A morphometric study of bone marrow angiogenesis in hairy cell leukaemia with clinicopathological correlations

Bone marrow angiogenesis has recently been implicated in the pathophysiology and course of various haematological malignancies. Little is known, however, about the significance of this phenomenon in hairy cell leukaemia (HCL). We evaluated various morphometric characteristics of microvessels, highlighted by means of anti-CD34 immunohistochemistry, in the bone marrow of 44 patients with typical HCL, before and after treatment with interferon-alpha (IFN-alpha). Overall, bone marrow from 103 HCL patients and 20 controls was examined. Microvessel density (MVD) and several size- and shape-related parameters were quantified in the region of most intense vascularization using image analysis. MVD, size-related parameters and the percentage of branching microvessels were higher in HCL than in controls. Likewise, perimeter counts were higher in partial/non-responders than in complete responders. Achievement of complete response was accompanied by smaller calibre microvessels. IFN-alpha induced a decrease in MVD and branching values in cases with diffuse marrow involvement. In univariate analysis, progression-free survival was adversely affected by MVD, branching and major axis length. Multivariate analysis indicated that MVD/branching independently affected progression-free survival and the likelihood of complete response. Our data suggest that the generation of bone marrow microvessels indicated an increased risk of progression and IFN-alpha treatment failure in HCL. Furthermore, the prognostic significance of angiogenesis requires the concomitant assessment of MVD and the complexity of the microvascular network.     

Sjögren's syndrome associated with multiple myeloma

Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown etiology characterized by lymphocytic infiltration of the exocrine glands and a polyclonal B-cell activation; it is demonstrated by the presence of multiple autoantibodies against organ- and non-organ-specific autoantigens. SS is associated with malignant lymphomas, Waldenstrom's macroglobulinemia and benign monoclonal gammopathy, while its relationship with multiple myeloma is extremely rare. The association between multiple myeloma and rheumatoid arthritis and other autoimmune diseases has been established, but it is not clear why a B-cell proliferation like myeloma occurs more rarely than other B-cell disorders in patients with SS. We describe a patient who presented with multiple myeloma and SS that might have existed for at least 2?years prior to the appearance of myeloma.     

The association of physical activity with novel adipokines in patients with type 2 diabetes

BackgroundAdipose-tissue derivatives, known as adipokines, have been involved in the inflammatory-mediated metabolic and cardiovascular disorders of type 2 diabetes mellitus (T2DM). This study examined the association between novel adipokines and self-reported physical activity, a potential anti-inflammatory mediator.MethodsWe enrolled 247 men and women with T2DM, free from overt cardiovascular disease. Based on a physical activity questionnaire, patients were classified into groups: A) sedentary, who did not report any physical activity or reported light activities < 2 h/week and B) active, referring to low or moderate-intensity physical activities > 2 h/week. Among them, 88 patients were randomly selected to perform a cardiorespiratory ergocycle testing. Clinical parameters, glycemic and lipid profiles, HOMA-IR, and serum levels of visfatin, apelin, vaspin, ghrelin and adiponectin were assessed.ResultsWith the exception of fat-mass, our groups did not differ in anthropometric parameters and pharmaceutical regimen. Active patients showed ameliorated glucose regulation, HOMA-IR, hsCRP and exercise capacity compared to sedentary counterparts (p < 0.01). Active rather than sedentary patients showed lower visfatin (10.16 ± 5.53 ng/ml vs 14.77 ± 8.48 ng/ml, p = 0.013), higher apelin (1.39 ± 0.65 ng/ml vs 1.04 ± 0.35 ng/ml, p = 0.018) and adiponectin (11.82 ± 3.06 μg/ml vs 7.81 ± 2.11 μg/ml, p = 0.033) levels. There were non-significant differences in the rest of parameters between groups. After adjusting for age, sex and BMI, physical activity along with hsCRP and ghrelin remained independent determinants of visfatin levels (R² = 0.328, p = 0.032), while physical activity was independently associated with apelin (R² = 0.221, p = 0.022).ConclusionsSelf-controlled physical activity of, even, moderate intensity ameliorates adipokines, such as visfatin, apelin and adiponectin, in patients with T2DM. Prospective interventional studies will confirm our results.The ClinicalTrials.gov identifier is: NCT00306176.     

