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Colon cancer
The risk of colorectal cancer in ulcerative colitis: a meta-analysis
  1. J A Eadena,
  2. K R Abramsb,
  3. J F Mayberrya
  1. aGastrointestinal Research Unit, Leicester General Hospital, Gwendolen Road, Leicester LE5 4PW, UK, bDepartment of Epidemiology and Public Health, University of Leicester, 22–28 Princess Road West, Leicester LE1 6TP, UK
  1. Dr J Eaden.Jayne.A.Eaden{at}btinternet.com

Abstract

BACKGROUND AND AIMS Controversy surrounds the risk of colorectal cancer (CRC) in ulcerative colitis (UC). Many studies have investigated this risk and reported widely varying rates.

METHODS A literature search using Medline with the explosion of references identified 194 studies. Of these, 116 met our inclusion criteria from which the number of patients and cancers detected could be extracted. Overall pooled estimates, with 95% confidence intervals (CI), of cancer prevalence and incidence were obtained using a random effects model on either the log odds or log incidence scale, as appropriate.

RESULTS The overall prevalence of CRC in any UC patient, based on 116 studies, was estimated to be 3.7% (95% CI 3.2–4.2%). Of the 116 studies, 41 reported colitis duration. From these the overall incidence rate was 3/1000 person years duration (pyd), (95% CI 2/1000 to 4/1000). The overall incidence rate for any child was 6/1000 pyd (95% CI 3/1000 to 13/1000). Of the 41 studies, 19 reported results stratified into 10 year intervals of disease duration. For the first 10 years the incidence rate was 2/1000 pyd (95% CI 1/1000 to 2/1000), for the second decade the incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000 to 12/1000), and in the third decade the incidence rate was 12/1000 pyd (95% CI 7/1000 to 19/1000). These incidence rates corresponded to cumulative probabilities of 2% by 10 years, 8% by 20 years, and 18% by 30 years. The worldwide cancer incidence rates varied geographically, being 5/1000 pyd in the USA, 4/1000 pyd in the UK, and 2/1000 pyd in Scandinavia and other countries. Over time the cancer risk has increased since 1955 but this finding was not significant (p=0.8).

CONCLUSIONS Using new meta-analysis techniques we determined the risk of CRC in UC by decade of disease and defined the risk in pancolitics and children. We found a non-significant increase in risk over time and estimated how risk varies with geography.

  • ulcerative colitis
  • colorectal cancer
  • risk
  • meta-analysis

  • Abbreviations used in this paper

    CRC
    colorectal cancer
    UC
    ulcerative colitis
    pyd
    person years duration

    • https://doi.org/10.1136/gut.48.4.526

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      Colorectal cancer (CRC) was first recognised as a complication of ulcerative colitis (UC) by Crohn and Rosenberg in 19251and since then a multitude of epidemiological studies have confirmed this increased risk. The exact magnitude of the risk remains a subject of controversy because of various biases and methodological errors in published studies.2-6 Although CRC in UC only accounts for 1% of all cases of CRC seen in the general population,7 it is a serious sequel of the disease and accounts for one sixth of all deaths in UC patients.8 As a result it deserves our attention.

      Early estimates of CRC complicating UC were based on crude percentages and all were from major medical institutions, predominantly tertiary referral centres. These centres saw a greater proportion of patients who had more severe recalcitrant disease and also patients who had been referred with a diagnosis of cancer. These series were based on patients admitted to hospital and risks were related to the hospital population rather than the larger population of the host community. These and other factors led to an initial over reporting of the cancer risk. Later population based studies covered defined geographical areas and aimed for complete case ascertainment. These studies are superior with respect to methodological standards and lean to more conservative risk estimates. However, population based series probably include more patients with limited disease and therefore may underestimate the risk.

      There is a general consensus from all studies that the CRC risk is highest in those with extensive disease of long duration. There is less certainty concerning how the risk may vary with geographical location. The worldwide variations reported may represent true differences relating to genetic or environmental factors. However, again the methods employed were not uniform and consequently it is not surprising that the CRC risk has been reported to be as low as 1.4% at 18 years9 and as high as 34% after 25 years of disease.10

      The aim of this paper is to give an overall estimate of the risk in all patients with UC by decade, define the risk for children and those with extensive colitis, and give CRC incidence rates by country where possible.

      Method

      The meta-analysis was conducted according to the guidelines produced by the NHS Centre for Reviews and Dissemination at York University.11

      IDENTIFICATION OF PRIMARY STUDIES

      All published reports citing the risk of CRC in UC were collected by conducting a literature search on Medline using the following keywords: colorectal cancer, ulcerative colitis, surveillance studies, dysplasia, risk factors, and children. A comprehensive search of reference lists of all review articles and of the retrieved original studies was performed to find studies not identified by the Medline search. This identified 194 independent studies dating back to 1925.

      INCLUSION AND EXCLUSION CRITERIA

      English language articles were included where there was a clear definition of the population of patients being studied and where the criteria for diagnosing UC and CRC, together with their outcomes, were well described. Studies citing cancer mortality statistics (not cancer incidence) were excluded as this is not a true representation of cancer incidence. Duplicate publications and studies that obviously combined patients with UC and Crohn's disease in a common analysis were also excluded.

      DATA EXTRACTION

      One author (JE) read each paper and extracted several study and patient population characteristics using a predefined review form (see appendix). Studies that were suitable for inclusion (from which a minimum data set of number of patients and number of cancers detected could be extracted) were placed in to one of three categories:

      (1)
      Crude cancer prevalence only reported.
      (2)
      Cancer incidence and duration of patient follow up reported.
      (3)
      Cancer incidence stratified by decade and duration of patient follow up reported.

      STATISTICAL ANALYSIS

      All analyses were performed using Stata and macros (meta-analysis programs) for conducting meta-analyses.12-14 Overall pooled estimates, together with 95% confidence intervals (CI), of the prevalence and incidence of CRC were obtained using a random effects model on either the log odds or log incidence scale, as appropriate.15 Changes in the log incidence rate over time were assessed using mixed effects meta-regression techniques.16 The size of the circles in fig 2 are inversely proportional to the variance associated with the estimate of the log incidence rate in each study and the regression line was estimated using mixed effects meta-regression techniques. Where possible the actual observed number of cases of CRC and the person years duration (pyd) of follow up were extracted from papers. When only the number of cases of CRC and cumulative probabilities were reported, pyd was calculated.17 In addition to estimating the magnitude of the CRC risk in UC, and how that risk varies temporally, subgroup analyses were performed to explore between study heterogeneity.

      Figure 2
      Figure 2

      Temporal relationship of colorectal cancer, overall and by geographical location.

      Results

      A total of 194 studies were identified. Of these, five reported cancer mortality data,8 ,18-21 10 did not give details concerning the background population,22-31 two included patients with Crohn's disease,32 ,33 four were reviews only,34-37 26 were updated by subsequent studies,9 ,38-62 and 31 overlapped with other studies or included the same patients.59 ,63-92 This left 116 studies suitable for inclusion in the analysis.7 ,10 ,81-121 ,122 ,123-150 ,151 ,152-179 ,180 ,181-205

      OVERALL ANALYSIS

      Overall 54 478 patients were studied and a total of 1698 CRCs were detected: 9846 patients had total colitis, among whom 700 cancers were found. Fifty four studies (with 22 730 patients and 844 cancers) included data on age at cancer diagnosis with a mean of 43.2 years (95% CI 40.5–45.9) and 61 studies reported the duration of colitis at cancer diagnosis with a mean of 16.3 years (95% CI 15.0–17.6). There were 75 studies in category 1, 22 in category 2, and 19 in category 3. Table 1 summarises the characteristics of the included trials by category. In the analyses that follow, all studies were not given equal weighting but were weighted proportionally to the number of cases of cancer that were included in the study.

      View this table:
      Table 1

      Characteristics of studies included

      Considering the overall prevalence of CRC in any patient with UC, based on the total 116 studies, a χ2 test for heterogeneity yielded χ2=799.1, p<0.0001, and therefore a random effects model produced an overall pooled estimate of the prevalence to be 3.7% (95% CI 3.2–4.2). Of the 116 studies, 35 included adequate data on patients with total colitis to calculate the prevalence in this group. In these 35 studies there were 8351 patients with pancolitis and 451 cases of cancer. The χ2=127.5, p<0.0001 and a random effects model produced an overall pooled estimate of the prevalence to be 5.4% (95% CI 4.4–6.5).

      ANALYSIS OF STUDIES REPORTING DURATION OF COLITIS (CATEGORIES 2 AND 3)

      Of the 116 studies, 41 reported duration of colitis (fig 1). From these studies the overall incidence rate of CRC for any patient with colitis was 3 per 1000 pyd (95% CI 2/1000 to 4/1000). The corresponding annual incidence rate of CRC in the general population given by the Office of National Statistics is 0.6 per 1000 population.206 As 21 of 41 studies did not report the cancer rates at 10 year intervals (and simply gave an overall risk) we had to assume that the cancer risk, in terms of the log incidence rate, remains constant over time. The cumulative probabilities based on this unstratified data gives a risk of 3% (95% CI 2.2–3.8) at 10 years, 5.9% (95% CI 4.3–7.4) at 20 years, and 8.7% (95% CI 6.4–10.9) at 30 years.

      Figure 1
      Figure 1

      Incidence rate of colorectal cancer for any patient with ulcerative colitis, overall and by decade. Ca/pyd, cancer per person years duration.

      Twenty six studies in categories 2 and 3 reported data for patients with total colitis and in this group the incidence rate of CRC was 4 per 1000 pyd (95% CI 3/1000 to 6/1000). The unstratified cumulative probabilities gave a risk of 4.4% (95% CI 2.0–6.8) at 10 years, 8.6% (95% CI 4.0–13.3) at 20 years, and 12.7% (95% CI 6.0–19.3) at 30 years.

