EUS with EUS-guided fine-needle aspiration as the first endoscopic test for the evaluation of obstructive jaundice

Richard A. Erickson, MD, Aldo A. Garza, MD

Temple, Texas

Background: This study assesses the cost savings associated with using endoscopic ultrasound (EUS) before endoscopic retrograde cholangiopancreatography (ERCP) for evaluating patients with suspected obstructive jaundice. Methods: One hundred forty-seven patients with obstructive jaundice of unknown or possibly neoplastic origin had EUS as their first endoscopic procedure. With knowledge of the final diagnosis and actual management for each patient, their probable evaluation and outcomes and their additional costs were reassessed assuming that ERCP would have been performed as the first endoscopic procedure. Also calculated were the additional costs incurred if EUS were unavailable for use after ERCP and had to be replaced by computed tomography or other procedures. Results: The final diagnoses in these patients included malignancies (65%), choledocholithiasis or cholecystitis (18%), medical jaundice (11%), and miscellaneous benign conditions (6%). Fiftyfour percent had EUS-guided fine-needle aspiration but only 53% required ERCP after EUS. An EUS-first approach saved an estimated $1007 to $1313/patient, but the cost was $2200 more if EUS was unavailable for use after ERCP. Significant savings persisted through sensitivity analysis. Conclusions: Performing EUS with EUS-guided fine-needle aspiration as the first endoscopic procedure in patients suspected to have obstructive jaundice can obviate the need for about 50% of ERCPs, helps direct subsequent therapeutic ERCP, and can substantially reduce costs in these patients. (Gastrointest Endosc 2001;53:475-84.)

The evaluation of the patient with obstructive jaundice is a common clinical problem. Most algorithms for evaluating these patients1-3 recommend clinical and laboratory assessment first, then confirmation of extrahepatic obstruction by using a noninvasive imaging method such as transcutaneous abdominal ultrasound (TUS), CT, or more recently magnetic resonance imaging or magnetic resonance cholangiopancreatography (MRCP). If these studies support a diagnosis of extrahepatic obstruction or if the clinical suspicion for obstruction is still high despite a nonsupportive result of TUS, CT, or MRCP, then ERCP is usually recommended to definitively image the biliary tree, obtain a tissue diagnosis if a neoplasm is suspected, and provide therapy for the underlying disorder if appropriate.

Received April 25, 2000. For revision July 31, 2000. Accepted September 22, 2000. From the Departments of Medicine, Scott & White Hospital and Clinic, Texas A&M Health Science Center, College of Medicine, Temple, Texas. Presented in part at the American College of Gastroenterology meeting, October 1999, Phoenix, Arizona, and at the EUS 2000 International Symposium, February 2000, Monte Carlo. Reprint requests: Richard A. Erickson, MD, Gastroenterology Division, Scott & White, 2401 S. 31st St., Temple, TX 76508. Copyright 2001 by the American Society for Gastrointestinal Endoscopy 0016-5107/2001/$35.00 + 0 37/1/111772 doi:10.1067/mge.2001.111772 VOLUME 53, NO. 4, 2001

