Downloaded from http://gut.bmj.com/ on May 11, 2015 - Published by group.bmj.com
PostScript with virological relapse (HBV DNA >2000 IU/mL) alone need to be treated again for a remote and unrealistic treatment goal. Cessation of long-term NA therapy adds to caring physicians and patients the burden of frequent follow-up visits, with uncertainty regarding long-term outcomes and with a high cost of multiple but necessary laboratory tests. However, in the long run, when discontinuation of long-term NA therapy terminates to sustained remission and particularly to HBsAg loss, it proves cost saving and beneficial to the patients in terms of close-to-cure outcomes of chronic liver disease and regarding their long-term psychology. Stephanos Hadziyannis,1 Yun-Fan Liaw2 1
Liver Unit and its Molecular Biology Laboratory of the National and Kapodistrian University of Athens, Evgenidion Hospital, Athens, Greece 2 Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan Correspondence to Professor Stephanos Hadziyannis, Liver Unit and its Molecular Biology Laboratory of the National and Kapodistrian University of Athens, Evgenidion Hospital, Athens, Greece, 20 Papadiamantopoulou Str, Athens 11527, Greece; [email protected] Contributors Both authors have contributed equally to the writing of the letter. Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed.
To cite Hadziyannis S, Liaw Y-F. Gut 2015;64:1005– 1006. Received 20 October 2014 Revised 28 October 2014 Accepted 30 October 2014 Published Online First 19 November 2014
▸ http://dx.doi.org/10.1136/gutjnl-2014-307237 Gut 2015;64:1005–1006. doi:10.1136/gutjnl-2014-308677
REFERENCES 1
2
3
Seto WK, Hui AJ, Wong VW, et al. Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study. Gut 2015;64:667–72. Jeng WJ, Sheen IS, Chen YC, et al. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology 2013;58:1888–96. Hadziyannis SJ, Vassilopoulos D, Sevastianos V, et al. Can Nucleos(t)ide Analogue (NA) Therapy Ever be Stopped in HBeAg-Negative Chronic Hepatitis B? Curr Hepatol Rep 2014;13:256–63.
1006
4
5
Hadziyannis SJ, Sevastianos V, Rapti I, et al. Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. Gastroenterology 2012;143: 629–36. Brunetto MR, Oliveri F, Colombatto P, et al. Use of hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers. Gastroenterology 2010;139:483–90.
Comment on impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test Sir, Zorzi et al1 are to be commended for their timely analysis of the impact of using a faecal immunochemical test (FIT) on colorectal cancer mortality in their screening programme. The 24% colorectal cancer mortality reduction they report will surely give impetus to efforts to introduce FIT into other screening programmes. As they rightly observe, the impact of these newer screening tests is likely only to be determined from observational studies such as their study rather than further randomised trials. Nevertheless, some of their findings are quite surprising. It is remarkable that the mortality reduction they report should have been evident so early, within 5 years of starting to screen, when in the randomised trials a lower mortality from colorectal cancer was not apparent until over 5 years after screening started and for the reduction to be substantially greater in women than men when in these same trials the mortality reduction was similar.2–4 It is also remarkable that their colorectal cancer incidence, after peaking in the 2002–2004 roll-out period, should already have fallen below the prescreening incidence level when uptake of their screening programme was about 50% and only reached in 2006. While removal of advanced colorectal neoplasia might be expected to have some effect on incidence, it is difficult to conceive that such an effect would be clearly detectable within 5 years considering the fall in incidence of distal cancers in three of the flexible sigmoidoscopy trials was only just discernible at 5–6 years.5–7 As the authors recognise, ecological analyses are prone to ecological fallacies and confounding from other unrecognised differences between areas. In their analysis, is it possible that there are differences in
colorectal incidence and mortality in the early-screening areas and late-screening areas affecting all age groups? The findings in their analysis would be more convincing if the colorectal cancer mortality and incidence trends for the age groups not invited for screening in the early-screening areas had also been reported. Inclusion of these data would address the critical issue of the comparability of the early-screening and latescreening areas. If Zorzi et al can show that the decline in colorectal cancer mortality in the early-screening areas is only evident in the age group offered screening (60–74) and not in the older or younger age groups in these areas, this would surely accelerate efforts to introduce FIT-based screening elsewhere. Richard F Logan,1,2 Stephen P Halloran3 1 Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals Nottingham, Nottingham, UK 2 Epidemiology and Public Health, University of Nottingham, Nottingham, UK 3 Southern Hub, Bowel Cancer Screening Programme, University of Surrey, Guildford, UK
Correspondence to Professor Richard F Logan, Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals Nottingham, Nottingham NG7 2UH, UK; [email protected] Contributors RFL and SPH both contributed to the drafting of this letter. Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed.
