Suspected Sphincter of Oddi Dysfunction Type II: Empirical Biliary Sphincterotomy or Manometry-Guided Therapy?

• Introduction
• Patients and Methods
• Patients
• Overview of Analysis
• Description of the Decision Tree
• Assumptions of the Decision Tree
• Costs
• Incremental Cost-Effectiveness Ratios
• Results
• Baseline Analysis
• Sensitivity Analysis
• Discussion
• Acknowledgment
• References

Background and Study Aims: Sphincter of Oddi manometry is considered to be the gold standard for diagnosing sphincter of Oddi dysfunction (SOD). Elevated basal sphincter pressures are found in about half of the patients with findings consistent with biliary type II SOD, and most of these patients will symptomatically improve after endoscopic sphincterotomy. Since manometric sphincter evaluation is not widely available, a decision analysis was used to compare the overall costs and outcomes of manometry-directed therapy with ”empirical” sphincterotomy in patients with suspected biliary type II SOD.
Patients and Methods: A decision analysis model was constructed using a software program. In a hypothetical cohort of 100 patients with suspected type II SOD, the following strategies were evaluated: a) endoscopic retrograde cholangiopancreatography (ERCP) with manometry followed by biliary sphincterotomy only if an elevated sphincter of Oddi basal pressure was found; and b) ”empirical” biliary sphincterotomy without manometry. Data on the probability of an elevated sphincter of Oddi basal pressure at the time of ERCP in patients with suspected biliary SOD type II, the proportion of patients who improved after biliary sphincterotomy (with and without elevated basal pressures), the proportion of patients who improved without biliary sphincterotomy, complications, and death were obtained from the literature and from our center. The procedural and hospitalization costs represented the average Medicare reimbursement at our institution. The expected overall costs and numbers of patients improving with each strategy were compared.
Results: The strategy of ERCP with manometry resulted in total costs of $ 2790 per patient, whereas a strategy of ”empirical” biliary sphincterotomy resulted in total costs of $ 2244. In a cohort of 100 patients with suspected SOD, 55 % of patients would be expected to improve if manometry were performed, compared to 60 % of patients improving with ”empirical” biliary sphincterotomy. Univariate sensitivity analyses demonstrated that ”empirical” biliary sphincterotomy continued to be a cost-saving strategy in comparison with ERCP with manometry as long as the probability of spontaneous improvement in patients with ”normal” manometry was less than 41 %, the probability of complications associated with manometry was greater than 6 %, and the probability of complications due to biliary sphincterotomy was less than 19 %.
Conclusions: For patients with suspected biliary SOD type II, empirical biliary sphincterotomy performed by experienced endoscopists appears to be cost-saving in comparison with a strategy based on the results of manometry.

Introduction

Sphincter of Oddi dysfunction (SOD) is increasingly being recognized as a cause of chronic abdominal pain following cholecystectomy. The suspicion of SOD can be stratified by categorizing patients using the modified Milwaukee classification into types I, II, or III [1]. Using this classification, it is estimated that the frequency of elevated sphincter pressures on sphincter of Oddi manometry (SOM) is 52 - 90 % in type I patients, 32 - 65 % in type II patients, and 28 - 60 % in type III patients [2] [3] [4] [5] [6] [7]. Although it is not controversial to carry out sphincterotomy empirically in type I patients, studies have shown a clinical response rate after biliary sphincterotomy of more than 90 % in manometrically defined type II patients [2] [3]. The long-term efficacy of sphincterotomy in type III patients continues to be controversial [8].

Conducting sphincter of Oddi manometry at the time of ERCP has been associated with a high risk of postprocedural pancreatitis, with reported rates of up to 21 % [9]. However, prospective studies using multivariate analysis have shown that SOM itself is not an independent risk factor [10] [11]. Given the response rate to sphincterotomy and the relatively high prevalence of elevated sphincter pressures in type II patients, coupled with the lack of widespread availability of SOM, it was hypothesized in the present study that empirical endoscopic biliary sphincterotomy may be more cost-effective than a strategy using manometry in patients with suspected type II SOD.