EUS can likewise diagnose most of the causes of obstructive jaundice such as pancreaticobiliary malignancies4-7 and choledocholithiasis8-10 with the same or better accuracy than ERCP. With the more recent introduction of EUS-guided fine-needle aspiration (EUS-FNA),11-13 EUS can now provide a tissue diagnosis of underlying pancreaticobiliary malignancy with higher success rates than ERCP.11-17 In addition, EUS provides important staging information for pancreaticobiliary malignancies,18,19 which is difficult to obtain by ERCP.20,21 EUS and EUS-FNA do not carry the significant level of risk of pancreatitis or cholangitis of ERCP,22 and they do not mandate biliary stent placement in obstructed patients as does ERCP.22,23 The diagnostic capabilities and lower morbidity of EUS have led us24 and others25,26 to propose that the ideal endoscopic approach to obstructive jaundice may be the combination of EUS/EUS-FNA followed by ERCP if necessary for therapy or to obtain further diagnostic information. The purpose of this study was to quantitate the impact on the subsequent need for diagnostic or therapeutic ERCP and to estimate the change in costs associated with using EUS/EUS-FNA before ERCP in patients with suspected obstructive jaundice.
METHODS Two hundred sixteen consecutive adult patients were referred for evaluation of probable obstructive jaundice
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Figure 1. Algorithm used in this study for managing patients with suspected obstructive jaundice. between June 1995 and March 2000. Patients were managed according to the basic algorithm outlined in Figure 1. The aim of this algorithm was to optimize endoscopic evaluation by placing the diagnostically more powerful procedures EUS/EUS-FNA before ERCP in those patients in whom a pancreaticobiliary malignancy was clinically a significant possibility1,2 and thus EUS/EUS-FNA would ultimately be performed in any case. In addition, EUS was used first in those patients in whom it was thought clinically that the likelihood of needing a therapeutic ERCP was not high and would therefore be better served by EUS, a test with a lower morbidity. This algorithm is similar to that recently published by Dancygier and Lightdale.26 Patients with probable obstructive jaundice were defined as those with a total bilirubin of 3 mg% or greater (51 mol/L) and a clinical history, physical examination and laboratory evaluation suggesting extrahepatic obstruction.1,2 Usually these patients were then evaluated by either TUS or CT (usually spiral) (MRCP was used in only 1 patient). EUS/EUS-FNA was used as the first endoscopic study in jaundiced patients unless one of the following clinical situations existed for which ERCP was considered more appropriate: (1) high likelihood (greater than 50%) of choledocholithiasis by clinical or radiologic evaluation27 (35 patients); (2) suspected bacterial cholangitis (1 patient); (3) jaundice that by clinical evaluation or abdominal imaging appeared to be due to a previously diagnosed malignancy or where tissue diagnosis was thought to be clinically unnecessary (20 patients); (4) previously diagnosed benign cause for obstructive jaundice (3 patients); (5) known Billroth II anatomy (2 patients); (6) suspected sclerosing cholangitis (1 patient); (7) EUS was unavailable (1 patient); (8) the attending gastroenterologist preferred ERCP first (6 patients). A total of 69 of the 216 patients (32%) had ERCP first because of one of the above clinical situations. This left 147 consecutive patients with obstructive jaundice who had EUS as the first endoscopic procedure. Included among these 147 patients were 6 in whom ERCP was attempted first but was unsuccessful in terms of diagnostic information. Thus, these 6 patients were included in the analysis of the EUS-first approach.
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Diagnostic EUS and any subsequent EUS-guided FNA were performed by one endosonographer (R.A.E.), as previously described13,28 by using sector scanning echoendoscopes (UM20, UM130; Olympus America, Inc., Melville, N.Y.). If a pancreaticobiliary neoplasm was detected, it was staged with radial endosonography. EUS-guided FNA was done using the linear array echoendoscopes (FG32UA, FG-36UX or FG-3631U; Pentax Precision Instrument Corp., Orangeburg, N.Y.) with either the Mediglobe (GIP-Medi-Globe, Grassau, Germany) or the EchoTip (Wilson-Cook Medical Inc., Winston-Salem, N.C.) 22-gauge aspiration needles. A cytopathologist was always present during the EUS-guided FNA.13,28,29 All patients gave informed consent for EUS and possible EUS-FNA and/or diagnostic or therapeutic ERCP under the same sedation depending on the findings of the initial EUS/EUS-FNA. Patients with obstructive jaundice undergoing EUS alone and/or EUS-FNA were not given antibiotics prophylactically.11 If ERCP was believed to be indicated after EUS, it was performed, usually while the patient was still sedated and by the same endoscopist. Stents were occasionally placed on a day other than that of the EUS if on subsequent evaluation the patient was not believed to be an operative candidate or a significant delay before surgery was anticipated because of schedule, preoperative evaluation or the use of neoadjuvant chemoradiation. If a stent was placed, a metallic stent was used in patients with an estimated survival of greater than 6 months as judged by a combination of tumor size, the presence of metastatic disease and performance status and comorbidities.30-32 For the purpose of this analysis, a stent placed more than 90 days after the initial EUS was not counted as a post-EUS ERCP. Each patients clinical course, including the results of subsequent diagnostic or therapeutic tests, was prospectively followed and pertinent data were entered into an electronic EUS database up to the point of definitive diagnosis and therapy. Survival data for patients with malignancies were also collected for our institutional tumor registry. Once the final outcome and therapy of the patient were known, the course of each patients evaluation was reassessed with an assumption that instead of EUS, ERCP had been the first endoscopic procedure performed. The probable findings on ERCP and the patients subsequent evaluation were reassessed by using information gathered either from actual findings on an ERCP subsequent to EUS or from the probable ERCP findings given the known diagnosis made by EUS and/or other evaluations. The following assumptions were made, based on published information and our experience with ERCP for obstructive jaundice, as to how ERCP would have been used in these patients with obstructive jaundice if performed as the first endoscopic procedure: 1. If the patient was found to have a biliary stricture at ERCP, a plastic stent would be placed to minimize the risk of ERCP-induced cholangitis.22,23,33 2. If a malignant-appearing stricture of the bile duct or pancreatic duct was seen by ERCP, an attempt at cytologic or tissue diagnosis by brush cytology, transpapilVOLUME 53, NO. 4, 2001