      A further analysis was performed after excluding studies that included referred cancers (two studies) and those that had missing data for this variable (eight studies). This made no statistically significant difference to the results as the overall risk was then 2/1000 pyd (95% CI 2/1000 to 3/1000) and the risk for patients with pancolitis was 4/1000 pyd (95% CI 3/1000 to 5/1000). It was therefore decided to include these 10 studies in further analyses as important information would be lost if they were excluded.

      Using overall incidence rates, Egger's test207 was employed to check whether the results could possibly be explained by publication bias. Overall it was found that publication bias was not a statistically significant factor (p=0.46). Egger's test was also used to determine whether language bias could have possibly explained the findings. Studies from countries where English is the first language were compared with those where it is not (and thus one might expect that studies with negative results may have been published in non-English language journals). Again, Egger's test found that language bias was not statistically significant: for studies from the UK, p=0.37; studies from the USA, p=0.47; studies from Scandinavia, p=0.37; and for studies from other countries (namely Iran, Israel, Oman, Czechoslovakia, and Turkey), p=0.90. Furthermore, when English speaking countries were considered collectively, the p value from Egger's test was 0.72 compared with 0.61 from the non-native English speaking countries.

      VARIATION OF RISK WITH GEOGRAPHICAL LOCATION

      Of the 41 studies, 11 were from the USA,112 ,123 ,129 ,130 ,134 ,144 ,146 ,147 ,153 ,154 ,168 ,18411 from the UK,97 ,98 ,109 ,111 ,118 ,131 ,156 ,160 ,162 ,174 ,190eight from Scandinavia,10 ,119 ,141 ,149 ,152 ,158 ,166 ,183 and 11 were from other countries including Israel, Turkey, Italy, Oman, Iran, Czechoslovakia, and Australia.93 ,100 ,125 ,126 ,139 ,151 ,164 ,169 ,175 ,178 ,179The overall incidence rate for CRC in the USA was 5/1000 pyd (95% CI 3/1000–7/1000), in the UK 4/1000 pyd (95% CI 3/1000–5/1000), in Scandinavia 2/1000 pyd (95% CI 1/1000–3/1000), and in other countries 2/1000 pyd (95% CI 1/1000–4/1000). None of the studies exerted a strong drive towards a particular trend in the meta-analysis.

      The geographical incidence rates quoted are based on an overall analysis (of the 41 studies), which therefore assumes that the log incidence rate is constant over time. Because of the smaller numbers of studies that reported results by decade of duration, it was felt that these were insufficient to conduct analyses broken down by country for specific decades.

      When the cancer risk for all 41 studies was plotted against the mid point of each study it can be seen that the overall reported cancer incidence has increased from 1955 to the present day (fig 2; size of the circles is proportional to the number of subjects in each study) but the increase is not statistically significant (slope 0.003, p=0.80). The slope can be used to calculate that from studies with a mid point of 1950 to studies with a mid point of 1990 there would be 0.31 extra cases per 1000 pyd. The temporal relationship of CRC risk in each country is also demonstrated. The reported cancer incidence is increasing in all countries but the increase is not statistically significant.

      VARIATION OF RISK WITH COLORECTAL SURGERY

      The panproctocolectomy rate alone did not exert a statistically significant effect on the CRC risk (z=0.4, p=0.7). When all forms of surgery were considered (panproctocolectomy + resections of varying degree), the reported CRC incidence rateincreased with higher rates of surgical intervention.

      ANALYSIS OF STUDIES REPORTING RISK STRATIFIED INTO 10 YEAR INTERVALS (CATEGORY 3)

      Of the 41 studies, 19 reported results at 10 yearly intervals of disease duration (fig 1). From these studies we were able to estimate how the CRC risk increased with increasing duration of disease and thus stratify the results at 10 year intervals. For the first 10 years duration the overall incidence rate was 2/1000 pyd (95% CI 1/1000–2/1000) while for the second decade of disease the overall incidence rate was estimated to be 7/1000 pyd (95% CI 4/1000–12/1000), and in the third decade of disease the incidence rate was estimated to be 12/1000 pyd (95% CI 7/1000–19/1000). These decade specific incidence rates correspond to a cumulative risk of 1.6% (95% CI 1.2–2) by 10 years, 8.3% (95% CI 4.8–11.7) by 20 years, and 18.4% (95% CI 15.3–21.5) by 30 years (fig 3). The data represented in fig 3 assume that the log incidence rate of CRC is linear over timewithin each 10 year interval, and that changes in the log incidence rate occur at 10, 20, and 30 years. These 10 year intervals correspond with the time points reported in the majority of studies included.

      Figure 3
      Figure 3

      Cumulative risk of developing colorectal cancer for any patient with ulcerative colitis based on stratified data (using stratified incidence, n=19).

      Of the 19 studies in category 3, six reported data for patients with total colitis. The stratified decade specific incidence rates for this group were estimated to be 2/1000 pyd (95% CI 1/1000–4/1000) in the first decade, 7/1000 pyd (95% CI 3/1000–14/1000) in the second, and 11/1000 pyd (95% CI 4/1000–28/1000) in the third decade of disease. These decade specific incidence rates correspond to a cumulative risk of 2.1% (95% CI 1.0–3.2%) at 10 years, 8.5% (95% CI 3.8–13.3%) at 20 years, and 17.8% (95% CI 8.3–27.4%) at 30 years.

      Table 2 provides a summary of the estimated CRC risks using the separate methods employed.

      View this table:
      Table 2

      Summary of estimated cancer risks

      To determine if age at onset of UC in adults affected the log incidence rate of CRC, a meta-analysis regression was conducted on 21 studies that reported the age at onset of UC (over 20 years of age). Studies which reported the age at diagnosis of UC were not included as a patient may have had colitis for several years prior to the diagnosis being made. Overall, a negative trend emerged indicating that a younger age at onset in adults was associated with a slightly increased risk of developing cancer, but this was not statistically significant (z=−1.61, p=0.11). A further meta-regression analysis of 11 studies that reported the age at onset of UC together with the risk at 10 yearly intervals also showed that age at onset in adults appeared to have no statistically significant bearing on cancer risk.

      ANALYSIS OF STUDIES REPORTING DATA ON CHILDREN ONLY

      Eighteen studies in the published literature estimated the incidence of CRC in children with UC. Of these, five were updated by subsequent studies38 ,45-47 ,52 and one included patients with Crohn's disease.83 This left 12 studies suitable for analysis.63 ,66 ,88 ,114 ,134 ,135 ,146 ,147 ,150 ,173 ,180 ,181 ,203Of these only five reported the duration of patient follow up.52 ,63 ,134 ,146 ,147 From these five studies the overall incidence rate of CRC for any child with colitis was 6/1000 pyd (95% CI 3/1000–13/1000). As these studies did not report the numbers of cancers at 10 year intervals, the log incidence rate had to be assumed to be constant. Based on this assumption the cumulative probabilities of any child developing cancer were estimated to be 5.5% (95% CI 2.5–12.3) at 10 years, 10.8% (95% CI 4.8–23.1) at 20 years, and 15.7% (95% CI 7.2–32.6) at 30 years. These rates are higher than the corresponding calculations for adults (3%, 5.9%, and 8.7% respectively). The average age of onset of childhood UC in the five studies was 10 years and the mean duration of follow up was 12 years. Although the other seven studies did not report the mean duration of follow up, the average age of onset of UC was also 10 years and thus it is possible that they too would have given similar rates if they had been included in the analysis.

      Discussion

      This is the first comprehensive systematic review and meta-analysis assessing the risk of CRC in UC although several reviews have been published addressing this issue.6 ,35 ,76 ,208 ,209 It is also the first meta-analysis of stratified (by duration of disease) cancer incidence rates. The precision of the pooled estimates, both overall and stratified, is due to the relatively large numbers of observations, but the pooled estimates also take into account the between study heterogeneity, as they are based on random effects meta-analysis models. The shortcomings of this meta-analysis are accepted. The methods used have made a number of assumptions and must be applied with caution. Consequently, the results must be interpreted warily. However, in the absence of any large multicentre studies or individual patient data analysis we feel they provide the most accurate method of determining the CRC risk in the current climate.

      Most meta-analyses are subject to publication bias as studies with “negative” conclusions are less likely to result in a publication. As there is much debate concerning the risk of CRC in UC, our meta-analysis avoids this bias as authors reporting low rates of CRC in UC are just as likely to have their work published as those reporting very high cancer incidences. This was demonstrated using Egger's test which also showed that language bias does not appear to explain the findings. Although desirable, it was impossible to include unpublished studies in the meta-analysis. There are no registers of observational studies (as there are for clinical trials) and so it is very difficult to identify unpublished data. It could be argued that the analysis was incomplete as only publications in the English language were included. The reason for excluding foreign language studies was the difficulty in extracting information accurately from such studies. If papers in foreign languages had been translated, one would have been dependent on the accuracy of those translations and their not having missed out or misinterpreted data. Furthermore, a Medline search for non-English language articles from the period 1966 to 1999 using CRC, dysplasia, surveillance, and UC as keywords resulted in only three foreign language studies. One of these was in Japanese210 and two were in Portuguese.211 ,212 If this search over the last 33 years is representative of the whole time span since CRC in UC was first reported in 1925, we do not believe a significant number of studies have been missed in the meta-analysis and thus the results are representative.

