- Email: [email protected]
Do ASGE guidelines for the appropriate use of colonoscopy enhance the probability of finding relevant pathologies in an open access service?
Digestive and Liver Disease 37 (2005) 609–614
Digestive Endoscopy
Do ASGE guidelines for the appropriate use of colonoscopy enhance the probability of finding relevant pathologies in an open access service? G. Bersani a,b,∗ , A. Rossi a,b , G. Ricci a,b , V. Pollino a,b , G. DeFabritiis a,b , A. Suzzi a,b , V. Alvisi a,b a
Gastrointestinal Endoscopy Service of Malatesta Novello Hospital, Cesena, Italy Post-graduate School of Gastroenterology, University of Ferrara, Ferrara, Italy
b
Received 30 September 2004; accepted 20 March 2005 Available online 27 April 2005
Abstract Background. This prospective study examined the appropriate use of colonoscopy in an open-access system with the American Society for Gastrointestinal Endoscopy guidelines and determined whether the American Society for Gastrointestinal Endoscopy guidelines were associated with relevant endoscopic findings. Methods. In a cohort of 2221 consecutive patients referred for colonoscopy, the proportion of patients who underwent colonoscopy for appropriate indications was prospectively assessed. The relationship between appropriateness and the presence of clinically relevant endoscopic diagnoses was assessed by calculating (1) the positive and negative likelihood ratio of the indications; and (2) the change in the probability of relevant endoscopic diagnoses in the presence of the American Society for Gastrointestinal Endoscopy criteria. Results. The rate for ‘generally not indicated’ colonoscopies was 37%. Relevant endoscopic diagnoses were present in 28.5% of cases with American Society for Gastrointestinal Endoscopy indications versus 20.1% of patients without appropriate indications. However, the risk of finding relevant diagnoses was significantly increased by American Society for Gastrointestinal Endoscopy criteria application (odds ratio (OR) 1.58; 99% CI 1.20–2.07; p < 0.01). Furthermore, in both endoscopic situations (appropriate and not appropriate), the likelihood ratio, positive and negative, varied very little, suggesting a low predictivity for serious pathologies by the appropriate procedure. Conclusions. The use of an appropriateness evaluation system makes it possible to increase the probability of finding relevant endoscopic diseases. However, the exclusive use of such a system for selecting patients to undergo colonoscopy involves a relatively high risk of colorectal neoplasms going undetected. © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Colonoscopy; Colorectal neoplasms
1. Introduction The demand for GI endoscopies in most developed countries, such as Italy, is progressively increasing with unavoidable financial consequences on the management of Health care. The rational utilisation of resources, the intention to reduce the risk of complications related to endoscopic in∗ Corresponding author. Present address: Via R. Serra 2, 47023 Cesena (FC), Italy. Tel.: +39 0547 370737; fax: +39 0547 22336. E-mail address: [email protected] (G. Bersani).
vestigations as far as possible, as well as the rapid growth and achievements of evidenced-based medicine require the adoption of appropriateness criteria as well as guidelines [1,2]. Specific guidelines for GI endoscopy have been published and periodically updated by American Society for Gastrointestinal Endoscopy (ASGE) [3]. Nevertheless the available data concerning the utilisation of such criteria for lower GI tract endoscopy have up to now produced few and conflicting reports [4–7]. In Italy, endoscopic procedures are performed on an open access system basis, so that several examinations
1590-8658/$30 © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2005.03.008
610
G. Bersani et al. / Digestive and Liver Disease 37 (2005) 609–614
Table 1 Number and percentage of colonscopies performed following indications included and not included in ASGE criteria No. Indications included in ASGE guidelines Evaluation of an abnormality by barium enema Evaluation of haematochezia Melena after exclusion of source with EGD Presence of occult faecal blood Unexplained iron deficiency anaemia Surveillance after resection of cancer within 3 yrs. Surveillance after resection of colonic polyps at 3–5 yr intervals Evaluation of families with HNPCC at 1–2 yr intervals Evaluation of families with sporadic polyps at 3–5 yr intervals Evaluation of ulcerative colitis at 1–2 yr intervals Evaluation of IBD of the colon with influence on the therapy Clinically significant diarrhoea of unexplained Origin Adenomatous polyp resection Others (ASGE criteria) Overall Indications not included in ASGE guidelines Chronic constipation Abdominal pain and bloating Altered bowel habits Surveillance after resection of colonic polyps <3 yrs Others Overall
are generally not indicated according to the ASGE guidelines [7]. The aim of this study was to investigate the applicability of the ASGE guidelines in the appropriateness evaluation of the indication for colonoscopy in an ‘open access’ digestive endoscopy service in Northern Italy. We therefore assessed: (a) the probability, according to ASGE criteria, of relevant endoscopic diagnosis in the group of patients with appropriate indication, compared to the group without appropriate indication; (b) the number and percentage of serious diseases (in particular neoplasms) found in the group of patients, without appropriate indication, compared to the group with appropriate indication.