To cite Logan RF, Halloran SP. Gut 2015;64:1006– 1007. Received 25 November 2014 Accepted 27 November 2014 Published Online First 15 December 2014
▸ http://dx.doi.org/10.1136/gutjnl-2014-307508 Gut 2015;64:1006–1007. doi:10.1136/gutjnl-2014-308902
REFERENCES 1
2
Zorzi M, Fedeli U, Schievano E, et al. Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test. Gut 2015;64:784–90. Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996;348: 1472–7.
Gut June 2015 Vol 64 No 6
Downloaded from http://gut.bmj.com/ on May 11, 2015 - Published by group.bmj.com
PostScript 3
4
5
6
7
Kronborg O, Fenger C, Olsen J, et al. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996;348:1467–71. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993;328:1365–71. Atkin WS, Edwards R, Kralj-Hans I, et al.; UK Flexible Sigmoidoscopy Trial Investigators. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet 2010;375:1624–33. Schoen RE, Pinsky PF, Weissfeld JL, et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 2012;366:2345–57. Segnan N, Armaroli P, Bonelli L, et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial—SCORE. J Natl Cancer Inst 2011;103:1310–22.
Early effect of screening programmes on incidence and mortality rates of colorectal cancer We thank Logan and Halloran for their interest in our study1 and admit that we were equally surprised at the early impact of screening programmes on colorectal cancer mortality rates.2 With respect to incidence trends, rates peaked during the prevalence round and showed a sharp reduction below the prescreening values within 5 years of screening set-up.2 These results are in line with the few evidences in the literature that evaluated the effect of population screening programmes based on the faecal occult blood test. Ventura et al3 compared the cumulative incidence between cohorts of screened and non-screened individuals. The rise of cumulative incidence was higher in screened individuals than in controls only during the first 2 years, then the value dropped and equalised with that of the non-attendees’ cohort around year 6. These figures translate into an initial increase of incidence rates followed by a decline in values below those of controls already after 3–4 years after screening. In our study, notwithstanding the impact of screening that is diluted because we collected data at a population level, we obtained similar results, probably due to the high sensitivity of the faecal immunochemical test. Furthermore, at the population level, incidence rates of the Scottish pilot study4 showed a similar pattern: the excess in incidence was limited to the first round of the screening pilot and fell below prescreening values during the second round. In conclusion, our results and the few additional published data Gut June 2015 Vol 64 No 6
Figure 1 Mortality rates of colorectal cancer in early screening areas, by year and age group, during the period 1995–2011. demonstrate an early effect of population screening programmes on incidence rates. We also reported a very early mortality reduction. Figure 1 shows that in early screening areas the decrease in mortality in the age group of 50–74 years started after 2005, while there was no time trend in subjects aged 75–89 years. Some reduction in subjects aged 40–49 years took place, but limited numbers do not allow to draw any conclusion in this younger age group. We applied to the two extrascreening age groups the same Poisson regression models adopted in the paper, and in both groups no statistically significant time trend or any difference in trends with respect to control (late screening) areas could be found. These additional findings reinforce the impact of faecal immunochemical test-based screening programmes on colorectal cancer mortality. Manuel Zorzi,1 Ugo Fedeli2 1
Veneto Tumour Registry, Veneto Region, Padua, Italy SER—Epidemiological Department, Veneto Region, Padua, Italy
2
Correspondence to Dr Manuel Zorzi, Veneto Tumour Registry, Veneto Region, Padua, Italy; manuel.zorzi@ regione.veneto.it Contributors MZ and UF: drafting and final approval of the manuscript. Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed.
To cite Zorzi M, Fedeli U. Gut 2015;64:1007. Received 5 December 2014 Accepted 6 December 2014
Published Online First 24 December 2014 Gut 2015;64:1007. doi:10.1136/gutjnl-2014-308970
REFERENCES 1
2
3
4
Logan RF, Halloran SP. Comment on Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test. Gut 2015;64:1009–10. Zorzi M, Fedeli U, Schievano E, et al. Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test. Gut 2015;64:784–90. Ventura L, Mantellini P, Grazzini G, et al. The impact of immunochemical faecal occult blood testing on colorectal cancer incidence. Dig Liver Dis 2014;46:82–6. McClements PL, Madurasinghe V, Thomson CS, et al. Impact of the UK colorectal cancer screening pilot studies on incidence, stage distribution and mortality trends. Cancer Epidemiol 2012;36:e232–42.