      Other possible biases have been considered. One may argue that the meta-analysis is subject to selection bias in that there may have been a greater chance of inclusion of cases treated by gastroenterologists with the exclusion of cases not treated by gastroenterologists. We feel this to be unlikely as many of the studies in the meta-analysis were population based and their inclusion did not rely on contact with a gastroenterologist. Another possible source of bias is ascertainment bias with a greater likelihood that cancers were detected among those having active follow up. We accept that this may have played a role as the majority of cases came from surveillance programmes or tertiary referral centres and very few studies included in the meta-analysis used national cancer registry data.

      From 116 published studies we found that the overall prevalence of CRC in any patient with UC is 3.7% which increases to 5.4% for those with pancolitis. Of the 41 studies that reported duration of disease, the overall incidence of CRC in any patient with UC is estimated at 3/1000 pyd. There is dispute in the literature as to whether young age at onset of colitis is an independent risk factor for CRC. We have found that for any child with UC (irrespective of disease extent) the incidence of CRC is estimated to be 6/1000 pyd which is higher than that calculated for adults. However, this estimate is based on only five studies compared with the 41 in the adult analysis and is thus less accurate, as can be seen by the width of the corresponding confidence intervals.

      From the studies that reported the number of cancers at 10 year intervals, we were able to stratify the risk. That is to say we were able to calculate the increase in CRC risk with increasing duration of disease. Such studies led to an estimation of the cumulative risk for any patient with UC to be 2% at 10 years, 8% at 20 years, and 18% at 30 years. Only six studies reported the results by decade for patients with pancolitis and these gave similar cumulative cancer estimates. One expects that the risk of pancolitics would be higher than for any patient with less extensive disease but we feel that the small number of studies in the pancolitis group (n=6) accounts for the similarity in the results, as evidenced by the wide confidence intervals in our calculations. Another factor may have contributed to this apparent similarity in risk. It is unusual that in the articles selected, approximately 20% had total colitis, a value that has been found to pertain to clinical series when it is known that publications must tend towards inclusion of more extensive cases. In this respect, it is noted that only 35 studies in the whole meta-analysis included data on total colitis with other studies not providing sufficient information on disease extent. As over half the cancers developed in patients not stated to have extensive colitis, it suggests that many of these cases did in fact have extensive disease. In this context the similarity of risks between total colitics and all colitics is understandable.

      Overall, the incidence of CRC in UC is increasing slightly but this was not statistically significant (fig 2). However, this finding agrees with those of Lashner et al who stated that there was a dramatic increase in the risk of developing CRC in patients with longstanding UC whose disease onset was after 1972 compared with those with disease onset during or before 1972.153 The small increase in the reported cancer incidence may be related to the virtual abolition of performing prophylactic colectomy after approximately 10 years of disease. The period of the meta-analysis also saw the introduction of surveillance strategies for CRC in UC. Although the reported CRC incidence has increased this does not necessarily mean that surveillance has failed. Rather, it is possible that surveillance programmes have led to increased cancer detection.

      The incidence of CRC varies with geographical location. In the USA and UK we found that the rate was higher than in Scandinavia and other countries. There are several possible explanations for this finding. It could represent true genetic/environmental population differences relating to the severity or course of the illness, although there is little evidence to suggest that the course of UC varies with country. It is possible that the Western diet plays a role exerting an influence in a similar way to CRC in the general population. Alternatively, it may reflect more active medical therapy strategies to severe disease, particularly in Scandinavia. Aminosalicylates are known to modify disease activity and there is some evidence that they exert some protection against CRC.170 ,213-215 Their protective effect is thought to be mediated in a similar way to aspirin in the general population—that is, by inhibiting mucosal prostaglandin synthesis.216 Indeed, a study from Copenhagen which took an aggressive approach with medical therapy found a very low CRC risk and is the only large published study to report no excess cancer risk.152 Another possible explanation may be variation between countries in the approach to surveillance for CRC. Obviously, centres with a comprehensive programme having high rates of patient follow up (such as St Marks in London) are likely to detect a significantly higher proportion of cancers than centres with less aggressive policies. Finally, studies from hospitals serving a defined catchment area provide a good estimate of cancer risk as it is assumed that cases of all grades of severity are seen. Most of the good data of this type come from Scandinavia119 ,131 and this fact may be part of the reason why the incidence appears lower than in the USA or UK.

      It has been suggested that high colectomy rates in patients with UC will reduce the incidence of cancer. This would appear logical as resected bowel obviously no longer has malignant potential. When we analysed this relationship the opposite was found to be true—that is, as more colectomies/resections are performed, cancer incidence is also higher. This is at odds with what one would initially expect but perhaps centres having a low threshold for surgery are also more aggressive in their surveillance strategies and are consequently detecting more cancers by regular colonoscopy. We reviewed the studies with the highest operation rates10 ,112 ,149 as it was not entirely clear whether colectomies had been carried out for cancer prophylaxis or because a cancer had already been identified on barium examination/colonoscopy. However, when these studies were no longer taken into consideration the relationship remained unchanged. It is possible that inclusion of surgical series in this analysis biases the results as some cancers would have been found in operation specimens where the operation was not being carried out for cancer prophylaxis.

      In summary, we have estimated as accurately as possible the risk of CRC in UC, having found it to be 2% at 10 years, 8% at 20 years, and 18% at 30 years (irrespective of disease extent). Estimates for patients with total colitis are less reliable due to the smaller number of studies in the analysis. The incidence of CRC in children is higher than that in adults. Incidence rates for CRC are higher in the USA and the UK compared with Scandinavia and other countries. Since 1955 the overall number of cases of CRC in UC has increased but this finding was not statistically significant.

      A long term prospective study of colitics with complete follow up would be the most accurate method of assessing the cancer risk in these patients. However, this is an enormous undertaking and is unlikely to be achieved. We have therefore determined the risk from the next best method available to us, a meta-analysis. However, a meta-analysis relies heavily on the quality of data that is reported in published studies. Another option to further refine the estimation of cancer risk would be a meta-analysis of individual patient data from the published literature. However, this assumes that the raw data from studies are still accessible and would require international collaboration between large centres of excellence. The techniques employed here have not been used in this context before and we hope that they may be utilised in future studies to estimate the risk of other diseases in other similar conditions where the incidence is disputed.

      Acknowledgments

      Part of this meta-analysis was kindly funded by a grant from the Crohn's in Childhood Research Association (CICRA).

      STUDY AND PATIENT POPULATION CHARACTERISTICS EXTRACTED

      (1)
      Country of origin.
      (2)
      Type of centre conducting the study and study design.
      (3)
      Period over which the study was conducted.
      (4)
      Number of patients in the study.
      (5)
      Number of patients with total and left sided colitis in the study.
      (6)
      Numbers who developed colorectal cancer (and whether they had total or left sided colitis).
      (7)
      Whether referred cancers were included in the analysis.
      (8)
      The duration of follow up of each study.
      (9)
      The ages of patients at time of onset of UC.
      (10)
      The ages of patients at the time of cancer diagnosis.
      (11)
      The duration of colitis at cancer diagnosis.
      (12)
      The number of patients in the study undergoing panproctocolectomy/partial colectomy.
      (13)
      The cumulative cancer incidence (if reported).
      (14)
      The relative cancer risk (if reported).
      (15)
      The number of patients followed up.

      Abbreviations used in this paper

      CRC
      colorectal cancer
      UC
      ulcerative colitis
      pyd
      person years duration

