- Email: [email protected]
Perioperative analgesia in hepato-pancreato-biliary surgery
Comment
and stage of liver disease. So far, short therapies have been used only in patients without advanced fibrosis. Treatment failure after exposure to direct-acting antivirals might also have an effect on future rescue therapies, although short-term direct-acting antiviral exposure seems to be less likely to select clinically relevant resistance-associated variants.10 Lau and colleagues9 defined uRVR based on the sensitivity of generally available HCV RNA test kits in China (<500 IU/mL), whereas in Europe and the USA HCV kinetics analyses are based on HCV RNA assays with different limits of detection. Different assays can give different results8 and the exact timing of analysis is perhaps more important in the very early phase of therapy compared with the previous 4-week RVR concept. In conclusion, Lau and colleagues show for the first time that response-guided ultrashort therapy in easy-to-treat patients is possible. If treatment costs remain prohibitive, this approach could save resources and should be further investigated in larger studies and in other patient groups. This study revives the debate about individualised therapy versus a one-pill-fits-all concept—at least for hepatitis C. Markus Cornberg, *Michael P Manns
MC has received financial compensation for lectures and advisory boards from Abbvie, Bristol-Myers-Squibb, Boehringer-Ingelheim, Biodec Idec, Falk, Gilead Sciences, Janssen-Cilag, MSD/Merck, Roche Diagnostics, Roche Pharma, and Siemens. MPM has received financial compensation for lectures and advisory boards from Abbvie, Boehringer-Ingelheim, Bristol-Myers-Squibb, Gilead Sciences, Janssen-Cilag, Merck/MSD, Novartis, and Roche Pharma. 1 2
3 4
5
6
7 8
9
10
Dore GJ, Feld JJ. Hepatitis C virus therapeutic development: in pursuit of “perfectovir”. Clin Infect Dis 2015; 60: 1829–36. Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015; 373: 2599–607. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med 2015; 373: 2608–17. Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med 2015; 373: 2618–28. Gane EJ, Schwabe C, Hyland RH, et al. Efficacy of the combination of sofosbuvir, velpatasvir, and the NS3/4A protease inhibitor GS-9857 in treatment-naïve or previously treated patients with HCV genotype 1 or 3 infections. Gastroenterology 2016; published online May 27. DOI:10.1053/j.gastro.2016.05.021. Ioannou GN, Beste LA, Chang MF, et al. Effectiveness of sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir regimens for treatment of patients with hepatitis C in the Veterans Affairs National Healthcare System. Gastroenterology 2016; published online June 4. DOI:10.1053/j.gastro.2016.05.049. Manns MP, Wedemeyer H, Cornberg M. Treating viral hepatitis C: efficacy, side effects, and complications. Gut 2006; 55: 1350–59. Maasoumy B, Vermehren J, Welker MW, et al. Clinical value of on-treatment HCV RNA levels during different approved sofosbuvir-based antiviral regimens. J Hepatol 2016; published online April 13. DOI:10.1016/ j.jhep.2016.04.006. Lau G, Benhamou Y, Chen G, et al. Efficacy and safety of 3-week response-guided triple direct-acting antiviral therapy for chronic hepatitis C infection: a phase 2, open-label, proof-of-concept study. Lancet Gastroenterol Hepatol 2016; published online July 25. http://dx.doi.org/10.1016/S2468-1253(16)30015-2. Pawlotsky JM. Hepatitis C virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology 2016; 151: 70–86.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, German Center for Infection Research (DZIF), Carl Neuberg Strasse 1, 30625 Hannover, Germany [email protected]
Perioperative analgesia in hepato-pancreato-biliary surgery For many years epidural analgesia has been considered the gold standard for provision of perioperative pain control in patients undergoing liver and pancreas surgery. The reasons for this are many, but include a perception of superior post-operative analgesia1 and a belief that epidural analgesia suppressed the inflammatory response to surgery.2 In the context of liver surgery, epidural analgesia was also promoted in the belief that this technique produced lower intraoperative central venous pressure and thus contributed to reduced blood www.thelancet.com/gastrohep Vol 1 October 2016
loss. These perceptions were perpetuated through the priority given to epidural analgesia during the development of enhanced recovery after surgery (ERAS) protocols. As a consequence, a generation of anaesthetists has grown up believing that epidural analgesia is the preferred option for providing perioperative analgesia for patients undergoing hepatobiliary surgery. A number of recent studies have questioned the benefit of epidural analgesia and have challenged the evidence supporting their routine use, much of
