V) Updates in the Treatment of Functional GI Disorder

Symposium (V)

UPDATES IN THE TREATMENT OF FUNCTIONAL GI DISORDER

GUT DYSFUNCTION IN DIABETES: DIAGNOSIS AND TREATMENT

Ping-Huei Tseng Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Diabetes mellitus has been associated a myriad of upper and lower gastrointestinal complications, including reflux esophagitis, gastroparesis, diarrhea and constipation, all of which may affect the quality of life and glycemic control. The pathogenesis of gastrointestinal complications in diabetic patients is multi-factorial and has been mainly attributed to autonomic neuropathy, which can impair both gastric acid secretion and gastrointestinal motility. Various gut hormones, including ghrelin, pancreatic polypeptide-fold peptides, amylin and glucagon-like peptide 1, also play crucial roles in regulation of food intake, gastrointestinal motility, energy balance, and body weight by working with the complex neural circuits in the brainstem, hypothalamus, and higher cortical centers. Normal gastric emptying is the result of coordinated activity in the proximal and distal regions of the stomach, and may be affected by several factors, such as the volume, composition and total calories of the ingested food, various neurohormonal factors and personal factors, such as pregnancy, anxiety and aging. Delayed or rapid gastric emptying has been associated with a number of gastrointestinal disorders, such as diabetic gastroparesis, functional dyspepsia, gastroesophageal reflux disease and dumping syndrome. Among them, diabetic gastroparesis is the most recognized and is characterized by the delayed gastric emptying, accompanied by severe nausea, vomiting and abdominal fullness, in the absence of mechanical obstruction of the stomach. Since delayed and rapid gastric emptying may cause similar gastrointestinal symptoms, such as nausea, vomiting and bloating, and therefore the importance of determining the rate of gastric emptying to guide the treatment choice has been stressed. Currently, gastric emptying scintigraphy with solid test meals remains the gold standard to assess delayed gastric emptying. Nevertheless, methodologies related to test meal and imaging protocols in determining gastric emptying time differ between institutions and regions. Other novel tests, including 13C-octanoate breath testing and wireless motility capsule, have been applied in several recent studies to determine gastric emptying, and each has its own advantages and limitations. Glycemic control, dietary measures, such as low fiber, low fat food, prokinetic drugs (e.g., domperidone, metoclopramide and erythromycin) and antiemetic drugs (e.g, phenothiazines, diphenhydramine) are generally effective for symptomatic relief in the majority of gastroparesis patients. When medical treatments become ineffective over time and associated with adverse events and tachyphylaxia, various interventional therapies may be initiated. The surgical laparoscopic pyloroplasty appeared efficacious but remained technically complicated and risky. Treatment with gastric electrical stimulation (GES) is reversible and may be a less invasive option compared to surgical intervention for the treatment of patients with chronic, drug-refractory nausea and vomiting secondary to gastroparesis. It has been proposed that GES could override the abnormal rhythms, stimulate gastric emptying and eliminate symptoms of gastroparesis. Nevertheless, the efficacy of GES remains unsatisfactory at present. Endoscopic approaches include intra-pyloric injection of botulinium toxin, stenting, and pyloric dilatation. Recently, gastric peroral endoscopic pyloromyotomy (G-POEM) has emerging as minimally invasive therapy for gastroparesis with a promising early and mid-term efficacy.

Symposium (V)

UPDATES IN THE TREATMENT OF FUNCTIONAL GI DISORDER

SHOULD WE MANIPULATE THE GUT MICROBIOTA IN FUNCTIONAL GUT DISORDER?

Yen-Po Wang Department of Internal Medicine, Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan Division of Internal Medicine, Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan

Functional gut disorder is characterized by chronic abdominal discomfort without a structural or biochemical cause that can adequate explain symptoms. The pathogenesis of functional gut disorder is multifactorial where brain-gut dysregulation was regarded as one of the most important issue. In Rome IV consensus, the intestinal microenvironment was regarded having important role in functional GI disorders, where diet and gut microbiota had substantial influence on metabolism and GI symptoms. Gut dysbiosis was also frequently observed in patients with FGID. Treatment towards alteration of gut microbiota was suggested to be promising in management of FGID. 14 days of rifaximin treatment was effective in to relieve irritable bowel syndrome (IBS) symptoms in 3 months. Rifaximin was also used in management of patients with small intestinal bacteria overgrowth (SIBO). In systemic review and meta-analysis, probiotics was shown effective in treatment of IBS. Fermented milk product with probiotic could further modulate brain activity through gut-brain-microbiome axis. Low Fermentable oligosaccharide disaccharide monosaccharide and polyol (FODMAP) diet could also improve IBS symptoms. The fecal bacterial dysbiosis status was found related to the treatment efficacy of low FODMAP diet. Gut microbiota composition could also be used to predict patients’ response to low FODMAP diet. Fecal microbiota transplant (FMT), which was primarily used for refractory clostridium difficile infection, was also experimented in treatment of IBS recently. The result was heterogenous among studies due to different protocols, fecal material donor, and patient’s characteristics. As gut microbiome also had impact on cardiovascular system, metabolism, immune system, neuropsychiatry and so on, the influence of manipulating gut microbiota on systems other than GI tract also warrants notice. Limited data about long-term efficacy and adverse events exist.

Symposium (V)

UPDATES IN THE TREATMENT OF FUNCTIONAL GI DISORDER

NEW PHARMACOLOGICAL TREATMENT FOR IRRITABLE BOWEL SYNDROME

Keng-Liang Wu Division of Hepato-Gastroenterology, Department of internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Department of Medicine, Chang Gung University, Taoyuan, Taiwan

Irritable bowel syndrome (IBS) is one of the most common diseases of the gut-brain axis. Rome IV criteria define IBS as chronic or recurrent abdominal pain associated with altered bowel habits. IBS patients are categorized in four subtypes: IBS with predominant constipation (IBS-C), predominant diarrhea (IBS-D), mixed bowel habits (IBS-M), and unclassified (IBS-U). Pharmacological treatment major target individual symptoms (bloating, abdominal pain and altered bowel habits). The current development of new treatment is focusing on different aspects of the complex pathophysiology of IBS: gut microenvironment, enterohepatic circulation of bile acids, gastrointestinal secretion, motility and sensation, gut–brain interactions, gut barrier function and the immune system within the gastrointestinal tract. In patients with IBS-C, plecanatide (peptide guanylate cyclase C receptor agonist) is a promising therapeutic option in patients with IBS-C. Tenapanor (inhibitor of the GI sodium/hydrogen exchanger NHE3) increases intestinal fluid volume and transit, leading to an improvement of constipation, bloating and pain. In patients with IBS-D, ACG suggest rifaximin to treat global IBS-D. Another drug also evaluated for IBS-D is ebastine, an antagonist of histamine receptor H1. Supplements, including probiotics and plant-derived products are safe to use in clinical practice but, high-quality evidence of efficacy is currently lack. Obeticholic acid was shown to decrease bile acid synthesis and improve stool form and symptoms of diarrhea in patients with bile acid diarrhea, but high-quality evidence of efficacy is also lack.

Symposium (V)

UPDATES IN THE TREATMENT OF FUNCTIONAL GI DISORDER

HOW TO PERFORM A SUCCESSFUL BIOFEEDBACK FOR THE PATIENTS WITH ANORECTAL DYSFUNCTION?

Kee Wook Jung Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Biofeedback is a scientific approach that relies on instrumentation to measure the physiological activity relevant to the problems including anorectal dysfunction.1,2 It has been widely used to treat fecal incontinence and chronic constipation due to pelvic floor dyssynergia.1 The goal of biofeedback training is to restore a normal pattern of defecation.1 In patients with dyssynergic defecation, the goal of neuromuscular training is twofold: to correct dyssynergia in coordination with the abdominal, rectal, and anal sphincter muscles and to achieve normal and complete evacuation and enhance rectal sensory perception in patients with impaired rectal sensation.3,4 The training comprises improving abdominal push efforts (diaphragmatic muscle training) and manometricguided pelvic floor relaxation followed by simulated defecation training.

The symptomatic improvement rate varies from 44% to 80%, as shown in the recent randomized controlled trials involving adults with dyssynergic defecation.5-10 However, previous studies have concluded that biofeedback therapy is superior to controlled treatment approaches, such as diet, exercise, and laxatives; the use of polyethylene glycol, diazepam, or placebo; balloon defecation therapy; or sham feedback therapy.5-9 Moreover, the effect of biofeedback was maintained for over 2 years after biofeedback therapy in a considerable proportion of patients with constipation with dyssynergic defecation.11 The ANMS-ESNM position paper recommended biofeedback therapy for short- and long-term treatments of fecal incontinence with Level II, Grade B evidence.12 However, a metaanalysis that assessing the role of biofeedback in fecal incontinence is difficult because of limited data.13 For constipation, more than three-fold superiority of biofeedback to non-biofeedback, but equal efficacy of electromyographic biofeedback to other applications, was demonstrated.12 The ANMS-ESNM position paper recommended biofeedback therapy for short- and long-term treatments of constipation with dyssynergic defecation with Level I, Grade A evidence.12 However, a Cochrane systematic review suggested that several studies had poor methodological quality.14 Thus, evidence is insufficient for any robust conclusion.14