The natural course of serrated lesions: a difficult enigma to resolve To the editor, The serrated pathway is an established sequence to colorectal cancer (CRC), but little is known about the exact malignant potential of serrated polyps (SPs). Therefore, we have read with great interest the article by Holme et al1 who evaluated the long-term risk of CRC in individuals with large (≥10 mm) SPs as well as the natural course of these lesions. Based on their results, the authors state that the increased CRC risk for individuals with large SPs may not be due to the malignant growth of the SP itself, but rather to an overall field effect in patients with these lesions. However, this statement warrants careful interpretation as we 1007
Downloaded from http://gut.bmj.com/ on May 11, 2015 - Published by group.bmj.com
Comment on impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test Richard F Logan and Stephen P Halloran Gut 2015 64: 1006-1007 originally published online December 15, 2014
doi: 10.1136/gutjnl-2014-308902 Updated information and services can be found at: http://gut.bmj.com/content/64/6/1006
These include:
References Email alerting service
This article cites 6 articles, 1 of which you can access for free at: http://gut.bmj.com/content/64/6/1006#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
PostScript with virological relapse (HBV DNA >2000 IU/mL) alone need to be treated again for a remote and unrealistic treatment goal. Cessation of long-term NA therapy adds to caring physicians and patients the burden of frequent follow-up visits, with uncertainty regarding long-term outcomes and with a high cost of multiple but necessary laboratory tests. However, in the long run, when discontinuation of long-term NA therapy terminates to sustained remission and particularly to HBsAg loss, it proves cost saving and beneficial to the patients in terms of close-to-cure outcomes of chronic liver disease and regarding their long-term psychology. Stephanos Hadziyannis,1 Yun-Fan Liaw2 1
Liver Unit and its Molecular Biology Laboratory of the National and Kapodistrian University of Athens, Evgenidion Hospital, Athens, Greece 2 Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan Correspondence to Professor Stephanos Hadziyannis, Liver Unit and its Molecular Biology Laboratory of the National and Kapodistrian University of Athens, Evgenidion Hospital, Athens, Greece, 20 Papadiamantopoulou Str, Athens 11527, Greece; [email protected] Contributors Both authors have contributed equally to the writing of the letter. Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed.
To cite Hadziyannis S, Liaw Y-F. Gut 2015;64:1005– 1006. Received 20 October 2014 Revised 28 October 2014 Accepted 30 October 2014 Published Online First 19 November 2014
▸ http://dx.doi.org/10.1136/gutjnl-2014-307237 Gut 2015;64:1005–1006. doi:10.1136/gutjnl-2014-308677
REFERENCES 1
2
3
Seto WK, Hui AJ, Wong VW, et al. Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: a multicentre prospective study. Gut 2015;64:667–72. Jeng WJ, Sheen IS, Chen YC, et al. Off-therapy durability of response to entecavir therapy in hepatitis B e antigen-negative chronic hepatitis B patients. Hepatology 2013;58:1888–96. Hadziyannis SJ, Vassilopoulos D, Sevastianos V, et al. Can Nucleos(t)ide Analogue (NA) Therapy Ever be Stopped in HBeAg-Negative Chronic Hepatitis B? Curr Hepatol Rep 2014;13:256–63.
1006
4
5
Hadziyannis SJ, Sevastianos V, Rapti I, et al. Sustained responses and loss of HBsAg in HBeAg-negative patients with chronic hepatitis B who stop long-term treatment with adefovir. Gastroenterology 2012;143: 629–36. Brunetto MR, Oliveri F, Colombatto P, et al. Use of hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers. Gastroenterology 2010;139:483–90.