Published Online July 7, 2016 http://dx.doi.org/10.1016/ S2468-1253(16)30017-6 See Articles page 105
87
Comment
P Marazzi/Science Photo Library
which is now quite dated. Among some members of the liver surgery community there were concerns regarding high failure rates and rare but potentially devastating neurological complications of epidural analgesia, particularly in the context of procedures with the potential for altered coagulation as a consequence of perioperative liver dysfunction.3 Additionally, prolonged postoperative stay due to sodium and fluid overload, recognised to be more common after epidural analgesia, fuelled the search for alternative analgesic strategies in this patient group. The Basingstoke liver surgery group challenged the paradigm of epidural analgesia by reporting their initial experiences with local anaesthetic continuous wound infiltration with favourable results, but the technique achieved only limited support in terms of routine adoption.4 The LIVER trial randomly assigned surgical patients undergoing liver resection to receive either epidural analgesia or continuous local anaesthetic wound infiltration with bupivacaine.5 This study showed better early dynamic pain control with epidural but otherwise similar pain scores. Where patients receiving wound catheter infiltration benefited was from greater early mobility, shorter critical care unit stay, and shorter time to fitness for medical discharge. The larger LIVER2 trial also randomly assigned patients undergoing liver surgery to receive thoracic epidural or continuous wound infiltration of local anaesthetic but on this occasion added early transversus abdominis plane blocks to the wound infiltration group.6 This addition resulted in comparatively better early pain scores than in the LIVER study and again showed improved mobility, reduced critical care unit stay, and earlier achievement of discharge criteria compared with epidural. In this latter study there was also a comparison of central venous pressure measurements and inflammatory markers between the two groups, which showed no advantage for thoracic epidural analgesia on either count. There is now reasonable evidence that both wound infiltration or thoracic epidural analgesia offer good perioperative pain control and there may be some advantages for wound catheters in terms of early mobilisation and functional recovery. The most important stakeholders in this decision are 88
of course the patients undergoing surgery. That is why the POP-UP study7 from Timothy Mungroop and colleagues in The Lancet Gastroenterology & Hepatology is so important. Their study also randomly assigned patients to receive either continuous local anaesthetic wound infiltration or thoracic epidural, but had two important differences from the LIVER trials. First, the inclusion criteria were broadened to include any patient undergoing liver or pancreas surgery. Second, the principal outcome measure was a validated composite score—the Overall Benefit of Analgesic Score (OBAS)—which includes pain scores, opioid side-effects, and patient satisfaction. The inclusion of patient-reported outcome measures is a novel and sensible inclusion for this type of study. Such outcomes are an important consideration in analgesia trials. POP-UP shows that continuous wound infiltration was non-inferior to epidural analgesia in terms of pain scores and patient satisfaction. Interestingly, both groups had relatively modest scores on the OBAS scale, indicating that both were highly effective treatments. In clinical practice it is quite common for patients to hold strong opinions—either positive or negative—on the type of analgesia that they wish to receive. The validation of continuous wound infiltration for patients having hepato-pancreato-biliary surgery is an advantage in terms of increasing patient choice. In addition, there is a potential role for continuous wound infiltration in patients who have laparoscopic hepato-pancreato-biliary procedures but who require conversion of their procedure to an open procedure, since this is a group where epidural analgesia is not commonly used. Stephen J Wigmore Clinical Surgery, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh EH16 4SA, UK [email protected] I declare no competing interests. 1 2
3
4
Rawal N, Sjöstrand U, Dahlström B. Postoperative pain relief by epidural morphine. Anesth Analg 1981; 60: 726–31. Christensen P, Brandt MR, Rem J, Kehlet H. Influence of extradural morphine on the adrenocortical and hyperglycaemic response to surgery. Br J Anaesth 1982; 54: 23–27. Revie EJ, Massie LJ, McNally SJ, McKeown DW, Garden OJ, Wigmore SJ. Effectiveness of epidural analgesia following open liver resection. HPB (Oxford) 2011; 13: 206–11. Basu S, Tamijmarane A, Bulters D, Wells JK, John TG, Rees M. An alternative method of wound pain control following hepatic resection: a preliminary study. HPB (Oxford) 2004; 6: 186–89.
