Research progress of functional constipation
Functional constipation (FD) is a kind of functional bowel disease, which manifests as persistent difficulty in defecation, reduced frequency of defecation or a sense of incomplete defecation, and does not meet the diagnostic criteria of irritable bowel syndrome (IBS).
With the change of diet structure and psychosocial factors, the incidence of FD is increasing year by year, which seriously affects the quality of life of patients. In this paper, we briefly review the latest research progress in the pathogenesis, diagnostic tests, and treatment of FD, taking into account the relevant reports of the 2014 DDW conference in the United States.
Pathogenesis
The pathogenesis of FD has not been fully elucidated, and is currently thought to be related to colonic motility dysfunction, anorectal dysfunction, psychosomatic abnormalities, and other factors. According to the current pathophysiological mechanism, FD is divided into four types: slow-transmission constipation, defecation disorder constipation, mixed constipation, and normal-transmission constipation.
1, colonic motility dysfunction
Patients with FD have colonic motility dysfunction, mainly characterized by prolonged colonic transmission time and reduced high-amplitude propulsive contractions, which may be related to abnormal intestinal neurons and neurotransmitters, intestinal glial cell lesions, abnormal intestinal neurochemical signals, abnormal intestinal Cajal interstitial cell (ICC) network, intestinal smooth muscle lesions, colonic aging, chloride channel dysfunction, and other factors. Chen et al. studied colonic motility in 8 healthy volunteers and 22 patients with chronic constipation using a colonoscope with high-resolution manometry fixed to the distal colon for 6-8 h. They found a lack of high-amplitude propulsive contractions, the presence of low-amplitude synchronous contractions and retrograde contractions, and an enrichment of rhythmic low-amplitude colonic pouch motility in patients with chronic constipation.Chen et al. found that in a mouse model of slow-transmission constipation, brain-derived neurotrophic The reduced expression of brain-derived neurotrophic factors, reduced intestinal nerve fiber density, and degeneration of the ultrastructure of intestinal mucosal nerve fibers suggest that brain-derived neurotrophic factors may play an important regulatory role in intestinal motility by altering intestinal nerve structure and activating the TrkB-PLC/IPS pathway to improve intestinal smooth muscle lesions.Mathilde Cohen et al. found that in patients with severe colonic weakness, ICC was significantly Broad et al. found that the contractile response of colonic smooth muscle to electrical stimulation diminished with age, and this change was more pronounced in the ascending colon, and this phenomenon was also confirmed in C57 BL/6 female mice.
2. Anorectal dysfunction
Mugie et al. found higher rectal thresholds in children with FD and for the first time found different patterns of brain activation and deactivation during rectal dilatation in children with FD compared to normal controls, suggesting that the two have different brain processing mechanisms during defecation Burgell et al. conducted a case-control study on 668 patients with abnormal defecation function and 668 normal controls and found that patients with impaired rectal sensation were more prone to constipation, emphasizing the importance of rectal sensory function in patients with abnormal defecation.
3. Psychosomatic abnormalities
The current increase in the incidence of FD is closely related to the accelerated pace of society and the increased pressure of survival. Depression, anxiety, tension and other emotions often disrupt the normal bowel movement pattern and inhibit bowel movement. Some scholars believe that psychosomatic factors may lead to gastrointestinal dysfunction through the cerebral cortex – limbic system – blue spot nucleus – dorsal nucleus of the vagus nerve – autonomic nervous system – sympathetic vagus nerve malfunction of the enteric nervous system.
Diagnostic tests
The diagnosis of FD is mainly based on symptoms, and currently the diagnostic criteria of Rome III are mainly used. Natasha et al. conducted a 1-year follow-up of 2781 patients diagnosed using Rome III criteria and found that the diagnosis of FD, IBS, and constipated IBS (IBS-C) by Rome III criteria had sustained stability, independent of psychological factors and quality of life. Gambaccini et al. found that patient-defined “constipation” was generally, but not completely, consistent with the Rome ID criteria for constipation, and that some of the symptoms of patient-defined “constipation” were not included in the Rome III diagnostic criteria.
Bowel dynamics and anorectal function tests are necessary for constipation typing, treatment selection, and assessment of efficacy. The tests currently used include colonic transmission tests, anorectal manometry, balloon force-out tests, x-ray fecography, and magnetic resonance fecography.Lee et al. found that high-resolution rectal pressure topography and waveform manometry not only correlated well on most manometric parameters, but also determined the length of the anal canal high-pressure zone.Spierings et al. used a fixed-point manometry device mounted on disposable gloves and found that it was comparable to conventional anal canal manometry. Dhanekula et al. found that methane levels in the lactose hydrogen breath test (LBT) correlated with constipation symptoms, and that higher methane levels may indicate more severe constipation symptoms.
