OC-06 - Pro-thrombotic biomarkers in pancreatic diseases: are they specific of cancer?

INTRODUCTION: Venous thrombo-embolic events (VTE) occur frequently in patients with pancreatic cancer and contribute to elevated morbidity and mortality. Clinical risk factors for thrombosis such as cancer stage and tumor grade have been clearly identified. Recently, several biomarkers have been proposed which may help identifying cancer patients at high risk of thrombosis. Those biomarkers have been studied in heterogeneous cohorts of patients with different cancer types. AIM: To compare pro-thrombotic biomarkers in pancreatic cancer and in chronic pancreatitis to determine whether these biomarkers are related to cancer or inflammation and to validate their association with thrombotic risk in a pancreatic cancer population. MATERIALS AND METHODS: 45 patients with pancreatic cancer, 49 with intraductal papillary mucinous tumor of the pancreas (IPMN), a precancerous lesion, and 50 with chronic pancreatitis were recruited. Plasma levels of factor VIII, D-dimers, thrombin-antithrombin complexes, soluble p-selectin, tissue factor-dependent procoagulant activity of MP (TF-MP), free Tissue Factor Pathway Inhibitor (TFPI) and extracellular DNA were measured. Thrombin generation triggered by 1pM of TF was evaluated with the Calibrated Automated Thrombogram assay. RESULTS: Levels of factor VIII, D-dimers, TF-MP, TFPI and extracellular DNA were significantly higher in cancer patients compared to IPMN or chronic pancreatitis (Table 1). Patients with metastatic cancer (n=27) presented higher levels of D-dimers (mean±sd 1.77±1.28 vs 0.80±0.96 µg/ml, p=0.004) and MP-TF (54.3±53.2 vs 15.8±10.4 fM, p=0.02) compared to patients with localized lesions (n=18). Among cancer patients, 42 were followed for a median duration of 187 days (min 21-max 802 days). VTE occurred in 10 (23%) patients. All had metastatic cancer at the time of thrombosis. Only D-dimers were significantly elevated in cancer patients with VTE compared to patients without VTE (median 1.85 vs 0.7 µg/ml, p=0.02). CONCLUSIONS: Elevation of factor VIII, D-dimers, TF-MP, TFPI and extracellular DNA seems to be related to cancer process, not to local or systemic inflammation as these parameters differentiate cancer from chronic pancreatitis. Interestingly, D-dimers and TF-MP are related to the disseminated cancer stage, suggesting that vascular invasion is a prerequisite to the release of TF-MP from the primary tumor into the bloodstream and to coagulation activation. However, only D-dimers are associated with the occurrence of future VTE. We propose that D-dimers could be a useful tool to predict thrombotic events in pancreatic cancer patients. This should be confirmed in a larger population.

Endothelial markers are associated with thrombolysis resistance in acute stroke patients.

BACKGROUND AND PURPOSE: The endothelium is crucial in maintaining the haemostatic balance between pro- and anti-thrombotic factors. In this pilot study, the association of endothelial biomarkers with arterial recanalization and clinical outcome in the setting of acute ischaemic stroke (AIS) was evaluated amongst patients treated with recombinant tissue plasminogen activator (rt-PA). METHODS: Sixty-four AIS patients treated with rt-PA were prospectively recruited. Blood was collected before thrombolysis and analysed for von Willebrand factor (vWF), soluble thrombomodulin (sTM) and soluble endothelial protein C receptor (sEPCR). Complete recanalization was defined by a Thrombolysis in Myocardial Infarction Score of 3. Favourable clinical outcome was defined by a modified Rankin Score of 0-2 at 90 days. RESULTS: Amongst the 64 patients, 31 had no documented occlusion, 19 had persistent occlusion and 14 had complete recanalization. After adjustment for confounding factors, these patients presented lower sTM and sEPCR levels than patients with persistent occlusion (median sTM, 21 vs. 48 ng/ml, P = 0.008; median sEPCR, 78 vs. 114 ng/ml, P = 0.018), but similar levels compared with patients without occlusion. vWF levels did not differ between groups. None of these biomarkers was significantly associated with favourable outcome. CONCLUSIONS: Recanalization after thrombolytic therapy is associated with low sTM and sEPCR levels but not with vWF levels. If corroborated in further larger studies, these findings could be helpful in the identification of patients resistant to rt-PA thrombolysis who could benefit from a modified recanalization therapy.

