A Prospective Evaluation of Computerized Tomographic(CT) Scanning as a Screening Modality for Esophageal Varices
Condition: Esophageal Varices; Portal Hypertension; Gastric Varices
MeSH terms: Hypertension, Portal; Esophageal and Gastric Varices; Hypertension; Varicose Veins
Study type: Observational

Summary: 
      Patients with cirrhosis require endoscopic screening for large esophageal varices. The aims
      of this study were to determine the cost -effectiveness and patient preferences of a strategy
      employing abdominal computerized tomography (CT) as the initial screening test for
      identifying large esophageal varices. In a prospective evaluation,102 patients underwent both
      CT and endoscopic screening for gastroesophageal varices. Two radiologists read each CT
      independently; standard upper gastrointestinal endoscopy was the reference standard.
      Agreement between radiologists, and between endoscopists regarding size of varices was
      determined using kappa statistic. Cost-effectiveness analysis was performed to determine the
      optimal screening strategy for varices. Patient preference was assessed by questionnaire. CT
      was found to have an approximately 90% sensitivity in the identification of esophageal
      varices determined to be large on endoscopy, but only about 50% specificity. The sensitivity
      of CT in detecting gastric varices was 87%. In addition, a significant additional number of
      gastric varices, peri-esophageal varices, and extraluminal pathology were identified by CT
      but not identified by endoscopy. Patients overwhelmingly preferred CT over endoscopy .
      Agreement between radiologists was good regarding the size of varices (Kappa = 0.56), and
      exceeded agreement between endoscopists (Kappa = 0.36). Use of CT as the initial screening
      modality for the detection of varices was significantly more cost-effective compared to
      endoscopy irrespective of the prevalence of large varices. In conclusion, abdominal CT as the
      initial screening test for varices could be cost-effective. CT also permits evaluation of
      extra-luminal pathology that impacts management.
    

Detailed description: 
      Study Group -We screened a population of 581 consecutive patients with cirrhosis who were
      scheduled to undergo upper gastrointestinal endoscopy. Exclusion criteria included inability
      to provide consent, patients who had previously undergone liver transplantation, previous
      portosystemic shunt procedure, or had a recent history (< 7 days) of upper gastrointestinal
      bleeding . In addition, patients with renal insufficiency defined as a serum creatinine of >
      1.7 mg/dL in non-diabetics or >1.5 mg/dL in diabetics were excluded given concerns regarding
      the requirement of intravenous contrast during CT. Approximately 300 patients met inclusion
      criteria for screening for esophageal varices. Patients who had endoscopic variceal therapy
      (n=19) were also screened and 10 patients were included in the study to determine the role of
      CT imaging in determining the presence of varices in this group of patients. The last
      endoscopic therapy session in this group was greater than four weeks prior to the CT scan in
      order to eliminate any potential radiological artifact from the endoscopic treatment.
      Patients who met inclusion criteria (n=300) but declined entry into the study cited either
      scheduling conflicts (n=142),or fear of radiation (n=24) . The diagnosis of cirrhosis in the
      134 patients who consented to the study was based on histology (N = 76); or the presence of
      ascites, thrombocytopenia or splenomegaly combined with low serum albumin (<3.4 g/dL) and
      prolongation of the prothrombin time (INR > 1.3) with compatible abdominal imaging (N = 58).
      No endoscopies were performed purely for research purposes. Written informed consent was
      obtained from all patients who were enrolled into the study. Of the 134 patients who
      consented, 102 completed both endoscopic and CT examinations.

      To reflect practice in the real world, the endoscopic procedures were deliberately chosen to
      be carried out by regularly scheduled endoscopists rather than a small selected group of very
      experienced endoscopists. Varices were regarded as present or absent, with size recorded as
      either large (≥5 mm diameter) or small (<5 mm diameter) based on subjective assessment of
      diameter.. Titrated sedation was undertaken in all patients with midazolam and fentanyl.. The
      size of the esophageal varices was measured in the distal 5 cm of the esophagus during
      withdrawal of the instrument.

      Two gastrointestinal radiologists (R1 and R2), each with over 10 years of experience and
      blinded to each other's evaluation, as well as to the results of the endoscopy, read each CT
      study. Axial images were evaluated to determine the presence and size of esophageal and
      gastric varices.