2. Materials and methods The study was carried out between August 2000 and September 2002 in an ‘open-access’ digestive endoscopy service in Northern Italy, for primary care physicians and for hospital-based specialists. This service accounts for about one-third of endoscopic examinations in the population of this area, which is characterised by an incidence of colorectal cancer averaging 56 cases/100,000 per year [8]. All patients (n = 2221) referred for colonoscopy were included in this study. Informed written consent was obtained for colonoscopy and for reviewing confidential medical information and the study was conducted according to the rules established by the local Health Department
37 419 29 138 98 64 187 30 82 25 93 152 30 13
%
Cancer
2.7 30.0 2.1 9.8 7.0 4.6 13.4 2.1 5.9 1.8 6.6 10.9 2.1 0.9
5 34 8 6 8 2 9
1397 201 297 69 79 178 824
24.4 36.0 8.4 9.6 21.6
Polyps
IBD
4 6
4 52 3 35 8 5 42 2 10 1 4 19 16
84
201
3 4 3 5
25 35 9 23 30
2
15
122
6
1 1
12
1
11 42 14
80
4
and in accordance with the Helsinki Declaration (1989 revision). Data were collected prospectively and uniformly according to a previously defined protocol that included the following steps: (a) patient evaluation including personal medical history according to a structured model that included investigating the presence of the main symptoms that can affect the intestine (rectorrhagia, abdominal pain, alterations in bowel habits, intestinal obstruction, family history of neoplasms); (b) determination, when possible, of the indication category specified by the ASGE guidelines; (c) performance of colonoscopy; (d) report of the endoscopic findings including selection of a standard diagnosis from a predefined list. The first two steps were carried out by trainees in gastroenterology. The colonoscopy and the report of the findings (steps 3 and 4) were carried out by three experienced endoscopists, who were blinded with respect to the ASGE indication category to which the patient had been assigned. The colonoscopies were performed according to a predefined weekly schedule by one of the three endoscopists, all of whom had over 15 years of experience with standard procedures [9]. By agreement between the endoscopists, the endoscopic findings were reported, whenever possible, with internationally accepted terminology and definitions. Caecal intubation was achieved in 94% of cases. Patients in whom it was not possible to complete the colonoscopy were excluded from the study, except those in whom the lack of completion was due to a neoplastic stenosis of the lumen and who were therefore included in the subsequent analyses. The ASGE appropriate indications for colonoscopy are listed in Table 1 together with the number and frequency of
G. Bersani et al. / Digestive and Liver Disease 37 (2005) 609–614 Table 2 Endoscopic findings, clinically and not clinically relevant, also divided according to indications included in ASGE criteria and those not included (column labelled non-ASGE) Total no. Clinically relevant Polyps Colorectal cancer Ulcerative colitis Crohn’s colitis Diverticulitis Intestinal stenosis Ischemic colitis Rectal ulcer Total Not clinically relevant Normal Diverticular disease Haemorrhoids Post-surgical Aspecific colitis Proctitis Others Total
%
ASGE
Non-ASGE
323 99 52 34 34 16 10 1
14.5 4.4 2.2 1.5 1.5 0.7 0.4 0.04
201 84 49 31 17 11 8 0
122 15 3 3 17 5 2 1
569
25.4
401
168
645 467 315 51 37 31 106
29.0 21.1 14.2 2.3 1.7 1.4 4.8
350 271 215 37 28 24 64
295 196 100 14 9 7 102
1652
74.6
989
663
the procedures of the study by indication performed by the service during the period of the study. If it was not possible to assign an indication, one was chosen from a list (see second part of Table 1) prepared on the basis of the indications for colonoscopy according to our experience in the years prior to the study, and named ‘non-ASGE indications’. If more than one indication was present, an ASGE indication was always chosen over a non-ASGE indication. The standardised diagnoses used in the study and divided into ‘clinically relevant’ and ‘not clinically relevant’ categories are listed in Table 2. The former is defined as an endoscopic diagnosis that generally and directly affects therapeutic decisions and prognosis (e.g. diverticulosis with diverticulitis, defined as acute inflammation of the mucosa surrounding the diverticula, adenomatous polyps, ulcerative lesions, neoplastic and non-neoplastic stenosis) [4,6]. A maximum of four diagnoses could be selected for each patient. A relevant diagnosis was always reported first in the event of the joint presence of other non-relevant diagnoses. To evaluate the association between appropriateness and the presence of clinically relevant endoscopic diagnoses, patients in whom colonoscopy was performed because of an ASGE indication were compared with those in whom an ASGE indication did not occur. Appropriateness was classified as appropriate and non-appropriate; endoscopic diagnoses were classified as clinically relevant and not relevant. The extent of the association between these two variables was expressed as the odds ratio of finding a relevant diagnosis in patients with an appropriate indication compared with those with a non-appropriate indication. The association was considered statistically significant if the 99% CI of the odds ratio (OR) did not include the value of 1.0.
611
The ability of the ASGE indications to forecast relevant endoscopic diagnoses was evaluated by calculating the likelihood ratio (LR) (positive and negative), both globally and for each separate indication. This choice was made since the appropriateness criteria can be considered on the same level as a diagnostic test; in fact, when applied to a patient, they are assigned to one of two categories: whether it is appropriate to carry out the test (‘positive’ test result) or not appropriate (‘negative’ test result); it is therefore possible to apply all the analysis methods used in studying the performance of diagnostic systems: sensitivity, specificity, VPP, VPN, LR+ve and LR−ve [10,11]. The LR is the likelihood that a given test result (LR+ve for a positive result or LR−ve for a negative test result) would be expected in a patient with a target disorder, compared to the likelihood that the same result would occur in a patient without the target disorder [10]. The LR assesses the value of a diagnostic test and can be used to assist in the selection of an appropriate diagnostic test or sequence of tests. It can also be used to calculate the post-test probability for a target disorder [10]. A test is useless if the LR is equal to 1; a test has greater value the more the LR+ve is greater than 1 or the LR−ve is less than 1. We decided to use LRs because they are more advantageous in terms of sensitivity and specificity and because they are less likely to change with alterations in the prevalence of a disorder. The prevalence (or pre-test probability) of a relevant disorder was calculated as the percentage of cases in which the disease was found in the total of patients studied. The probability of a relevant pathology after the appropriateness evaluation (or post-test probability) was calculated according to Bayes’ theorem, defining the Ppost-test+ as the probability of a relevant pathology in the case of an appropriate indication (‘positive test’) and the Ppost-test− as the probability of a relevant pathology in the absence of an appropriate indication (‘negative test’). The formulas are defined in Appendix A. All data analyses were carried out with Excel® (Microsoft Corp., Redmond, WA).
