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Only for medical professionals to read the reference dry goods! This article grasps the latest developments in the diagnosis and treatment of functional constipation.
This year's American Digestive Disease Week (DDW) was held online on May 21-23, bringing together experts and scholars in the field of gastroenterology from around the world to discuss the research results and clinical standards of digestive system diseases.
On May 22, 2021, 5:30-7:00 in the morning, Beijing time, the American Gastroenterology Association (AGA) gave a lecture on the clinical challenges of digestive tract diseases at the DDW conference.
Professor Brooks D.
Cash, director of the Department of Digestive Diseases and Nutrition of Texas State University Health Science Center, shared his experience in the diagnosis and treatment of chronic idiopathic constipation in this DDW seminar.
The prevalence of chronic constipation in the general population of our country is 4.
0%~10.
0%, and the prevalence rate of the elderly is as high as 11.
5%.
With changes in dietary structure, faster pace of life and the influence of social and psychological factors, the prevalence of chronic constipation is on the rise.
Chronic constipation is closely related to anorectal diseases, and may play an important role in the occurrence of colorectal cancer, hepatic encephalopathy, breast disease, Alzheimer's disease and other diseases; forced defecation may lead to acute myocardial infarction, cerebrovascular accident and other diseases aggravated .
Among them, Chronic idiopathic constipation (CIC) (also known as idiopathic constipation or functional constipation) has complex etiology and unknown pathophysiological mechanisms, which has become one of the clinical problems faced by the gastroenterology department.
Functional constipation: OTC treatment progress The prevalence of CIC in the United States is about 10-15%, and the annual cost of OTC laxatives alone is US$821 million.
Moreover, many patients and doctors have different descriptions of the symptoms of constipation, and even misunderstand the problem.
In addition, the causes of CIC are complex and diverse, which increases the difficulty of diagnosis and treatment.
Therefore, Professor Cash pointed out that the key to successful CIC management is first a comprehensive and systematic evaluation.
Combined with the chronic constipation diagnosis and treatment process shown in the figure above, Professor Cash gave a detailed introduction to some new treatment methods and effect evaluation of CIC.
The first is the adjustment of diet.
Many global chronic constipation guidelines and consensuses all regard increasing dietary fiber and drinking water as the basic treatment measures for chronic constipation.
In addition, there is new evidence that kiwifruit also has a positive effect on CIC.
A randomized controlled trial published on Am J Gastroenterol in 2021 included 79 patients with CIC, randomly divided into three groups, receiving dried plums (100g/day), kiwifruit (2 pcs/day) and Plantago seeds ( 12g/day) 4 weeks of treatment.
The number of completely spontaneous bowel movements (CSBM), stool hardness and shape of the three groups of patients were significantly improved compared with the previous ones, and the adverse reactions of kiwifruit were the least, and the satisfaction of the subjects was the highest.
Therefore, among the dietary adjustment recommendations provided to patients, kiwi fruit with higher acceptance can be selected.
Polyethylene glycol (PEG) is an osmotic laxative, which is often used for the treatment of occasional constipation in previous cognitions.
Generally, the medication should not exceed 2 weeks.
But in fact, its long-term efficacy and safety have been verified.
A multi-center randomized controlled trial conducted by DiPaima J in 2007 included 304 CIC patients in 50 centers.
Compared with patients taking placebo, patients who received PEG 17g/day for 6 months had a significantly higher treatment success rate (55/204 vs 11/100), and there was no difference in the incidence of adverse events between the two groups.
Therefore, the current major guidelines also use PEG as the first-line over-the-counter drug for the initial treatment of CIC.
However, it is not enough to treat CIC with over-the-counter drugs.
The results of a large retrospective study involving 1482 patients with CIC suggest that among these patients who took over-the-counter medications for CIC for more than 6 months, 62% of patients believed that over-the-counter drugs failed to improve their bowel movements, and 78% of patients believed that non-prescription drugs failed to improve their bowel movements.
Abdominal symptoms, and 40% of patients discontinued the drug because the symptoms did not improve.
