High-dose lanreotide in the treatment of poorly differentiated pancreatic neuroendocrine carcinoma: a case report.

Pancreatic neuroendocrine tumors (NETs), including poorly differentiated carcinomas (NECs), are rarely encountered. The majority of these tumors do not secrete excess hormones, but functioning NETs produce large amounts of vasoactive peptides and may cause carcinoid syndrome. Synthetic somatostatin analogs (SSAs) have been widely used in NETs for control of hormonal syndromes. Here, we present a case of poorly differentiated, grade 3 pancreatic NEC associated with carcinoid syndrome, for which adequate symptom control was achieved for 2 years and 4 months using the long-acting SSA lanreotide Autogel(®). In February 2009, a 55-year-old woman presented with episodes of flushing, diarrhea and epigastric pain. Imaging techniques revealed the presence of a metabolically active mass expressing somatostatin receptors in the hilar area of the liver. Histopathological examination confirmed the malignant nature of the mass, which was identified as a poorly differentiated grade 3 pancreatic NEC (TNM staging: T4NxM0). Therapeutic options were limited for the patient because of the extent of the primary mass involving the celiac axis, severe gastrointestinal toxicity experienced as a side effect of chemotherapy with cisplatin-etoposide and, later in the course of the disease, extensive liver metastases and carcinoid heart syndrome. Along with a palliative debulking surgery and right portal vein embolization, biotherapy with a high dose of lanreotide Autogel (120 mg/14 days) contributed to alleviation of symptoms caused by hormone overproduction, even after the development of liver metastases. These results suggest that patients with poorly differentiated NECs who exhibit signs of carcinoid syndrome can benefit from treatment with somatostatin analogs.

Spontaneous liver bleeding in a patient with congenital arterioportal fistulisation. Presentation of a casus princeps and review of the literature.

We present the first case reported in the literature describing spontaneous liver haemorrhage due to diffuse arterioportal fistulae. A 48-year old Caucasian woman was admitted to the hospital complaining of acute epigastric pain eradiating to the right shoulder. Patient never had any penetrating or blunt abdominal trauma in the past nor any intervention on the liver. CT scan of the abdomen revealed a subcapsular haematoma originating from two bleeding sites in the right liver lobe. Arteriography of the common hepatic artery showed opacification of the portal branches, indicative of an arterioportal fistula. A hypertrophic feeding branch of the right hepatic artery was then embolized, resulting in disappearance of the fistula. After complete resolution of the haematoma, investigations to detect underlying liver lesions were repeatedly negative. Therefore we conclude that a diffuse congenital arterioportal fistula was the cause of spontaneous bleeding. This is to our knowledge the first case in whom a spontaneous liver bleeding secondary to diffuse arterioportal fistulisation is reported. A review of the literature regarding arterioportal fistulas and regarding the possible aetiology of spontaneous liver haematomas is provided.

Clinical, biochemical and neuroimaging parameters after thrombolytic therapy predict long-term stroke outcome.

INTRODUCTION: We investigated the predictive value of standard neurological evaluation, a commercially available biomarker assay and neuroimaging in the subacute phase for outcome after thrombolytic therapy in ischemic stroke. METHODS: Thirty-four consecutive ischemic stroke patients were evaluated by means of the NIH Stroke Scale (NIHSS(72)), the Triage(R) Stroke Panel (MMX(72)) and standardized infarct volumetry at 72 h after treatment with intravenous recombinant tissue plasminogen activator or intra-arterial urokinase. Outcome was assessed by the modified Rankin Scale (mRS) at 3 months after the stroke. RESULTS: NIHSS(72), MMX(72) and infarct volume correlated significantly with the mRS score at month 3 and emerged as independent outcome predictors from logistic regression analysis. NIHSS(72) is the best predictor for outcome, but its accuracy increases by 9 and 6% when combined with MMX(72) and infarct volumetry, respectively. The combined use of NIHSS(72) and MMX(72) allows long-term outcome prediction with 97% accuracy, which is not further improved by infarct volumetry. CONCLUSIONS: Routine clinical evaluation, bedside testing of biochemical markers by the Triage Stroke Panel and infarct volumetry on neuroimaging at 72 h after thrombolytic therapy are predictors for long-term outcome of ischemic stroke patients. Clinical assessment is the most reliable parameter for outcome prediction, but its predictive value is substantially improved when combined with the biomarker panel.

Carboxypeptidase U (TAFIa) decreases the efficacy of thrombolytic therapy in ischemic stroke patients.

INTRODUCTION: Thrombolytic therapy improves clinical outcome in patients with acute ischemic stroke but is compromised by symptomatic intracranial hemorrhage and an unpredictable therapeutic response. In vitro and in vivo data suggest that activation of procarboxypeptidase U (proCPU) inhibits fibrinolysis. AIMS: To investigate whether the extent of proCPU activation is related to efficacy and safety of thrombolytic therapy in ischemic stroke patients. METHODS: In twelve patients with ischemic stroke who were treated with intravenous (n=7) or intra-arterial (n=5) thrombolysis, venous blood samples were taken at different time points before, during and after thrombolytic therapy. ProCPU and carboxypeptidase U (CPU, TAFIa) plasma concentrations were determined by HPLC. The maximal CPU activity (CPU(max)) and the percentage of proCPU consumption during thrombolytic therapy were calculated. The efficacy and safety of the thrombolytic therapy were assessed by evolution of the clinical deficit, recanalisation, final infarct volume, thrombolysis-induced intracranial hemorrhage and mortality. RESULTS: No correlations between CPU(max) or proCPU consumption and patient or stroke characteristics were found. However, CPU(max) is associated with evolution of the clinical deficit and achieved recanalisation. ProCPU consumption is related to the risk of intracranial hemorrhage, mortality and final infarct volume. CONCLUSIONS: Irrespective of patient and stroke characteristics, CPU(max) and proCPU consumption during thrombolytic treatment for ischemic stroke are parameters for therapeutic efficacy and safety. Further evaluation of the clinical applicability of these parameters and further investigation of the potential role for CPU inhibitors as adjunctive therapeutics during thrombolytic treatment may be of value.