3. Results A total of 2221 patients (52% men, 48% women; mean age 57 years, range 14–97 years) were included in the study (70% outpatients, 30% inpatients). Table 1 lists the ASGEappropriate indications for colonoscopy with the number and frequency of procedures; the number and frequency of procedures by indications not listed in the ASGE guideline are also shown. The indication for colonoscopy was considered appropriate according to ASGE criteria in 1390 (63%) patients, whereas in 831 (37%) patients the indication was not included among these criteria and was therefore judged as being not appropriate. The comparison of colonoscopies performed for an appropriate ASGE indication with those for non-appropriate ones shows that the percentage of clinically relevant diagnoses was 28.8% in the former group and 20.2% in the latter with a significant difference (p < 0.05).
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G. Bersani et al. / Digestive and Liver Disease 37 (2005) 609–614
Table 3 Endoscopic findings with and without relevant diseases, LR positive and negative, and post-test prevalence in the presence of the ASGE criteria (Ppost-test+ ) or in the absence (Ppost-test− ) of the ASGE criteria, calculated for the indications most frequently found in our study Class
ASGE criteria
No. with relevant disease
No. without relevant disease
LR+ve
LR−ve
Ppost-test+ (%)
Ppost-test− (%)
A B1 B2 B3 C
Evaluation of an abnormality by barium enema Evaluation of haematochezia Melena after exclusion of source with EGD Presence of occult faecal blood Unexplained iron deficiency anaemia Other ASGE criteria
12 106 12 47 19 205
26 308 18 93 84 460
1.34 0.9 2 1.47 0.66 1.3
0.99 1.09 0.99 0.97 1.01 0.88
32 25 41 34 18 30
25 25 25 25 26 23
Overall
401
989
1.17
0.74
29
20
No. without relevant disease
LR+ve
LR−ve
Ppost-test+ (%)
Ppost-test− (%)
38 56 10 26 38
171 251 59 60 122
0.65 0.65 0.49 1.26 0.90
1.04 1.06 1.02 0.99 1
18 18 14 30 24
26 27 26 25 26
168
663
0.74
1.17
20
29
Non-ASGE criteria
No. with relevant disease
Chronic constipation Abdominal pain Altered bowel habits Surveillance after resection of colonic polyps <3 years Others Overall
In patients in whom colonoscopy was performed according to ASGE indications, the risk of finding clinically relevant pathologies was significantly increased (OR 1.60; 95% CI 1.30–1.96; p < 0.05). In patients in whom colonoscopy was performed according to non-ASGE indications, the risk of finding clinically relevant pathologies was also significantly reduced (OR 0.62; 95% CI 0.51–0.77; p < 0.05). The LR+ve and the LR−ve for both ASGE appropriateness categories and non-appropriate indications are summarised in Table 3, which also shows the variation of pre-test probability (i.e. the prevalence) of finding a relevant pathology. Table 3 shows that ASGE criteria, whenever applied in our patients, could consistently modify the probability of finding pathologies related to clinically relevant diagnoses; it is important to point out that for some ASGE classes the observed LR value may have been affected by the small size of the sample. In both groups of colonoscopies (appropriate and non-appropriate), a total of 569 cases with relevant diagnoses [99 cases of colon cancer (4.4%); 323 cases of adenomatous polyps (14.5%)] were recorded. In the group of patients with polyps, 282 colonoscopies showed ≤3 polyps and 41 colonoTable 4 Number of patients (%) with colorectal cancer or adenomatous polyps in whom colonoscopy was performed with indications not included in ASGE criteria Non-ASGE indication Abdominal pain Constipation Polypectomy <3 years Abdominal bloating Altered bowel habits Other Total
Colorectal cancer
Adenomatous polyps
4 3 3 – – 5
34 25 23 1 9 30
15
122
scopies showed >3 polyps. In this group, 122 cases of adenomatous polyps were recorded without appropriate ASGE indications (Table 4). In the patients with colon cancer, 15 cases (15% of the total number of tumours detected) were recorded without an appropriate ASGE indication. Four of these presented with abdominal pain that had begun 6 months earlier and three with recent onset of constipation; the average age of these patients was 65 years (Table 4).
