Invited Editorials Table 1 | Comparison of week 52 outcomes among different treatment groups, stratified according to week 8 response Week 8 responders (NRI) Outcome Remission, n/N (%) Response, n/N (%) Mucosal healing, n/N (%)
Week 8 nonresponders (NRI)
EOW ADA
EW ADA
EOW ADA
EW ADA
4/19 (21.1)
4/20 (20.0)
4/29 (13.8)
1/48 (2.1)
8/19 (42.1)
9/20 (45.0)
13/29 (44.8)
12/48 (25.0)
8/19 (42.1)
9/20 (45.0)
10/29 (34.5)
14.48 (29.2)
burden of UC is high and therefore at least equal, or even higher, doses of biologics may be required in UC compared to Crohn’s disease. Hopefully future studies, most likely directed by therapeutic drug monitoring, will help confirm the optimal dose of ADA for UC. Meanwhile, dose optimisation of anti-TNF therapy should remain a priority, even with the recent availabil-
Editorial: unsedated transnasal endoscopy S. S. Sami & K. Ragunath NIHR Biomedical Research Unit, Nottingham Digestive Diseases Centre, Queens Medical Centre, Nottingham, UK. E-mail: [email protected] doi:10.1111/apt.12897
Alexandridis et al. performed a randomised controlled trial comparing unsedated transnasal endoscopy (TNE) to standard upper endoscopy (SOGD).1 The authors concluded that TNE was superior to SOGD in terms of comfort, acceptability and cardiovascular stress. It is worth noting that these results are consistent with findings from multiple other studies performed over the last decade across different continents.2–5 So this raises the question: are we reinventing the wheel? Indeed, TNE technology is very appealing not least because it cuts the cost of sedation while remaining favoured by the majority of patients.5 However, as stated by the authors, it is not widely used and remains under-utilised in clinical practice. Endoscopy units are faced with unprecedented high demands,6 and low Aliment Pharmacol Ther 2014; 40: 727-734 ª 2014 John Wiley & Sons Ltd
ity of alternate agents (vedolizumab) for refractory UC patients.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Wolf D, D’Haens G, Sandborn WJ, et al. Escalation to weekly dosing recaptures response in adalimumab-treated patients with moderately to severe active ulcerative colitis. Aliment Pharmacol Ther 2014; 40: 486–97. 2. Sandborn WJ, Van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2012; 142: 257–65. 3. Colombel J-F, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology 2007; 132: 52–65. 4. Brandse JF, Wildenberg M, de Bruyn JR, et al. 157 fecal loss of infliximab as a cause of lack of response in severe inflammatory bowel disease. Gastroenterology 2013; 144: S–36. 5. Brandse JF, van der Kleij D, Wolbink G-J, et al. 786 the pharmacokinetics of infliximab induction therapy in patients with moderate to severe ulcerative colitis. Gastroenterology 2014; 146: S–134.
referral rates for gastroscopy will put patients at risk of worse outcomes from cancer.7 Hence, it is possible that more efficient and innovative ways of working are needed to increase capacity at endoscopy units. For instance, the majority (94%) of patients referred on the 2-week wait cancer pathway do not have cancer8 and 25% of patients with dyspepsia do not require gastroscopy.9 Therefore, open access endoscopy alone may not be adequate while referral to the out-patient clinic is also not ideal, because those patients will likely need a second visit for SOGD (or utilise the over-stretched endoscopy facilities in case of one stop dyspepsia clinics). One solution could be to ‘realign’ the clinical assessment with the endoscopic test in one visit. Future research should focus on whether providing a one-stop, nurse-led, office-based TNE clinic can be effective. TNE can be performed by Endoscopy nurses after a short training programme.10 In summary, we may simply need to realign the wheel rather than reinventing it. The advent of portable and disposable transnasal oesophagoscopes may further increase the potential utility and mobility of this technology for use in the community outside the hospital setting.11, 12
731
Invited Editorials ACKNOWLEDGEMENTS Declaration of personal interests: Professor Krish Ragunath has received research grant support from Olympus (Keymed, UK) and Intromedic Ltd. (Seoul, South Korea). Dr. Sarmed S. Sami is funded by a Core-Olympus national endoscopy research fellowship and received travel grant support from Intromedic Ltd. (Seoul, South Korea). Declaration of funding interests: No funding support was needed for the production of this manuscript.
5.
6.
7.
8.