      References

      1. ↵
        1. Crohn B,
        2. Rosenberg H
        (1925) The sigmoidoscopic picture of chronic ulcerative colitis (non- specific). Am J Med Sci 170:220–228.
        OpenUrlCrossRef
      2. ↵
        1. Collins RH,
        2. Feldman M,
        3. Fordtran JS
        (1987) Colon cancer, dysplasia and surveillance in patients with ulcerative colitis: a critical review. N Engl J Med 316:1654–1658.
        OpenUrlCrossRefPubMedWeb of Science
      3. ↵
        1. Gyde S
        (1990) Screening for colorectal cancer in ulcerative colitis: dubious benefits and high costs. Gut 31:1089–1092.
        OpenUrlFREE Full Text
      4. ↵
        1. Sackett DL,
        2. Whelan G
        (1980) Cancer risk in ulcerative colitis: Scientific requirements for the study of prognosis. Gastroenterology 78:1632–1635.
        OpenUrlPubMed
      5. ↵
        1. Sackett DL
        (1979) Bias in analytic research. J Chronic Dis 32:51–63.
        OpenUrlCrossRefPubMedWeb of Science
      6. ↵
        1. Whelan G
        (1991) Ulcerative colitis. What is the risk of developing colorectal cancer? Aust NZ J Med 21:71–77.
        OpenUrlPubMed
      7. ↵
        1. Choi PM,
        2. Zelig MP
        (1994) Similarity of colorectal cancer in Crohn's disease and ulcerative colitis: implications for carcinogenesis and prevention. Gut 35:950–954.
        OpenUrlAbstract/FREE Full Text
      8. ↵
        1. Gyde S,
        2. Prior P,
        3. Dew NJ,
        4. et al.
        (1982) Mortality in ulcerative colitis. Gastroenterology 83:36–43.
        OpenUrlPubMedWeb of Science
      9. ↵
        1. Hendriksen C,
        2. Kreiner S,
        3. Binder V
        (1985) Long term prognosis in ulcerative colitis—based on results from a regional patient group from the county of Copenhagen. Gut 26:158–163.
        OpenUrlAbstract/FREE Full Text
      10. ↵
        1. Kewenter J,
        2. Ahlman H,
        3. Hulten L
        (1978) Cancer risk in extensive ulcerative colitis. Ann Surg 188:824–828.
        OpenUrlCrossRefPubMedWeb of Science
      11. ↵
        1. The University of York
        (1996) NHS Centre for Reviews and Dissemination. Undertaking systematic reviews of research on effectiveness: CRD guidelines for those carrying out or commissioning reviews. (York Publishing Services Ltd, York).
      12. ↵
        1. Sharp SJ
        (1998) Meta-analysis regression. Stata Tech Bull 42:16–22.
        OpenUrl
      13. ↵
        1. Sharp SJ,
        2. Sterne JAC
        (1997) Meta-analysis. Stata Tech Bull 38:9–14.
      14. ↵
        (1997) Stata Statistical Software (computer program). Stata Corp. College Station. (Stata Corporation, Texas).
      15. ↵
        1. Fleiss JL
        (1993) The statistical basis of meta-analysis. Stat Methods Med Res 2:121–145.
        OpenUrlCrossRefPubMed
      16. ↵
        1. Berkey CS,
        2. Hoaglin DC,
        3. Mosteller F,
        4. et al.
        (1995) A random effects regression model for meta-analysis. Stat Med 14:395–411.
        OpenUrlCrossRefPubMedWeb of Science
      17. ↵
        1. Collett D
        (1993) Modelling survival data in medical research. (CRC Press LLC, London).
      18. ↵
        1. Perrson PG,
        2. Bernell O,
        3. Leijonmarck CE,
        4. et al.
        (1996) Survival and cause specific mortality in inflammatory bowel disease: a population based cohort study. Gastroenterology 110:1339–1345.
        OpenUrlCrossRefPubMedWeb of Science
      19. ↵
        1. Bonnevie O,
        2. Riis P,
        3. Anthonisen P
        (1968) An epidemiological study of ulcerative colitis in Copenhagen county. Scand J Gastroenterol 3:432–438.
        OpenUrlCrossRefPubMedWeb of Science
      20. ↵
        1. Mosbech J
        (1960) Mortality from ulcerative colitis in Denmark. Gastroenterology 39:690–693.
        OpenUrlPubMed
      21. ↵
        1. Svartz N
        (1954) The treatment of ulcerative colitis. Gastroenterology 26:26–28.
        OpenUrlPubMed
      22. ↵
        1. Bargen JA,
        2. Dixon CF
        (1935) Chronic ulcerative colitis with associated carcinoma. Arch Surg 30:854–864.
        OpenUrlCrossRef
      23. ↵
        1. Bargen JA
        (1928) Chronic ulcerative colitis associated with malignant disease. Arch Surg 17:561–576.
        OpenUrlCrossRefWeb of Science
      24. ↵
        1. Cattell RB
        (1944) Indications for colectomy in ulcerative colitis. Surg Clin North Am 24:656–660.
        OpenUrl
      25. ↵
        1. Coffey RJ
        (1939) Multiple polyposis associated with chronic ulcerative colitis:a clinicopathological study. Proc Staff Meetings Mayo Clinic 14:11–13.
      26. ↵
        1. Devroede GJ,
        2. Dockerty MB,
        3. Sauer WG,
        4. et al.
        (1972) Cancer of the colon in patients with ulcerative colitis since childhood. Can J Surg 15:369–374.
        OpenUrlPubMed
      27. ↵
        1. Hinton JM
        (1966) Risk of malignant change in ulcerative colitis. Gut 7:427–432.
        OpenUrlFREE Full Text
      28. ↵
        1. Sauer WG,
        2. Bargen JA
        (1949) Chronic ulcerative colitis and carcinoma. JAMA 141:982–985.
        OpenUrl
      29. ↵
        1. Shands WC,
        2. Dockerty MB,
        3. Bargen JA
        (1952) Adenocarcinoma of the large intestine associated with chronic ulcerative colitis. Surg Gynecol Obstet 94:302–310.
      30. ↵
        1. Muto T,
        2. Konishi F,
        3. Shiratori T,
        4. et al.
        , eds (1984) Inflammatory bowel disease. (University & Tokyo Press, Tokyo), pp 151–160.
      31. ↵
        1. Sauer WG,
        2. Bargen JA
        (1944) Chronic ulcerative colitis followed by carcinoma: report of twenty-six cases. Staff Meetings of the Mayo Clinic, pp 311–315.
      32. ↵
        1. Manning AP,
        2. Bulgim OR,
        3. Dixon MF,
        4. et al.
        (1987) Screening by colonoscopy for colonic epithelial dysplasia in inflammatory bowel disease. Gut 28:1489–1494.
        OpenUrlAbstract/FREE Full Text
      33. ↵
        1. Bargen JA,
        2. Coffey RJ
        (1935) Two intestinal carcinomas in the same case of chronic ulcerative colitis and the management of the resulting obstruction. Med Clin North Am 19:403–409.
        OpenUrl
      34. ↵
        1. Brooke BN
        (1961) Malignant change in ulcerative colitis. Dis Colon Rectum 4:393–398.
        OpenUrlPubMed
      35. ↵
        1. Lynn DH
        (1945) The relationship of chronic lesions to carcinoma of the colon—chronic ulcerative colitis. Int Abstract Surg 81:269–276.
      36. ↵
        1. Poley JR
        (1978) Chronic inflammatory bowel disease in children and adolescents: Part II. South Med J 71:1123–1133.
        OpenUrlPubMed
      37. ↵
        1. Poley JR
        (1978) Chronic inflammatory bowel disease in children and adolescents: Part I. South Med J 71:935–948.
        OpenUrlPubMed
      38. ↵
        1. Bargen JA,
        2. Kennedy RLJ
        (1955) Chronic ulcerative colitis in children. Postgrad Med 17:127–131.
      39. ↵
        1. Bargen JA,
        2. Jackman RJ,
        3. Kerr JG
        (1938) Studies on the life histories of patients with chronic ulcerative colitis (thrombo-ulcerative colitis) with some suggestions for treatment. Ann Intern Med 12:339–352.
        OpenUrlWeb of Science
      40. ↵
        1. Bonnevie O,
        2. Binder V,
        3. Anthonisen P,
        4. et al.
        (1974) The prognosis of ulcerative colitis. Scand J Gastroenterol 9:81–91.
        OpenUrlPubMedWeb of Science
      41. ↵
        1. Brostrom O,
        2. Lofberg R,
        3. Ost A,
        4. et al.
        (1986) Cancer surveillance of patients with long-standing ulcerative colitis: a clinical, endoscopical and histological study. Gut 27:1408–1413.
        OpenUrlAbstract/FREE Full Text
      42. ↵
        1. Cave HW
        (1946) Late results in the treatment of ulcerative colitis. Am Surg 124:716–724.
        OpenUrl
      43. ↵
        1. Choi PM,
        2. Nugent FW,
        3. Schoetz DJ,
        4. et al.
        (1993) Colonoscopic surveillance reduces mortality from colorectal cancer in ulcerative colitis. Gastroenterology 105:418–424.
        OpenUrlPubMedWeb of Science
      44. ↵
        1. Fuson JA,
        2. Farmer RG,
        3. Hawk WA,
        4. et al.
        (1980) Endoscopic surveillance for cancer in chronic ulcerative colitis. Am J Gastroenterol 73:120–126.
        OpenUrlPubMedWeb of Science
      45. ↵
        1. Helmholz HF
        (1923) Chronic ulcerative colitis in childhood. Am J Dis Child 26:418–430.
        OpenUrlCrossRef
      46. ↵
        1. Jackman RJ,
        2. Bargen JA,
        3. Helmholz HF
        (1940) Life histories of ninety-five children with chronic ulcerative colitis. Am J Dis Child 59:459–467.
        OpenUrlCrossRef
      47. ↵
        1. Lagerkrantz R
        (1949) Ulcerative colitis in children. Acta Paediatr 37 (suppl 75):89–151.
        OpenUrl
      48. ↵
        1. Lennard-Jones JE,
        2. Morson BC,