Patients and Methods

Patients

A decision tree was constructed with a hypothetical cohort of 100 patients with clinical criteria meeting suspected biliary type II SOD according to the modified Milwaukee classification [1]. Patients meeting type II criteria had ”biliary-type” pain and one of the following: a common bile duct diameter larger than 10 mm, and serum alanine aminotransferase, aspartate aminotransferase, or alkaline phosphatase more than or equal to two times the upper limit of normal on any occasion. Patients with suspected biliary SOD types I and III, as well as patients with suspected pancreatic SOD of any type, were also excluded. The decision was taken not to use hepatobiliary scintigraphy or fatty meal sonography as criteria for classification of these patients, given the limited information available to date.

Overview of Analysis

A decision tree was constructed using the DATA program version 3.5 (TreeAge Software, Inc., Williamstown, Massachusetts, USA). Two strategies in the management of a hypothetical cohort of 100 patients with suspected biliary type II SOD were compared. The strategies evaluated were: ERCP with manometry followed by biliary endoscopic sphincterotomy if the basal pressure was equal to or greater than 40 mmHg; and ERCP with biliary endoscopic sphincterotomy (without manometry).

Decision analysis uses data to produce a model of possible outcomes associated with a particular disease to facilitate the determination of the most desirable health-care strategy among different alternatives. To create the model, the following steps were used: 1. definition of the decision problem and listing of the alternatives; 2. attachment of clinical outcomes associated with each decision alternative; 3. representation of the sequence of events leading to the particular outcome (governed by transition probabilities); and 4. calculation of the expected value of each decision alternative by the process known as ”averaging out and folding back” [12].

The transition probabilities (Table [1]) used in the model were derived from the medical literature with a Medline search using the terms ”SOD,” ”endoscopic retrograde cholangiopancreatography”, and ”SOM”. Data from our center measuring the prevalence, complication rates, and outcome of sphincterotomy in type II patients were also incorporated [8] [13].

Description of the Decision Tree

An attempt was made to identify the optimal management strategy for patients presenting with suspected biliary type II SOD, as described above. The alternative strategies were: ERCP with manometry followed by biliary endoscopic sphincterotomy if the basal pressure was equal to or greater than 40 mmHg; and ERCP with biliary endoscopic sphincterotomy (without manometry). A control group in whom nothing was done was not included, as this is beyond the scope of this study and may not affect clinical practice.

Patients in whom ERCP and manometry was performed would undergo endoscopic sphincterotomy only if the sphincter basal pressure was equal to or greater than 40 mmHg, whereas in the other strategy, all patients would undergo ERCP with endoscopic sphincterotomy without manometry. After each procedure, there is a probability of procedure-related morbidity and mortality. In uncomplicated cases and in survivors of complications, a certain proportion of patients would experience improvement at 1 year (Figure [1]). The expected costs and health outcomes (improvement/no improvement) for each strategy were calculated by a process known as ”averaging out and folding back”. With this process, costs and outcomes are multiplied by their probability of occurrence (transition probability) and are calculated consecutively at each chance node beginning by the later events (from right to left in the decision tree). Discounting (assigning a ”present value” for future costs and health outcomes) was not performed due to the short time horizon of the analysis.

Assumptions of the Decision Tree

• Data regarding symptom improvement after endoscopic sphincterotomy in biliary type II SOD patients were obtained from published studies [2] [3] [6] [14]. It was assumed that a similar proportion of patients would experience improvement after endoscopic sphincterotomy in the absence of prior manometry.

• The probability of complications of ERCP with manometry with or without endoscopic sphincterotomy was obtained from published studies [10] [11] and experience in our institution [13].

• All of the patients had a total of three clinic visits in addition to the procedure. For those patients who did not experience improvement after the procedure, two additional clinic visits were included.

• The decision tree was modified to incorporate the need for repeat procedures due to ongoing abdominal pain in the cohort of patients who underwent endoscopic sphincterotomy only without manometry. Specifically, based on local experience (unpublished observations), it was assumed that 5 % of patients who underwent endoscopic sphincterotomy would undergo manometry for persistent pain. At our center, patients who undergo manometry in whom sphincterotomy has previously been performed have elevated sphincter pressures in less than 10 % of cases (unpublished data). In the latter patients, endoscopic sphincterotomy would be repeated.