Comment on impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test Sir, Zorzi et al1 are to be commended for their timely analysis of the impact of using a faecal immunochemical test (FIT) on colorectal cancer mortality in their screening programme. The 24% colorectal cancer mortality reduction they report will surely give impetus to efforts to introduce FIT into other screening programmes. As they rightly observe, the impact of these newer screening tests is likely only to be determined from observational studies such as their study rather than further randomised trials. Nevertheless, some of their findings are quite surprising. It is remarkable that the mortality reduction they report should have been evident so early, within 5 years of starting to screen, when in the randomised trials a lower mortality from colorectal cancer was not apparent until over 5 years after screening started and for the reduction to be substantially greater in women than men when in these same trials the mortality reduction was similar.2–4 It is also remarkable that their colorectal cancer incidence, after peaking in the 2002–2004 roll-out period, should already have fallen below the prescreening incidence level when uptake of their screening programme was about 50% and only reached in 2006. While removal of advanced colorectal neoplasia might be expected to have some effect on incidence, it is difficult to conceive that such an effect would be clearly detectable within 5 years considering the fall in incidence of distal cancers in three of the flexible sigmoidoscopy trials was only just discernible at 5–6 years.5–7 As the authors recognise, ecological analyses are prone to ecological fallacies and confounding from other unrecognised differences between areas. In their analysis, is it possible that there are differences in
colorectal incidence and mortality in the early-screening areas and late-screening areas affecting all age groups? The findings in their analysis would be more convincing if the colorectal cancer mortality and incidence trends for the age groups not invited for screening in the early-screening areas had also been reported. Inclusion of these data would address the critical issue of the comparability of the early-screening and latescreening areas. If Zorzi et al can show that the decline in colorectal cancer mortality in the early-screening areas is only evident in the age group offered screening (60–74) and not in the older or younger age groups in these areas, this would surely accelerate efforts to introduce FIT-based screening elsewhere. Richard F Logan,1,2 Stephen P Halloran3 1 Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals Nottingham, Nottingham, UK 2 Epidemiology and Public Health, University of Nottingham, Nottingham, UK 3 Southern Hub, Bowel Cancer Screening Programme, University of Surrey, Guildford, UK
Correspondence to Professor Richard F Logan, Eastern Hub, Bowel Cancer Screening Programme, Nottingham University Hospitals Nottingham, Nottingham NG7 2UH, UK; [email protected] Contributors RFL and SPH both contributed to the drafting of this letter. Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed.
To cite Logan RF, Halloran SP. Gut 2015;64:1006– 1007. Received 25 November 2014 Accepted 27 November 2014 Published Online First 15 December 2014
▸ http://dx.doi.org/10.1136/gutjnl-2014-307508 Gut 2015;64:1006–1007. doi:10.1136/gutjnl-2014-308902
REFERENCES 1
2
Zorzi M, Fedeli U, Schievano E, et al. Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test. Gut 2015;64:784–90. Hardcastle JD, Chamberlain JO, Robinson MH, et al. Randomised controlled trial of faecal-occult-blood screening for colorectal cancer. Lancet 1996;348: 1472–7.
Gut June 2015 Vol 64 No 6
Downloaded from http://gut.bmj.com/ on May 11, 2015 - Published by group.bmj.com
PostScript 3
4
5
6
7
Kronborg O, Fenger C, Olsen J, et al. Randomised study of screening for colorectal cancer with faecal-occult-blood test. Lancet 1996;348:1467–71. Mandel JS, Bond JH, Church TR, et al. Reducing mortality from colorectal cancer by screening for fecal occult blood. Minnesota Colon Cancer Control Study. N Engl J Med 1993;328:1365–71. Atkin WS, Edwards R, Kralj-Hans I, et al.; UK Flexible Sigmoidoscopy Trial Investigators. Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer: a multicentre randomised controlled trial. Lancet 2010;375:1624–33. Schoen RE, Pinsky PF, Weissfeld JL, et al. Colorectal-cancer incidence and mortality with screening flexible sigmoidoscopy. N Engl J Med 2012;366:2345–57. Segnan N, Armaroli P, Bonelli L, et al. Once-only sigmoidoscopy in colorectal cancer screening: follow-up findings of the Italian Randomized Controlled Trial—SCORE. J Natl Cancer Inst 2011;103:1310–22.