        3. Ritchie JK,
        4. et al.
        (1983) Cancer surveillance in ulcerative colitis. Experience over 15 years. Lancet ii:149–152.
        OpenUrl
      49. ↵
        1. Lennard-Jones JE,
        2. Morson BC,
        3. Ritchie JK,
        4. et al.
        (1977) Cancer in colitis: assessment of the individual risk by clinical histological criteria. Gastroenterology 73:1280–1289.
        OpenUrlPubMedWeb of Science
      50. ↵
        1. Lennard-Jones JE,
        2. Parrish JA,
        3. Misiewicz JJ,
        4. et al.
        (1974) Prospective study of outpatients with extensive colitis. Lancet i:1065–1067.
        OpenUrlCrossRef
      51. ↵
        1. Maratka Z
        (1961) Ulcerative colitis and carcinoma of the colon. Gastroenterology 40:854–855.
        OpenUrl
      52. ↵
        1. Michener WM,
        2. Gage RP,
        3. Sauer WG,
        4. et al.
        (1961) The prognosis of chronic ulcerative colitis in children. N Engl J Med 265:1075–1079.
      53. ↵
        1. Nedbal J,
        2. Maratka Z
        (1968) Ulcerative proctocolitis in Czechoslovakia. Am J Proctol 19:106–114.
        OpenUrlPubMed
      54. ↵
        1. Nugent FW,
        2. Haggitt RC,
        3. Gilpin PA
        (1991) Cancer surveillance in ulcerative colitis. Gastroenterology 100:1241–1248.
        OpenUrlPubMedWeb of Science
      55. ↵
        1. Rice-Oxley JM,
        2. Truelove S
        (1950) Complications of ulcerative colitis. Lancet i:607–611.
        OpenUrlCrossRef
      56. ↵
        1. Ritchie JK,
        2. Powell-Tuck J,
        3. Lennard-Jones JE
        (1978) Clinical outcome of the first ten years of ulcerative colitis and proctitis. Lancet i:1140–1143.
        OpenUrlCrossRef
      57. ↵
        1. Rutegard J,
        2. Ahsgren L,
        3. Stenling R,
        4. et al.
        (1988) Cancer surveillance in an unselected population. Scand J Gastroenterol 23:139–145.
        OpenUrlCrossRefPubMedWeb of Science
      58. ↵
        1. Sedlack RE,
        2. Nobrega FT,
        3. Kurland LT,
        4. et al.
        (1972) Inflammatory colon disease in Rochester, Minnesota 1935–1964. Gastroenterology 62:935–941.
        OpenUrlPubMedWeb of Science
      59. ↵
        1. Sloan WP,
        2. Bargen JA,
        3. Baggentoss AH
        (1950) Local complications of chronic ulcerative colitis based on the study of 2000 cases. Mayo Clinic Proc 25:240–244.
        OpenUrl
      60. ↵
        1. Storgaard L,
        2. Bischoff N,
        3. Henriksen FW,
        4. et al.
        (1979) Survival rate in Crohn's disease and ulcerative colitis. Scand J Gastroenterol 14:225–230.
        OpenUrlPubMedWeb of Science
      61. ↵
        1. Svartz N,
        2. Ernberg T
        (1949) Cancer coli in cases of colitis ulcerosa. Acta Med Scand 135:444–447.
        OpenUrl
      62. ↵
        1. Tidrick RT,
        2. Hickey RC
        (1956) The catastrophic complications of ulcerative colitis: cancer, perforation and massive bleeding. J Iowa Med Soc 46:485–492.
        OpenUrlPubMed
      63. ↵
        1. Ashgren L,
        2. Jonsson B,
        3. Stenling R,
        4. et al.
        (1993) Prognosis after early onset of ulcerative colitis. A study from an unselected patient population. Hepatogastroenterolgy 40:467–470.
        OpenUrlPubMed
      64. ↵
        1. Aylett S
        (1971) Cancer and ulcerative colitis. BMJ 2:203–205.
      65. ↵
        1. Bargen JA
        (1929) Complications and sequelae of chronic ulcerative colitis. Ann Intern Med 3:335–352.
        OpenUrlCrossRefWeb of Science
      66. ↵
        1. Binder V,
        2. Bonnevie O,
        3. Gertz TCL,
        4. et al.
        (1973) Ulcerative colitis in children: treatment, course and prognosis. Scand J Gastroenterol 8:161–167.
        OpenUrlPubMedWeb of Science
      67. ↵
        1. Brown ML,
        2. Kasich AM,
        3. Weingarten B
        (1951) Complications of chronic ulcerative colitis. Am J Dig Dis 18:52–54.
      68. ↵
        1. Cattell RB,
        2. Boehme EJ
        (1947) The importance of malignant degeneration as a complication of chronic ulcerative colitis. Gastroenterology 8:695–710.
        OpenUrlPubMedWeb of Science
      69. ↵
        1. Culinan ER,
        2. MacDougall IP
        (1957) The natural history of ulcerative colitis. Lancet i:487–489.
        OpenUrlCrossRef
      70. ↵
        1. Dawson IMP,
        2. Pryse-Davies J
        (1959) The development of carcinoma of the large intestine in ulcerative colitis. Br J Surg 47:113–128.
        OpenUrlCrossRefPubMedWeb of Science
      71. ↵
        1. Dukes CE,
        2. Lockhart-Mummery HE
        (1957) Practical points in the pathology and surgical treatment of ulcerative colitis. A critical review. Br J Surg 45:25–36.
        OpenUrlPubMed
      72. ↵
        1. Edling NPG,
        2. Eklof O
        (1961) Radiologic findings and prognosis in ulcerative colitis. Acta Chir Scand 121:299–308.
        OpenUrlPubMed
      73. ↵
        1. Ekbom AM
        (1995) Cancer risk in inflammatory bowel disease. Can J Gastroenterol 9:23–26.
      74. ↵
        1. Fennessy JJ,
        2. Sparberg MB,
        3. Kirsner JB
        (1968) Radiological findings in carcinoma of the colon complicating chronic ulcerative colitis. Gut 9:388–397.
        OpenUrlFREE Full Text
      75. ↵
        1. Goldgraber MB,
        2. Kirsner JB
        (1964) Carcinoma of the colon complicating ulcerative colitis. Report of ten cases. Dis Colon Rectum 7:336–344.
        OpenUrlPubMed
      76. ↵
        1. Goldgraber MB,
        2. Kirsner JB
        (1964) Carcinoma of the colon in ulcerative colitis. Cancer 17:657–665.
        OpenUrlCrossRefPubMed
      77. ↵
        1. Goldgraber MB,
        2. Humphreys EM,
        3. Kirsner JB,
        4. et al.
        (1958) Carcinoma and ulcerative colitis: a clinical-pathologic study. II Statistical analysis. Gastroenterology 34:840–846.
        OpenUrlPubMed
      78. ↵
        1. Goligher JC,
        2. De Dombal FT,
        3. Watts JMK,
        4. et al.
        , eds (1968) Ulcerative colitis. (Williams and Wilkins, Baltimore), pp 175–188.
      79. ↵
        1. Greenstein AJ,
        2. Sachar DB
        (1983) Cancer in inflammatory bowel disease. Surv Dig Dis 1:8–18.
      80. ↵
        1. Greenstein AJ,
        2. Sachar DB,
        3. Smith H,
        4. et al.
        (1981) A comparison of cancer risk in Crohn's disease and ulcerative colitis. Cancer 48:2742–2745.
        OpenUrlCrossRefPubMedWeb of Science
      81. ↵
        1. Gyde SN,
        2. Prior P,
        3. Thompson H,
        4. et al.
        (1984) Survival of patients with colorectal cancer complicating ulcerative colitis. Gut 25:228–231.
        OpenUrlAbstract/FREE Full Text
      82. ↵
        1. Kiefer ED,
        2. Eytinge EJ,
        3. Johnson AC
        (1951) Malignant degeneration in chronic ulcerative colitis. Gastroenterology 19:51–57.
        OpenUrlPubMed
      83. ↵
        1. King RC,
        2. Linder AE,
        3. Pollard HM
        (1959) Chronic ulcerative colitis in childhood. A follow-up study. Arch Dis Child 34:257–261.
      84. ↵
        1. Kirsner JB,
        2. Palmer WL,
        3. Maimon SN,
        4. et al.
        (1948) Clinical course of chronic nonspecific ulcerative colitis. JAMA 137:922–928.
        OpenUrlCrossRefPubMed
      85. ↵
        1. Lahey FH
        (1950) The management of ulcerative colitis. Postgrad Med 8:93–100.
        OpenUrl
      86. ↵
        1. Lennard-Jones JE
        (1983) The clinical outcome of ulcerative colitis depends on how much of the colonic mucosa is involved. Scand J Gastroenterol 18 (suppl 88):48–53.
      87. ↵
        1. MacDougall IPM
        (1954) Ulcerative colitis and carcinoma of the large intestine. BMJ i:852–854.
        OpenUrl
      88. ↵
        1. Michener WM,
        2. Farmer RG,
        3. Mortimer EA
        (1979) Long-term prognosis of ulcerative colitis with onset in childhood or adolescence. J Clin Gastroenterol 1:301–305.
        OpenUrlPubMedWeb of Science
      89. ↵
        1. Renshaw RJF,
        2. Brownell TS
        (1945) Carcinoma complicating ulcerative colitis. Cleve Clin Q 12:123–127.
        OpenUrl
      90. ↵
        1. Rosenstock E,
        2. Farmer RG,
        3. Petras R,
        4. et al.
        (1985) Surveillance for colonic carcinoma in ulcerative colitis. Gastroenterology 89:1342–1346.
        OpenUrlCrossRefPubMedWeb of Science
      91. ↵
        1. Rutegard JN,
        2. Ahsgren LR,
        3. Janunger KG
        (1988) Ulcerative colitis: colorectal cancer risk in an unselected population. Ann Surg 6:721–724.
        OpenUrl
      92. ↵
        1. Sugita A,
        2. Sachar DB,
        3. Bodian C,
        4. et al.
        (1991) Colorectal cancer in ulcerative colitis. Influence of anatomical extent and age at onset on colitis-cancer interval. Gut 32:167–169.
        OpenUrlAbstract/FREE Full Text
      93. ↵
        1. Aktan H,
        2. Paykoc Z,
