Venous Thromboembolism and Haemostatic Disturbances in Patients With Upper Gastrointestinal Cancer
Condition: Thrombosis; Deep Venous Thrombosis; Pulmonary Embolism; Venous Thromboembolism; Pancreas Cancer; Esophagus Cancer; Gastric Cancer
MeSH terms: Gastrointestinal Neoplasms; Pancreatic Neoplasms; Esophageal Neoplasms; Pulmonary Embolism; Thrombosis; Embolism; Thromboembolism; Venous Thromboembolism; Venous Thrombosis
Study type: Observational

Summary: 
      Cancer is a well known risk factor for venous thromboembolism (VTE) such as deep venous
      thrombosis (DVT) and pulmonary embolism (PE). Today we know that patients with
      adenocarcinomas of the gastro intestinal tract (GI-tract) often is in a hypercoagulable
      state.

      In our observational study we collect patients admitted to department with a tentative
      diagnosis of upper GI cancer including pancreas cancer and offer them flow doppler
      ultrasounds of both legs for diagnosis of DVT in the entire treatment time. The routine
      CT-scan of the chest is modified to diagnose PE. This will be compared with blood samples
      analysed for coagulation markers including D-dimer - a fibrinogen degradation product.
    

Detailed description: 
      Armand Troussau observed back in 1865 a particular condition of the blood that predisposes to
      spontaneous coagulation in patients with gastric cancer. Today it is known that
      adenocarcinomas in the gastrointestinal (GI) tract including tumours of colon and rectum is
      accompanied by an hypercoagulable state.

      Cancer is a well known risk factor for venous thromboembolism (VTE) such as deep venous
      thrombosis (DVT) and pulmonary embolism (PE). In fact PE in cancer patients is the second
      most common cause of death.

      In an analysis of 13 cohort studies published with observational data Otten and Prins
      concludes that the prevalence of VTE in cancer patients varied between 10 and 20%. Variation
      could be explained with inconsistency. Patients suffering from thrombosis secondary to hemi
      paresis and paraplegia were included. Patients where included at time of VTE and not at time
      of cancer diagnosis.

      Levitan et al looked at discharge diagnosis in 1211944 cancer patients and found among
      gastric cancer patients a frequency of VTE at 85 per 10000 patients and in pancreatic cancer
      110 per 10000. Gastric cancer patients had a relative risk of 1.49 compared to non-cancer
      patients and pancreatic cancer patients a relative risk of 2.05 compared to non-cancer
      patients. This put pancreatic cancer among the most prone malignancy to cause thromboembolic
      complications. In a newly published study of 202 pancreatic cancer patients 19 developed
      venous thrombosis resulting in a 58 fold increased risk compared to general population with
      an incidence of 108/1000 patient-years and cumulative incidence after 6 months of 74/1000. 15
      out of 19 cases of VTE occurred in the first 6 months since diagnosis of cancer. Tumours
      located in the corpus or cauda had twice the risk of caput. Chemotherapy resulted in a 4.8
      fold risk of venous thrombosis.

      Postoperatively VTE is higher in cancer patients than in non-cancer patients after surgery. A
      multicenter study including Danish patients - using phlebography - has shown VTE in 23% of
      patients after surgery for colorectal cancer. Coagulation activity - as assessed by sensitive
      biochemical markers - was related to tumour load.

      Stender et al has in a newly published study shown a high preoperative prevalence of DVT in
      193 colorectal cancer patients with a prevalence of 16% in women and 2.6% in men. In another
      newly published study asymptomatic DVT is found ovarian cancer patients with elevated levels
      of D-Dimer before treatment. The mechanism by which cancer induce VTE is at present subject
      to great interest.

      Plasma D-dimer (DD), a degradation product of cross-linked fibrin, is routinely used to
      support or exclude the tentative diagnosis of DVT, combined with clinical assessment and
      ultrasonography (US).

      The accuracy of DD assays in cancer patients is unknown, despite their high negative
      predictive values (NPV) in non cancer patients. A negative DD seems to exclude PE in cancer
      patients, but DD in combination imaging techniques such as US or computed tomography (CT)
      seems to improve diagnostic work-up but needs further investigation.
    

Observational model: Cohort
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        From February 2008 to December 2009 all patients admitted to The Department of Surgical
        Gastroenterology with upper GI cancer or pancreatic cancer will be included.

        Depending on the disease nature and progression, the patients will be followed as
        palliation or surgery cohorts.
      
Biospecimen description: 
      Blood samples with seperation in plasma and serum. Urin samples. tumour tissue samples.
    
Keywords: DVT; PE; D-dimer; cancer; VTE