Therefore, for patients who are ineffective in taking over-the-counter laxatives, prescription drugs should be considered.
Next, Professor Cash summarized some of the latest clinical studies on CIC prescription drugs.
Functional constipation: Advances in prescription drug treatments in recent years, popular guanylate cyclase C activators (such as linaclotide, pucanatide), increase intestinal epithelial cells by activating guanylate cyclase C receptors Cyclic guanosine phosphate (cGMP) activates cystic fibrosis transmembrane transport regulator (CFTR), increases the secretion of luminal chloride and bicarbonate, accelerates intestinal peristalsis, and improves visceral hypersensitivity.
Linaclotide also significantly increases the number of patients' spontaneous bowel movements per week, improves bowel effort and stool characteristics, and can effectively relieve abdominal discomfort such as bloating.
Linaclotide increases the number of bowel movements per week and is effective within the first week of taking the drug (5.
69 vs 1.
37), and the number of bowel movements is relatively stable throughout the course of treatment.
Studies have shown that the response ratio of patients taking two doses of linaclotide (72μg and 145μg) is similar, and there is no significant difference in efficacy.
Procapride is a highly selective and high-affinity serotonin (5-HT4) receptor agonist, which can increase cholinergic neurotransmitters after binding to 5-HT4 receptors in the intestinal myenteric plexus The release of X-ray stimulates the colon to produce high-amplitude propulsive contraction waves, which accelerates gastric emptying, small intestinal transit and colonic transit in patients with constipation who are not accompanied by anorectal dysfunction.
A meta-analysis of 6 randomized controlled trials showed that at 12 weeks of treatment, the proportion of patients with CSBM ≥ 3 times per week in the prucalopride group was 31.
6%, which was significantly higher than the 16.
7% in the placebo group.
Procapride is recommended for patients whose symptoms of constipation cannot be improved by conventional laxatives.
When taking Procapride for 4 weeks and still has no effect, it is necessary to reassess the patient's condition and whether to continue taking the drug. For patients with fecal excretion disorders, anorectal pressure measurement should be used to evaluate anorectal motility and sensory function.
Pelvic floor synergy is caused by insufficient rectal and/or abdominal propulsion, impaired anal relaxation (resting pressure relaxation <20%), or increased resistance to the anal outlet due to abnormal contraction of the external anal sphincter and puborectalis, during defecation Inability to coordinate the abdomen, rectum, anus, and pelvic floor muscles.
Pelvic floor synergy is most suitable for biofeedback therapy.
Biofeedback therapy belongs to behavior regulation therapy.
Abdominal wall electrodes and anorectal baroreceptors can perceive and show the patient's abdominal wall, rectum, and anal canal muscles to force the patient.
The patient can use this to self-regulate and correct the uncoordinated defecation force method and train the patient to coordinate The abdominal and pelvic floor muscles restore normal bowel patterns.
The results of a randomized controlled trial showed that the effectiveness of biofeedback treatment can be as high as 70%, which can bring long-term benefits to patients for more than 2 years.
There is no uniform standard for the frequency, single training time, and treatment course of using biofeedback to treat constipation, and there are differences between studies.
For refractory CIC, the colorectal and anal morphology and function should be checked again.
Colorectal anus morphology examination methods include colonoscopy, barium enema, defecation contrast and anorectal ultrasound examination.
The functional examination methods include measurement of colon transit time, balloon expulsion test, pelvic floor electromyography, pudendal nerve terminal potential latency, and anorectal pressure measurement.
Finally, Professor Cash summarized some of his experience with refractory CIC: 1.
Using higher doses of osmotic laxatives (especially PEG); 2.
Using different types of over-the-counter laxatives (such as osmotic laxatives combined with stimulant laxatives) ); 3.
For patients with neurological diseases, consider taking over-indication drugs, such as misoprostol, colchicine or pistigmine; 4.
For patients who do not respond to first-line drug treatment, consider pelvic floor synergy and Chronic transit constipation; 5.