        3. Ertan A
        (1970) Ulcerative colitis in Turkey: clinical review of sixty cases. Dis Colon Rectum 13:62–65.
        OpenUrlPubMed
      94. ↵
        1. Al-Nakib B,
        2. Radhakrishnan S,
        3. Jacob GS,
        4. et al.
        (1984) Inflammatory bowel disease in Kuwait. Am J Gastroenterol 79:191–194.
        OpenUrlPubMed
      95. ↵
        1. Albrechtsen D,
        2. Bergan A,
        3. Gjone E,
        4. et al.
        (1981) Elective surgery for ulcerative colitis: colectomy in 158 patients. Scand J Gastroenterol 16:825–831.
        OpenUrlPubMed
      96. ↵
        1. Bacon HE,
        2. OuYang LM,
        3. Carroll PT,
        4. et al.
        (1956) Non-specific ulcerative colitis with reference to mortality, morbidity, complications and long-term survivals following colectomy. Am J Surg 92:688–695.
        OpenUrlPubMed
      97. ↵
        1. Baker WNW,
        2. Glass RE,
        3. Ritchie JK,
        4. et al.
        (1978) Cancer of the rectum following colectomy and ileorectal anastomosis for ulcerative colitis. Br J Surg 65:862–868.
        OpenUrlCrossRefPubMedWeb of Science
      98. ↵
        1. Banks BM,
        2. Korelitz BI,
        3. Zetzel L
        (1957) The course of nonspecific ulcerative colitis: review of twenty years' experience and late results. Gastroenterology 32:983–1012.
        OpenUrlPubMed
      99. ↵
        1. Bargen JA,
        2. Gage RP
        (1960) Carcinoma and ulcerative colitis: prognosis. Gastroenterology 39:385–393.
        OpenUrlPubMed
      100. ↵
        1. Biasco G,
        2. Brandi G,
        3. Pagannelli GM,
        4. et al.
        (1995) Colorectal cancer in patients with ulcerative colitis. A prospective cohort study in Italy. Cancer 75:2045–2050.
        OpenUrlCrossRefPubMed
      101. ↵
        1. Blackstone MO,
        2. Riddell RH,
        3. Rogers G,
        4. et al.
        (1981) Dysplasia-associated lesion or mass (DALM) detected by colonoscopy in long-standing ulcerative colitis: an indication for colectomy. Gastroenterology 80:366–374.
        OpenUrlPubMedWeb of Science
      102. ↵
        1. Brostrom O,
        2. Lofberg R,
        3. Nordenvall B,
        4. et al.
        (1987) The risk of colorectal cancer in ulcerative colitis. An epidemiologic study. Scand J Gastroenterol 22:1193–1199.
        OpenUrlCrossRefPubMedWeb of Science
      103. ↵
        1. Bruce D,
        2. Cole WH
        (1962) Complications of ulcerative colitis. Ann Surg 155:768–779.
        OpenUrlCrossRefPubMed
      104. ↵
        1. Carleson R,
        2. Fristedt B,
        3. Philipson J
        (1962) A follow-up investigation of a 20-year primary material. Acta Med Scand 172:647–656.
        OpenUrlPubMed
      105. ↵
        1. Cattell RB,
        2. Sachs E
        (1948) Surgical treatment of ulcerative colitis. JAMA 137:929–933.
        OpenUrlCrossRefPubMed
      106. ↵
        1. Cazacu M,
        2. Dejica D,
        3. Badea R,
        4. et al.
        (1997) Colorectal cancer and pre-existing pathological conditions: ulcerative colitis, Crohn's disease, colonic diverticulosis and polyposis. A retrospective analysis of 286 surgical patients. Rom J Gastroenterol 6:239–241.
      107. ↵
        1. Chuttani HK,
        2. Nigam SP,
        3. Sama SK,
        4. et al.
        (1967) Ulcerative colitis in the tropics. BMJ 4:204–207.
      108. ↵
        1. Colcock BP,
        2. Mathiesen WL
        (1956) Complications of the surgical treatment of chronic ulcerative colitis. Arch Surg 72:399–404.
        OpenUrl
      109. ↵
        1. Connell WR,
        2. Lennard-Jones JE,
        3. Williams CB,
        4. et al.
        (1994) Factors affecting the outcome of endoscopic surveillance for cancer in ulcerative colitis. Gastroenterology 107:934–944.
        OpenUrlPubMedWeb of Science
      110. ↵
        1. Counsell PB,
        2. Dukes CE
        (1952) The association of chronic ulcerative colitis and carcinoma of the rectum and colon. Br J Surg 39:485–495.
      111. ↵
        1. De Dombal FT,
        2. Watts J,
        3. Watkinson G,
        4. et al.
        (1966) Local complications of ulcerative colitis: stricture, pseudopolyposis and carcinoma of colon and rectum. BMJ 1:1442–1447.
      112. ↵
        1. Dennis C,
        2. Karlson KE
        (1961) Cancer risk in ulcerative colitis: formidability per patient-year of late disease. Surgery 50:568–571.
        OpenUrlWeb of Science
      113. ↵
        1. Dennis C,
        2. Karlson KE
        (1952) Surgical measures as supplements to the management of idiopathic ulcerative colitis: cancer, cirrhosis and arthritis as frequent complications. Surgery 32:892–912.
        OpenUrlPubMedWeb of Science
      114. ↵
        1. Devroede GJ,
        2. Taylor WF,
        3. Sauer WG,
        4. et al.
        (1971) Cancer risk and life expectancy of children with ulcerative colitis. N Engl J Med 285:17–21.
      115. ↵
        1. Diaz RJ,
        2. Farmer RG,
        3. Brown CH
        (1965) Carcinoma of the colon and ulcerative colitis. Am J Dig Dis 10:643–656.
        OpenUrlCrossRefPubMed
      116. ↵
        1. Dickinson RJ,
        2. Dixon MF,
        3. Axon ATR
        (1980) Colonoscopy and the detection of dysplasia in patients with longstanding ulcerative colitis. Lancet ii:620–622.
        OpenUrlCrossRef
      117. ↵
        1. Dolcini H,
        2. Arabehety JT,
        3. Stapler NM
        (1967) Ulcerative colitis. Follow-up of 100 patients with some comments on the general features of this disease in Argentina. Am J Proctol 18:132–135.
        OpenUrlPubMed
      118. ↵
        1. Edwards FC,
        2. Truelove SC
        (1964) The course and prognosis of ulcerative colitis. Part IV: carcinoma of the colon. Gut 5:15–22.
      119. ↵
        1. Ekbom A,
        2. Helmick C,
        3. Zack M,
        4. et al.
        (1990) Ulcerative colitis and colorectal cancer. A population-based study. N Engl J Med 323:1228–1233.
        OpenUrlCrossRefPubMedWeb of Science
      120. ↵
        1. Farmer RG,
        2. Hawk WA,
        3. Turnbull RB
        (1971) Carcinoma associated with mucosal ulcerative colitis and with transmural colitis and enteritis (Crohn's disease). Cancer 28:289–292.
        OpenUrlCrossRefPubMed
      121. ↵
        1. Feder IA
        (1938) Chronic ulcerative colitis: an analysis of 88 cases. Am J Dig Dis 2:239–245.
      122. ↵
        1. Felsen J,
        2. Wolarsky W
        (1949) Chronic ulcerative colitis and carcinoma. Arch Intern Med 84:293–304.
        OpenUrlCrossRefPubMed
      123. ↵
        1. Flood CA,
        2. Lepore MJ,
        3. Hiatt RB,
        4. et al.
        (1956) Prognosis in chronic ulcerative colitis. J Chronic Dis 4:267–282.
        OpenUrlCrossRefPubMed
      124. ↵
        1. Fung WP,
        2. Monteiro EH,
        3. Murugasu JJ,
        4. et al.
        (1971) Non-specific ulcerative colitis in Chinese and Indians in Singapore. Med J Aust 2:361–365.
        OpenUrlPubMed
      125. ↵
        1. Gilat T,
        2. Fireman Z,
        3. Grossman A,
        4. et al.
        (1988) Colorectal cancer in patients with ulcerative colitis. A population study in central Israel. Gastroenterology 94:870–877.
        OpenUrlPubMed
      126. ↵
        1. Gilat T,
        2. Zemishlany Z,
        3. Ribak J,
        4. et al.
        (1974) Ulcerative colitis in the Jewish population of Tel-Aviv Yafo II: The rarity of malignant degeneration. Gastroenterology 67:933–938.
        OpenUrlPubMed
      127. ↵
        1. Gleckler WJ,
        2. Brown CH
        (1950) Carcinoma of the colon complicating chronic ulcerative colitis. Gastroenterology 14:455–464.
        OpenUrlPubMed
      128. ↵
        1. Granqvist S,
        2. Gabrielsson N,
        3. Sundelin P,
        4. et al.
        (1980) Precancerous lesions in the mucosa in ulcerative colitis. A radiographic, endoscopic and histopathologic study. Scand J Gastroenterol 15:289–296.
        OpenUrlPubMed
      129. ↵
        1. Greenstein AJ,
        2. Sachar DB,
        3. Smith H,
        4. et al.
        (1979) Cancer in universal and left-sided ulcerative colitis: factors determining risk. Gastroenterology 77:290–294.
        OpenUrlPubMedWeb of Science
      130. ↵
        1. Grundfest SF,
        2. Fazio V,
        3. Weiss RA,
        4. et al.
        (1981) The risk of cancer following colectomy and ileorectal anastomosis for extensive mucosal ulcerative colitis. Ann Surg 193:9–14.
        OpenUrlPubMed
      131. ↵
        1. Gyde SN,
        2. Prior P,
        3. Allan RN,
        4. et al.
        (1988) Colorectal cancer in ulcerative colitis: a cohort study of primary referrals from three centres. Gut 29:206–217.
        OpenUrlAbstract/FREE Full Text
      132. ↵
        1. Hayes MA
        (1949) Chronic ulcerative colitis and associated carcinoma. Am J Surg 77:363–370.
        OpenUrlPubMed
      133. ↵
        1. Hickey RC,
        2. Tidrick RT