• All procedures were performed by experienced endoscopists. Given the emerging data on the use of prophylactic pancreatic stents in this setting [7] [9] [11], it was assumed that these stents would be used in both groups and that the complication rates would therefore be similar.

Costs

The in-patient costs involved in the management of patients with procedure-related complications represented the average Medicare reimbursement rates at the University of Alabama at Birmingham. The costs were based on current procedural terminology (CPT) for the year 2001 (CPT codes: 43 262, 43 263) and diagnosis-related group (DRG) codes (ICD-9 code 577.0). The costs used in the model are summarized in Table [1].

Incremental Cost-Effectiveness Ratios

After calculating total patient costs, incremental cost-effectiveness ratios were computed using a third-party payer perspective. The strategies were ordered according to increasing cost, and the incremental cost-effectiveness ratio was obtained by dividing the difference in expected total costs by the difference in the expected number of patients experiencing improvement between the two strategies.

Sensitivity analyses were performed by changing the value of variables used in the decision tree, particularly those in which there is a certain degree of uncertainty that could alter the study’s conclusions.

Results

Baseline Analysis

The strategy of performing ERCP with manometry followed by endoscopic sphincterotomy if the basal pressure was equal to or greater than 40 mmHg was associated with a total cost of $ 2790 per patient. In this strategy, it would be expected that 55 % of the cohort would experience improvement at 1 year.

The strategy of performing ERCP with endoscopic sphincterotomy (without manometry) was associated with a total expected cost per patient of $ 2244. At 1 year, improvement with this strategy would be expected to occur in 60 % of the cohort.

Therefore, under baseline assumptions, the strategy of performing ERCP with endoscopic sphincterotomy (without manometry) is considered ”dominant” compared to a strategy of performing ERCP and manometry, as it is less expensive ($ 2244 vs. $ 2790) and more effective (improvement in 60 % vs. 55 %).

Sensitivity Analysis

In most sensitivity analyses, ERCP with endoscopic sphincterotomy (without manometry) remained cost-saving compared to ERCP with manometry. For example, when varying the prevalence of type II SOD over a wide range (0 - 100 %), the strategy of empirical endoscopic sphincterotomy was always associated with lower costs and a higher proportion of patients experiencing clinical improvement in comparison with ERCP with manometry. One-way sensitivity analyses demonstrated that the expected costs of ERCP with endoscopic sphincterotomy (without manometry) exceeded the costs of ERCP with manometry when the cost of endoscopic sphincterotomy was higher than $ 1728, the probability of complications due to endoscopic sphincterotomy was higher than 19 %, and the probability of complications associated with manometry was less than 6 %.

Similarly, ERCP with endoscopic sphincterotomy was cost-saving as long as the proportion of patients without elevated basal pressures who improve spontaneously remains less than 41 % and the proportion of patients without elevated basal pressures who improve with endoscopic sphincterotomy remains above 33 %. Table [2] demonstrates the results of one-way sensitivity analyses for selected values.

Figure [2] demonstrates the results of two-way sensitivity analysis on the probability of an abnormal manometry (prevalence of type II SOD) and the proportion of patients who improve after endoscopic sphincterotomy with normal sphincter pressures. For the baseline analysis, the prevalence of type II SOD was 41 % and the proportion of patients with ”normal” manometry improving after endoscopic sphincterotomy was 42 %. As the figure demonstrates, at a higher prevalence of type II SOD, endoscopic sphincterotomy becomes the preferred strategy even as the proportion of patients improving decreases, due to the high probability of improvement in those with documented high pressures [2] [3].

The decision tree was modified to incorporate the need for manometry in patients who had undergone ERCP with endoscopic sphincterotomy (without manometry) with ongoing symptoms. The strategy of ERCP with endoscopic sphincterotomy (without manometry) would remain cost-saving as long as less than 45 % of the patients underwent repeat ERCP with manometry for persistent symptoms.