Anticoagulation for atrial fibrillation in active cancer

Atrial fibrillation (AF) may often pre-exist in patients with newly diagnosed cancer or occur with increased frequency shortly after cancer diagnosis. Patients with active cancer and AF have a particularly high risk of thromboembolic complications, as both conditions carry a risk of thrombosis. Thromboembolic risk is determined by several factors, including advanced age, sex (females), cancer histology (adenocarcinomas), location (e.g., pancreas, stomach), advanced stage, anticancer regimens (e.g., platinum compounds, anti-angiogenic therapies, immune modulators), comorbidities (e.g., obesity, kidney disease) and concurrent therapies (e.g., surgery, central catheters). Physicians are often reluctant to prescribe anticoagulants to patients with active cancer and AF, mainly due to fear of bleeding complications, which is partly related to the paucity of evidence in the field. Decision making regarding anticoagulation for the prevention of ischemic stroke and systemic embolism in patients with active cancer and AF may be challenging and should not simply rely on the risk prediction scores used in the general AF population. By contrast, the administration and choice of anticoagulants should be based on the comprehensive, individualized and periodic evaluation of thromboembolic and bleeding risk, drug-drug interactions, patient preferences and access to therapies.     

The prognostic significance of beta(2)-microglobulin in patients with Hodgkin's lymphoma

BACKGROUND AND OBJECTIVES: Serum beta(2)-microglobulin (s beta(2)m) is an established prognostic factor for multiple myeloma and non-Hodgkin's lymphoma, but only limited data suggest an adverse prognostic significance for Hodgkin's lymphoma (HL). This study was undertaken to examine the impact of s beta(2)m on the prognosis of patients with HL. DESIGN AND METHODS: s beta(2)m was measured by a radioimmunoassay (upper normal limit 2.4 mg/L), in pretreatment serum samples of 232 patients with HL, who were then treated with ABVD or equivalent regimens with or without radiotherapy. Multivariate survival analysis was based on Cox's proportional hazards model. RESULTS: Main patients' characteristics: median age 30.5 years (14-78); 58% males; 68% nodular sclerosis, 20% mixed cellularity and 12% lymphocyte predominance; 34% B-symptoms; 24% Ann Arbor stage I, 49% II, 18% III and 9% IV. Elevated s beta(2)m levels were detected in 65/232 patients (28%) and correlated with older age (p<0.001), mixed cellularity (p=0.03), B-symptoms (p=0.002), advanced stage (p=0.02), > or = 5 involved sites (p=0.02), inguinal/iliac involvement (p=0.009), lymphocytopenia (p=0.002) and elevated lactate dehydrogenase (p=0.01). The 7-year failure free survival (FFS) was 75% vs. 72% for patients with normal vs. elevated s beta(2)m (p=0.15). The corresponding 7-year overall survival (OS) rates were 86% vs. 52% (p=0.003). In multivariate analysis, elevated s beta(2)m was not predictive of FFS, but was independently associated with inferior OS (p=0.01), along with the number of involved sites (p<0.001). INTERPRETATION AND CONCLUSIONS: s beta(2)m is not a potent prognostic factor for FFS in optimally treated patients with HL. However s beta(2)m may be predictive of OS, probably due to its effect on the timing of treatment failure.     

Does octreotide impair anastomotic healing after small bowel resection?

Seventy two rats underwent small bowel resection followed by end-to-end anastomosis. The octreotide group consisted of 36 rats treated with octreotide (subcutaneously, 7 microg/kg/day, in two equal doses), and the control group consisted of 36 rats treated with the same volume saline. Twelve animals from each group were re-explored on the 4th, 8th and 15th postoperative day. Leakages, adhesions, obstructions were the clinical postoperative findings identified and recorded. Anastomotic bursting pressures were measured. Histochemical studies included haematoxylin-eosin and Van Gieson staining techniques and focused on the microscopic characterization of the healing process. Adhesions, leakages and obstructions were not different between octreotide and control groups. Anastomoses of the octreotide group had increased bursting pressures on the 8th and the 15th day (p < .05 , p < .05, respectively). Regarding the histogical results, on the 8th day the octreotide group compared to the control group, showed healing in more layers (p < .05), increased bright red collagen fibers and quantity of fibroblasts (p < .05), and on the 15th day, the octreotide group showed fewer gaps (p < .05), increased bright red collagen fibers and quantity of fibroblasts (p < .05). In this experimental model, it appeared that octreotide does not impair healing of small bowel anastomoses, but in contrast, there is some evidence that it enhances healing on the 8th and the 15th postoperative day.