直腸前切除患者術(shù)后生活質(zhì)量調(diào)查及5-HT、TRPA1在ARS發(fā)病中的作用
發(fā)布時間：2018-11-29 08:27
【摘要】：目的前切除綜合征(Anterior resection syndrome,ARS)是直腸癌括約肌保留術(shù)后病人出現(xiàn)的一個廣泛的排便障礙癥候群的總稱,其發(fā)生率高達(dá)90%,常見的癥狀包括便急、便意頻繁、排便次數(shù)增多、排便不盡感、排便失禁、排便困難等。ARS嚴(yán)重影響患者術(shù)后的生活質(zhì)量目前臨床上尚未建立有關(guān)ARS的確切定義,且缺乏統(tǒng)一的癥狀評估標(biāo)準(zhǔn),其發(fā)病機(jī)制尚不完全清楚。研究認(rèn)為新建直腸的容量減少、腸神經(jīng)系統(tǒng)損傷、自主神經(jīng)損傷等都是ARS發(fā)生的原因。新近的研究發(fā)現(xiàn)腸黏膜感覺信號在腸動力紊亂性疾病的發(fā)生中發(fā)揮重要作用。前切除術(shù)后患者突出表現(xiàn)為便意頻繁、排便不盡感等癥狀提示結(jié)直腸黏膜感覺功能異常。研究發(fā)現(xiàn)腸黏膜瞬時受體電位通道家族的錨蛋白亞家族成員1(transient receptor potential channel-ankyrin subfamily member 1,TRPA1)是存在于腸嗜鉻(enterochromaffinl,EC)細(xì)胞的感受器分子,可感知腸腔內(nèi)的物理與化學(xué)信號,通過引起Ca2+內(nèi)流介導(dǎo)EC釋放5-羥色胺(5-hydroxytryptamine,5-HT)來調(diào)控腸道動力。有關(guān)5-HT及TRPA1在ARS發(fā)生中的作用迄今未見報道。為此,本課題回顧性分析我院直腸前切除患者術(shù)后生活質(zhì)量、排便功能變化情況,并觀察了直腸前切除患者術(shù)后吻合口附近直腸的黏膜相關(guān)分子感受器表達(dá)變化,初步探討5-HT、TRPA1在前切除患者發(fā)病中的作用,為深入研究其病理生理機(jī)制提供基礎(chǔ)。方法一.研究對象及方法回顧性分析大坪醫(yī)院胃結(jié)直腸肛門外科2012年11月至2014年10月確診直腸癌行Dixon手術(shù)治療并符合納入標(biāo)準(zhǔn)的105名患者,通過門診及電話隨訪填寫術(shù)后胃腸道生活質(zhì)量評分(Gastrointestinal quality of life questionnaire,GIQLI)、Wexner便秘評分(wexner constipation scale,WCS)、Wexner失禁評分(wexner incontinence scale,WIS)及SF-36(the MOS item short from health survey,SF-36)健康問卷,按術(shù)后隨訪時的時間對病人進(jìn)行分組。其中10例患者在知情同意的前提下愿意進(jìn)行術(shù)后吻合口免疫組化觀察,我們?nèi)∑湫g(shù)前直腸切緣黏膜標(biāo)本與術(shù)后吻合口附近黏膜活檢行5-HT、TRPA1免疫組化染色,采用圖像分析軟件分析免疫組化陽性表達(dá)情況。檢查前研究對象均簽署了知情同意書,本研究經(jīng)第三軍醫(yī)大學(xué)大坪醫(yī)院野戰(zhàn)外科研究所倫理委員會批準(zhǔn)。二.檢測指標(biāo)1.直腸前切除術(shù)后患者生活質(zhì)量評分:包括胃腸道生活質(zhì)量評分、Wexner失禁評分、Wexner便秘評分及SF-36生活質(zhì)量評分(包括:生理機(jī)能、軀體疼痛、社會功能、一般健康狀況、精神健康、生理職能、精力、情感職能等8個維度,還包含另一項健康指標(biāo):健康變化)。2.直腸吻合口附近黏膜TRPA1受體表達(dá)。3.直腸吻合口附近黏膜5-羥色胺表達(dá)。結(jié)果一.ARS術(shù)后患者生活質(zhì)量評分1.胃腸道生活質(zhì)量評分:與術(shù)后0-6月組的評分相比,術(shù)后7-24月組的胃腸道生活質(zhì)量評分有顯著提高(P0.05)。2.Wexner便秘評分:與術(shù)后0-6月組的評分相比,術(shù)后7-24月組的便秘評分有顯著下降(P0.05)。3.Wexner失禁評分:與術(shù)后0-6月組的評分相比,術(shù)后7-24月組的失禁評分有顯著下降(P0.05)。4.SF-36生活健康調(diào)查問卷:直腸前切除術(shù)后患者SF-36評分中生理機(jī)能、生理職能、精力、社會功能、軀體疼痛、情感職能、一般健康狀況、精神健康8個子項及健康變化在術(shù)后7-24月組均較術(shù)后0-6月組有顯著改善(P0.05)。二.直腸下段黏膜TRPA1受體表達(dá)對比分布于直腸黏膜區(qū)域的TRPA1免疫組化陽性表達(dá)。與術(shù)前組相比,術(shù)后ARS患者吻合口上組直腸黏膜TRPA1陽性表達(dá)顯著降低(P0.05);同時吻合口下組直腸黏膜TRPA1陽性表達(dá)也顯著降低(P0.05);而吻合口上、下組之間的TRPA1表達(dá)未見顯著差異(P0.05)。三.直腸下段黏膜5-羥色胺表達(dá)對比分布于直腸黏膜區(qū)域的5-HT免疫組化陽性表達(dá)。與術(shù)前組相比,術(shù)后ARS患者吻合口上組直腸黏膜5-HT陽性表達(dá)顯著降低(P0.05);同時吻合口下組直腸黏膜5-HT陽性表達(dá)也顯著降低(P0.05);而吻合口上、下組之間的5-HT表達(dá)未見顯著差異(P0.05)。結(jié)論通過本課題研究,我們發(fā)現(xiàn)直腸前切除患者術(shù)后隨著時間延長,其胃腸道生活質(zhì)量、便秘、大便失禁情況以及健康狀況等方面有著顯著改善。直腸前切除術(shù)后的排便功能紊亂可能與直腸黏膜TRPA1表達(dá)下調(diào)、5-HT表達(dá)下調(diào)有關(guān),腸黏膜感覺信號異常在ARS發(fā)病中的作用機(jī)制值得深入研究。