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Table 1. Medicare and fee-for-service total procedure charges (professional and technical charges and supplies) and miscellaneous costs and values used in cost analysis
Procedure Diagnostic EUS EUS-FNA Diagnostic CT CT-FNA-pancreas Diagnostic ERCP ERCP with sphincterotomy and stone extraction ERCP with plastic stent, no brush cytology ERCP with plastic stent and brush cytology ERCP with plastic stent and brush cytology, FNA and biopsy ERCP with metallic stent, no brush cytology Upper endoscopy for stent removal Other values used in cost analysis Cost for therapeutic ERCP complication40 Cost of a day of hospitalization39 Cost of a significant delay in diagnosis of unsuspected acute cholecystitis41 Cost of major abdominal operation39,40,42 Yield of positive diagnosis after ERCP sampling of malignant biliary stricture3,14-17 Cost factor for underrepresentation of EUS charges to true cost of EUS relative to ERCP Yield of positive cytologic diagnosis after EUS-FNA Hospitalization rate after planned outpatient therapeutic ERCP43 % of jaundiced patients who are inpatients Post-therapeutic ERCP major complications22 $4000 $800 $5000 $20,000 40% 1.0 96% 15% 33% 5.0% Medicare charges $822 $1542 $350 $909 $930 $1132 $1056 $1298 $1440 $2063 $427 Fee-for-service charges $1873 $3481 $1143 $1956 $1704 $2757 $2418 $2796 $3244 $3425 $1149 Range used for sensitivity analysis $1-10,000 $300-1500 $2-10,000 $5-40,000 20%-80% 1.0-2.6 50%-100% 5%-75% 0-100% 2%-10%

lary FNA and/or biopsy3,14-17 would be made. If the definitive diagnostic tissue yields from ERCP assessment of malignant pancreaticobiliary strictures were assumed to be greater than 40% for the sensitivity analysis of our study, then ERCP with brush cytology, FNA and duct biopsy17 along with their attendant additional costs would all have to be used. 3. If a stent was placed for malignancy, a plastic stent would be placed initially and changed by ERCP at a later date to a metallic stent if subsequent evaluation showed the patient to not be an operative candidate and to have a potential survival of more than 6 months.30-32 4. As per the policy of Medicare34 and most insuring agencies, the professional charges for EUS done on the same day as ERCP would be reduced by 50%. 5. Although most authorities recommend that antibiotics be given intravenously as a prophylactic measure when performing therapeutic ERCP in obstructed patients,3,23,35 this approach is controversial.36 In addition, antibiotics given orally may be as efficacious as intravenously.37 In our institution combinations are used of intravenous ciprofloxacin or cephtriaxone and/or oral ciprofloxacin selectively depending on the perceived risk of infection and adequacy of biliary drainage. Therefore only $50 was added per the cost of ERCP to cover the average cost of prophylactic antibiotics. 6. If a malignant-appearing stricture was found by ERCP, an EUS, if available, would be done within a day to help stage the lesion and to make a cytologic diagnosis by EUS-FNA if the definitive cytologic or tissue diagVOLUME 53, NO. 4, 2001