www.thelancet.com/gastrohep Vol 1 October 2016
Comment
5
6
Revie EJ, McKeown DW, Wilson JA, Garden OJ, Wigmore SJ. Randomized clinical trial of local infiltration plus patient-controlled opiate analgesia vs. epidural analgesia following liver resection surgery. HPB (Oxford) 2012; 14: 611–18. Hughes MJ, Harrison EM, Peel NJ, et al. Randomized clinical trial of perioperative nerve block and continuous local anaesthetic infiltration via wound catheter versus epidural analgesia in open liver resection (LIVER 2 trial). Br J Surg 2015; 102: 1619–28.
7
Mungroop TH, Veelo DP, Busch OR, et al. Continuous wound infiltration versus epidural analgesia after hepato-pancreato-biliary surgery (POP-UP): a randomised controlled, open-label, non-inferiority trial. Lancet Gastroenterol Hepatol 2016; published online July 7. http://dx.doi. org/10.1016/S2468-1253(16)30012-7.
A specific link between migraine and functional GI disorders
www.thelancet.com/gastrohep Vol 1 October 2016
that there is a strong association with particular disorders that is different from what is seen for other similar disorders, and that there is evidence that directly suggests a common mechanism. In The Lancet Gastroenterology & Hepatology, Julie Le Gal and colleagues8 report a robust case-control study that fills these requirements. In the study, done in the emergency departments of four European hospitals, the investigators compared the prevalence of ten functional gastrointestinal disorders in three groups of children and adolescents aged 6–18 years (257 with migraine, 167 with tension-type headache, and a control group of 648 headache-free individuals). Headaches were diagnosed by a neurologist using the International Classification of Headache Disorders. The ten functional gastrointestinal disorder diagnoses were based on the Rome III diagnostic criteria and were made by investigators masked to the headache diagnosis of each child. The researchers found that three of the four painpredominant functional gastrointestinal disorders
Published Online August 24, 2016 http://dx.doi.org/10.1016/ S2468-1253(16)30074-7 See Articles page 114
Girand/BSIP/Science Photo Library
A substantial body of published research over the past 40 years has established that functional gastrointestinal disorders have an unusually large overlap with several non-gastrointestinal pain syndromes, including fibromyalgia, chronic pelvic pain, and temporomandibular joint disorder.1 Migraine has also been found to have such excess comorbidity with functional gastrointestinal disorders. For example, a meta-analysis2 of six studies reported an overall odds ratio (OR) of 2·66 for migraine in individuals with irritable bowel syndrome (IBS). Most of the published research has been limited to assessments of the association between gastrointestinal disorders and one or a few other disorders. However, a few large studies3,4 with a broader scope have reported that individuals with functional gastrointestinal disorders have significantly higher odds than comparison groups of the great majority of all medical diagnoses. These observations call into question the typical assumption that excess overlap must signify a common underlying pathophysiological mechanism. The obvious alternative suggested by the broad pattern of comorbidity is that the cause is simply a heightened tendency to experience and report varied body symptoms and visit doctors for them; a characteristic typically called somatisation.5 The more different symptoms experienced and reported to the doctor, the more likely an individual is to meet criteria for multiple different medical diagnoses. Indeed, those with functional gastrointestinal disorders tend to score unusually high on somatisation questionnaires, reporting all kinds of non-specific body symptoms at increased rates.1,6,7 Therefore, there is a need to determine whether anything more specific than such tendency toward somatisation is the cause of the overlap of functional gastrointestinal disorders with other medical disorders. Studies need to demonstrate