Early effect of screening programmes on incidence and mortality rates of colorectal cancer We thank Logan and Halloran for their interest in our study1 and admit that we were equally surprised at the early impact of screening programmes on colorectal cancer mortality rates.2 With respect to incidence trends, rates peaked during the prevalence round and showed a sharp reduction below the prescreening values within 5 years of screening set-up.2 These results are in line with the few evidences in the literature that evaluated the effect of population screening programmes based on the faecal occult blood test. Ventura et al3 compared the cumulative incidence between cohorts of screened and non-screened individuals. The rise of cumulative incidence was higher in screened individuals than in controls only during the first 2 years, then the value dropped and equalised with that of the non-attendees’ cohort around year 6. These figures translate into an initial increase of incidence rates followed by a decline in values below those of controls already after 3–4 years after screening. In our study, notwithstanding the impact of screening that is diluted because we collected data at a population level, we obtained similar results, probably due to the high sensitivity of the faecal immunochemical test. Furthermore, at the population level, incidence rates of the Scottish pilot study4 showed a similar pattern: the excess in incidence was limited to the first round of the screening pilot and fell below prescreening values during the second round. In conclusion, our results and the few additional published data Gut June 2015 Vol 64 No 6
Figure 1 Mortality rates of colorectal cancer in early screening areas, by year and age group, during the period 1995–2011. demonstrate an early effect of population screening programmes on incidence rates. We also reported a very early mortality reduction. Figure 1 shows that in early screening areas the decrease in mortality in the age group of 50–74 years started after 2005, while there was no time trend in subjects aged 75–89 years. Some reduction in subjects aged 40–49 years took place, but limited numbers do not allow to draw any conclusion in this younger age group. We applied to the two extrascreening age groups the same Poisson regression models adopted in the paper, and in both groups no statistically significant time trend or any difference in trends with respect to control (late screening) areas could be found. These additional findings reinforce the impact of faecal immunochemical test-based screening programmes on colorectal cancer mortality. Manuel Zorzi,1 Ugo Fedeli2 1
Veneto Tumour Registry, Veneto Region, Padua, Italy SER—Epidemiological Department, Veneto Region, Padua, Italy
2
Correspondence to Dr Manuel Zorzi, Veneto Tumour Registry, Veneto Region, Padua, Italy; manuel.zorzi@ regione.veneto.it Contributors MZ and UF: drafting and final approval of the manuscript. Competing interests None. Provenance and peer review Not commissioned; internally peer reviewed.
To cite Zorzi M, Fedeli U. Gut 2015;64:1007. Received 5 December 2014 Accepted 6 December 2014
Published Online First 24 December 2014 Gut 2015;64:1007. doi:10.1136/gutjnl-2014-308970
REFERENCES 1
2
3
4
Logan RF, Halloran SP. Comment on Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test. Gut 2015;64:1009–10. Zorzi M, Fedeli U, Schievano E, et al. Impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test. Gut 2015;64:784–90. Ventura L, Mantellini P, Grazzini G, et al. The impact of immunochemical faecal occult blood testing on colorectal cancer incidence. Dig Liver Dis 2014;46:82–6. McClements PL, Madurasinghe V, Thomson CS, et al. Impact of the UK colorectal cancer screening pilot studies on incidence, stage distribution and mortality trends. Cancer Epidemiol 2012;36:e232–42.
The natural course of serrated lesions: a difficult enigma to resolve To the editor, The serrated pathway is an established sequence to colorectal cancer (CRC), but little is known about the exact malignant potential of serrated polyps (SPs). Therefore, we have read with great interest the article by Holme et al1 who evaluated the long-term risk of CRC in individuals with large (≥10 mm) SPs as well as the natural course of these lesions. Based on their results, the authors state that the increased CRC risk for individuals with large SPs may not be due to the malignant growth of the SP itself, but rather to an overall field effect in patients with these lesions. However, this statement warrants careful interpretation as we 1007
Downloaded from http://gut.bmj.com/ on May 11, 2015 - Published by group.bmj.com
Comment on impact on colorectal cancer mortality of screening programmes based on the faecal immunochemical test Richard F Logan and Stephen P Halloran Gut 2015 64: 1006-1007 originally published online December 15, 2014
doi: 10.1136/gutjnl-2014-308902 Updated information and services can be found at: http://gut.bmj.com/content/64/6/1006
These include:
References Email alerting service
This article cites 6 articles, 1 of which you can access for free at: http://gut.bmj.com/content/64/6/1006#BIBL Receive free email alerts when new articles cite this article. Sign up in the box at the top right corner of the online article.
Notes
To request permissions go to: http://group.bmj.com/group/rights-licensing/permissions To order reprints go to: http://journals.bmj.com/cgi/reprintform To subscribe to BMJ go to: http://group.bmj.com/subscribe/