4. Discussion The digestive endoscopic services work in Italy on the basis of an ‘open access’ system. The increasing demand for colonoscopies in routine use leads to a lack of appropriateness because of indications not considered in the ASGE guidelines [3]. However, the relatively high percentage (37%) of colonoscopies in this study, performed for indications not included in ASGE criteria, did not differ from those reported in previous studies carried out with the same system of access [4,6]. On the other hand, the colonoscopies performed following ASGE indications were able to demonstrate relevant diseases with a higher prevalence (28.8%) than those performed without ASGE indications (20.2%, p < 0.05). With regard to less relevant pathologies, the use of ASGE criteria did not enhance the diagnostic performance of the examination. On the other hand, whenever the procedure was performed for an appropriate ASGE indication, the risk of serious pathologies increased only slightly (OR 1.6; 95% CI 1.30–1.96). Furthermore, in both endoscopic situations (appropriate and non-appropriate) the calculation of LR showed only slight variations, LR+ve 1.17 and LR−ve 0.74, respectively. This behaviour suggests an unsatisfactory level of diagnostic predictivity even for those colonoscopies performed
G. Bersani et al. / Digestive and Liver Disease 37 (2005) 609–614
following ASGE indications. We therefore argue that the failure to find significant differences between appropriate and non-appropriate endoscopic situations is related to the ‘open-access’ system; one important discussion point, which could modify the interpretation of our data (and those of similar studies), concerns the definition of a relevant endoscopic pathology; in our case we also made use of definitions already present in the literature [4,6]. There is, however, still plenty of room for discussion; for example, on normal endoscopic findings in patients undergoing colonoscopy for screening purposes or for surveillance after polypectomy or surgical resection of the intestine. In these cases, the clinical value of a normal test result is, in fact, undeniable. The method we chose nevertheless offers the advantage of being simple, reproducible and transferable for comparison with other studies; the best alternative would in fact be a case-by-case assessment of the usefulness and relevance of the endoscopic diagnosis in the individual clinical situation of the patient in question; this would, however, make the analysis much more subjective and difficult to compare with other experiences. However, in the present study another two main aspects must be taken into consideration: (a) the importance of the pre-test prevalence for relevant pathologies in the population undergoing colonoscopies; (b) the number of colonoscopies performed without appropriateness that demonstrated serious pathologies, such as neoplasms. As regards the former question, it could be suggested that for those indications listed in the ASGE criteria with a medium–low predictive diagnostic value, the safety may mainly depend on the pre-test prevalence for relevant diseases. As regards the latter aspect, we must point out that in our experience the exclusive use of ASGE criteria cannot be considered a safe approach to endoscopic procedures. This consideration is mainly due to the fact that 15% of cases of colorectal cancer would have been missed if only ASGE indications had been followed. In our opinion, therefore, appropriateness criteria can only be safely used in a context of reviewing the probability of diagnosing a relevant pathology, according to the Bayesian point of view [12,13]. The comparison of our results with other previous studies performed with similar working conditions shows that: (i) the percentage of relevant diagnoses obtained with the appropriate use of colonoscopy is higher in both previous studies, 40% for Froehlich et al. [4] and 35% for Morini et al. [6]; (ii) the diagnostic performance of the appropriate and non-appropriate colonoscopies, especially those referring to relevant diagnoses, would be better evaluated by means of LR+ve and LR−ve ; LRs are in fact considered a powerful way of expressing the accuracy of a diagnostic system in a format that is clinically relevant [10,11]. Even though these previous similar studies did not include the calculation of LR, we determined the figures from their data and compared them with our values. A significant difference was observed only for LR−ve calculated from Morini’s data [6] (Table 5). This difference may be due to the prior exclusion of the cases performed with indications not included in ASGE guidelines;
613
Table 5 LRs (LR+ve , LR−ve ) calculated for relevant diagnoses from the data of previous similar studies and compared with the values of the present study
No. of patients LR+ve LR−ve
Present study
Morini et al. [6]
Froehlich et al. [4]
2221 1.17 0.74
1123 1.402 0.337
553 1.282 0.639
(iii) the percentage of relevant diagnoses, e.g. colorectal cancers, obtained with indications not included in the ASGE guidelines is significantly higher in our study, 14% versus 0% and 2% in the respective studies of Froehlich et al. [4] and Morini et al. [6]. The causes underlying such differences cannot yet be sufficiently clarified, since further investigations are needed with comparison of data obtained in similar working conditions. The aim would be to find new appropriateness criteria and to test their effectiveness in terms of how they are tailored to the specific clinical setting of the endoscopic services. In our experience, therefore, the risk of missing neoplastic diseases is too high to allow us to safely use the ASGE appropriateness criteria to select patients for colonoscopy. The reasons for using these criteria are, in our opinion, as follows: • in a context of reviewing disease probability, application of the criteria allows us to calculate by how much the probability of finding relevant endoscopic diseases increases or decreases, both in general and for each individual disease considered; • inclusion in a program of ensuring quality/continuous improvement of quality, in which appropriateness evaluation can be considered a process indicator, where process is the provision of the diagnostic endoscopy service; • the definition of a list of appropriate indications geared to the local situation in which the service operates. The use of an appropriateness evaluation system makes it possible to increase the probability of finding relevant endoscopic diseases. However, the exclusive use of such a system for selecting patients to undergo colonoscopy involves a relatively high risk of colorectal neoplasms going undetected. Conflict of interest statement None declared.
Acknowledgements This work was partly supported by the Grant for Local Research of the Ministry of Universities (M.I.U.R.). We thank Ms. Susan West (IC-DOC s.r.l) for the Help in translation of the text.
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G. Bersani et al. / Digestive and Liver Disease 37 (2005) 609–614
Appendix A
References
Ppre-test = pre-test probability for a target disorder Ppost-test = post-test probability for a target disorder ODDSpre-test = Ppre-test =
ODDSpost-test = Ppost-test =
Ppre-test 1 − Ppre-test
and
ODDSpre-test 1 + ODDSpre-test Ppost-test 1 − Ppost-test
and
ODDSpost-test 1 + ODDSpost-test
According to Bayes’ theorem we find ODDSpost-test = ODDSpre-test × LR By means of LR, we can evaluate how the test, adopted in a defined clinical setting, is able to modify the probability of finding a corresponding disease. The LR may be easily derived from the sensitivity and specificity of a test: • In the case of a positive test LR+ve =
Sensitivity 1 − Specificity
• In the case of a negative test LR−ve =
1 − Sensitivity Specificity
[1] Minoli G. Effectiveness of colonoscopy. Dig Liver Dis 2005;37:85–6. [2] Fasoli R, Repaci G, Comin U, Minoli G. A multi-centre North Italian prospective survey on some quality parameters in lower gastrointestinal endoscopy. Dig Liver Dis 2002;34:833–41. [3] Appropriate use of gastrointestinal endoscopy: a consensus statement from the American Society for Gastrointestinal Endoscopy. Gastrointest Endosc 2000;52:831–7. [4] Froehlich F, Pache I, Burnand B, Vader JP, Fried M, Beglinger C, et al. Performance of panel-based guidelines for colonoscopy: an international comparison. Gastrointest Endosc 1998;48:128– 36. [5] Charles RJ, Chak A, Cooper GS, Wong RC, Sivak Jr MV. Use of open access in GI endoscopy at an academic medical center. Gastrointest Endosc 1999;50:480–5. [6] Morini S, Hassan C, Meucci G, Toldi A, Zullo A, Minoli G. Diagnostic yield of open access colonoscopy according to appropriateness. Gastrointest Endosc 2001;54:175–9. [7] Rossi A, Bersani G, Ricci G, Defabritiis G, Pollino V, Suzzi A, et al. ASGE guidelines for the appropriate use of upper endoscopy: association with endoscopic findings. Gastrointest Endosc 2002;56: 714–9. [8] Zanetti R, Gaf`a L, Pannelli F, Conti E, Rosso S. Cancer in Italy. Incidence data from cancer registries. Roma: Il Pensiero Scientifico Editore; 2002. [9] Cotton PB, Williams B. Practical gastrointestinal endoscopy. Oxford: Blackwell Scientific Publications; 1982. [10] Suchman AL, Dolan JG. Odds and likelihood ratios. In: Panzer RJ, Black ER, Griner PF, editors. Diagnostic strategies for common medical problems. Philadelphia: ACP; 1991. p. 29–34. [11] Moayyedi P, Axon ATR. The usefulness of the likelihood ratio in the diagnosis of dyspepsia and gastroesophageal reflux disease. Am J Gastroenterol 1999;94:3122–5. [12] Phelps CE. The methodologic foundations of studies of the appropriateness of medical care. N Engl J Med 1993;329:1241–5. [13] Shekelle PG. Are appropriateness criteria ready for use in clinical practice. N Engl J Med 2001;344:677–8.
