Transorbital endoscopic approaches to the skull base: a systematic literature review and anatomical description

Neurosurgical Review - Transorbital endoscopic approaches are increasing in popularity as they provide corridors to reach various areas of the ventral skull base through the orbit. They can be used...     

Thrombocytosis and leukocytosis interaction in vascular complications of essential thrombocythemia

To elucidate the role of thrombocytosis, alone or in combination with standard (age, previous cardiovascular events) and novel (leukocytosis, JAK2(V617F) mutational status) risk factors, in the cardiovascular events of essential thrombocythemia (ET), we analyzed a cohort of 1063 patients. We found that a platelet count at diagnosis greater than 1000 x 10(9)/L was associated with significantly lower rate of thrombosis in multivariable analysis and, if combined with leukocytes less than 11 x 10(9)/L, pointed to a "low-risk" category with a rate of thrombosis of 1.59% of patients/year. On the contrary, the highest risk category (thrombosis rate, 2.95% of patients/year) was constituted of patients with leukocytosis, lower platelet count, and a JAK2(V617F) mutated genotype in most cases (77% vs 26% in the low-risk group), independently from standard risk factors. These data challenge the theory that elevated platelet count increases thrombosis risk in ET and suggest prospective clinical trials to support this hypothesis.     

Cerebral vein thrombosis in patients with Philadelphia‐negative myeloproliferative neoplasms An European Leukemia Net study

To investigate the characteristics and clinical course of cerebral vein thrombosis (CVT) in patients with myeloproliferative neoplasms (MPN) we compared 48 patients with MPN and CVT (group MPN‐CVT) to 87 with MPN and other venous thrombosis (group MPN‐VT) and 178 with MPN and no thrombosis (group MPN‐NoT) matched by sex, age at diagnosis of MPN (±5 years) and type of MPN. The study population was identified among 5,500 patients with MPN, from January 1982 to June 2013. Thrombophilia abnormalities were significantly more prevalent in the MPN‐CVT and MPN‐VT than in MPN‐NoT group (P = 0.015), as well as the JAK2 V617F mutation in patients with essential thrombocythemia (P = 0.059). Compared to MPN‐VT, MPN‐CVT patients had a higher rate of recurrent thrombosis (42% vs. 25%, P = 0.049) despite a shorter median follow‐up period (6.1 vs. 10.3 years, P = 0.019), a higher long‐term antithrombotic (94% vs. 84%, P = 0.099) and a similar cytoreductive treatment (79% vs. 70%, P = 0.311). The incidence of recurrent thrombosis was double in MPN‐CVT than in MPN‐VT group (8.8% and 4.2% patient‐years, P = 0.022), and CVT and unprovoked event were the only predictive variables in a multivariate model including also sex, blood count, thrombophilia, cytoreductive, and antithrombotic treatment (HR 1.97, 95%CI 1.05–3.72 and 2.09, 1.09–4.00, respectively). Am. J. Hematol. 89:E200–E205, 2014. © 2014 Wiley Periodicals, Inc.     

Masked polycythemia Vera (mPV): Results of an international study

We examined the baseline features and clinical outcomes of 140 patients presenting with JAK2V617F positivity and a bone marrow morphology conforming with WHO criteria of polycythemia vera (PV), but a hemoglobin level of <18.5 g/dL in males (range 16.0–18.4) and <16.5 g/dL in females (range 15.0–16.4). This cohort operationally referred to as masked PV (mPV) was compared with 257 patients with overt PV and displayed male predominance, a more frequent history of arterial thrombosis and thrombocytosis. Incidence of thrombosis was similar between the two groups but mPV displayed significantly higher rates of progression to myelofibrosis and acute leukemia and inferior survival. In multivariable analysis mPV diagnosis was an independent predictor of poor survival along with age >65 years and leukocyte count >10 × 10⁹/L. Our data suggest that mPV is a heterogeneous myeloproliferative neoplasia and not necessarily an early/ pre‐polycythemic form of classical PV that at onset in a small fraction of patients clinically may mimic essential thrombocythemia. On the other hand, the majority mPV may have a longer prodrome of undiagnosed PV or a disease biology akin to primary myelofibrosis‐post PV myelofibrosis that could explain the worsening of outcome in comparison to overt/classical manifestations. Am. J. Hematol. 89:52–54, 2014. © 2013 Wiley Periodicals, Inc.     