nosis of malignancy was not made at ERCP and/or the prior CT did not yield enough information to stage the patient as inoperable. 7. In order not to overestimate the impact of EUS, the assumption was made that the failure rate for ERCP was zero, even though in most series failure rates run between 1% and 15%.38 8. EUS/EUS-FNA would not be done on the same day after an ERCP because it would be unreasonable to use another biopsy technique (EUS-FNA) until the results of the samples taken at ERCP were available (usually the next afternoon). By using a spread sheet based cost analysis previously described,39 the difference in estimated costs of evaluating the patients by using EUS first (their actual management) was compared with the probable management if they had been evaluated with ERCP first. Incorporated into this analysis were variables such as actual fee-forservice and regional Medicare charges for each procedure, the estimated cost per hospital day, the percentage of jaundiced patients managed as inpatients versus outpatients, publication-derived complication rates for ERCP, post-therapeutic ERCP hospitalization rates and the frequency of a definitive tissue diagnosis by EUS-FNA and ERCP (Table 1). The relative true cost of EUS and ERCP is difficult to derive and is the subject of a recent multicenter study.44 Fully recognizing that procedure charges and costs are not the same thing, our institutions fee-for-service and Medicare procedure charges were used as the most reaGASTROINTESTINAL ENDOSCOPY 477

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Table 2. Final diagnoses and actual procedures performed in 147 patients undergoing EUS first for suspected obstructive jaundice
EUS-FNA site Diagnosis Malignant obstruction Pancreatic carcinoma Cholangiocarcinoma Gallbladder carcinoma Ampullary carcinoma Metastatic disease Choledocholithiasis Cholecystitis Miscellaneous benign lesions No biliary obstruction detected Total No. 63 9 5 10 9 18 8 9 16 147 Mass 54 5* 5 2 1 3 70 7 80 6 3 (2) Node 3 2 Liver 4* 1 Failed 3 (2) ERCP after EUS Diagnostic 2 (1) 4 (2) ES Plastic stent 17 (10) 4 (2) 2 3 1 2 (2) 29 (11) 16 (3) 1 37 Metallic stent 10 (2) 1 3 (1) 1 Surgical therapy Resection 25 5 6 Bypass 12

1*

2 1 (1) 1 3 4 (1) 17 (5)

1 1

16 (3) 2 18 (3)

1 15

Numbers in parentheses designate the total number of ERCPs done on a separate day from the EUS/EUS-FNA. ES, Endoscopic sphincterotomy. *EUS-FNA also positive in an aspirated lymph node(s) in this patient. Includes unknown primary (3), lymphoma (2) and 1 each of breast, renal, gastric and multiple myeloma. Includes 1 patient also found to have an unsuspected pancreatic carcinoma. Confirmatory diagnostic ERCPs done within the first 18 months of the study. Each symbol denotes an individual patient. None of these ERCPs demonstrated new findings. Includes chronic pancreatitis (3), choledochocele (2), and 1 each of postoperative stricture, acquired immune deficiency syndrome cholangiopathy, peribiliary fibrosis and biloma.

sonable range estimates for true procedural costs and the relative cost ratio of one procedure to another. To account for the possibility that the charges for EUS relative to ERCP may underrepresent the true costs of EUS relative to ERCP, the impact of selectively increasing the charges for EUS/EUS-FNA relative to ERCP was examined in the sensitivity analysis. The cost analysis also included the estimated cost of a delayed diagnosis of a life-threatening disease (4 patients with unsuspected acute cholecystitis and 1 with an unsuspected pancreatic carcinoma) found on EUS that would not have been detected by ERCP and had not been recognized by prior diagnostic procedures. To examine the costs associated with unavailability of EUS/EUS-FNA for patients with obstructive jaundice, the analysis was also run assuming that EUS was unavailable and would have to be replaced by TUS or CT-guided FNA or, if the lesion was not evident at TUS or CT, by other investigations such as diagnostic laparotomy. Sensitivity analysis of the results of the cost analysis was done by varying the values in Table 1 through reasonable ranges, individually and in combination, as supported by the published data and/or clinical experience.42,43