Digestive Endoscopy
Do ASGE guidelines for the appropriate use of colonoscopy enhance the probability of finding relevant pathologies in an open access service? G. Bersani a,b,∗ , A. Rossi a,b , G. Ricci a,b , V. Pollino a,b , G. DeFabritiis a,b , A. Suzzi a,b , V. Alvisi a,b a
Gastrointestinal Endoscopy Service of Malatesta Novello Hospital, Cesena, Italy Post-graduate School of Gastroenterology, University of Ferrara, Ferrara, Italy
b
Received 30 September 2004; accepted 20 March 2005 Available online 27 April 2005
Abstract Background. This prospective study examined the appropriate use of colonoscopy in an open-access system with the American Society for Gastrointestinal Endoscopy guidelines and determined whether the American Society for Gastrointestinal Endoscopy guidelines were associated with relevant endoscopic findings. Methods. In a cohort of 2221 consecutive patients referred for colonoscopy, the proportion of patients who underwent colonoscopy for appropriate indications was prospectively assessed. The relationship between appropriateness and the presence of clinically relevant endoscopic diagnoses was assessed by calculating (1) the positive and negative likelihood ratio of the indications; and (2) the change in the probability of relevant endoscopic diagnoses in the presence of the American Society for Gastrointestinal Endoscopy criteria. Results. The rate for ‘generally not indicated’ colonoscopies was 37%. Relevant endoscopic diagnoses were present in 28.5% of cases with American Society for Gastrointestinal Endoscopy indications versus 20.1% of patients without appropriate indications. However, the risk of finding relevant diagnoses was significantly increased by American Society for Gastrointestinal Endoscopy criteria application (odds ratio (OR) 1.58; 99% CI 1.20–2.07; p < 0.01). Furthermore, in both endoscopic situations (appropriate and not appropriate), the likelihood ratio, positive and negative, varied very little, suggesting a low predictivity for serious pathologies by the appropriate procedure. Conclusions. The use of an appropriateness evaluation system makes it possible to increase the probability of finding relevant endoscopic diseases. However, the exclusive use of such a system for selecting patients to undergo colonoscopy involves a relatively high risk of colorectal neoplasms going undetected. © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. Keywords: Colonoscopy; Colorectal neoplasms
1. Introduction The demand for GI endoscopies in most developed countries, such as Italy, is progressively increasing with unavoidable financial consequences on the management of Health care. The rational utilisation of resources, the intention to reduce the risk of complications related to endoscopic in∗ Corresponding author. Present address: Via R. Serra 2, 47023 Cesena (FC), Italy. Tel.: +39 0547 370737; fax: +39 0547 22336. E-mail address: [email protected] (G. Bersani).
vestigations as far as possible, as well as the rapid growth and achievements of evidenced-based medicine require the adoption of appropriateness criteria as well as guidelines [1,2]. Specific guidelines for GI endoscopy have been published and periodically updated by American Society for Gastrointestinal Endoscopy (ASGE) [3]. Nevertheless the available data concerning the utilisation of such criteria for lower GI tract endoscopy have up to now produced few and conflicting reports [4–7]. In Italy, endoscopic procedures are performed on an open access system basis, so that several examinations
1590-8658/$30 © 2005 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.dld.2005.03.008
610
G. Bersani et al. / Digestive and Liver Disease 37 (2005) 609–614
Table 1 Number and percentage of colonscopies performed following indications included and not included in ASGE criteria No. Indications included in ASGE guidelines Evaluation of an abnormality by barium enema Evaluation of haematochezia Melena after exclusion of source with EGD Presence of occult faecal blood Unexplained iron deficiency anaemia Surveillance after resection of cancer within 3 yrs. Surveillance after resection of colonic polyps at 3–5 yr intervals Evaluation of families with HNPCC at 1–2 yr intervals Evaluation of families with sporadic polyps at 3–5 yr intervals Evaluation of ulcerative colitis at 1–2 yr intervals Evaluation of IBD of the colon with influence on the therapy Clinically significant diarrhoea of unexplained Origin Adenomatous polyp resection Others (ASGE criteria) Overall Indications not included in ASGE guidelines Chronic constipation Abdominal pain and bloating Altered bowel habits Surveillance after resection of colonic polyps <3 yrs Others Overall
are generally not indicated according to the ASGE guidelines [7]. The aim of this study was to investigate the applicability of the ASGE guidelines in the appropriateness evaluation of the indication for colonoscopy in an ‘open access’ digestive endoscopy service in Northern Italy. We therefore assessed: (a) the probability, according to ASGE criteria, of relevant endoscopic diagnosis in the group of patients with appropriate indication, compared to the group without appropriate indication; (b) the number and percentage of serious diseases (in particular neoplasms) found in the group of patients, without appropriate indication, compared to the group with appropriate indication.