Treatment
1.Lifestyle modification
Lisoni et al. conducted a study of 66 patients with slow-transit constipation randomized to a Mediterranean diet or a general diet (55% carbohydrate, 15%-20% protein, 30% fat) for a 2-week introductory period, an 8-week treatment period, and a 2-week washout period, and found that the 8-week Mediterranean diet significantly improved constipation symptoms and reduced colonic transit time.
2.Medication
Yiannakou et al. first conducted a multicenter randomized controlled study of prucalopride in 374 male patients with chronic constipation and found that prucalopride significantly increased the rate of spontaneous completion of bowel movements >3 times per week in male patients compared to placebo, and no new safety issues were identified. However, a multicenter randomized controlled study of 213 pediatric FD patients by Benninga et al. found that prucalopride was moderately well tolerated in children, but there were no significant differences in constipation symptoms or disease-related quality of life compared with placebo.Gatta et al. conducted a systematic review of randomized controlled trials of prucalopride for chronic constipation and found that at the current therapeutic dose, prucalopride Lacy et al. conducted a 12-week randomized controlled trial in 483 patients with chronic idiopathic constipation with abdominal distension and found that linalotide at 145 μg/d and 290 μg/d significantly improved intestinal and abdominal symptoms in patients with chronic idiopathic constipation. Acosta et al. found that 100 μg/d of RM-131 (a selective gastric growth hormone receptor agonist) accelerated colonic transit time, promoted gastric emptying, and evenly promoted upper and lower GI motility in patients with chronic constipation. Cho et al. found that DA-6886, a 5-HT4 agonist, increased colonic activity and promoted defecation in constipated mice.
3.Biofeedback therapy
Biofeedback is an effective treatment for constipation caused by pelvic floor muscle dysfunction. 82 cases of children with chronic constipation were retrospectively analyzed by Kessler et al. They found that pelvic floor muscle training and biofeedback therapy had significant effects on children with chronic constipation (especially constipation caused by pelvic floor muscle dysfunction), and sustained symptom relief may be obtained.
4.Other methods
Other methods of FD treatment include sacral nerve stimulation, acupuncture, massage and tui-na, Chinese herbal medicine, probiotic preparations, etc. The efficacy of these methods is still unclear. Ron et al. conducted an open trial on 20 patients with chronic idiopathic constipation or IBS-C to investigate the safety and efficacy of colonic vibration capsules for the first time, and the results of the study suggested that colonic vibration capsules are safe and can increase the spontaneous completion of chronic idiopathic constipation or IBS-C. Dinning et al. found no significant efficacy of sacral nerve stimulation in the long-term treatment of severe slow-transit constipation. Meij et al. analyzed the fecal flora of children with FD and normal controls and found no significant differences in the type and number of intestinal flora, suggesting that dysbiosis may not be the cause of FD and that probiotic therapy may not be a good option for children with FD. Bignell et al. showed that naloxone hydrochloride extended-release capsules had no therapeutic effect on FD patients, suggesting that the endogenous opioid system is not the causative mechanism of FD. Kumar et al. found that transcutaneous electrical stimulation (using posterior tibial nerve stimulation) had no significant effect on patients with chronic constipation.
5.Surgical treatment
When the patient’s symptoms seriously affect work and life, and after a period of strict non-surgical treatment is ineffective, surgical treatment can be considered. A retrospective analysis of patients with chronic constipation who underwent colectomy (excluding inflammatory and neoplastic diseases) was conducted by Dudekula et al. using a national hospitalization sample from 1998 to 2011 and data from California and Florida from 2005 to 2011. A retrospective analysis of patients with chronic constipation (excluding inflammatory and neoplastic disease) undergoing colectomy in the United States found that the rate of colectomy in patients with chronic constipation is increasing, accounting for at least 2% of colectomies performed annually in the United States. Despite the relatively young age of patients undergoing colectomy, intraoperative complications and 30-d postoperative hospitalization rates remain high. Also, persistently high postoperative patient readmission rates suggest limited benefit from surgery.
In conclusion, combined with the report on FD related to the 2014 DDW meeting, it makes us understand the pathogenesis, diagnosis and detection of FD (18) The pathophysiological mechanism of FD is complex, the treatment is unsatisfactory, and the quality of life of patients is seriously affected, and further research is still needed to be strengthened.