Discussion

A decision analysis model was constructed to determine whether empirical biliary sphincterotomy or a strategy of manometry-directed therapy is the optimal strategy for patients with suspected type II SOD. This model demonstrates that for patients with suspected type II SOD, manometry followed by sphincterotomy (if sphincter pressures are elevated) would cost $ 2790 per patient and empirical sphincterotomy without manometry would cost $ 2244 per patient - suggesting that empirical sphincterotomy without manometry is cost-saving. For the most part, the assumptions in the model were robust within the ranges used in our sensitivity analyses. The results persist as long as less than 41 % of patients without elevated sphincter pressures improve spontaneously and more than one-third of patients without elevated sphincter pressures respond to sphincterotomy.

An important element in this model is the fact that patients with normal sphincter pressures may improve after sphincterotomy. Previous studies have found a favorable response to sphincterotomy in patients with suspected SOD but normal sphincter pressures. Geenen et al. [2] demonstrated that 94 % of patients with elevated sphincter pressures and 33 % of patients without elevated pressures responded favorably to sphincterotomy. Toouli et al. [3] showed that 85 % of patients with elevated pressures improved after sphincterotomy, while 62 % of patients without elevated sphincter pressures also improved after sphincterotomy.

The results of this analysis must be interpreted in the appropriate context. As with any decision analysis, the results are dependent not only on the findings of previous studies, but on the assumption of the model as well. Firstly, the model only explores this strategy in biliary type II SOD patients. Given the prevalence of sphincter hypertension and clinical response to sphincterotomy, it was considered that this would be an appropriate group to examine. The results should not be extrapolated to suspected biliary type III patients. These patients have a lower prevalence of elevated pressures, are at risk for ERCP-related pancreatitis, and have a poor long-term response to sphincterotomy even if pressures are found to be mildly elevated [2] [8]. Secondly, emerging evidence suggests that pancreatic ductal stenting decreases the rate of pancreatitis after sphincter manometry and sphincterotomy. It was assumed that either strategy would be performed by experienced endoscopists at centers in which these procedures are commonly performed. The study also shows that a difference in the pancreatitis rate of more than 13 % between two endoscopists, for example, would negate the cost-effectiveness of an empirical approach. Thirdly, the use of sensitivity analysis confirms the robustness of these results. Importantly, the model can be used to determine the cost-effectiveness of such a strategy on the basis of other local procedural complication rates. In addition, the decision was taken not to include a ”do-nothing” group as a control group, as the clinical question being investigated revolves around manometry.

Based on this model, for patients with suspected SOD type II, empirical biliary sphincterotomy performed by experienced endoscopists appears to be a cost-saving strategy in comparison with one based on the findings sphincter of Oddi manometry. Although it is cost-saving, this strategy does not reduce the potential for symptomatic improvement. Before this strategy can be recommended, randomized trials including cost data would be warranted, as well as additional cost-effectiveness analyses.

Acknowledgment

A portion of this work was presented in abstract form at the annual meeting of the American College of Gastroenterology October 2001 and was published previously in abstract form (American Journal of Gastroenterology 2001; 96(9S): AB 286).

References

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• 4 Eversman D, Fogel E L, Rusche M. et al . Frequency of abnormal pancreatic and biliary sphincter manometry compared with clinical suspicion of sphincter of Oddi dysfunction.  Gastrointest Endosc. 1999;  50 637-641
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• 9 Tarnasky P R, Palesch Y Y, Cunningham J T. et al . Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction.  Gastroenterology. 1998;  115 1518-1524
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• 10 Freeman M L, Nelson D B, Sherman S. et al . Complications of endoscopic biliary sphincterotomy.  N Engl J Med. 1996;  335 909-918
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• 11 Freeman M L, DiSario J A, Nelson D B. et al . Risk factors for post-ERCP pancreatitis: a prospective, multicenter study.  Gastrointestinal Endosc. 2001;  54 425-434
  CrossrefPubMedSearch in Google Scholar
• 12 Sox H C, Blatt M A, Higgins M C, Marton K I (eds). Expected value decision making. Boston, MA; Butterworth-Heinemann 1988: 147-166
  Search in Google Scholar
• 13 Linder J D, Geels W, Wilcox C M. Pancreatic endotherapy as a risk factor for endoscopic retrograde cholangiopancreatography (ERCP)-related complications.  Gastrointest Endosc. 2001;  53 AB 3350
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C. M. Wilcox, M. D. 