2. Materials and methods The study was carried out between August 2000 and September 2002 in an ‘open-access’ digestive endoscopy service in Northern Italy, for primary care physicians and for hospital-based specialists. This service accounts for about one-third of endoscopic examinations in the population of this area, which is characterised by an incidence of colorectal cancer averaging 56 cases/100,000 per year [8]. All patients (n = 2221) referred for colonoscopy were included in this study. Informed written consent was obtained for colonoscopy and for reviewing confidential medical information and the study was conducted according to the rules established by the local Health Department
37 419 29 138 98 64 187 30 82 25 93 152 30 13
%
Cancer
2.7 30.0 2.1 9.8 7.0 4.6 13.4 2.1 5.9 1.8 6.6 10.9 2.1 0.9
5 34 8 6 8 2 9
1397 201 297 69 79 178 824
24.4 36.0 8.4 9.6 21.6
Polyps
IBD
4 6
4 52 3 35 8 5 42 2 10 1 4 19 16
84
201
3 4 3 5
25 35 9 23 30
2
15
122
6
1 1
12
1
11 42 14
80
4
and in accordance with the Helsinki Declaration (1989 revision). Data were collected prospectively and uniformly according to a previously defined protocol that included the following steps: (a) patient evaluation including personal medical history according to a structured model that included investigating the presence of the main symptoms that can affect the intestine (rectorrhagia, abdominal pain, alterations in bowel habits, intestinal obstruction, family history of neoplasms); (b) determination, when possible, of the indication category specified by the ASGE guidelines; (c) performance of colonoscopy; (d) report of the endoscopic findings including selection of a standard diagnosis from a predefined list. The first two steps were carried out by trainees in gastroenterology. The colonoscopy and the report of the findings (steps 3 and 4) were carried out by three experienced endoscopists, who were blinded with respect to the ASGE indication category to which the patient had been assigned. The colonoscopies were performed according to a predefined weekly schedule by one of the three endoscopists, all of whom had over 15 years of experience with standard procedures [9]. By agreement between the endoscopists, the endoscopic findings were reported, whenever possible, with internationally accepted terminology and definitions. Caecal intubation was achieved in 94% of cases. Patients in whom it was not possible to complete the colonoscopy were excluded from the study, except those in whom the lack of completion was due to a neoplastic stenosis of the lumen and who were therefore included in the subsequent analyses. The ASGE appropriate indications for colonoscopy are listed in Table 1 together with the number and frequency of
G. Bersani et al. / Digestive and Liver Disease 37 (2005) 609–614 Table 2 Endoscopic findings, clinically and not clinically relevant, also divided according to indications included in ASGE criteria and those not included (column labelled non-ASGE) Total no. Clinically relevant Polyps Colorectal cancer Ulcerative colitis Crohn’s colitis Diverticulitis Intestinal stenosis Ischemic colitis Rectal ulcer Total Not clinically relevant Normal Diverticular disease Haemorrhoids Post-surgical Aspecific colitis Proctitis Others Total
%
ASGE
Non-ASGE
323 99 52 34 34 16 10 1
14.5 4.4 2.2 1.5 1.5 0.7 0.4 0.04
201 84 49 31 17 11 8 0
122 15 3 3 17 5 2 1
569
25.4
401
168
645 467 315 51 37 31 106
29.0 21.1 14.2 2.3 1.7 1.4 4.8
350 271 215 37 28 24 64
295 196 100 14 9 7 102
1652
74.6
989
663
the procedures of the study by indication performed by the service during the period of the study. If it was not possible to assign an indication, one was chosen from a list (see second part of Table 1) prepared on the basis of the indications for colonoscopy according to our experience in the years prior to the study, and named ‘non-ASGE indications’. If more than one indication was present, an ASGE indication was always chosen over a non-ASGE indication. The standardised diagnoses used in the study and divided into ‘clinically relevant’ and ‘not clinically relevant’ categories are listed in Table 2. The former is defined as an endoscopic diagnosis that generally and directly affects therapeutic decisions and prognosis (e.g. diverticulosis with diverticulitis, defined as acute inflammation of the mucosa surrounding the diverticula, adenomatous polyps, ulcerative lesions, neoplastic and non-neoplastic stenosis) [4,6]. A maximum of four diagnoses could be selected for each patient. A relevant diagnosis was always reported first in the event of the joint presence of other non-relevant diagnoses. To evaluate the association between appropriateness and the presence of clinically relevant endoscopic diagnoses, patients in whom colonoscopy was performed because of an ASGE indication were compared with those in whom an ASGE indication did not occur. Appropriateness was classified as appropriate and non-appropriate; endoscopic diagnoses were classified as clinically relevant and not relevant. The extent of the association between these two variables was expressed as the odds ratio of finding a relevant diagnosis in patients with an appropriate indication compared with those with a non-appropriate indication. The association was considered statistically significant if the 99% CI of the odds ratio (OR) did not include the value of 1.0.