Some non-drug alternative treatments can be considered, such as transanal enema, sacral nerve stimulation, cecal fistula, ileorectal anastomosis, etc.
Expert profile Wang Xiaoze, post-doctorate in the Department of Gastroenterology, West China Hospital, Sichuan University, Doctor of Medicine.
He is good at digestive system and peripheral vascular interventional therapy.
He is engaged in basic and clinical research on the pathogenesis of portal hypertension and interventional therapy in liver cirrhosis.
He won the first prize of Sichuan Science Progress Award.
He has published many SCI papers and participated in editing 2 books/monographs. References: [1] Gastrointestinal Dynamics Group, Functional Gastrointestinal Disease Cooperative Group, Chinese Medical Association Gastroenterology Branch.
Expert consensus on chronic constipation in China (2019, Guangzhou)[J].
Chinese Journal of Digestion,2019,39( 9):577-598.
DOI:10.
3760/cma.
j.
issn.
0254-1432.
2019.
09.
001[2]Tse Y,Armstrong D,Andrews CN,Bitton A,Bressler B,Marshall J,Liu LW.
Treatment Algorithm for Chronic Idiopathic Constipation and Constipation-Predominant Irritable Bowel Syndrome Derived from a Canadian National Survey and Needs Assessment on Choices of Therapeutic Agents.
Can J Gastroenterol Hepatol.
2017;2017:8612189.
doi:10.
1155/2017/8612189[3]Chey,Samuel W.
MPH1;Chey,William D.
MD1;Jackson,Kenya BS1,2;Eswaran,Shanti MD1 Exploratory Comparative Effectiveness Trial of Green Kiwifruit,Psyllium,or Prunes in US Patients With Chronic Constipation,The American Journal of Gastroenterology:February 5,2021- Volume Latest Articles-Issue-doi:10.
14309/ajg.
0000000000001149[4]Dipalma JA,Cleveland MV,McGowan J,Herera JL.
A randomized,multicenter,placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation.
Am J Gastroenterol.
2007 Jul;102(7):1436-41.
doi:10.
1111/j.
1572-0241
This year's American Digestive Disease Week (DDW) was held online on May 21-23, bringing together experts and scholars in the field of gastroenterology from around the world to discuss the research results and clinical standards of digestive system diseases.
On May 22, 2021, 5:30-7:00 in the morning, Beijing time, the American Gastroenterology Association (AGA) gave a lecture on the clinical challenges of digestive tract diseases at the DDW conference.
Professor Brooks D.
Cash, director of the Department of Digestive Diseases and Nutrition of Texas State University Health Science Center, shared his experience in the diagnosis and treatment of chronic idiopathic constipation in this DDW seminar.
The prevalence of chronic constipation in the general population of our country is 4.
0%~10.
0%, and the prevalence rate of the elderly is as high as 11.
5%.
With changes in dietary structure, faster pace of life and the influence of social and psychological factors, the prevalence of chronic constipation is on the rise.
Chronic constipation is closely related to anorectal diseases, and may play an important role in the occurrence of colorectal cancer, hepatic encephalopathy, breast disease, Alzheimer's disease and other diseases; forced defecation may lead to acute myocardial infarction, cerebrovascular accident and other diseases aggravated .
Among them, Chronic idiopathic constipation (CIC) (also known as idiopathic constipation or functional constipation) has complex etiology and unknown pathophysiological mechanisms, which has become one of the clinical problems faced by the gastroenterology department.
Functional constipation: OTC treatment progress The prevalence of CIC in the United States is about 10-15%, and the annual cost of OTC laxatives alone is US$821 million.
Moreover, many patients and doctors have different descriptions of the symptoms of constipation, and even misunderstand the problem.
In addition, the causes of CIC are complex and diverse, which increases the difficulty of diagnosis and treatment.
Therefore, Professor Cash pointed out that the key to successful CIC management is first a comprehensive and systematic evaluation.
Combined with the chronic constipation diagnosis and treatment process shown in the figure above, Professor Cash gave a detailed introduction to some new treatment methods and effect evaluation of CIC.