Division of Gastroenterology and Hepatology, 633 ZRB, UAB Station

Birmingham, AL 35294-0007 · USA

Fax: +1-205-934-1546

Email: melw@uab.edu

References

• 1 Hogan W J, Geenen J E. Biliary dyskinesia.  Endoscopy. 1988;  20 (Suppl 1) 179-183
  PubMedSearch in Google Scholar
• 2 Geenen J E, Hogan W J, Dodds W J. et al . The efficacy of endoscopic sphincterotomy after cholecystectomy in patients with sphincter-of-Oddi dysfunction.  N Engl J Med. 1989;  320 82-87
  PubMedSearch in Google Scholar
• 3 Toouli J, Craig A. Sphincter of Oddi function and dysfunction.  Can J Gastroenterol. 2000;  14 411-419
  PubMedSearch in Google Scholar
• 4 Eversman D, Fogel E L, Rusche M. et al . Frequency of abnormal pancreatic and biliary sphincter manometry compared with clinical suspicion of sphincter of Oddi dysfunction.  Gastrointest Endosc. 1999;  50 637-641
  CrossrefPubMedSearch in Google Scholar
• 5 Sherman S, Troiano F P, Hawes R H. et al . Frequency of abnormal sphincter of Oddi manometry compared with the clinical suspicion of sphincter of Oddi dysfunction.  Am J Gastroenterol. 1991;  86 586-590
  PubMedSearch in Google Scholar
• 6 Botoman V A, Kozarek R A, Novell L A. et al . Long-term outcome after endoscopic sphincterotomy in patients with biliary colic and suspected sphincter of Oddi dysfunction.  Gastrointest Endosc. 1994;  40 165-170
  CrossrefPubMedSearch in Google Scholar
• 7 Fogel E L, Eversman D, Jamidar P. et al . Sphincter of Oddi dysfunction: pancreaticobiliary sphincterotomy with pancreatic stent placement has a lower rate of pancreatitis than biliary sphincterotomy alone.  Endoscopy. 2002;  34 280-285
  Thieme ConnectPubMedSearch in Google Scholar
• 8 Linder J D, Klapow J C, Geels W. et al . Long term follow-up of patients undergoing sphincter of Oddi manometry (SOM) and sphincterotomy (S): evidence for a chronic pain disorder.  Gastrointest Endosc. 2001;  53 AB 3327
  PubMedSearch in Google Scholar
• 9 Tarnasky P R, Palesch Y Y, Cunningham J T. et al . Pancreatic stenting prevents pancreatitis after biliary sphincterotomy in patients with sphincter of Oddi dysfunction.  Gastroenterology. 1998;  115 1518-1524
  PubMedSearch in Google Scholar
• 10 Freeman M L, Nelson D B, Sherman S. et al . Complications of endoscopic biliary sphincterotomy.  N Engl J Med. 1996;  335 909-918
  CrossrefPubMedSearch in Google Scholar
• 11 Freeman M L, DiSario J A, Nelson D B. et al . Risk factors for post-ERCP pancreatitis: a prospective, multicenter study.  Gastrointestinal Endosc. 2001;  54 425-434
  CrossrefPubMedSearch in Google Scholar
• 12 Sox H C, Blatt M A, Higgins M C, Marton K I (eds). Expected value decision making. Boston, MA; Butterworth-Heinemann 1988: 147-166
  Search in Google Scholar
• 13 Linder J D, Geels W, Wilcox C M. Pancreatic endotherapy as a risk factor for endoscopic retrograde cholangiopancreatography (ERCP)-related complications.  Gastrointest Endosc. 2001;  53 AB 3350
  PubMedSearch in Google Scholar
• 14 Toouli J, Roberts-Thomson I C, Kellow J. et al . Manometry based randomized trial of endoscopic sphincterotomy for sphincter of Oddi dysfunction.  Gut. 2000;  46 98-102
  CrossrefPubMedSearch in Google Scholar

C. M. Wilcox, M. D. 

Division of Gastroenterology and Hepatology, 633 ZRB, UAB Station

Birmingham, AL 35294-0007 · USA

Fax: +1-205-934-1546

Email: melw@uab.edu