      Multidetector CT scans (four detectors or higher)were performed using 0.5 second rotation
      time ,scanner settings of 250 mAs and 120 kVp, slice thickness 3 mm, and 3 mm reconstruction
      interval. Intravenous low osmolar iodinated contrast (Omnipaque 300; GE Healthcare) was
      administrated at a rate of 4ml/second, with late arterial phase scanning initiated 35 seconds
      after contrast injection, and carried out from the liver dome through the liver and pancreas.
      Portal phase imaging was initiated 70 seconds after contrast injection, and was carried out
      from above the diaphragm to the iliac crest. Partial phase images were also reconstructed to
      a nominal slice thickness of 0.75-1.5 mm and a 20cm field of view to maximize spatial
      resolution.. The total effective radiation dose for this protocol was 15mSv. There was a
      possible clinical indication to perform CT of the abdomen in 44 of the patients; CT was
      performed solely for research purposes in 58 patients. Large esophageal varices on CT scan
      were defined as those that were measured as greater than or equal to 5 mm in diameter, with
      small varices being those that measured less than 5 mm in diameter.

      To determine degree of interobserver variability regarding characterization of variceal size
      between endoscopists, photographs of esophageal varices were taken during endoscopies and
      randomly selected images were circulated among 5 endoscopists, 2 with <5 years' experience in
      practice and 3 with >15 years' experience. The endoscopists were blinded to the results of
      the other's interpretation and were asked to characterize the endoscopic images as either
      small,large, or absent varices.

      Patient satisfaction with endoscopy and CT was determined by administering a questionnaire
      for each patient to complete 24 hours after the procedure. The questionnaire determined the
      patient's opinion regarding elements of comfort and convenience during each test. In
      addition, patient preference for either study and the reason for preference were elicited.

      Statistical Analysis - Sensitivity, specificity, positive and negative predictive values of
      CT in determining characteristics of varices were determined for both radiologists with
      endoscopy regarded as the reference standard.

      The sensitivity of CT for detecting large varices was determined by identifying which of
      those patients with large varices at endoscopy were identified by CT as having esophageal
      varices. The specificity of CT for identifying esophageal varices was defined by correctly
      identifying the absence of varices in those patients in whom no varices were found
      endoscopically. Dilated and tortuous veins that protruded into the lumen of the stomach on CT
      were termed gastric varices. Variceal channels that coursed along the adventitia of the
      esophagus, but did not protrude into the esophageal lumen were termed peri-esophageal
      varices. Kappa statistic was used to determine agreement between observers in grading the
      size of the varices, both on endoscopy and on CT.

      We assumed a 40% prevalence rate of esophageal varices, and a 20 % rate of large varices
      (2,8). To detect a 15% difference in detection rate of esophageal varices between CT and
      endoscopy, 95 patients would require to be studied for an alpha of 0.05 (one tailed test), or
      alpha of 0.10 (two tailed test), and beta of 0.20.

      Decision Model We compared the cost-effectiveness of three strategies for the detection of
      large varices in patients with cirrhosis using a decision tree approach. The comparison
      strategies were 1) Endoscopy, 2) CT and 3) CT + Endoscopy only for patients with small
      varices on CT. The model was contructed using Treeage Pro Suite 2007 (Treeage Software,
      Williamstown, MA). Patients considered in this analysis are assumed to have compensated
      cirrhosis in whom the presence or absence of esophageal varices is not known. The decision
      tree assumed a two year time horizon. The efficacy and costs of the three approaches were
      compared using the incremental cost-effectiveness ratios (ICERs). The decision tree is
      presented in the Appendix (Figure 1) We made a number of assumptions for this analysis. The
      full set of assumptions are presented in the appendix (Table 1). We assumed the sensitivity
      of testing strategies and subsequent complication and bleeding rates from various sources.
      The sensitivity of detection of large varices with CT was derived from the results presented
      in this paper. The analysis was conducted from the perspective of a third party payer,
      considering only direct health care costs. Costs were not discounted due to the relatively
      short time horizon of the analysis (two years). The main outcome of the analysis was the cost
      per variceal bleed prevented. The incremental cost-effectiveness ratios (ICER) were
      calculated compared to the "Do Nothing" strategy.

      The study protocol was approved by the Institutional Review Board.
    

Observational model: Case-Only
Time perspective: Prospective
Sampling method: Non-Probability Sample
Study population: 
        patients with cirrhosis
      
Keywords: esophageal varices; portal hypertension; gastric varices; cost effectiveness