[Fixation of nasogastric tubes in agitated and uncooperative patients]. / Fixation des sondes naso-gastriques chez les patients agités et peu compliants.

To prevent extubation, nasogastric tubes (NGT) were attached to a fine bore polyurethane tube, which loops loosely around the nasal septum. In a prospective study 180 cases were evaluated concerning the efficacy and possible complications related to this techniques. On average, a nasal septal loop (NSL) remained 20.1 +/- 1.3 days and a NGT 14 +/- 0.9 days. Complications were rare. In 45 of the cases NGT had to be replaced after self extubation and in 2.2% extubation presented more than twice. We think NSL is an easy and useful technique to secure NGT in non-cooperative and/or agitated patients for a relatively short term enteral nutrition or gastric decompression.

Posterior epistaxis: our experience with transantral ligation and embolisation.

Transantral ligation of the arteria maxillares internae (AMI) (with or without ligation of the arteria ethmoidalis) and percutaneous embolisation of AMI in cases of intractable epistaxis (i.e. epistaxis not responding to classical posterior packing) are compared. Except when ethmoidal bleeding is suspected, we recommend embolisation for epistaxis not responding to classical measures as it leads to fewer complications and recurrences, to shorter hospital stay and to improved postoperative comfort.

Premalignant lesions of the vocal cords. A retrospective study of 62 cases treated with CO2 laser.

A series of 62 patients treated by (repeated) CO2 laser excision and/or vaporization for premalignant lesions of the vocal cords was analysed retrospectively. Of the 54 patients available for follow-up (ranging from 1 to 15 years), five patients (9%) developed an invasive glottic carcinoma and needed radiotherapy. Only two patients (4%) needed extensive surgery (total laryngectomy). One patient (2%) died of a recurrent carcinoma despite radiotherapy and laryngectomy, and six patients (11%) died of a metachronic lung carcinoma. The therapeutic results of (repeated) laser therapy were comparable to those in other reports regarding radiotherapy or stripping. The subjective functional results were satisfactory and tended to improve along with refinement of laser surgery techniques. Follow-up of patients who once had a premalignant laryngeal lesion is mandatory ad vitam, regardless of the grade of the lesion. For the screening of lung cancer, there is still no consensus on a standard-of-care. The classical chest X-ray remains the most accessible and comfortable screening procedure.

Our technique of partial inferior turbinoplasty: long-term results evaluated by rhinomanometry.

Conservative surgical technique (Partial inferior turbinoplasty) for enlarged inferior turbinates, not responding to adequate local and systemic therapy is described. Short and long term results are evaluated. Relief of nasal obstruction is reported in 94.7% of the patients. There is a good correlation between this success-rate and the objective measurements of the nasal resistance by active anterior rhinomanometry. Rhinorrhea or postnasal drip was still present in 34.2%. Atrophic changes in the nasal mucosa were not observed. Early post-operative epistaxis was found in 5.3% of the patients. Late post-operative epistaxis did not occur.

Securing nasogastric tubes in non-cooperative patients.

To prevent extubation, nasogastric tubes (NGT) were attached to a fine bore polyurethane tube, which loops loosely around the nasal septum. In a prospective study, 124 cases were evaluated for the efficiency and possible complications. On average, a Nasal Septal Loop (NSL) remained 21,2 +/- 1,8 days and a NGT 13,8 +/- 1,1 days. Complications were rare. In 16,9% of the cases NGT had to be replaced after self extubation and in 2.4% extubation occurred more than twice. We think NSL is an easy and useful technique for securing NGT in non-cooperative and/or agitated patients for relatively short term enteral nutrition or gastric decompression.