Brachial plexus tumors extending into the cervicothoracic spine: a review with operative nuances and outcomes

Background The rarity and anatomical complexity of brachial plexus tumors (BPTs) impose many challenges onto surgeons performing surgical resections, especially when these tumors invade the cervicothoracic spine. Treatment choices and surgery outcomes heavily depend on anatomical location and tumor type. Methods The authors performed an extensive review of the published literature (PubMed) focusing on “brachial plexus tumors” that identified invasion of the cervicothoracic spine. Result The search yielded 2774 articles pertaining to “brachial plexus tumors”. Articles not in the English language or involving cervicothoracic spinal invasion were excluded. Conclusions Recent research has shown that the most common method used to resect tumors of the proximal roots is the dorsal subscapular approach. Despite its association with high morbidity rate, this technique offers excellent exposure to the spinal roots and intraforaminal portion of the spinal nerve. The dorsal approach is used to resect recurrent lower trunk tumors and dumbbell-shaped neurofibromas, yet it is also the least common overall approach used in brachial plexus tumor resections. The ventral or anterior technique is commonly used to resect tumors at the cord to division level, and root to trunk level. Motor complications, transient nerve palsy, and bleeding are among the most common complications of the anterior supraclavicular approach. Further controlled studies are needed to fully determine the optimal surgical approach used to obtain the best outcomes and least complications for each type of brachial plexus tumor (AU)

Brachial plexus tumors extending into the cervicothoracic spine: a review with operative nuances and outcomes.

BACKGROUND: The rarity and anatomical complexity of brachial plexus tumors (BPTs) impose many challenges onto surgeons performing surgical resections, especially when these tumors invade the cervicothoracic spine. Treatment choices and surgery outcomes heavily depend on anatomical location and tumor type. METHODS: The authors performed an extensive review of the published literature (PubMed) focusing on "brachial plexus tumors" that identified invasion of the cervicothoracic spine. RESULTS: The search yielded 2774 articles pertaining to "brachial plexus tumors". Articles not in the English language or involving cervicothoracic spinal invasion were excluded. CONCLUSIONS: Recent research has shown that the most common method used to resect tumors of the proximal roots is the dorsal subscapular approach. Despite its association with high morbidity rate, this technique offers excellent exposure to the spinal roots and intraforaminal portion of the spinal nerve. The dorsal approach is used to resect recurrent lower trunk tumors and dumbbell-shaped neurofibromas, yet it is also the least common overall approach used in brachial plexus tumor resections. The ventral or anterior technique is commonly used to resect tumors at the cord to division level, and root to trunk level. Motor complications, transient nerve palsy, and bleeding are among the most common complications of the anterior supraclavicular approach. Further controlled studies are needed to fully determine the optimal surgical approach used to obtain the best outcomes and least complications for each type of brachial plexus tumor.

Lymphadenectomy in colorectal cancer liver metastases resection: incidence of hilar lymph nodes micrometastasis.

BACKGROUND: Liver resection is considered the best treatment for metastatic colorectal cancer. Several prognostic factors have been investigated, and many studies have shown that hepatic hilum lymph nodes involvement has a negative impact on prognosis. The present study evaluated the frequency of microscopic involvement of hilar lymph nodes, through systematic lymphadenectomy and analysis of micrometastases in patients undergoing hepatectomy due to colorectal metastasis. METHODS: A total of 28 patients underwent hepatic resection with hilar lymphadenectomy. Lymph nodes considered negative by conventional hematoxylin and eosin (H&E) staining were analyzed by serial sectioning with 100-microm intervals and immunohistochemistry (IHC) with anti-human pancytokeratin antibody AE1/AE3. RESULTS: In average, 6.18 lymph nodes were dissected per patient. No morbidity or mortality was associated to lymphadenectomy. In two patients, conventional H&E analysis showed presence of microscopic lymph node metastasis. IHC analysis allowed the identification of three other patients with lymph node micrometastases. The overall frequency of microscopic metastases, including micrometastasis, was 18%. CONCLUSIONS: Systematic lymphadenectomy allowed the detection of microscopic lymph node metastases, resulting in more accurate staging of extrahepatic disease. The inclusion of IHC increased the detection of lymph node micrometastasis.