REFERENCES 1. Alexandridis E, Inglis S, McAvoy NC, et al. Randomised clinical study: comparison of acceptability, patient tolerance, cardiac stress and endoscopic views in transnasal and transoral endoscopy under local. Aliment Pharmacol Ther 2014; 40: 467–76. 2. Shariff MK, Bird-Lieberman EL, O’Donovan M, et al. Randomized crossover study comparing efficacy of transnasal endoscopy with that of standard endoscopy to detect Barrett’s esophagus. Gastrointest Endosc 2012; 75: 954–61. 3. Garcia RT, Cello JP, Nguyen MH, et al. Unsedated ultrathin EGD is well accepted when compared with conventional sedated EGD: a multicenter randomized trial. Gastroenterology 2003; 125: 1606–12. 4. Trevisani L, Cifala V, Sartori S, Gilli G, Matarese G, Abbasciano V. Unsedated ultrathin upper endoscopy is better than conventional endoscopy in routine outpatient gastroenterology
Editorial: metabolomic analysis of breath volatile organic compounds – a new scent for inflammatory bowel disease R. P. Arasaradnam*,†, J. Covington‡ & C. U. Nwokolo† *Clinical Sciences Research Institute, University of Warwick, Coventry, UK. † School of Engineering, University of Warwick, Coventry, UK. ‡ Department of Gastroenterology, University Hospitals Coventry & Warwickshire, Coventry, UK. E-mail: [email protected] doi:10.1111/apt.12901
Patel et al. describe a unique set of breathprints in children with inflammatory bowel disease (IBD).1 Analyses of breath volatile organic compounds (VOCs) were assessed using selected ion-flow tube mass spectroscopy (SIFT-MS). Having pre-selected 21 ionic compounds, three specific VOCs were deemed significant (1-octene, 1-decene, (E)-2-nonene). Analysis using linear discriminant analysis (pre-classified) as we all as principal component analysis (unclassified), demonstrated an impressive reclassification 732
9.
10.
11.
12.
practice: a randomized trial. World J Gastroenterol 2007; 13: 906–11. Yagi J, Adachi K, Arima N, et al. A prospective randomized comparative study on the safety and tolerability of transnasal esophagogastroduodenoscopy. Endoscopy 2005; 37: 1226–31. NHS Bowel Cancer Screening Programme: Bowel scope screening – 2nd wave Advice to the NHS and bidding process. Online: Public Health England, 2013. Available at: http://www. cancerscreening.nhs.uk/bowel/publications/ bowel-scope-screening-2nd-wave.pdf (Accessed April 07 2014) Shawihdi M, Thompson E, Kapoor N, et al. Variation in gastroscopy rate in English general practice and outcome for oesophagogastric cancer: retrospective analysis of Hospital Episode Statistics. Gut 2014; 63: 250–61. Spahos T, Hindmarsh A, Cameron E, et al. Endoscopy waiting times and impact of the two week wait scheme on diagnosis and outcome of upper gastrointestinal cancer. Postgrad Med J 2005; 81: 728–30. Rutter MD, Michie AF, Trewby PN. The one-stop dyspepsia clinic–an alternative to open-access endoscopy for patients with dyspepsia. J R Soc Med 1998; 91: 524–7. Alashkar B, Faulx AL, Hepner A, et al. Development of a program to train physician extenders to perform transnasal esophagoscopy and screen for Barrett’s esophagus’. Clin Gastroenterol Hepatol 2013; 12: 785–92. Chung JW, Park S, Chung MJ, et al. A novel disposable, transnasal esophagoscope: a pilot trial of feasibility, safety, and tolerance. Endoscopy 2012; 44: 206–9. Sami SS, Ragunath K, Iyer PG. Screening for Barrett’s esophagus and esophageal adenocarcinoma: rationale, recent progress, challenges, and future directions. Clin Gastroenterol Hepatol 2014; June 2nd [Epub ahead of print].