611
The ability of the ASGE indications to forecast relevant endoscopic diagnoses was evaluated by calculating the likelihood ratio (LR) (positive and negative), both globally and for each separate indication. This choice was made since the appropriateness criteria can be considered on the same level as a diagnostic test; in fact, when applied to a patient, they are assigned to one of two categories: whether it is appropriate to carry out the test (‘positive’ test result) or not appropriate (‘negative’ test result); it is therefore possible to apply all the analysis methods used in studying the performance of diagnostic systems: sensitivity, specificity, VPP, VPN, LR+ve and LR−ve [10,11]. The LR is the likelihood that a given test result (LR+ve for a positive result or LR−ve for a negative test result) would be expected in a patient with a target disorder, compared to the likelihood that the same result would occur in a patient without the target disorder [10]. The LR assesses the value of a diagnostic test and can be used to assist in the selection of an appropriate diagnostic test or sequence of tests. It can also be used to calculate the post-test probability for a target disorder [10]. A test is useless if the LR is equal to 1; a test has greater value the more the LR+ve is greater than 1 or the LR−ve is less than 1. We decided to use LRs because they are more advantageous in terms of sensitivity and specificity and because they are less likely to change with alterations in the prevalence of a disorder. The prevalence (or pre-test probability) of a relevant disorder was calculated as the percentage of cases in which the disease was found in the total of patients studied. The probability of a relevant pathology after the appropriateness evaluation (or post-test probability) was calculated according to Bayes’ theorem, defining the Ppost-test+ as the probability of a relevant pathology in the case of an appropriate indication (‘positive test’) and the Ppost-test− as the probability of a relevant pathology in the absence of an appropriate indication (‘negative test’). The formulas are defined in Appendix A. All data analyses were carried out with Excel® (Microsoft Corp., Redmond, WA).
3. Results A total of 2221 patients (52% men, 48% women; mean age 57 years, range 14–97 years) were included in the study (70% outpatients, 30% inpatients). Table 1 lists the ASGEappropriate indications for colonoscopy with the number and frequency of procedures; the number and frequency of procedures by indications not listed in the ASGE guideline are also shown. The indication for colonoscopy was considered appropriate according to ASGE criteria in 1390 (63%) patients, whereas in 831 (37%) patients the indication was not included among these criteria and was therefore judged as being not appropriate. The comparison of colonoscopies performed for an appropriate ASGE indication with those for non-appropriate ones shows that the percentage of clinically relevant diagnoses was 28.8% in the former group and 20.2% in the latter with a significant difference (p < 0.05).
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Table 3 Endoscopic findings with and without relevant diseases, LR positive and negative, and post-test prevalence in the presence of the ASGE criteria (Ppost-test+ ) or in the absence (Ppost-test− ) of the ASGE criteria, calculated for the indications most frequently found in our study Class
ASGE criteria
No. with relevant disease
No. without relevant disease
LR+ve
LR−ve
Ppost-test+ (%)
Ppost-test− (%)
A B1 B2 B3 C
Evaluation of an abnormality by barium enema Evaluation of haematochezia Melena after exclusion of source with EGD Presence of occult faecal blood Unexplained iron deficiency anaemia Other ASGE criteria
12 106 12 47 19 205
26 308 18 93 84 460
1.34 0.9 2 1.47 0.66 1.3
0.99 1.09 0.99 0.97 1.01 0.88
32 25 41 34 18 30
25 25 25 25 26 23
Overall
401
989
1.17
0.74
29
20
No. without relevant disease
LR+ve
LR−ve
Ppost-test+ (%)
Ppost-test− (%)
38 56 10 26 38
171 251 59 60 122
0.65 0.65 0.49 1.26 0.90
1.04 1.06 1.02 0.99 1
18 18 14 30 24
26 27 26 25 26
168
663
0.74
1.17
20
29
Non-ASGE criteria
No. with relevant disease
Chronic constipation Abdominal pain Altered bowel habits Surveillance after resection of colonic polyps <3 years Others Overall
In patients in whom colonoscopy was performed according to ASGE indications, the risk of finding clinically relevant pathologies was significantly increased (OR 1.60; 95% CI 1.30–1.96; p < 0.05). In patients in whom colonoscopy was performed according to non-ASGE indications, the risk of finding clinically relevant pathologies was also significantly reduced (OR 0.62; 95% CI 0.51–0.77; p < 0.05). The LR+ve and the LR−ve for both ASGE appropriateness categories and non-appropriate indications are summarised in Table 3, which also shows the variation of pre-test probability (i.e. the prevalence) of finding a relevant pathology. Table 3 shows that ASGE criteria, whenever applied in our patients, could consistently modify the probability of finding pathologies related to clinically relevant diagnoses; it is important to point out that for some ASGE classes the observed LR value may have been affected by the small size of the sample. In both groups of colonoscopies (appropriate and non-appropriate), a total of 569 cases with relevant diagnoses [99 cases of colon cancer (4.4%); 323 cases of adenomatous polyps (14.5%)] were recorded. In the group of patients with polyps, 282 colonoscopies showed ≤3 polyps and 41 colonoTable 4 Number of patients (%) with colorectal cancer or adenomatous polyps in whom colonoscopy was performed with indications not included in ASGE criteria Non-ASGE indication Abdominal pain Constipation Polypectomy <3 years Abdominal bloating Altered bowel habits Other Total
Colorectal cancer
Adenomatous polyps
4 3 3 – – 5
34 25 23 1 9 30
15
122
scopies showed >3 polyps. In this group, 122 cases of adenomatous polyps were recorded without appropriate ASGE indications (Table 4). In the patients with colon cancer, 15 cases (15% of the total number of tumours detected) were recorded without an appropriate ASGE indication. Four of these presented with abdominal pain that had begun 6 months earlier and three with recent onset of constipation; the average age of these patients was 65 years (Table 4).