The biofeedback protocol in our center is as follows1,11: at the first visit, the biofeedback therapist discusses the patient’s current problems and their solutions. Instructions about prepared treatment plans and individualized education regarding ideal defecation or continence practices are provided to patients. The second phase comprises improving the abdominal push effort and biofeedback-guided pelvic floor relaxation followed by simulated defecation training. Patients with fecal incontinence are taught Kegel exercises. After insertion of sensory probes, patients are asked to simulate defecation. Immediate feedback

is provided to the patient about the pressure changes in both the abdomen and anal sphincter, and the patient is asked to modify inappropriate responses through trial and error. The patient starts to become aware of coordinated defecation through this rectoanal coordination training, and subsequently, simulated defecation training is imparted using a water-filled balloon. In conclusion, biofeedback therapy is considered to be a safe behavioral treatment that can result in symptomatic improvement beyond the active treatment period in patients with anorectal dysfunction.

Reference:

1. Lee HJ, Jung KW, Myung SJ. Technique of functional and motility test: how to perform biofeedback for constipation and fecal incontinence. J Neurogastroenterol Motil 2013;19:532-537. 2. Yang DH, Myung SJ, Jung KW, et al. Anorectal function and the effect of biofeedback therapy in ambulatory spinal cord disease patients having constipation. Scand J Gastroenterol 2010;45:1281-1288. 3. Ahn JY, Myung SJ, Jung KW, et al. Effect of biofeedback therapy in constipation according to rectal sensation. Gut Liver 2013;7:157-162. 4. Jung KW, Yang DH, Yoon IJ, et al. Electrical stimulation therapy in chronic functional constipation: five years’ experience in patients refractory to biofeedback therapy and with rectal hyposensitivity. J Neurogastroenterol

Motil 2013;19:366-373. 5. Heymen S, Scarlett Y, Jones K, Ringel Y, Drossman D, Whitehead WE. Randomized, controlled trial shows biofeedback to be superior to alternative treatments for patients with pelvic floor dyssynergia-type constipation. Dis Colon Rectum 2007;50:428-441. 6. Rao SS, Seaton K, Miller M, et al. Randomized controlled trial of biofeedback, sham feedback, and standard therapy for

dyssynergic defecation. Clin Gastroenterol Hepatol 2007;5:331-338. 7. Rao SS, Valestin J, Brown CK, Zimmerman B, Schulze K. Long-term efficacy of biofeedback therapy for dyssynergic defecation: randomized controlled trial. Am J

Gastroenterol 2010;105:890-896. 8. Chiarioni G, Whitehead WE, Pezza V, Morelli A, Bassotti G. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology 2006;130:657-664. 9. Chiarioni G, Salandini L, Whitehead WE. Biofeedback benefits only patients with outlet dysfunction, not patients with isolated slow transit constipation. Gastroenterology 2005;129:86-97. 10. Skardoon GR, Khera AJ, Emmanuel AV, Burgell RE. Review article: dyssynergic defaecation and biofeedback therapy in the pathophysiology and management of functional constipation. Aliment Pharmacol

Ther 2017;46:410-423. 11. Lee HJ, Boo SJ, Jung KW, et al. Long-term efficacy of biofeedback therapy in patients with dyssynergic defecation: results of a median 44 months follow-up. Neurogastroenterol

Motil 2015;27:787-795. 12. Rao SS, Benninga MA, Bharucha AE, Chiarioni G, Di Lorenzo C, Whitehead WE. ANMS-ESNM position paper and consensus guidelines on biofeedback therapy for anorectal disorders. Neurogastroenterol Motil 2015;27:594-609. 13. Norton C, Cody JD. Biofeedback and/or sphincter exercises for the treatment of faecal incontinence in adults. Cochrane Database Syst Rev 2012:CD002111. 14. Woodward S, Norton C, Chiarelli P. Biofeedback for treatment of chronic idiopathic constipation in adults. Cochrane Database Syst Rev 2014:CD008486.