Tomatoes have natural anti-thrombotic effects.

The prevention of arterial thrombotic diseases has a high priority in developed countries. An inappropriate diet may be an important risk factor for thrombotic events. The daily intake of an anti-thrombotic diet may offer a convenient and effective way of prevention. The aim of the present study was to test tomato extracts for anti-thrombotic effects and to identify those varieties that have such an effect. A shear-induced platelet-function test (haemostatometry) was used to test anti-thrombotic potential in vitro. Extracts from those tomato varieties that showed a significant anti-thrombotic activity in vitro were further assessed in vivo, using a laser-induced thrombosis test in mice. One tomato variety (KG99-4) showed significant anti-thrombotic activity both in vitro and in vivo. KG99-4 inhibited not only platelet-rich thrombus formation but also had a thrombolytic effect. It is concluded that haemostatometry can detect and classify the anti-thrombotic potential of fruits and vegetables and offers a simple way of screening for such effects.

There is no valid evidence presented as to an impaired endothelial NO system in the stroke-prone spontaneously hypertensive rats.

Platelet reactivity in stroke-prone spontaneously hypertensive rats (SHRSP) and normotensive Wistar-Kyoto rats (WKY) were compared. In vivo platelet reactivity was tested by the He-Ne laser-induced thrombosis model. The number of laser pulses needed to reach thrombotic occlusion of the targeted vessel was used as an index of thrombogenicity. SHRSP rats needed significantly less number of irradiation to reach occlusion than WKY rats (SHRSP vs. WKY, 5.1+/-0.3 vs. 8.1+/-0.6), indicating enhanced thrombotic response in SHRSP rats. Further, acetylcholine administration significantly increased the number of laser pulses until occlusion in WKY but not in SHRSP rats. This suggests an impaired thrombotic reaction in acetylcholine-treated WKY but not in SHRSP rats. Platelet reactivity in vitro was measured in native blood by a shear-induced haemostasis test (haemostatometry). Indexes of this test (H1/H2), which inversely correlated with platelet reactivity, were significantly greater in SHRSP than in WKY rats (SHRSP vs. WKY, H1: 1815+/-192 vs. 763+/-75; H2: 7547+/-723 vs. 3536+/-264). This suggests reduced platelet reactivity in SHRSP compared with WKY rats. Thus, the present findings show increased thrombotic tendency in SHRSP rats in vivo despite reduced platelet reactivity in vitro. To explain this contradiction, we suggest that an increased in vivo thrombotic tendency may be due to impaired nitric oxide (NO) release from endothelial cells in SHRSP rats, and that a reduced platelet reactivity in vitro may be due to an adaptation of SHRSP rats to survive at extremely high blood pressure.

Artificial trachea and long term follow-up in carinal reconstruction in dogs.

We have already reported successful carinal reconstruction of the trachea with an observation period of 1 - 2 years. In this study, we evaluate the long-term safety and efficacy of the reconstruction after 5-years of follow-up. The Y-shaped Marlex mesh tube was reinforced with a polypropylene spiral and coated with atelocollagen made from porcine skin. The prosthesis was 60 mm long with an outer diameter of 18 mm. Replacement of the tracheobronchial bifurcation was preformed through a right thoracotomy in a beagle dog. Bronchoscopical examination and sampling of the tracheal epithelium was performed periodically to check the function of cilia. The implanted prothesis was promptly infiltrated by the surrounding connective tissue and completely incorporated by the host trachea and bronchus. Bronchoscopically, sufficient epithelization was confirmed from the upper to the lower site of anastomosis. After 5 years neither stenosis nor dehiscence was observed. In spite of there being mesh-exposure at the luminal surface, the dog had no clinical symptoms until sacrifice for pathological examination. The bent frequency of the cilia was maintained within the normal range, indicating functional recovery of the regenerating airway. Our tracheal prosthesis is promising for clinical repair of the tracheobronchial bifurcation.

Inhibitory effect of various thrombin inhibitors on shear-induced platelet function and dynamic coagulation.