RESULTS Actual patient management The final diagnoses in the 147 patients are summarized in Table 2. Sixty-two percent of the patients were men and the average age was 69.4 years with a range of 26 to 91 years. Ninety-six of these patients (65%) had malignancy as the cause of jaundice. Two thirds of these were pancreatic cancers with the rest
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fairly equally divided between metastatic disease, papillary and biliary (bile duct and gallbladder) cancers. Of the benign causes of obstructive jaundice, 26 patients (18%) had choledocholithiasis or cholecystitis, 9 (6%) had miscellaneous benign conditions and 16 (11%) had no evidence of biliary obstruction, that is, medical jaundice. One patient had obstructive jaundice caused by a common duct stone but also had a clinically unsuspected carcinoma found in the neck of the pancreas. EUS was successful in all 147 patients. Eighty (54%) of the patients had EUS-FNA as part of their EUS evaluation. EUS-FNA provided a positive cytologic diagnosis of malignancy in 74 of the 77 patients (96%) who underwent the procedure and eventually had the diagnosis of underlying neoplasm confirmed. The average number of EUS-guided FNA passes for the 55 pancreatic masses was 3.40 2.20 (SD) (range 1 to 10), for 17 lymph nodes 1.53 0.51 (range 1 to 2) and for 13 other masses and 4 liver metastases 2.94 2.05 (range 1 to 10). There were 2 cardiorespiratory complications in the 147 patients undergoing EUS/EUS-FNA. One 88-year-old man with severe congestive heart failure and jaundice was admitted for 2 days after EUS because of a prolonged recovery from sedation. Another patient was hospitalized for 1 day after developing sudden hypoxia in the recovery room, which spontaneously cleared after a few minutes and was later attributed to mucous plugging.
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There was 1 patient (0.7%) misdiagnosed by the EUS-first approach. This 46-year-old man was found on EUS to have chronic pancreatitis with a distal biliary stricture and a proximal bile duct stone with echogenic biliary sludge but no definite pancreatic mass. At ERCP, the stone could not be removed because of the stricture. Brush cytology of the stricture at ERCP was also negative. The patient was believed to have either chronic pancreatitis or a small pancreaticobiliary malignancy and underwent choledochojejunostomy after transduodenal intraoperative biopsies of the strictured area were interpreted as benign. However, the patient represented with metastatic pancreatic carcinoma 10 months later. The actual procedures performed in these 147 patients are also shown in Table 2. One third (48) of the patients were inpatients at the time of evaluation. Eighty-three (56%) of the patients had an ERCP within 90 days of the EUS. Five of these ERCPs were confirmatory and were done during the first 18 months of our institutions experience with EUS. None of these confirmatory ERCPs demonstrated additional findings. This left 78 patients (53%) who underwent ERCP as an aid to diagnosis or therapy. Other than providing endoscopic therapy, additional useful diagnostic information was provided by ERCP in 14 (17%) of the patients who underwent ERCP after EUS. However, the information provided by ERCP was clearly superior to that provided by EUS in only 2 of these 14 patients. In 1 patient, ERCP demonstrated a small Klatskins tumor not seen by EUS, although hilar level of obstruction was evident. ERCP brush cytology of this lesion suggested but was not diagnostic of malignancy; this was confirmed at resection. Unbeknown to the endosonographer, another patient had had sphincterotomy and when EUS was performed, air within the biliary tree prevented adequate examination of the porta hepatis. Subsequent ERCP demonstrated this region. The EUS findings were clearly superior to those of ERCP in 20 patients (4 because the prior ERCP was unsuccessful); EUS and ERCP revealed similar biliary findings in 51 patients. Because major therapeutic decisions are based on EUS staging, the accuracy of this information must be considered in an EUS-first approach. In a previous study of our surgically confirmed TNM staging accuracy for pancreatic cancer45 our T stage accuracy was 88% and N stage accuracy was 64%, similar to that reported by others.18,19,46,47 However, patients considered to have unresectable tumors in the current study based primarily on EUS criteria did not undergo surgery to verify the accuracy of
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staging. Survival was substituted for staging accuracy in this group of patients. If these patients truly had a more advanced stage of disease, survival should be similar to that reported for patients with surgically unresectable pancreatic cancer. Of the 64 patients with pancreatic cancer in this study, 37 had operations (25 resections and 12 bypasses) where operability could be assessed surgically. Four patients had metastatic liver disease confirmed by EUS-guided FNA. Four patients had resectable tumors by EUS but were deemed inoperable because of major comorbidities or extreme age. This left 19 patients who were considered by EUS criteria (i.e., substantial major vessel invasion) to have unresectable tumors. The median survival of these 19 patients was 158 days (range 11 to 283 days), which is the same as that previously reported for patients with unresectable pancreatic cancer: 6 months,31 5 months,48 and 5 months.49 Cost analysis The procedures that probably would have been done in these 147 patients if ERCP were to be the first endoscopic procedure are detailed in Table 3. The primary change with respect to the types and numbers of procedures done with an ERCP-first strategy relate to the use of more than 80 ERCPs than with the EUS-first approach. Because of the information provided including that by tissue diagnosis at ERCP, the estimated number of EUS or EUS-FNAs needed with an ERCP-first approach would be reduced by 20 and 31, respectively. However, because the yield of an unequivocally positive brush cytology, FNA or biopsy at ERCP for a pancreaticobiliary malignancy is generally low,14-17 a significant number of post-ERCP procedures to obtain a tissue diagnosis would still be required, either EUS-FNA, CT-FNA, or occasionally exploratory laparotomy if the lesion was not evident on spiral CT and EUS-FNA was not available. The estimated additional cost associated with the ERCP-first approach to obstructive jaundice with the assumptions of our standard analysis are shown in Table 3. Overall, an additional $1007 would be spent per patient if Medicare charges are used for procedural costs or $1313 if fee-for-service charges are used. If EUS or EUS-FNA were not available after ERCP and CT-FNA or laparotomy had to be used to obtain a tissue diagnosis, then the extra cost per patient increases significantly to $2139 and $2229, respectively (Table 4). Sensitivity analysis The impact of varying the assumptions and variable parameters in the cost analysis (sensitivity
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Table 3. Actual procedures performed in 147 patients having EUS first for obstructive jaundice compared with probable procedures that would be done if an ERCP-first approach was used and the estimated cost savings with an EUS-first approach with the values of our standard analysis and Medicare and fee-forservice procedure costs in Table 2
Actual procedures EUS-first Diagnostic EUS EUS-FNA Diagnostic ERCP Therapeutic ERCP ERCP with endoscopic sphincterotomy ERCP with plastic stent placement, no cytology ERCP with plastic stent and brush cytology ERCP with metallic stent placement Endoscopy to remove a stent Additional inpatient days to complete evaluation using ERCP-first approach Calculated post-ERCP major complications Calculated inpatient observation days after outpatient ERCP Nondiagnostic EUS-FNA requiring another biopsy technique if ERCP biopsy also negative Delayed or missed diagnoses of a major morbid condition with ERCP-first (4 acute cholecystitis, 1 pancreatic carcinoma) 50% reduction of professional charges only for 59 EUS done on same day as ERCP plus 19.2 inpatient days saved for same day EUS and ERCP Total Divided by 147 patients Additional major diagnostic operations with ERCP-first if EUS/EUS-FNA not available 67 80 20 18 27 2 16 0 0 4.2 8.4 2 0 Probable procedures ERCP-first* 47 49 37 18 3 89 17 2 43 8.2 16.6 2 5 5 Difference (20) (31) 17 0 (24) 87 1 2 43 4 8.3 Estimated cost savings for EUS-first Medicare ($16,594) ($47,493) $15,804 0 ($25,229) $112,771 $2063 $853 $34,165 $16,200 $6551 $44 $25,000 Fee-for-service ($37,836) ($107,205) $28,970 0 ($57,744) $242,924 $3425 $2298 $34,165 $16,200 $6551 $94 $25,000