Second cancers in MPN: Survival analysis from an international study

One out of ten patients with Philadelphia-negative myeloproliferative neoplasms (MPN) develop a second cancer (SC): in such patients we aimed at assessing the survival impact of SC itself and of MPN-specific therapies. Data were therefore extracted from an international nested case-control study, recruiting 798 patients with SC diagnosed concurrently or after the MPN. Overall, 2995 person-years (PYs) were accumulated and mortality rate (MR) since SC diagnosis was 5.9 (5.1-6.9) deaths for every 100 PYs. A “poor prognosis” SC (stomach, esophagus, liver, pancreas, lung, ovary, head-and-neck or nervous system, osteosarcomas, multiple myeloma, aggressive lymphoma, acute leukemia) was reported in 26.3% of the patients and was the cause of death in 65% of them (MR 11.0/100 PYs). In contrast, patients with a “non-poor prognosis” SC (NPPSC) incurred a MR of 4.6/100 PYs: 31% of the deaths were attributed to SC and 15% to MPN evolution. At multivariable analysis, death after SC diagnosis was independently predicted (HR and 95% CI) by patient age greater than 70 years (2.68; 1.88-3.81), the SC prognostic group (2.57; 1.86-3.55), SC relapse (1.53; 10.6-2.21), MPN evolution (2.72; 1.84-4.02), anemia at SC diagnosis (2.32; 1.49-3.59), exposure to hydroxyurea (1.89; 1.26-2.85) and to ruxolitinib (3.63; 1.97-6.71). Aspirin was protective for patients with a NPPSC (0.60; 0.38-0.95). In conclusion, SC is a relevant cause of death competing with MPN evolution. Prospective data are awaited to confirm the role of cytoreductive and anti-platelet drugs in modulating patient survival after the occurrence of a SC.     

Leukocytosis is a risk factor for thrombosis in essential thrombocythemia: interaction with treatment, standard risk factors, and Jak2 mutation status

Leukocytes contribute to the pathogenesis of thrombosis in essential thrombocythemia (ET) through recently discovered mechanisms of activation and interaction with platelets and endothelial cells. To evaluate whether an increased leukocyte count was associated with thrombosis and whether this effect can be modulated by therapy, we analyzed the clinical course of 439 patients with ET followed at the Ospedali Riuniti di Bergamo. The strength of the association was measured at diagnosis or before thrombotic events by multivariable analyses carried out using data at baseline as well as time-varying covariates. The results showed that (1) an increased leukocyte count at diagnosis was associated with thrombosis during follow-up ("baseline analysis," relative risk [RR] 2.3, 95% confidence interval [CI] 1.4-3.9, P = .001); (2) hydroxyurea (HU) lowered leukocytosis and reduced the strength of the association between leukocytosis and thrombosis ("time-dependent analysis," RR 1.6, 95% CI 0.9-2.0, not significant [NS]); (3) the association of leukocytosis and thrombosis was more evident in untreated low-risk patients (RR 2.7, 95% CI 1.2-6.4, P = .01) compared with HU-treated high-risk patients (RR 1.6, 95% CI 0.8-3.2, NS); and (4) the presence of JAK2 V617F was not identified as a risk factor for thrombosis during follow-up despite a significant association between the mutation and leukocytosis. We suggest validation of these findings in prospective clinical studies.     

Palliative care of cancer patients: audit of current hospital procedures

The palliative care of cancer patients admitted for tumour-related symptoms to three different departments (medical oncology, radiotherapy, internal medicine) of a general hospital was prospectively audited. The physicians directly responsible for the patients provided prospective data by reporting both the diagnostic and therapeutic interventions performed and the degree of control achieved for each symptom. A patient form for evaluation of the control achieved in the case of each symptom by means of linear analogue scales was also provided. The appropriateness of all procedures was evaluated by two external auditors. Over 6 months, 125 such admissions were recorded: 24 patients entered the study and the management of 56 symptoms, the most common of which were pain and dyspnoea, was reviewed. A total of 72 diagnostic procedures were performed, deemed necessary for only 50% of symptoms, optional for 15%, and performed as part of a logical sequence for 38%. A total of 130 therapeutic interventions were undertaken, deemed necessary for 55% of symptoms, optional for 15% and carried out as part of a logical sequence for 44%. Re-evaluations of symptoms and physician and patient evaluations of the degree of control achieved could not be assessed because of lack of information. The audit could not be repeated owing to the low accrual of patients and incompleteness of the data collection. Reasons for failure of the study and proposals for feasible methods of auditing the management of symptoms in cancer patients are discussed.