the 1-year group of 18,882 unique patients visits the percentage of patients who were <1, 1 to 5, 6 to 10, and >10 years postdiagnosis were 18.7%, 48.7%, 18.9%, and 13.8%, respectively. During the selected week, 74% of the total office visits were with patients who were being actively treated for a new cancer, relapse, or a second cancer, whereas 24% were not being seen for treatment of an active malignancy. The percentage of total office visits with patients who were <6, 6 to 10, or >10 years postdiagnosis and had completed their initial treatment were 21.4%, 3.7%, and 1%, respectively. Approximately 5% of oncology office visits were with cancer survivors who were 5 or more years postdiagnosis and not receiving treatment. CONCLUSIONS: In a database of over 18,000 unique patients who were seen at a major cancer center in 2010, approximately 68% were 5 or less and 32% were 6 or more years postdiagnosis. A review of the medical oncology notes in a random sample of cases of oncology visits demonstrated that approximately 5% of office visits were with long-term cancer survivors who were >5 years postdiagnosis and not receiving active treatment. IMPLICATIONS FOR CANCER SURVIVORS: Cancer survivors often indicate a preference to receive long-term follow-up care from their oncologist. These findings suggest that long-term cancer survivorship care represents only a small component of care at a comprehensive cancer center and also that alternative models for long-term survivorship health care need to be considered.

Unusual Paraneoplastic Presentation of Cholangiocarcinoma.

Introduction. Cutaneous paraneoplastic syndromes are a heterogeneous group of skin manifestations that occur in relation to many known malignancies. Paraneoplastic occurrence of SCLE has been noted but is not commonly reported. SCLE association with cholangiocarcinoma is rare. Case Presentation. A 72-year-old man with a history of extrahepatic stage IV cholangiocarcinoma presented with a pruritic rash. Cholangiocarcinoma had been diagnosed three years earlier and was treated. Five months after interruption of his chemotherapy due to a semiurgent surgery, he presented with explosive onset of a new pruritic rash, arthralgias, and lower extremity edema. Physical exam revealed a scaly erythematous rash on his arms, hands, face, neck, legs, and trunk. It was thick and scaly on sun exposed areas. Skin biopsy revealed vacuolar interface dermatitis. Immunofluorescence revealed IgM positive cytoid bodies scattered along the epidermal basement membrane zone. PET-CT scanning revealed metabolically active recurrent disease in peripancreatic and periportal region with hypermetabolic lymph nodes. Oral steroids and new regimen of chemotherapy were started. Rash improved and steroids were tapered off. Discussion. Paraneoplastic syndromes demonstrate the complex interaction between the immune system and cancer. Treatment resistant SCLE should raise a suspicion for paraneoplastic etiology.