$23,864

$36,096

$148,000 $1007/patient 0 12 12

$192,938 $1,313/patient

*In the actual cost analysis some of these values are calculated numbers and therefore may be fractions of whole numbers. For simplicity in the table they are displayed rounded to the nearest integer.

Table 4. Estimated additional costs per patient incurred if an ERCP-first approach were to be used for the 147 patients instead of the EUS-first approach actually used
Additional cost per patient Medicare Standard analysis Only CT/CT-FNA available Confirmatory ERCPs not included ERCP done on separate day from EUS All patients outpatients versus all inpatients 5% versus 75% of patients hospitalized after ERCP ERCP complications 2% versus 10% Great ERCP, poor EUS (ERCP tissue yield 70%, ERCP complications 2%, post-ERCP hospitalization 5%, 90% outpatients, EUS must be on separate day, EUS-FNA yield only 70%) With true cost of EUS 1.5 ERCP Standard analysis With malignant diagnoses only (96 patients) With benign diagnoses only (51 patients) With pancreatic cancers only (64 patients) With resectable pancreatic cancers only (25 patients) With EUS unresectable pancreatic cancers only (19 patients) Only CT/CT-FNA available, pancreatic cancers only $1007 $2139 $1044 $844 $691/$1659 $977/$1185 $941/$1117 $538 Fee-for-service $1313 $2229 $1370 $1067 $997/$1965 $1283/$1491 $1246/$1423 $772