4. Discussion The digestive endoscopic services work in Italy on the basis of an ‘open access’ system. The increasing demand for colonoscopies in routine use leads to a lack of appropriateness because of indications not considered in the ASGE guidelines [3]. However, the relatively high percentage (37%) of colonoscopies in this study, performed for indications not included in ASGE criteria, did not differ from those reported in previous studies carried out with the same system of access [4,6]. On the other hand, the colonoscopies performed following ASGE indications were able to demonstrate relevant diseases with a higher prevalence (28.8%) than those performed without ASGE indications (20.2%, p < 0.05). With regard to less relevant pathologies, the use of ASGE criteria did not enhance the diagnostic performance of the examination. On the other hand, whenever the procedure was performed for an appropriate ASGE indication, the risk of serious pathologies increased only slightly (OR 1.6; 95% CI 1.30–1.96). Furthermore, in both endoscopic situations (appropriate and non-appropriate) the calculation of LR showed only slight variations, LR+ve 1.17 and LR−ve 0.74, respectively. This behaviour suggests an unsatisfactory level of diagnostic predictivity even for those colonoscopies performed
G. Bersani et al. / Digestive and Liver Disease 37 (2005) 609–614
following ASGE indications. We therefore argue that the failure to find significant differences between appropriate and non-appropriate endoscopic situations is related to the ‘open-access’ system; one important discussion point, which could modify the interpretation of our data (and those of similar studies), concerns the definition of a relevant endoscopic pathology; in our case we also made use of definitions already present in the literature [4,6]. There is, however, still plenty of room for discussion; for example, on normal endoscopic findings in patients undergoing colonoscopy for screening purposes or for surveillance after polypectomy or surgical resection of the intestine. In these cases, the clinical value of a normal test result is, in fact, undeniable. The method we chose nevertheless offers the advantage of being simple, reproducible and transferable for comparison with other studies; the best alternative would in fact be a case-by-case assessment of the usefulness and relevance of the endoscopic diagnosis in the individual clinical situation of the patient in question; this would, however, make the analysis much more subjective and difficult to compare with other experiences. However, in the present study another two main aspects must be taken into consideration: (a) the importance of the pre-test prevalence for relevant pathologies in the population undergoing colonoscopies; (b) the number of colonoscopies performed without appropriateness that demonstrated serious pathologies, such as neoplasms. As regards the former question, it could be suggested that for those indications listed in the ASGE criteria with a medium–low predictive diagnostic value, the safety may mainly depend on the pre-test prevalence for relevant diseases. As regards the latter aspect, we must point out that in our experience the exclusive use of ASGE criteria cannot be considered a safe approach to endoscopic procedures. This consideration is mainly due to the fact that 15% of cases of colorectal cancer would have been missed if only ASGE indications had been followed. In our opinion, therefore, appropriateness criteria can only be safely used in a context of reviewing the probability of diagnosing a relevant pathology, according to the Bayesian point of view [12,13]. The comparison of our results with other previous studies performed with similar working conditions shows that: (i) the percentage of relevant diagnoses obtained with the appropriate use of colonoscopy is higher in both previous studies, 40% for Froehlich et al. [4] and 35% for Morini et al. [6]; (ii) the diagnostic performance of the appropriate and non-appropriate colonoscopies, especially those referring to relevant diagnoses, would be better evaluated by means of LR+ve and LR−ve ; LRs are in fact considered a powerful way of expressing the accuracy of a diagnostic system in a format that is clinically relevant [10,11]. Even though these previous similar studies did not include the calculation of LR, we determined the figures from their data and compared them with our values. A significant difference was observed only for LR−ve calculated from Morini’s data [6] (Table 5). This difference may be due to the prior exclusion of the cases performed with indications not included in ASGE guidelines;
613
Table 5 LRs (LR+ve , LR−ve ) calculated for relevant diagnoses from the data of previous similar studies and compared with the values of the present study
No. of patients LR+ve LR−ve
Present study
Morini et al. [6]
Froehlich et al. [4]
2221 1.17 0.74
1123 1.402 0.337
553 1.282 0.639
(iii) the percentage of relevant diagnoses, e.g. colorectal cancers, obtained with indications not included in the ASGE guidelines is significantly higher in our study, 14% versus 0% and 2% in the respective studies of Froehlich et al. [4] and Morini et al. [6]. The causes underlying such differences cannot yet be sufficiently clarified, since further investigations are needed with comparison of data obtained in similar working conditions. The aim would be to find new appropriateness criteria and to test their effectiveness in terms of how they are tailored to the specific clinical setting of the endoscopic services. In our experience, therefore, the risk of missing neoplastic diseases is too high to allow us to safely use the ASGE appropriateness criteria to select patients for colonoscopy. The reasons for using these criteria are, in our opinion, as follows: • in a context of reviewing disease probability, application of the criteria allows us to calculate by how much the probability of finding relevant endoscopic diseases increases or decreases, both in general and for each individual disease considered; • inclusion in a program of ensuring quality/continuous improvement of quality, in which appropriateness evaluation can be considered a process indicator, where process is the provision of the diagnostic endoscopy service; • the definition of a list of appropriate indications geared to the local situation in which the service operates. The use of an appropriateness evaluation system makes it possible to increase the probability of finding relevant endoscopic diseases. However, the exclusive use of such a system for selecting patients to undergo colonoscopy involves a relatively high risk of colorectal neoplasms going undetected. Conflict of interest statement None declared.
Acknowledgements This work was partly supported by the Grant for Local Research of the Ministry of Universities (M.I.U.R.). We thank Ms. Susan West (IC-DOC s.r.l) for the Help in translation of the text.
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Appendix A
References
Ppre-test = pre-test probability for a target disorder Ppost-test = post-test probability for a target disorder ODDSpre-test = Ppre-test =
ODDSpost-test = Ppost-test =
Ppre-test 1 − Ppre-test
and
ODDSpre-test 1 + ODDSpre-test Ppost-test 1 − Ppost-test
and
ODDSpost-test 1 + ODDSpost-test
According to Bayes’ theorem we find ODDSpost-test = ODDSpre-test × LR By means of LR, we can evaluate how the test, adopted in a defined clinical setting, is able to modify the probability of finding a corresponding disease. The LR may be easily derived from the sensitivity and specificity of a test: • In the case of a positive test LR+ve =
Sensitivity 1 − Specificity
• In the case of a negative test LR−ve =
1 − Sensitivity Specificity
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