The first is the adjustment of diet.
Many global chronic constipation guidelines and consensuses all regard increasing dietary fiber and drinking water as the basic treatment measures for chronic constipation.
In addition, there is new evidence that kiwifruit also has a positive effect on CIC.
A randomized controlled trial published on Am J Gastroenterol in 2021 included 79 patients with CIC, randomly divided into three groups, receiving dried plums (100g/day), kiwifruit (2 pcs/day) and Plantago seeds ( 12g/day) 4 weeks of treatment.
The number of completely spontaneous bowel movements (CSBM), stool hardness and shape of the three groups of patients were significantly improved compared with the previous ones, and the adverse reactions of kiwifruit were the least, and the satisfaction of the subjects was the highest.
Therefore, among the dietary adjustment recommendations provided to patients, kiwi fruit with higher acceptance can be selected.
Polyethylene glycol (PEG) is an osmotic laxative, which is often used for the treatment of occasional constipation in previous cognitions.
Generally, the medication should not exceed 2 weeks.
But in fact, its long-term efficacy and safety have been verified.
A multi-center randomized controlled trial conducted by DiPaima J in 2007 included 304 CIC patients in 50 centers.
Compared with patients taking placebo, patients who received PEG 17g/day for 6 months had a significantly higher treatment success rate (55/204 vs 11/100), and there was no difference in the incidence of adverse events between the two groups.
Therefore, the current major guidelines also use PEG as the first-line over-the-counter drug for the initial treatment of CIC.
However, it is not enough to treat CIC with over-the-counter drugs.
The results of a large retrospective study involving 1482 patients with CIC suggest that among these patients who took over-the-counter medications for CIC for more than 6 months, 62% of patients believed that over-the-counter drugs failed to improve their bowel movements, and 78% of patients believed that non-prescription drugs failed to improve their bowel movements.
Abdominal symptoms, and 40% of patients discontinued the drug because the symptoms did not improve.
Therefore, for patients who are ineffective in taking over-the-counter laxatives, prescription drugs should be considered.
Next, Professor Cash summarized some of the latest clinical studies on CIC prescription drugs.
Functional constipation: Advances in prescription drug treatments in recent years, popular guanylate cyclase C activators (such as linaclotide, pucanatide), increase intestinal epithelial cells by activating guanylate cyclase C receptors Cyclic guanosine phosphate (cGMP) activates cystic fibrosis transmembrane transport regulator (CFTR), increases the secretion of luminal chloride and bicarbonate, accelerates intestinal peristalsis, and improves visceral hypersensitivity.
Linaclotide also significantly increases the number of patients' spontaneous bowel movements per week, improves bowel effort and stool characteristics, and can effectively relieve abdominal discomfort such as bloating.
Linaclotide increases the number of bowel movements per week and is effective within the first week of taking the drug (5.
69 vs 1.
37), and the number of bowel movements is relatively stable throughout the course of treatment.
Studies have shown that the response ratio of patients taking two doses of linaclotide (72μg and 145μg) is similar, and there is no significant difference in efficacy.
Procapride is a highly selective and high-affinity serotonin (5-HT4) receptor agonist, which can increase cholinergic neurotransmitters after binding to 5-HT4 receptors in the intestinal myenteric plexus The release of X-ray stimulates the colon to produce high-amplitude propulsive contraction waves, which accelerates gastric emptying, small intestinal transit and colonic transit in patients with constipation who are not accompanied by anorectal dysfunction.
A meta-analysis of 6 randomized controlled trials showed that at 12 weeks of treatment, the proportion of patients with CSBM ≥ 3 times per week in the prucalopride group was 31.
6%, which was significantly higher than the 16.
7% in the placebo group.
Procapride is recommended for patients whose symptoms of constipation cannot be improved by conventional laxatives.
When taking Procapride for 4 weeks and still has no effect, it is necessary to reassess the patient's condition and whether to continue taking the drug. For patients with fecal excretion disorders, anorectal pressure measurement should be used to evaluate anorectal motility and sensory function.