$259 $1186 $722 $1072 $1424 $2302 $3002

$144 $1792 $516 $1746 $2221 $2348 $3328

Additional rows show the alterations (sensitivity analysis) in these additional costs per patient when the assumptions or values used in the analysis are taken to their extremes. Further sensitivity analyses are displayed in Figure 2. 480 GASTROINTESTINAL ENDOSCOPY VOLUME 53, NO. 4, 2001

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analysis) are shown in Table 4 and Figure 2. Because confirmatory ERCPs are no longer performed after EUS at our institution, if the 5 confirmatory diagnostic ERCPs done in the first 18 months of this study are excluded from the EUS-first costs, the savings associated with performing EUS-first increases by about $50 per patient. In addition, some of the cost savings of the EUS-first approach derive from performing EUS on the same day as ERCP. These savings result primarily from inpatient days saved by a more expeditious evaluation and to a lesser extent from the decrease in professional charges for a same-day procedure. If ERCP had to be performed as a separate procedure on the day after EUS/EUSFNA, the cost savings per patient of an EUS-first approach are reduced by about 20%. Our sensitivity analysis suggested the cost savings accrued from an EUS-first approach were relatively insensitive to wide variations in the percentage of major complications occurring as a result of ERCP, the costs attributed to ERCP complications, the cost of a hospital day, or the cost of a delayed diagnosis or major operation. However, the additional costs if EUS/EUS-FNA were unavailable and had to be replaced by CT/CT-biopsy were significantly decreased by decreasing the cost of an unneeded major abdominal operation. The primary factors that affected the additional cost per patient of an ERCP-first approach were the inpatient versus outpatient status of the patient, the yield of a positive cytologic or tissue diagnosis by ERCP and EUS-FNA, the hospitalization rate after an outpatient ERCP and the true cost of EUS relative to ERCP. The EUS-first strategy saves even more money per hospitalized patient or if the hospitalization rate after outpatient ERCP is high (Table 4). The amount of money saved drops as the yield of ERCP tissue diagnosis increases or the yield of EUS-FNA decreases (Fig. 2). Obviously, if EUS/EUS-FNA actually costs substantially more than that estimated by current Medicare or fee-for-service charges, then the cost savings must be less. However, as shown in Figure 2, the relative cost of EUS/EUS-FNA to ERCP must be more than doubled in our standard analysis to effectively eliminate the cost savings of an EUS-first approach. Multiple combinations of changes in the variables used in this analysis were made to determine under which assumptions the cost savings associated with an EUS-first approach persist. If these combinations are taken to clinically unrealistic extremes, highly favoring ERCP (see Great ERCP, poor EUS in Table 4), then the cost savings of an EUS-first approach are effectively negated. However, using the values of our standard analysis,
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EUS/ERCP cost factor

Figure 2. Sensitivity analysis curves for the standard cost analysis assumptions used in this study while varying the relative cost of EUS/EUS-FNA to ERCP. Also shown are the effects on dollars saved with various combinations of changes in the variables used in the cost analysis (Table 4).

