A Prospective Evaluation of Computerized Tomographic(CT) Scanning as a Screening Modality for Esophageal Varices
A Prospective Evaluation of Computerized Tomographic(CT) Scanning as a Screening Modality for Esophageal Varices
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.
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.
Inclusion Criteria:

 -  Cirrhosis

 Exclusion Criteria:

 -  Recent bleed

 -  Previous TIPS

 -  Inability to provide consent

 -  Renal insufficiency