        (1958) Cancer in patients with chronic ulcerative colitis. Cancer 11:35–39.
        OpenUrlCrossRefPubMedWeb of Science
      134. ↵
        1. Hijmans JC,
        2. Enzer NB
        (1962) Ulcerative colitis in childhood. A study of 43 cases. Pediatr 29:389–403.
        OpenUrlAbstract/FREE Full Text
      135. ↵
        1. Holowach J,
        2. Thurston DL
        (1956) Chronic ulcerative colitis in childhood. J Pediatr 48:279–291.
        OpenUrlCrossRefPubMedWeb of Science
      136. ↵
        1. Hughes RG,
        2. Hall TJ,
        3. Block GE,
        4. et al.
        (1978) The prognosis of carcinoma of the colon and rectum complicating ulcerative colitis. Surg Gynecol Obstet 146:46–48.
        OpenUrlPubMedWeb of Science
      137. ↵
        1. Hurt LE
        (1954) The relationship of chronic ulcerative colitis to malignancy. Ann Surg 139:838–843.
        OpenUrlPubMed
      138. ↵
        1. Johnson TM,
        2. Orr TG
        (1948) Carcinoma of the colon secondary to chronic ulcerative colitis. Am J Dig Dis 15:21–23.
        OpenUrlCrossRefPubMed
      139. ↵
        1. Johnson WR,
        2. McDermott FT,
        3. Hughes ESR,
        4. et al.
        (1983) Carcinoma of the colon and rectum in inflammatory disease of the intestine. Surg Gynecol Obstet 156:193–197.
        OpenUrlPubMed
      140. ↵
        1. Jones HW,
        2. Grogono J,
        3. Hoare AM
        (1988) Surveillance in ulcerative colitis: burdens and benefit. Gut 29:325–331.
        OpenUrlAbstract/FREE Full Text
      141. ↵
        1. Jonsson B,
        2. Ashgren L,
        3. Andersson LO,
        4. et al.
        (1994) Colorectal cancer surveillance in patients with ulcerative colitis. Br J Surg 81:689–691.
        OpenUrlCrossRefPubMedWeb of Science
      142. ↵
        1. Kapel O
        (1950) Medical and modern surgical treatment of chronic ulcerative colitis. Acta Med Scand 138:328–339.
      143. ↵
        1. Kasich AM,
        2. Weingarten B,
        3. Brown ML
        (1949) Malignant degeneration in ulcerative colitis. Med Clin North Am 33:1421–1437.
        OpenUrlPubMed
      144. ↵
        1. Katzka I,
        2. Brody RS,
        3. Morris E,
        4. et al.
        (1983) Assessment of colorectal cancer risk in patients with ulcerative colitis: experience from a private practice. Gastroenterology 85:22–29.
        OpenUrlPubMedWeb of Science
      145. ↵
        1. Kochhar R,
        2. Goenka MK,
        3. Kaushik SP,
        4. et al.
        (1992) Colorectal carcinoma in Indian patients with idiopathic ulcerative colitis. Eur J Cancer Prev 1:293–296.
        OpenUrlCrossRefPubMed
      146. ↵
        1. Korelitz BI,
        2. Gribetz D,
        3. Danziger I
        (1962) The prognosis of ulcerative colitis with onset in childhood. I. The pre-steroid era. Ann Intern Med 57:582–591.
      147. ↵
        1. Korelitz BI,
        2. Gribetz D
        (1962) The prognosis of ulcerative colitis with onset in childhood. II. The steroid era. Ann Intern Med 57:592–597.
      148. ↵
        1. Kusakcioglu O,
        2. Kusakcioglu A,
        3. Oz F
        (1979) Idiopathic ulcerative colitis in Istanbul: clinical review of 204 cases. Dis Colon Rectum 22:350–355.
        OpenUrlPubMed
      149. ↵
        1. Kvist N,
        2. Jacobsen O,
        3. Kvist HK,
        4. et al.
        (1989) Malignancy in ulcerative colitis. Scand J Gastroenterol 24:497–506.
        OpenUrlPubMedWeb of Science
      150. ↵
        1. Ladd WE,
        2. Fothergill LD
        (1935) Idiopathic ulcerative colitis in children. Med Clin North Am 19:1673–1683.
        OpenUrl
      151. ↵
        1. Lanfranchi GA,
        2. Brignola C,
        3. Michelini M,
        4. et al.
        (1980) Clinical course of ulcerative colitis in Italy. Digestion 20:106–110.
        OpenUrlPubMed
      152. ↵
        1. Langholz E,
        2. Munkholm P,
        3. Davidsen M,
        4. et al.
        (1992) Colorectal cancer risk and mortality in patients with ulcerative colitis. Gastroenterology 103:1444–1451.
        OpenUrlCrossRefPubMedWeb of Science
      153. ↵
        1. Lashner BA,
        2. Provencher KS,
        3. Bosdech JM,
        4. et al.
        (1995) Worsening risk for the development of dysplasia or cancer in patients with chronic ulcerative colitis. Am J Gastroenterol 90:377–380.
        OpenUrlPubMed
      154. ↵
        1. Lashner BA,
        2. Silverstein MD,
        3. Hanauer SB
        (1989) Hazard rates for dysplasia and cancer in ulcerative colitis. Results from a surveillance program. Dig Dis Sci 34:1536–1541.
        OpenUrlCrossRefPubMedWeb of Science
      155. ↵
        1. Leidenius M,
        2. Kellokumpu I,
        3. Husa A,
        4. et al.
        (1991) Dysplasia and carcinoma in longstanding ulcerative colitis: an endoscopic and histological surveillance programme. Gut 32:1521–1525.
        OpenUrlAbstract/FREE Full Text
      156. ↵
        1. Lennard-Jones JE,
        2. Melville DM,
        3. Morson BC,
        4. et al.
        (1990) Precancer and cancer in extensive ulcerative colitis: findings among 401 patients over 22 years. Gut 31:800–806.
        OpenUrlAbstract/FREE Full Text
      157. ↵
        1. Lindner AE,
        2. King RC,
        3. Bolt RJ
        (1960) Chronic ulcerative colitis. A clinical appraisal and follow-up study. Gastroenterology 39:153–160.
        OpenUrlPubMed
      158. ↵
        1. Lofberg R,
        2. Brostrom O,
        3. Karlen P,
        4. et al.
        (1990) Colonoscopic surveillance in long-standing total ulcerative colitis—a 15 year follow-up study. Gastroenterology 99:1021–1031.
        OpenUrlCrossRefPubMedWeb of Science
      159. ↵
        1. Lumb G,
        2. Protheroe RHB
        (1958) Ulcerative colitis. A pathologic study of 152 surgical specimens. Gastroenterology 34:381–407.
        OpenUrlPubMed
      160. ↵
        1. Lynch DAF,
        2. Lobo AJ,
        3. Sobala GM,
        4. et al.
        (1993) Failure of colonoscopic surveillance in ulcerative colitis. Gut 34:1075–1080.
        OpenUrlAbstract/FREE Full Text
      161. ↵
        1. Lyons AS,
        2. Garlock JH
        (1951) The relationship of chronic ulcerative colitis to carcinoma. Gastroenterology 18:170–178.
        OpenUrlPubMed
      162. ↵
        1. MacDougall IPM
        (1964) The cancer risk in ulcerative colitis. Lancet ii:655–658.
        OpenUrl
      163. ↵
        1. Maltby EJ,
        2. Dickson RC,
        3. O'Sullivan PM
        (1956) The use of ACTH and cortisone in idiopathic ulcerative colitis. Can Med Assoc J 74:4–9.
        OpenUrl
      164. ↵
        1. Maratka Z,
        2. Nedbal J,
        3. Kocianova J,
        4. et al.
        (1985) Incidence of colorectal cancer in proctocolitis: a retrospective study of 959 cases over 40 years. Gut 26:43–49.
        OpenUrlAbstract/FREE Full Text
      165. ↵
        1. McMillan WO,
        2. Garbutt JT,
        3. Ruffin JM
        (1968) Problems of cancer in ulcerative colitis. South Med J 61:526–528.
        OpenUrlPubMed
      166. ↵
        1. Mellemkjaer L,
        2. Olsen JH,
        3. Frisch M,
        4. et al.
        (1995) Cancer in patients with ulcerative colitis. Int J Cancer 60:330–333.
        OpenUrlPubMedWeb of Science
      167. ↵
        1. Micames C,
        2. Zaiter J,
        3. Nigaglioni A
        (1983) Clinico-epidemiological features of 102 cases of ulcerative colitis in Puerto Rico. Bol Asoc Med P R 75:106–109.
        OpenUrlPubMed
      168. ↵
        1. Mir-Madjlessi SH,
        2. Farmer RG,
        3. Easley KA,
        4. et al.
        (1986) Colorectal and extracolonic malignancy in ulcerative colitis. Cancer 58:1569–1574.
        OpenUrlCrossRefPubMedWeb of Science
      169. ↵
        1. Mir-Madjlessi SH,
        2. Forouzandeh B,
        3. Ghadimi R
        (1985) Ulcerative colitis in Iran: a review of 112 cases. Am J Gastroenterol 80:862–866.
        OpenUrlPubMed
      170. ↵
        1. Moody GA,
        2. Jayanthi V,
        3. Probert CSJ,
        4. et al.
        (1996) Long term therapy with sulphasalazine protects against colorectal cancer in ulcerative colitis: a retrospective study of colorectal cancer risk and compliance with treatment in Leicestershire. Eur J Gastroenterol Hepatol 8:1179–1183.
        OpenUrlCrossRefPubMedWeb of Science
      171. ↵
        1. Nefzger MD,
        2. Acheson ED
        (1963) Ulcerative colitis in the United States army in 1944. Gut 4:183–192.
      172. ↵
        1. Odes HS,
        2. Fraser D,
        3. Krawiec J
        (1987) Ulcerative colitis in the Jewish population of Southern Israel 1961–1985: epidemiological and clinical study. Gut 28:1630–1636.
        OpenUrlAbstract/FREE Full Text
      173. ↵
        1. Patterson M,
        2. Castiglioni L,
        3. Sampson L
        (1971) Chronic ulcerative colitis. A review of 43 patients beginning in children and teenagers. Am J Dig Dis 16:289–297.
        OpenUrlCrossRefPubMedWeb of Science
      174. ↵
        1. Prior P,