89
and stage of liver disease. So far, short therapies have been used only in patients without advanced fibrosis. Treatment failure after exposure to direct-acting antivirals might also have an effect on future rescue therapies, although short-term direct-acting antiviral exposure seems to be less likely to select clinically relevant resistance-associated variants.10 Lau and colleagues9 defined uRVR based on the sensitivity of generally available HCV RNA test kits in China (<500 IU/mL), whereas in Europe and the USA HCV kinetics analyses are based on HCV RNA assays with different limits of detection. Different assays can give different results8 and the exact timing of analysis is perhaps more important in the very early phase of therapy compared with the previous 4-week RVR concept. In conclusion, Lau and colleagues show for the first time that response-guided ultrashort therapy in easy-to-treat patients is possible. If treatment costs remain prohibitive, this approach could save resources and should be further investigated in larger studies and in other patient groups. This study revives the debate about individualised therapy versus a one-pill-fits-all concept—at least for hepatitis C. Markus Cornberg, *Michael P Manns
MC has received financial compensation for lectures and advisory boards from Abbvie, Bristol-Myers-Squibb, Boehringer-Ingelheim, Biodec Idec, Falk, Gilead Sciences, Janssen-Cilag, MSD/Merck, Roche Diagnostics, Roche Pharma, and Siemens. MPM has received financial compensation for lectures and advisory boards from Abbvie, Boehringer-Ingelheim, Bristol-Myers-Squibb, Gilead Sciences, Janssen-Cilag, Merck/MSD, Novartis, and Roche Pharma. 1 2
3 4
5
6
7 8
9
10
Dore GJ, Feld JJ. Hepatitis C virus therapeutic development: in pursuit of “perfectovir”. Clin Infect Dis 2015; 60: 1829–36. Feld JJ, Jacobson IM, Hézode C, et al. Sofosbuvir and velpatasvir for HCV genotype 1, 2, 4, 5, and 6 infection. N Engl J Med 2015; 373: 2599–607. Foster GR, Afdhal N, Roberts SK, et al. Sofosbuvir and velpatasvir for HCV genotype 2 and 3 infection. N Engl J Med 2015; 373: 2608–17. Curry MP, O’Leary JG, Bzowej N, et al. Sofosbuvir and velpatasvir for HCV in patients with decompensated cirrhosis. N Engl J Med 2015; 373: 2618–28. Gane EJ, Schwabe C, Hyland RH, et al. Efficacy of the combination of sofosbuvir, velpatasvir, and the NS3/4A protease inhibitor GS-9857 in treatment-naïve or previously treated patients with HCV genotype 1 or 3 infections. Gastroenterology 2016; published online May 27. DOI:10.1053/j.gastro.2016.05.021. Ioannou GN, Beste LA, Chang MF, et al. Effectiveness of sofosbuvir, ledipasvir/sofosbuvir, or paritaprevir/ritonavir/ombitasvir and dasabuvir regimens for treatment of patients with hepatitis C in the Veterans Affairs National Healthcare System. Gastroenterology 2016; published online June 4. DOI:10.1053/j.gastro.2016.05.049. Manns MP, Wedemeyer H, Cornberg M. Treating viral hepatitis C: efficacy, side effects, and complications. Gut 2006; 55: 1350–59. Maasoumy B, Vermehren J, Welker MW, et al. Clinical value of on-treatment HCV RNA levels during different approved sofosbuvir-based antiviral regimens. J Hepatol 2016; published online April 13. DOI:10.1016/ j.jhep.2016.04.006. Lau G, Benhamou Y, Chen G, et al. Efficacy and safety of 3-week response-guided triple direct-acting antiviral therapy for chronic hepatitis C infection: a phase 2, open-label, proof-of-concept study. Lancet Gastroenterol Hepatol 2016; published online July 25. http://dx.doi.org/10.1016/S2468-1253(16)30015-2. Pawlotsky JM. Hepatitis C virus resistance to direct-acting antiviral drugs in interferon-free regimens. Gastroenterology 2016; 151: 70–86.
Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, German Center for Infection Research (DZIF), Carl Neuberg Strasse 1, 30625 Hannover, Germany [email protected]
Perioperative analgesia in hepato-pancreato-biliary surgery For many years epidural analgesia has been considered the gold standard for provision of perioperative pain control in patients undergoing liver and pancreas surgery. The reasons for this are many, but include a perception of superior post-operative analgesia1 and a belief that epidural analgesia suppressed the inflammatory response to surgery.2 In the context of liver surgery, epidural analgesia was also promoted in the belief that this technique produced lower intraoperative central venous pressure and thus contributed to reduced blood www.thelancet.com/gastrohep Vol 1 October 2016
loss. These perceptions were perpetuated through the priority given to epidural analgesia during the development of enhanced recovery after surgery (ERAS) protocols. As a consequence, a generation of anaesthetists has grown up believing that epidural analgesia is the preferred option for providing perioperative analgesia for patients undergoing hepatobiliary surgery. A number of recent studies have questioned the benefit of epidural analgesia and have challenged the evidence supporting their routine use, much of
Published Online July 7, 2016 http://dx.doi.org/10.1016/ S2468-1253(16)30017-6 See Articles page 105
87
Comment
P Marazzi/Science Photo Library
which is now quite dated. Among some members of the liver surgery community there were concerns regarding high failure rates and rare but potentially devastating neurological complications of epidural analgesia, particularly in the context of procedures with the potential for altered coagulation as a consequence of perioperative liver dysfunction.3 Additionally, prolonged postoperative stay due to sodium and fluid overload, recognised to be more common after epidural analgesia, fuelled the search for alternative analgesic strategies in this patient group. The Basingstoke liver surgery group challenged the paradigm of epidural analgesia by reporting their initial experiences with local anaesthetic continuous wound infiltration with favourable results, but the technique achieved only limited support in terms of routine adoption.4 The LIVER trial randomly assigned surgical patients undergoing liver resection to receive either epidural analgesia or continuous local anaesthetic wound infiltration with bupivacaine.5 This study showed better early dynamic pain control with epidural but otherwise similar pain scores. Where patients receiving wound catheter infiltration benefited was from greater early mobility, shorter critical care unit stay, and shorter time to fitness for medical discharge. The larger LIVER2 trial also randomly assigned patients undergoing liver surgery to receive thoracic epidural or continuous wound infiltration of local anaesthetic but on this occasion added early transversus abdominis plane blocks to the wound infiltration group.6 This addition resulted in comparatively better early pain scores than in the LIVER study and again showed improved mobility, reduced critical care unit stay, and earlier achievement of discharge criteria compared with epidural. In this latter study there was also a comparison of central venous pressure measurements and inflammatory markers between the two groups, which showed no advantage for thoracic epidural analgesia on either count. There is now reasonable evidence that both wound infiltration or thoracic epidural analgesia offer good perioperative pain control and there may be some advantages for wound catheters in terms of early mobilisation and functional recovery. The most important stakeholders in this decision are 88
of course the patients undergoing surgery. That is why the POP-UP study7 from Timothy Mungroop and colleagues in The Lancet Gastroenterology & Hepatology is so important. Their study also randomly assigned patients to receive either continuous local anaesthetic wound infiltration or thoracic epidural, but had two important differences from the LIVER trials. First, the inclusion criteria were broadened to include any patient undergoing liver or pancreas surgery. Second, the principal outcome measure was a validated composite score—the Overall Benefit of Analgesic Score (OBAS)—which includes pain scores, opioid side-effects, and patient satisfaction. The inclusion of patient-reported outcome measures is a novel and sensible inclusion for this type of study. Such outcomes are an important consideration in analgesia trials. POP-UP shows that continuous wound infiltration was non-inferior to epidural analgesia in terms of pain scores and patient satisfaction. Interestingly, both groups had relatively modest scores on the OBAS scale, indicating that both were highly effective treatments. In clinical practice it is quite common for patients to hold strong opinions—either positive or negative—on the type of analgesia that they wish to receive. The validation of continuous wound infiltration for patients having hepato-pancreato-biliary surgery is an advantage in terms of increasing patient choice. In addition, there is a potential role for continuous wound infiltration in patients who have laparoscopic hepato-pancreato-biliary procedures but who require conversion of their procedure to an open procedure, since this is a group where epidural analgesia is not commonly used. Stephen J Wigmore Clinical Surgery, Royal Infirmary of Edinburgh, University of Edinburgh, Edinburgh EH16 4SA, UK [email protected] I declare no competing interests. 1 2
3
4
Rawal N, Sjöstrand U, Dahlström B. Postoperative pain relief by epidural morphine. Anesth Analg 1981; 60: 726–31. Christensen P, Brandt MR, Rem J, Kehlet H. Influence of extradural morphine on the adrenocortical and hyperglycaemic response to surgery. Br J Anaesth 1982; 54: 23–27. Revie EJ, Massie LJ, McNally SJ, McKeown DW, Garden OJ, Wigmore SJ. Effectiveness of epidural analgesia following open liver resection. HPB (Oxford) 2011; 13: 206–11. Basu S, Tamijmarane A, Bulters D, Wells JK, John TG, Rees M. An alternative method of wound pain control following hepatic resection: a preliminary study. HPB (Oxford) 2004; 6: 186–89.