We assessed the effects of active site-directed, fibrinogen recognition exosite (FRE)-directed and bifunctional thrombin inhibitors, on shear-induced platelet reactivity (adhesion/aggregation) and dynamic coagulation (coagulation of flowing blood). An in vitro test for shear-induced haemostatic plug formation and dynamic coagulation (haemostatometry) was employed using non-anticoagulated rat blood. The active site-directed inhibitors (argatroban, P891, P899) caused inhibition of platelet reactivity and coagulation at 1-, 100- and 100-microM concentrations, respectively. Bifunctional inhibitors (P553, P1053) exerted inhibitory effects at 0.1 microM. A dimeric bifunctional inhibitor P824 caused significant inhibition at 1 microM. The FRE-directed inhibitor (P960) inhibited shear-induced platelet reactivity at 10 microM but the dynamic coagulation at 1 microM. Combination of active site-directed argatroban and FRE-directed P960 did not show any synergistic effect. The most potent inhibition was observed in monomeric bifunctional inhibitors. The inhibitory effects were compared with the K(i) values against human thrombin and with the IC(50) values against fibrin clot formation. The minimum effective concentrations on shear-induced platelet reactivity and dynamic coagulation were comparable with the IC(50) values, but not with the K(i) values.

Adjuvant effect of antibodies against von Willebrand Factor, fibrinogen, and fibronectin on staphylokinase-induced thrombolysis as measured using mural thrombi formed in rat mesenteric venules.

The change in thrombus mass during thrombolytic therapy is thought to be the difference between its growth and its degradation induced by thrombolytic agents. Platelets play a pivotal role in arterial thrombosis and bind to each other and to exposed subendothelial matrices via adhesive proteins such as von Willebrand Factor, fibrinogen, and fibronectin. The aim of the present study was to assess whether administration of antibodies against these adhesive proteins, in conjunction with plasminogen activator, could enhance the degradation of platelet-rich thrombus. Mural platelet-rich thrombi were formed in rat mesenteric venules using He-Ne laser irradiation. Recombinant staphylokinase was infused continuously and polyclonal antibodies against adhesive proteins were given by bolus injection. The thrombolytic process was analysed using computer-enhanced image analysis software. Administration of each of the antibodies enhanced staphylokinase-induced thrombolysis.

A global platelet test of thrombosis and thrombolysis detects a prothrombotic state in some patients with non-insulin dependent diabetes and in some patients with stroke.

Platelet aggregation and spontaneous thrombolytic activity were assessed in patients with non-insulin dependent diabetes and stroke using a shear-induced and agonist-induced platelet aggregation test. The Thrombotic Status Analyser (TSA), induces platelet-rich thrombus formation solely by shear forces, while whole blood platelet aggregometry measures platelet reactivity to different agonists. These tests were employed in the present study because in earlier studies they both demonstrated that platelet aggregability in healthy volunteers was unchanged with age. On the other hand, it is known that thrombolytic activity decreases with age in males, but not in females. In diabetic patients shear-induced platelet aggregability varied according to the stage of nephropathy but platelet aggregation to collagen was suppressed at all stages. Platelet reaction to shear stress was enhanced in stroke patients with haemorrhagic episodes but not in patients with lacunar infarction. In contrast, platelet reactivity to collagen was suppressed and changes in ADP-induced platelet aggregability were inconsistent. Suppressed thrombolysis was observed only in diabetes with minor renal defect. Fibrinogen was increased in diabetes with stage III and IV nephropathy. Fibrinopeptide A (FPA) and D-dimer were increased in stroke. Thus, the observed increase in fibrinogen, FPA and D-dimer is inconsistent with changes in platelet aggregability. Our present findings suggest that a shear-induced platelet aggregation test is superior to other tests such as agonist-induced platelet aggregation and thrombotic markers such as fibrinogen, FPA and D-dimer in detecting a prothrombotic state. It is concluded that elderly males may have a prothrombotic state not because of platelet hyper-aggregability but because of suppressed thrombolytic activity. On the other hand, a prothrombotic state in patients with non-insulin dependent diabetes and after stroke may be due to changes in age-independent platelet aggregability.