        2. Gyde SN,
        3. Macartney JC,
        4. et al.
        (1982) Cancer morbidity in ulcerative colitis. Gut 23:490–497.
        OpenUrlAbstract/FREE Full Text
      175. ↵
        1. Radhakrishnan S,
        2. Zubaidi G,
        3. Daniel M,
        4. et al.
        (1997) Ulcerative colitis in Oman: a prospective study of the incidence and disease pattern from 1987 to 1994. Digestion 58:266–270.
        OpenUrlCrossRefPubMedWeb of Science
      176. ↵
        1. Ricketts WE,
        2. Palmer WL
        (1946) Complications of chronic non-specific ulcerative colitis. Gastroenterology 7:55–66.
        OpenUrlPubMedWeb of Science
      177. ↵
        1. Rosenqvist H,
        2. Lagerkrantz R,
        3. Ohrling H,
        4. et al.
        (1959) Ulcerative colitis and carcinoma coli. Lancet i:906–908.
        OpenUrlCrossRef
      178. ↵
        1. Rozen P,
        2. Baratz M,
        3. Fefer F,
        4. et al.
        (1995) Low incidence of significant dysplasia in a successful endoscopic surveillance program of patients with ulcerative colitis. Gastroenterology 108:1361–1370.
        OpenUrlCrossRefPubMedWeb of Science
      179. ↵
        1. Russell IS,
        2. Hughes ESR
        (1961) Carcinoma of the colon complicating ulcerative colitis. Aust NZ J Surg 30:306–311.
        OpenUrlPubMed
      180. ↵
        1. Schlesinger B,
        2. Platt J
        (1958) Ulcerative colitis in childhood and a follow-up study. Proc R Soc Med 51:733–734.
        OpenUrlPubMed
      181. ↵
        1. Skyring A,
        2. Roberts R
        (1965) Childhood ulcerative colitis: an epidemiological study in NSW. Med J Aust 52:955–960.
        OpenUrl
      182. ↵
        1. Slaney G,
        2. Brooke BN
        (1959) Cancer in ulcerative colitis. Lancet ii:694–698.
      183. ↵
        1. Stewenius J,
        2. Adnerhill I,
        3. Anderson H,
        4. et al.
        (1995) Incidence of colorectal cancer and all cause mortality in non-selected patients with ulcerative colitis and indeterminate colitis in Malmo, Sweden. Int J Colorectal Dis 10:117–122.
        OpenUrlCrossRefPubMedWeb of Science
      184. ↵
        1. Stonnington CM,
        2. Phillips SF,
        3. Zinsmeister AR,
        4. et al.
        (1987) Prognosis of chronic ulcerative colitis in a community. Gut 28:1261–1266.
        OpenUrlAbstract/FREE Full Text
      185. ↵
        1. Strombeck JP
        (1949) The surgical treatment of ulcerative colitis. Acta Chir Scand 98:414–427.
      186. ↵
        1. Sugita A,
        2. Greenstein AJ,
        3. Ribeiro MB,
        4. et al.
        (1993) Survival with colorectal cancer in ulcerative colitis. A study of 102 cases. Ann Surg 218:189–195.
        OpenUrlCrossRefPubMedWeb of Science
      187. ↵
        1. Svartz N,
        2. Gillnas T
        (1958) In which phase of ulcerative colitis does colonic cancer occur ? Am J Dig Dis 3:537–548.
        OpenUrlCrossRefPubMed
      188. ↵
        1. Tandon BN,
        2. Mathur AK,
        3. Mohapatra LN,
        4. et al.
        (1965) A study of the prevalence and clinical pattern of non-specific ulcerative colitis in northern India. Gut 6:448–453.
      189. ↵
        1. Thompson JE
        (1961) Ulcerative colitis. South Med J 54:801–807.
        OpenUrlPubMed
      190. ↵
        1. Thorlakson RH
        (1956) Carcinoma of the colon and rectum associated with chronic ulcerative colitis. Surg Gynecol Obstet 103:41–50.
        OpenUrlPubMed
      191. ↵
        1. Turunen MJ,
        2. Jarvinen HJ
        (1985) Cancer in ulcerative colitis: what failed in follow-up? Acta Chir Scand 151:669–673.
        OpenUrlPubMed
      192. ↵
        1. Van Heerden JA,
        2. Beart RW
        (1980) Carcinoma of the colon and rectum complicating chronic ulcerative colitis. Dis Colon Rectum 23:155–159.
        OpenUrlCrossRefPubMedWeb of Science
      193. ↵
        1. Vilien M,
        2. Jorgensen MJ,
        3. Ouyang Q,
        4. et al.
        (1991) Colonic epithelial dysplasia or carcinoma in a regional group of patients with ulcerative colitis of more than 15 years duration. J Intern Med 230:259–263.
        OpenUrlPubMed
      194. ↵
        1. Warren S,
        2. Sommers SC
        (1949) Pathogenesis of ulcerative colitis. Am J Pathol 25:657–679.
        OpenUrlPubMedWeb of Science
      195. ↵
        1. Watanabe H,
        2. Hiwatashi N,
        3. Yamagata S
        (1977) Clinical observations on ulcerative colitis. Tohoku J Exp Med 123:197–213.
        OpenUrlPubMed
      196. ↵
        1. Waye JD
        (1983) Dysplasia and ulcerative colitis—A colonoscopic study. Scand J Gastroenterol 18 (suppl 88):44–47.
      197. ↵
        1. Weckesser EC,
        2. Chinn AB
        (1953) Carcinoma of the colon complicating chronic ulcerative colitis. JAMA 152:905–908.
        OpenUrl
      198. ↵
        1. Welch CE,
        2. Hedberg SE
        (1965) Colonic cancer in ulcerative colitis and idiopathic colonic cancer. JAMA 191:815–818.
      199. ↵
        1. Wheelock FC,
        2. Warren R
        (1955) Ulcerative colitis. Follow-up studies. N Engl J Med 252:421–425.
      200. ↵
        1. Willard JH,
        2. Pessel JF,
        3. Hundley JW,
        4. et al.
        (1938) Prognosis of ulcerative colitis. JAMA 111:2078–2083.
        OpenUrlCrossRef
      201. ↵
        1. Woolrich AJ,
        2. DaSilva MD,
        3. Korelitz BI
        (1992) Surveillance in the routine management of ulcerative colitis: The predictive value of low grade dysplasia. Gastroenterology 103:431–438.
        OpenUrlPubMedWeb of Science
      202. ↵
        1. Yardley JH,
        2. Keren DF
        (1974) “Precancer” lesions in ulcerative colitis. A retrospective study of rectal biopsy and colectomy specimens. Cancer 34:835–844.
      203. ↵
        1. Lagerkrantz R
        (1955) Follow-up investigation of children with ulcerative colitis. With special reference to indications for surgical therapy. Acta Paediatr 44:302–317.
        OpenUrlPubMed
      204. ↵
        1. Feher M
        (1972) Prognosis of ulcerative colitis. in Recent progress in the study of disorders of the colon and rectum. eds Drobini S, Feher M (Akademiai Kiado, Budapest), pp 389–393.
      205. ↵
        1. Pronay G,
        2. Molnar P,
        3. Horvath A,
        4. et al.
        (1972) Diagnosis and prognosis of proctitis and ulcerative colitis. in Recent progress in the study of disorders of the colon and rectum. eds Drobini S, Feher M (Akademiai Kiado, Budapest), pp 395–399.
      206. ↵
        1. Office of National Statistics
        (1993) 1993 Cancer Statistics Registrations. (Stationary Office, London), p 24, (series MB1 26).
      207. ↵
        1. Egger M,
        2. Smith GD,
        3. Schneider M,
        4. et al.
        (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634.
        OpenUrlAbstract/FREE Full Text
      208. ↵
        1. Butt JH,
        2. Lennard-Jones JE,
        3. Ritchie JK
        (1980) A practical approach to the risk of cancer in inflammatory bowel disease. Reassure, watch or act? Med Clin North Am 64:1203–1220.
        OpenUrlPubMed
      209. ↵
        1. Whelan G
        (1980) Cancer risk in ulcerative colitis: Why are results in the literature so varied? Clin Gastroenterol 9:469–476.
        OpenUrlPubMedWeb of Science
      210. ↵
        1. Matsui T,
        2. Iida M,
        3. Suekane H,
        4. et al.
        (1993) The long-term follow-up study of Japanese patients with ulcerative colitis. (Japanese). Jpn J Gastroenterol 90:134–143.
        OpenUrl
      211. ↵
        1. Martins P,
        2. Soares C,
        3. Batista A
        (1990) Idiopathic proctocolitis. Follow-up (1–13 years) of 71 patients. Acta Med Port 3:159–163.
        OpenUrlPubMed
      212. ↵
        1. Nahas SC
        (1994) Colonoscopy and digital cytometry in the clinical assessment of prolonged non-specific ulcerative rectocolitis. Revista do Hospital das Clinicas 49:152–156.
      213. ↵
        1. Bansal P,
        2. Sonnenberg A
        (1996) Risk factors for colorectal cancer in inflammatory bowel disease. Am J Gastroenterol 91:44–48.
        OpenUrlPubMedWeb of Science
      214. ↵
        1. Pinczowski D,
        2. Ekbom A,
        3. Baron J,
        4. et al.
        (1994) Risk factors for colorectal cancer in patients with ulcerative colitis: A case-control study. Gastroenterology 107:117–120.
        OpenUrlCrossRefPubMedWeb of Science
      215. ↵
        1. Eaden JA,
        2. Abrams K,
        3. Ekbom A,
        4. et al.
        (2000) Colorectal cancer prevention in ulcerative colitis: a case-control study. Aliment Pharmacol Ther 14:145–153.
        OpenUrlPubMedWeb of Science
      216. ↵
        1. Rosenberg L,
        2. Palmer JR,
        3. Zauber AG,
        4. et al.
        (1991) A hypothesis: nonsteroidal anti-inflammatory drugs reduce the incidence of large bowel cancer. J Natl Cancer Inst 83:355–358.
        OpenUrlCrossRefPubMedWeb of Science