| Background:Slow transit constipation is one of the most common colonic functional disorders, which arises from the colonic dysfunctional motility. The patients with STC affected by severe symptoms have to be ultimately recommended for surgery, who have been not responsive to all medical options. The main surgical options for STC are ileorectal anastomosis(IRA) and cecorectal anastomosis(CRA).Although the surgical options for STC have proven to be a definite treatment, the improvement on the defecation function and quality of life are rarely studied. Moreover, a few persistent symptoms with postoperative complications are still the factors that affect adversely the effectiveness of the surgical treatment. However, the outcomes of surgery for STC are rarely reported and most are small sample retrospective studies. Therefore, it is vital and essential to evaluate the effectiveness of surgery for STC, defecation function and quality of life after surgery for the further improvement on surgical treatment for STC.Additionally, with STC being the functional motility disorder, surgical treatment is the ultimate option for the patients. If the physiopathologic mechanism can be clarified, it is very significant to develop the management of STC. Recent studies have reported that the intestinal mucosa sensory signals play a major role in regulating intestinal motility. The highlight symptoms of colonic transit functional disorder and no feeling of defecation in the patients with STC suggest that the abnormality of the intestinal mucosa sensory signals may play a key role in the pathogenesis. Recently, transient receptor pot ential channel-ankyrin subfamily member 1(TRPA1) is suggested to act as a sensor molecule for enterochromaffin cells(ECC) to detect the physical and chemical signals from the lumen and regulate gastrointestinal motility by the release of 5-hydroxytryptamine(5-HT) from ECC. Furthermore, other studies have showed that transient receptor potential channel-vanilloid subfamily member 1(TRPV1) acts as a significant part to regulation of gastrointestinal motility and accumulating evidence has indicated that there is a synergistic role of TRPA1 and TRPV1 in various neural tissues and non-neural tissues. Are the expression of TRPA1 and TRPV1 abnormal in the colonic mucosa of the patients with STC? So far, no study has been reported in this field. It is greatly significant to explore preliminarily the pathogenesis of STC from the regulation of the intestinal mucosa sensory nerve.Objective:(1) To analyze the medical records of the patients with STC, retrospectively, and evaluate the effectiveness of surgical treatment, defecation function and quality of life.(2) To observe the alterations of TRPA1, TRPV1 and 5-HT expression in the colonic mucosa and explore their role in the pathogenesis of STC.Methods:Between August 2007 and February 2015, the medical records regarding clinical outcomes of 38(4 male) patients undergoing surgery for colonic inertia at our department were retrospectively obtained. 29 patients were successfully followed up after surgery, 9 patients were lost to follow-up(7 patients lost to follow-up, one refusing follow-up, and one died of respiratory disease companying with respiratory failure). All the patients experienced gastrointestinal quality of life index(GIQLI), Wexner constipation(WC), Wexner incontinence(WI) and 36-item short-form health survey(SF-36) so that an evaluation of surgical effectiveness and quality of life was performed. Meanwhile, each 10 surgical specimens of descending colon from patients with STC between March 2013 and March 2014 as well as sigmoid cancer(tumor edge measuring in controls >10cm) between December 2013 and May 2014 were allocated into the STC group and the control group, respectively. With the applications of immunofluorescence double staining and immunohistochemical assay, the expressions of TRPA1, TRPV1 and 5-HT(TPH) were determined in the colonic mucosa. The expressions of TRPA1 and TRPV1 were observed by Western Blotting. Detailed written informed consent was obtained from all patients.Results:1. To analyze the medical records of the patients with STC and evaluate the effectiveness of surgical treatment after surgery.(1)Complications and defecation function There was one patient deceased with respiratory disease companying with respiratory failure. Four(13.8%) patients had an ileus postoperatively, which could be managed by conservative therapy. Two(6.9%) patients had postoperative infection. One case was attacked by lung infection. The other one with lung and abdominal infection had a duodenum fistula that required duodenal leak repair surgery. Long-term complication occurred in 3(10.3%) patients, including small intestinal obstruction(2 patients undergoing reoperation of enterolysis, 6.6%), constipation recurrences(2 patients, 6.7%) and anastomotic stenosis(1 patient, 3.3%). Compared with that preoperatively, the number of bowel movements per week followed up for 3 months was significantly increased(P<0.01). A significant improvement was postoperatively observed in terms of straining during defecation, bloating and laxative use(P<0.01). 89.7% patients stated that surgery received benefits to their health.(2)WI Compared with the one followed up for 3 months, the scores of WI in the groups followed up for 6 months, 1-2 years and 2-7 years were not statistically different(P>0.05).(3)WC Compared with that in the preoperation, the scores of WC in the groups followed up for 3 months, 6 months, 1-2 years and 2-7 years were significantly improved(P<0.01).(4)GIQLI Compared with that in the preoperation, the scores of GIQLI in the groups followed up for 3 months, 6 months, 1-2 years and 2-7 years were significantly improved(P<0.01).(5)SF-36 Compared with that in the preoperation, the scores of 7 spheres(role physical, physical pain, general health, vitality, social function, role emotional and mental health) in the group followed up for 1-2 years significantly improved(P<0.05); the scores of role physical, role emotional, physical pain, vitality and social function spheres in the group followed up for 2-7 years significantly improved(P<0.05).2. The expressions of TRPA1, TRPV1 and 5-HT in the colonic mucosa of patients with STC(1)TRPA1 and TPH were co-located on the ECC in the human colonic mucosa, so were TRPV1 and TPH.(2)With the application of immunochemical assay, expressions of TRPA1 and TRPV1 were significantly lower in the colonic mucosa in STC compared with those in controls(P<0.05). However, the expression of 5-HT was overexpressed in STC compared with that in controls(P<0.05).(3)The similar results of TRPA1 and TRPV1 were confirmed by Western Blotting(P<0.05).Conclusions: 1. Surgery for appropriate patients with slow transit constipation is an effective and acceptable option. A majority of patients not only significantly receive symptom resolution in short-term, but also experience a significant trend toward recovery in their quality of life. 2. TRPA1 and TRPV1 were both located on the ECC suggesting that they regulated gastrointestinal motility by the release of 5-HT from ECC. TRPA1 and TRPV1 level lower accompanying 5-HT level higher in STC are closely related with the pathogenesis of STC. |
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