precision of 97%. Moreover the accuracy of predicting the presence of IBD using the combination of all three chemicals returned an area under the receiver operating characteristics curve of 0.96 (95% CI: 0.93–0.99). Volatile organic compounds are a heterogeneous group of compounds that can exist in the vapour phase at room temperature. In breath alone, there are over 1000 VOCs detectable; present in minute quantities – concentrations of parts per billion.2 Thus high end sensitive analytical equipment is required e.g. SIFT-MS, as this is challenging with almost all traditional gas sensors. SIFT-MS allows for rapid quantification of trace VOCs, but the chemical library is currently limited. There is, as yet, no consensus on breath chemicals detected in IBD. Earlier studies of breath in IBD utilising standard gas chromatography and mass spectroscopy had identified pentane3 and alkanes4 as potential markers. Pentane is a by product of lipid peroxidation; a consequence of lipid cellular degradation. Interestingly, pentane-1-thiol has been shown in vitro to inhibit phagocytosis through prevention of binding of antibody coated cells.5 Such disruption could have an effect on Aliment Pharmacol Ther 2014; 40: 727-734 ª 2014 John Wiley & Sons Ltd
Week 8 nonresponders (NRI)
EOW ADA
EW ADA
EOW ADA
EW ADA
4/19 (21.1)
4/20 (20.0)
4/29 (13.8)
1/48 (2.1)
8/19 (42.1)
9/20 (45.0)
13/29 (44.8)
12/48 (25.0)
8/19 (42.1)
9/20 (45.0)
10/29 (34.5)
14.48 (29.2)
burden of UC is high and therefore at least equal, or even higher, doses of biologics may be required in UC compared to Crohn’s disease. Hopefully future studies, most likely directed by therapeutic drug monitoring, will help confirm the optimal dose of ADA for UC. Meanwhile, dose optimisation of anti-TNF therapy should remain a priority, even with the recent availabil-
Editorial: unsedated transnasal endoscopy S. S. Sami & K. Ragunath NIHR Biomedical Research Unit, Nottingham Digestive Diseases Centre, Queens Medical Centre, Nottingham, UK. E-mail: [email protected] doi:10.1111/apt.12897
Alexandridis et al. performed a randomised controlled trial comparing unsedated transnasal endoscopy (TNE) to standard upper endoscopy (SOGD).1 The authors concluded that TNE was superior to SOGD in terms of comfort, acceptability and cardiovascular stress. It is worth noting that these results are consistent with findings from multiple other studies performed over the last decade across different continents.2–5 So this raises the question: are we reinventing the wheel? Indeed, TNE technology is very appealing not least because it cuts the cost of sedation while remaining favoured by the majority of patients.5 However, as stated by the authors, it is not widely used and remains under-utilised in clinical practice. Endoscopy units are faced with unprecedented high demands,6 and low Aliment Pharmacol Ther 2014; 40: 727-734 ª 2014 John Wiley & Sons Ltd
ity of alternate agents (vedolizumab) for refractory UC patients.
ACKNOWLEDGEMENT Declaration of personal and funding interests: None. REFERENCES 1. Wolf D, D’Haens G, Sandborn WJ, et al. Escalation to weekly dosing recaptures response in adalimumab-treated patients with moderately to severe active ulcerative colitis. Aliment Pharmacol Ther 2014; 40: 486–97. 2. Sandborn WJ, Van Assche G, Reinisch W, et al. Adalimumab induces and maintains clinical remission in patients with moderate-to-severe ulcerative colitis. Gastroenterology 2012; 142: 257–65. 3. Colombel J-F, Sandborn WJ, Rutgeerts P, et al. Adalimumab for maintenance of clinical response and remission in patients with Crohn’s disease: the CHARM trial. Gastroenterology 2007; 132: 52–65. 4. Brandse JF, Wildenberg M, de Bruyn JR, et al. 157 fecal loss of infliximab as a cause of lack of response in severe inflammatory bowel disease. Gastroenterology 2013; 144: S–36. 5. Brandse JF, van der Kleij D, Wolbink G-J, et al. 786 the pharmacokinetics of infliximab induction therapy in patients with moderate to severe ulcerative colitis. Gastroenterology 2014; 146: S–134.
referral rates for gastroscopy will put patients at risk of worse outcomes from cancer.7 Hence, it is possible that more efficient and innovative ways of working are needed to increase capacity at endoscopy units. For instance, the majority (94%) of patients referred on the 2-week wait cancer pathway do not have cancer8 and 25% of patients with dyspepsia do not require gastroscopy.9 Therefore, open access endoscopy alone may not be adequate while referral to the out-patient clinic is also not ideal, because those patients will likely need a second visit for SOGD (or utilise the over-stretched endoscopy facilities in case of one stop dyspepsia clinics). One solution could be to ‘realign’ the clinical assessment with the endoscopic test in one visit. Future research should focus on whether providing a one-stop, nurse-led, office-based TNE clinic can be effective. TNE can be performed by Endoscopy nurses after a short training programme.10 In summary, we may simply need to realign the wheel rather than reinventing it. The advent of portable and disposable transnasal oesophagoscopes may further increase the potential utility and mobility of this technology for use in the community outside the hospital setting.11, 12
731
Invited Editorials ACKNOWLEDGEMENTS Declaration of personal interests: Professor Krish Ragunath has received research grant support from Olympus (Keymed, UK) and Intromedic Ltd. (Seoul, South Korea). Dr. Sarmed S. Sami is funded by a Core-Olympus national endoscopy research fellowship and received travel grant support from Intromedic Ltd. (Seoul, South Korea). Declaration of funding interests: No funding support was needed for the production of this manuscript.
5.
6.
7.
8.