Norepinephrine, but not epinephrine, enhances platelet reactivity and coagulation after exercise in humans.

The effects of exercise and catecholamines on platelet reactivity or coagulation and fibrinolysis appear to be inconsistent. This may be partly due to the methods employed in previous studies. In the present study, we investigated the effects of acute aerobic exercise and catecholamines on the thrombotic status by a novel in vitro method, shear-induced hemostatic plug formation (hemostatometry), using nonanticoagulated (native) blood. Aerobic exercise (60% maximal O2 consumption) was performed by healthy male volunteers for 20 min, and the effect on platelet reactivity and coagulation was assessed by performing hemostatometry before and immediately after exercise. Exercise significantly increased shear-induced platelet reactivity, coagulation, and catecholamine levels. The effect of catecholamines on platelet reactivity and coagulation was assessed in vitro by adding catecholamines to blood collected in the resting state. The main findings of the present study are that elevation of circulating norepinephrine at levels that are attained during exercise causes platelet hyperreactivity and a platelet-mediated enhanced coagulation. This may be a mechanism of an association of aerobic exercise with thrombotic risk.

Effects of clopidogrel on platelet activation and coagulation of non-anticoagulated rat blood under high shear stress.

Clopidogrel is a new thienopyridine derivative similar to ticlopidine, which inhibits adenosine diphosphate-induced platelet aggregation. The in vitro effects of clopidogrel on shear-induced platelet activation and coagulation were assessed after oral administration to rats, by subjecting non-anticoagulated blood to haemostatometry. Clopidogrel significantly inhibited shear-induced platelet activation and coagulation 2 h after administration at doses of 7.5 and 15 mg/kg. Both ticlopidine (200 mg/kg) and aspirin (200 mg/kg) inhibited shear-induced platelet activation, but not coagulation. The peak inhibition of plaetelet activation by clopidogrel occurred 2 h after oral administration, but significant inhibition persisted even after 24 h. These results suggest that clopidogrel could be a more potent antithrombotic agent than ticlopidine or aspirin, and also that ADP plays an important role in shear-induced platelet activation.

A shear-induced in vitro platelet function test can assess clinically relevant anti-thrombotic effects.

Morphological features of haemostatic plugs formed in vitro under high shear forces were investigated. Electron microscopy confirmed the relevance of such haemostatic plug to a platelet-rich arterial thrombus, which is formed in vivo . In rat blood samples, the effects of anticoagulants and various antiplatelet agents on platelet reactivity (rate of haemostatic plug formation) and subsequent coagulation of the flowing blood were investigated. Haemostasis did not occur in citrated blood, and heparin greatly inhibited the shear-induced platelet reaction. Aspirin (1 mM), a thromboxane A(2) receptor antagonist (5 microM), a stable prostacyclin (0.55 nM), a stable prostaglandin E(1) (141 nM) and a phosphodiesterase inhibitor (100 microM) were tested. All these agents exerted significant inhibitory effect on shear-induced platelet reaction, including the inhibition of the very first phase of platelet plug formation, due to aggregation of shear-activated platelets. Except for the phosphodiesterase inhibitor, which prolonged clotting time, none of the above agents affected dynamic coagulation. These results suggest that the employed in vitro shear-induced thrombosis/haemostasis test can reveal in vivo the antithrombotic effect of various agents independently of their mechanism of action.

Effects of cyclosporine and FK506 on in vitro high shear-induced platelet reactivity in rat and human non-anticoagulated blood.

BACKGROUND: The immunosuppressants cyclosporine and FK506 have been used successfully in clinical transplantation, but both agents have various side effects. We have previously found that cyclosporine is prothrombotic and that FK506 is antithrombotic in an in vivo system. The aim of the present study was to assess the effects of these agents on platelet reactivity and coagulation using an in vitro shear-induced hemostatic platelet plug-forming instrument, the hemostatometer. METHODS: A purpose-built hemostatometer was constructed in our laboratory. The effects of cyclosporine and FK506 on platelet reactivity and coagulation were assessed under high shear stress using non-anticoagulated rat and human blood. RESULTS: FK506 significantly inhibited both platelet reactivity and coagulation. Cyclosporine also significantly inhibited coagulation, but a proaggregatory effect was observed at a final blood concentration of 0.05 mg/ml. CONCLUSIONS: The present in vitro results support our previous in vivo findings regarding the prothrombotic and antithrombotic effects of cyclosporine and FK506, respectively.