which represents the combination of high quality ERCP and EUS/EUS-FNA, the EUS-first strategy resulted in an estimated overall cost savings of between $150 and $200,000 for the 147 patients in this study. When subanalyses of our study population are made (Table 4) according to the various types of malignant obstructive jaundice, an EUS-first strategy saves substantially more per patient than was found in the overall analysis. Similar to the results of a prior study of the cost savings of using EUS/EUS-FNA in pancreatic cancer,29 if EUS is not used in patients with malignant biliary obstruction, the added cost (primarily because of unnecessary operations) is greater than $3000 per patient. DISCUSSION Because the procedures developed relatively recently, the potential role of EUS and EUS-FNA in the evaluation of obstructive jaundice is poorly defined. This study is the first to quantitate actual impact on the need for subsequent ERCP and to estimate the cost-effectiveness of using EUS/EUSFNA as the first endoscopic procedure in the investigation of obstructive jaundice. The use of EUS/EUS-FNA first correctly identified the cause of obstructive jaundice in all but 1 patient (also missed by ERCP and operation) and reduced the total number of patients needing ERCP by 47%. Our best estimate of the cost savings of an EUS-first strategy was between $1007 and $1313 per patient, and an estimated additional $2200 would be spent per patient if EUS/EUS-FNA were not used at all. Sensitivity analysis suggests that
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the cost savings realized by EUS/EUS-FNA remains significant despite varying the assumptions through a wide range of values. The reasons for the cost savings associated with an EUS-first approach for obstructive jaundice are multifactorial. (1) The high diagnostic accuracy of EUS/EUS-FNA (98% in the current study) makes ERCP unnecessary in patients found not to have extrahepatic obstruction or to have a lesion that does not require therapeutic ERCP. (2) Patients best served by operative biliary drainage (either resective or palliative) are reliably identified and therefore do not need ERCP. (3) The high positive yield of EUSFNA for cytology in malignant obstruction (96% in our study) obviates the need to obtain brush cytology, transductal FNA or ductal biopsy at ERCP, which have a disappointingly low yield in most series, especially for pancreatic carcinoma.3,14-17 This low yield often results in additional procedures (EUS-FNA, CT-FNA or operation) to make a tissue diagnosis of cancer. (4) Patients best served by implantation of a metal expandable stent undergo this procedure at their first ERCP because a definitive diagnosis, unresectability and prognosis have already been established by EUS and EUS/FNA. (5) For hospitalized patients (one third of patients in the present study), each extra day in hospital increases costs. Thus the expeditious diagnosis, tissue acquisition and appropriate therapy afforded by EUS/EUS-FNA result in substantial savings in terms of hospital days. (6) The significantly higher cost of the ERCPfirst approach when EUS/EUS-FNA are not available reflects the cost savings incurred when EUS identifies patients who are inoperable but would still undergo surgery when this assessment is made based on CT information alone. This type of cost savings has been shown previously for EUS/EUS-FNA in pancreatic carcinoma.29 A number of factors could significantly affect the cost savings estimated for an EUS-first approach in this study. Our yield for a definitive cytologic diagnosis with EUS-FNA (96%) is among the highest reported11-13 and may not be the norm. The impact of differences in tissue diagnosis yields with EUSFNA and ERCP was assessed in the sensitivity analysis. Because pancreatic cancer was present in 43% of the patients in our series, the way in which an institution approaches the management of this disease could significantly affect the relative roles and cost-effectiveness of EUS and ERCP in obstructive jaundice. If an attempt at preoperative tissue diagnosis is not made in patients with potentially operable disease, the advantages relating to the reliability of EUS-FNA for cytologic diagnosis decrease. If neoadjuvant therapy is used routinely before
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attempting resective surgery for pancreatic carcinoma,50 then plastic stents would usually be placed in all patients to allow 6 to 12 weeks of preoperative chemoradiation. In most institutions, same day EUS and ERCP may be impracticable because the procedures are done by different physicians or the endoscopy schedules may not permit it. Without same day EUS and ERCP, the cost savings of an EUS-first approach are reduced by about 20% (Table 4). In addition, some patients undoubtedly could be discharged after biliary stent placement to continue evaluation on an ambulatory basis. This would reduce the cost savings in our analysis attributed to the extra hospital days accrued with an ERCP-first approach (Table 3). However, as shown in Table 4, even if all the patients were managed as outpatients, the cost savings of an EUS-first approach would be reduced by only about 30%. Finally, although the attempt is made to expedite pancreaticoduodenectomy, in most institutions there is likely a significant delay between diagnosis and operation. This may relate to difficulties in scheduling a long operation or to the time required to complete preoperative medical and oncologic evaluation or treatment. If delays are likely, a patient with biliary obstruction is better served by biliary stent placement rather than have the patient suffer continued malaise and pruritus and risk of cholangitis. Indeed, in most of the patients who had stents placed on a day other than EUS in our series (14 of 45 patients receiving stents, Table 2) one of the above situations developed. Other imaging technologies are also achieving promising results in the evaluation of pancreaticobiliary diseases such as MRCP and advanced spiral CT. As computer technology increases, these techniques will only become more powerful. Thus, the roles of these radiologic procedures in obstructive jaundice are, like EUS, in a state of evolution. In conclusion, this study is believed to demonstrate that EUS and EUS-FNA as needed as first procedures in patients with suspected obstructive jaundice due to possible pancreaticobiliary neoplasm or of unclear origin obviate the need for almost half of the ERCPs that might otherwise be done and at considerable cost savings. Therefore, where high quality EUS/EUS-FNA is available, these patients are most efficiently managed by performing EUS as the first endoscopic procedure, with EUS-FNA if a possible malignancy is visualized, followed directly by therapeutic ERCP when indicated by the findings at EUS/EUS-FNA. EUS/EUS-FNA should be an integral and early part of the evaluation of patients when there is a suspicion of malignant obstructive jaundice.
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