www.thelancet.com/gastrohep Vol 1 October 2016
Comment
5
6
Revie EJ, McKeown DW, Wilson JA, Garden OJ, Wigmore SJ. Randomized clinical trial of local infiltration plus patient-controlled opiate analgesia vs. epidural analgesia following liver resection surgery. HPB (Oxford) 2012; 14: 611–18. Hughes MJ, Harrison EM, Peel NJ, et al. Randomized clinical trial of perioperative nerve block and continuous local anaesthetic infiltration via wound catheter versus epidural analgesia in open liver resection (LIVER 2 trial). Br J Surg 2015; 102: 1619–28.
7
Mungroop TH, Veelo DP, Busch OR, et al. Continuous wound infiltration versus epidural analgesia after hepato-pancreato-biliary surgery (POP-UP): a randomised controlled, open-label, non-inferiority trial. Lancet Gastroenterol Hepatol 2016; published online July 7. http://dx.doi. org/10.1016/S2468-1253(16)30012-7.
A specific link between migraine and functional GI disorders
www.thelancet.com/gastrohep Vol 1 October 2016
that there is a strong association with particular disorders that is different from what is seen for other similar disorders, and that there is evidence that directly suggests a common mechanism. In The Lancet Gastroenterology & Hepatology, Julie Le Gal and colleagues8 report a robust case-control study that fills these requirements. In the study, done in the emergency departments of four European hospitals, the investigators compared the prevalence of ten functional gastrointestinal disorders in three groups of children and adolescents aged 6–18 years (257 with migraine, 167 with tension-type headache, and a control group of 648 headache-free individuals). Headaches were diagnosed by a neurologist using the International Classification of Headache Disorders. The ten functional gastrointestinal disorder diagnoses were based on the Rome III diagnostic criteria and were made by investigators masked to the headache diagnosis of each child. The researchers found that three of the four painpredominant functional gastrointestinal disorders
Published Online August 24, 2016 http://dx.doi.org/10.1016/ S2468-1253(16)30074-7 See Articles page 114
Girand/BSIP/Science Photo Library
A substantial body of published research over the past 40 years has established that functional gastrointestinal disorders have an unusually large overlap with several non-gastrointestinal pain syndromes, including fibromyalgia, chronic pelvic pain, and temporomandibular joint disorder.1 Migraine has also been found to have such excess comorbidity with functional gastrointestinal disorders. For example, a meta-analysis2 of six studies reported an overall odds ratio (OR) of 2·66 for migraine in individuals with irritable bowel syndrome (IBS). Most of the published research has been limited to assessments of the association between gastrointestinal disorders and one or a few other disorders. However, a few large studies3,4 with a broader scope have reported that individuals with functional gastrointestinal disorders have significantly higher odds than comparison groups of the great majority of all medical diagnoses. These observations call into question the typical assumption that excess overlap must signify a common underlying pathophysiological mechanism. The obvious alternative suggested by the broad pattern of comorbidity is that the cause is simply a heightened tendency to experience and report varied body symptoms and visit doctors for them; a characteristic typically called somatisation.5 The more different symptoms experienced and reported to the doctor, the more likely an individual is to meet criteria for multiple different medical diagnoses. Indeed, those with functional gastrointestinal disorders tend to score unusually high on somatisation questionnaires, reporting all kinds of non-specific body symptoms at increased rates.1,6,7 Therefore, there is a need to determine whether anything more specific than such tendency toward somatisation is the cause of the overlap of functional gastrointestinal disorders with other medical disorders. Studies need to demonstrate
89