Detection of a prothrombotic state after acute aerobic exercise.

Angina, myocardial infarction, and sudden cardiac death are associated with thrombus formation in coronary arteries. It is generally believed that these conditions benefit from long-term exercise. However, the evidence for such amelioration or prevention is inconclusive and so is the mechanism through which long-term exercise exerts its beneficial effect on various ischaemic conditions. Because of the thrombotic events, the effects of exercise on platelet reactivity, blood coagulation and fibrinolysis have been extensively studied, but the findings are not consistent (1-9). This is mainly due to methodological problems. Analysis of platelet response to a variety of agonists and the dozen of coagulation and fibrinolysis variables makes the assessment of the overall platelet function, coagulation and fibrinolysis status extremely difficult.

Insulin-dependent diabetes mellitus in which glycemic control was improved during pregnancy but deteriorated after delivery with the occurrence of postpartum thyrotoxicosis: a case report.

We report a patient, a twin, with diabetes mellitus whose hyperglycemic state fluctuated during the course of the pregnancy and the subsequent delivery. She was diagnosed as having slowly progressive IDDM because of her clinical course and the findings of serum positive ICA/CF, positive HLA-DR4 and disconcordance of diabetes mellitus with her identical twin. Insulin therapy was not initially needed in the first two years because the endogenous insulin secretion was not completely reduced. After two years of insulin therapy the patient became pregnant. Her glycemic control was remarkably improved without changes in dietary intake and insulin dosage. After delivery glycemic control deteriorated after delivery with the occurrence of postpartum thyroiditis. Urinary excretion of CPR was increased during pregnancy but decreased after delivery. ICA/CF in serum were persistently detected in the whole observation period. It seems that the improved glycemic control during pregnancy was caused by the reduction in the autoimmune reaction and the deterioration in glycemic control during the postpartum period was induced by the acceleration of the autoimmune reaction by the same mechanism of postpartum autoimmune thyroiditis.

Nonamyloidotic nephrotic syndrome in Waldenström's macroglobulinemia.

Severe nephrotic syndrome developed in an 83-year-old Japanese man with Waldenström's macroglobulinemia. Treatment with corticoid remarkably improved the proteinuria. Autopsy disclosed no deposit of amyloid in the kidneys but a slight infiltration of atypical lymphocytes. A considerable number of glomeruli showed mesangial cell proliferation and global or segmental thickening of the basement membrane with occasional double tracks. Immunofluorescent studies revealed deposits of IgM but not IgG, IgA and C3 along the basement membrane in most glomeruli. Electron microscopy disclosed the splitting glomerular basement membrane and scattered electron-dense deposits.

Waldenström's macroglobulinemia. Report of an autopsy case presenting with a pulmonary manifestation.

An autopsy case of Waldenström's macroglobulinemia is reported, in whom an abnormal pulmonary shadow had already existed 2 years before the diagnosis of the disease and was proved to be pulmonary involvement. Immunoelectrophoresis demonstrated a monoclonal increase in immunoglobulin M with kappa light chain. A chest X-ray film showed a reticulo-nodular shadow in the right lower lobe of the lung. A bronchial biopsy specimen revealed a diffuse and dense lymphocytic infiltration. Bone marrow aspirate revealed no remarkable change except for a slight increase in plasma cells (1.7%) and an appearance of atypical lymphocytes (0.5%). At autopsy, more than half of the right lower lobe of the lung was occupied by a pale whitish, viscid and glossy tumour mass. Heptosplenomegaly and lymph node enlargement were not observed. Histological findings of the tumour tissue were similar to those of the biopsy specimen. Lymphocytic infiltration was observed also in the liver, kidneys, spleen, bone marrow and lymph nodes, but was of minor degree. Other reported cases of Waldenström's macroglobulinemia accompanied by pulmonary involvement are reviewed.