Pelvic floor synergy is caused by insufficient rectal and/or abdominal propulsion, impaired anal relaxation (resting pressure relaxation <20%), or increased resistance to the anal outlet due to abnormal contraction of the external anal sphincter and puborectalis, during defecation Inability to coordinate the abdomen, rectum, anus, and pelvic floor muscles.
Pelvic floor synergy is most suitable for biofeedback therapy.
Biofeedback therapy belongs to behavior regulation therapy.
Abdominal wall electrodes and anorectal baroreceptors can perceive and show the patient's abdominal wall, rectum, and anal canal muscles to force the patient.
The patient can use this to self-regulate and correct the uncoordinated defecation force method and train the patient to coordinate The abdominal and pelvic floor muscles restore normal bowel patterns.
The results of a randomized controlled trial showed that the effectiveness of biofeedback treatment can be as high as 70%, which can bring long-term benefits to patients for more than 2 years.
There is no uniform standard for the frequency, single training time, and treatment course of using biofeedback to treat constipation, and there are differences between studies.
For refractory CIC, the colorectal and anal morphology and function should be checked again.
Colorectal anus morphology examination methods include colonoscopy, barium enema, defecation contrast and anorectal ultrasound examination.
The functional examination methods include measurement of colon transit time, balloon expulsion test, pelvic floor electromyography, pudendal nerve terminal potential latency, and anorectal pressure measurement.
Finally, Professor Cash summarized some of his experience with refractory CIC: 1.
Using higher doses of osmotic laxatives (especially PEG); 2.
Using different types of over-the-counter laxatives (such as osmotic laxatives combined with stimulant laxatives) ); 3.
For patients with neurological diseases, consider taking over-indication drugs, such as misoprostol, colchicine or pistigmine; 4.
For patients who do not respond to first-line drug treatment, consider pelvic floor synergy and Chronic transit constipation; 5.
Some non-drug alternative treatments can be considered, such as transanal enema, sacral nerve stimulation, cecal fistula, ileorectal anastomosis, etc.
Expert profile Wang Xiaoze, post-doctorate in the Department of Gastroenterology, West China Hospital, Sichuan University, Doctor of Medicine.
He is good at digestive system and peripheral vascular interventional therapy.
He is engaged in basic and clinical research on the pathogenesis of portal hypertension and interventional therapy in liver cirrhosis.
He won the first prize of Sichuan Science Progress Award.
He has published many SCI papers and participated in editing 2 books/monographs. References: [1] Gastrointestinal Dynamics Group, Functional Gastrointestinal Disease Cooperative Group, Chinese Medical Association Gastroenterology Branch.
Expert consensus on chronic constipation in China (2019, Guangzhou)[J].
Chinese Journal of Digestion,2019,39( 9):577-598.
DOI:10.
3760/cma.
j.
issn.
0254-1432.
2019.
09.
001[2]Tse Y,Armstrong D,Andrews CN,Bitton A,Bressler B,Marshall J,Liu LW.
Treatment Algorithm for Chronic Idiopathic Constipation and Constipation-Predominant Irritable Bowel Syndrome Derived from a Canadian National Survey and Needs Assessment on Choices of Therapeutic Agents.
Can J Gastroenterol Hepatol.
2017;2017:8612189.
doi:10.
1155/2017/8612189[3]Chey,Samuel W.
MPH1;Chey,William D.
MD1;Jackson,Kenya BS1,2;Eswaran,Shanti MD1 Exploratory Comparative Effectiveness Trial of Green Kiwifruit,Psyllium,or Prunes in US Patients With Chronic Constipation,The American Journal of Gastroenterology:February 5,2021- Volume Latest Articles-Issue-doi:10.
14309/ajg.
0000000000001149[4]Dipalma JA,Cleveland MV,McGowan J,Herera JL.
A randomized,multicenter,placebo-controlled trial of polyethylene glycol laxative for chronic treatment of chronic constipation.
Am J Gastroenterol.
2007 Jul;102(7):1436-41.
doi:10.
1111/j.
1572-0241
