6 versus 30 months anticoagulation for recurrent venous thrombosis in patients with high factor VIII.

Patients with first venous thromboembolism (VTE) and high factor VIII (FVIII) are at increased risk of recurrence. It is unknown whether these patients benefit from prolonged secondary thrombophrophylaxis. In a prospective trial patients with first spontaneous VTE and FVIII levels >230 IU/dl were randomized to discontinue vitamin K Antagonist (VKA) after 6 months or to continue VKA for additional 24 months. Patients were excluded if they had a natural inhibitor deficiency, lupus anticoagulant, cancer, were pregnant, required long-term antithrombotic therapy or had acute-phase reaction. Primary study endpoints were symptomatic recurrent VTE or major bleeding within 2 years. Follow-up was continued beyond 2 years. Of 3,219 screened patients 34 met the inclusion criteria. Mean observation time was 37 months. Two of 17 patients allocated to discontinue VKA and two of 17 patients randomized to prolonged anticoagulation had recurrent VTE within 2 years. In the prolonged treatment group, one patient had recurrence during VKA therapy and one patient 4 weeks after voluntary discontinuation of VKA. One major nonfatal bleeding (severe epistaxis) after 10 months of VKA occurred in the prolonged treatment group. Five patients allocated to prolonged anticoagulation had recurrent VTE after discontinuation of VKA. The probability of recurrence at 2 years after discontinuation of VKA was 30% (95% CI 13-46%). Patients with high FVIII are at increased risk of recurrence. Our findings in a small number of patients indicate that prolonged anticoagulation seems to be effective but that the benefit is not maintained after discontinuation of anticoagulation.

Pathogenesis of diabetic macro- and microangiopathy.

Epidemiological investigations reveal that we must expect a rapid increase in cases of diabetes mellitus in the next few years. As a result, vascular complications in the form of macro- and microangiopathy are also expected to arise more frequently. A classical example of macroangiopathy is coronary arteriosclerosis, microangiopathy is exemplified by diabetic nephropathy. In patients suffering from diabetes, macroangiopathy manifests as atherosclerosis like in nondiabetic patients, characterized by formation of plaques that follows in stages but with an accelerated course due to the different risk factors, especially hyper- and dyslipidemia, with cumulative effects. Thus, atherosclerosis in diabetes begins earlier, is more markedly pronounced and progresses more rapidly. The pathogenetic concept is based on an endothelial lesion that occurs as a result of a diabetes-specific, endothelium-damaging parameters. In case of diabetic microangiopathy histologically characterized by a progressive glomerulosclerosis, arteriolosclerosis and interstitial fibrosis hyperglycemia, along with its consecutive and complex processes that induce matrix increase, is considered to be the primary pathogenetically relevant factor involved. Insulin resistance seems to be the major common denominator at the center of both diabetic macroangiopathy and microangiopathy.

Multiple skeletal metastases from a giant cell tumour of the distal fibula with fatal outcome.

A giant cell tumour is a primary lesion of bone of intermediate severity. Its histogenesis is unclear. In a few cases pulmonary metastases have been described. Multiple skeletal metastases in the absence of sarcomatous change have been observed. We present a case report of a 25-year-old woman with a recurrent giant cell tumour of the distal fibula. After a second recurrence and six years after the initial diagnosis, she rapidly developed multiple bony metastases. The outcome was fatal.

[Diagnosis of fibrolamellar cancer]. / Diagnostik des fibrolamellären Karzinoms.

A fibrolamellar carcinoma (FL-Ca) is a primary malignant tumor of the liver of unknown etiology, without cirrhosis and usually without an increase in tumor markers; it occurs mainly in young patients. As it can simulate malignant and benign tumors, particularly focal nodular hypoplasia (FNH), the diagnosis is difficult. Ultrasound and angiography show mostly uncharacteristic features, so ultrasound only has to ascertain that the tumor is there. Angiography can reveal vascular infiltrations and assess the resectability of the tumor, but diagnosis of FL-Ca is not always possible with angiography. CT has the highest specificity if calcifications are present, because calcifications in a tumor similar to FNH are pathognomonic for FL-Ca. By means of hepatobiliary functional scintigraphy FNH can be excluded. MRI seems to be important in differentiating the tumor from FNH, because the central scars of FL-Ca and FNH--if present--have a different signal intensity in T2-weighted images. The histological diagnosis of FL-Ca is also difficult. In patients with resectable tumors or prior to liver transplantation, an operative biopsy should be obtained to verify the diagnosis. In non-resectable tumors sonographic guided biopsy is justified.

CNS manifestations in non-Hodgkin lymphomas (NHL).

In a group of 241 patients with non-Hodgkin lymphoma investigated retrospectively, CNS manifestations occurred in 8%, mainly as meningeosis lymphoblastomatosa. Lymphoblastic and immunoblastic NHL showed the highest risk of CNS infiltration (40.7% and 12.5% respectively). Further risk factors were disseminated stage of the disease, prior involvement of the bone marrow and juvenile age. Characteristic symptoms were eye muscle paresis, paresthesias and pareses of peripheral muscles. The most fruitful diagnostic measure was lumbar puncture. More than 80% of the patients observed with CNS manifestations died within one year. The factor limiting life was less the CNS infiltration itself than the systemic progression. CNS prophylaxis should be incorporated in the treatment plan in patients with lymphoblastic and immunoblastic non-Hodgkin lymphoma at an early stage. In contrast CNS prophylaxis is not justified in uncontrollable systemic non-Hodgkin lymphoma spread.