REFERENCES 1. Alexandridis E, Inglis S, McAvoy NC, et al. Randomised clinical study: comparison of acceptability, patient tolerance, cardiac stress and endoscopic views in transnasal and transoral endoscopy under local. Aliment Pharmacol Ther 2014; 40: 467–76. 2. Shariff MK, Bird-Lieberman EL, O’Donovan M, et al. Randomized crossover study comparing efficacy of transnasal endoscopy with that of standard endoscopy to detect Barrett’s esophagus. Gastrointest Endosc 2012; 75: 954–61. 3. Garcia RT, Cello JP, Nguyen MH, et al. Unsedated ultrathin EGD is well accepted when compared with conventional sedated EGD: a multicenter randomized trial. Gastroenterology 2003; 125: 1606–12. 4. Trevisani L, Cifala V, Sartori S, Gilli G, Matarese G, Abbasciano V. Unsedated ultrathin upper endoscopy is better than conventional endoscopy in routine outpatient gastroenterology
Editorial: metabolomic analysis of breath volatile organic compounds – a new scent for inflammatory bowel disease R. P. Arasaradnam*,†, J. Covington‡ & C. U. Nwokolo† *Clinical Sciences Research Institute, University of Warwick, Coventry, UK. † School of Engineering, University of Warwick, Coventry, UK. ‡ Department of Gastroenterology, University Hospitals Coventry & Warwickshire, Coventry, UK. E-mail: [email protected] doi:10.1111/apt.12901
Patel et al. describe a unique set of breathprints in children with inflammatory bowel disease (IBD).1 Analyses of breath volatile organic compounds (VOCs) were assessed using selected ion-flow tube mass spectroscopy (SIFT-MS). Having pre-selected 21 ionic compounds, three specific VOCs were deemed significant (1-octene, 1-decene, (E)-2-nonene). Analysis using linear discriminant analysis (pre-classified) as we all as principal component analysis (unclassified), demonstrated an impressive reclassification 732
9.
10.
11.
12.
practice: a randomized trial. World J Gastroenterol 2007; 13: 906–11. Yagi J, Adachi K, Arima N, et al. A prospective randomized comparative study on the safety and tolerability of transnasal esophagogastroduodenoscopy. Endoscopy 2005; 37: 1226–31. NHS Bowel Cancer Screening Programme: Bowel scope screening – 2nd wave Advice to the NHS and bidding process. Online: Public Health England, 2013. Available at: http://www. cancerscreening.nhs.uk/bowel/publications/ bowel-scope-screening-2nd-wave.pdf (Accessed April 07 2014) Shawihdi M, Thompson E, Kapoor N, et al. Variation in gastroscopy rate in English general practice and outcome for oesophagogastric cancer: retrospective analysis of Hospital Episode Statistics. Gut 2014; 63: 250–61. Spahos T, Hindmarsh A, Cameron E, et al. Endoscopy waiting times and impact of the two week wait scheme on diagnosis and outcome of upper gastrointestinal cancer. Postgrad Med J 2005; 81: 728–30. Rutter MD, Michie AF, Trewby PN. The one-stop dyspepsia clinic–an alternative to open-access endoscopy for patients with dyspepsia. J R Soc Med 1998; 91: 524–7. Alashkar B, Faulx AL, Hepner A, et al. Development of a program to train physician extenders to perform transnasal esophagoscopy and screen for Barrett’s esophagus’. Clin Gastroenterol Hepatol 2013; 12: 785–92. Chung JW, Park S, Chung MJ, et al. A novel disposable, transnasal esophagoscope: a pilot trial of feasibility, safety, and tolerance. Endoscopy 2012; 44: 206–9. Sami SS, Ragunath K, Iyer PG. Screening for Barrett’s esophagus and esophageal adenocarcinoma: rationale, recent progress, challenges, and future directions. Clin Gastroenterol Hepatol 2014; June 2nd [Epub ahead of print].
precision of 97%. Moreover the accuracy of predicting the presence of IBD using the combination of all three chemicals returned an area under the receiver operating characteristics curve of 0.96 (95% CI: 0.93–0.99). Volatile organic compounds are a heterogeneous group of compounds that can exist in the vapour phase at room temperature. In breath alone, there are over 1000 VOCs detectable; present in minute quantities – concentrations of parts per billion.2 Thus high end sensitive analytical equipment is required e.g. SIFT-MS, as this is challenging with almost all traditional gas sensors. SIFT-MS allows for rapid quantification of trace VOCs, but the chemical library is currently limited. There is, as yet, no consensus on breath chemicals detected in IBD. Earlier studies of breath in IBD utilising standard gas chromatography and mass spectroscopy had identified pentane3 and alkanes4 as potential markers. Pentane is a by product of lipid peroxidation; a consequence of lipid cellular degradation. Interestingly, pentane-1-thiol has been shown in vitro to inhibit phagocytosis through prevention of binding of antibody coated cells.5 Such disruption could have an effect on Aliment Pharmacol Ther 2014; 40: 727-734 ª 2014 John Wiley & Sons Ltd