[Abstract]:Objective The anterior resection syndrome (ARS) is a general term of a wide bowel movement disorder in the patients with rectal cancer after the operation of the sphincter of rectal cancer. The incidence rate is up to 90%. The common symptoms include acute and frequent urination, increased defecation frequency, insatiety of defecation, and incontinent. and the like. ARS has a serious effect on the quality of life after operation, and the exact definition of ARS has not been established at present, and there is a lack of unified symptom assessment criteria, and the pathogenesis of ARS is not clear. It is suggested that the reduction of the capacity of the new rectum, the injury of the nervous system, the autonomic nerve injury, etc. are the causes of the ARS. The recent study found that the sensory signal of the intestinal mucosa plays an important role in the pathogenesis of the intestinal motility disorder. After the pre-resection, the patients had the symptoms of frequent occurrence, inexhaustible defecation, and the like, and the sensory function of the colorectal mucosa was abnormal. It was found that the transient receptor potential channel-ankyrin subfamily member 1 (TRPA1) of the transient receptor potential channel family of the intestinal mucosa is a receptor molecule present in the enterochromaffin (EC) cell, and can sense the physical and chemical signals in the intestinal cavity, The intestinal motility was regulated by causing a Ca2 + internal flow-mediated EC to release 5-hydroxytryptamine (5-HT). The role of 5-HT and TRPA1 in the occurrence of ARS has not been reported to date. To this end, this topic is a retrospective analysis of the quality of life and the change of the function of defecation in our hospital, and the changes of the expression of the mucosa-related molecules in the rectum near the anastomotic stoma of the patients with prerectal excision were also observed, and the 5-HT was initially discussed. The role of TRPA1 in the pathogenesis of the pre-resection of the patient is to provide the basis for the in-depth study of its pathophysiological mechanism. Method 1. The subject and method of the study retrospectively analyzed the treatment of the gastric junction of the Daping Hospital from November 2012 to October 2014 and the 105 patients who were included in the standard, and completed the post-operative gastrointestinal life of life score (GQLI) through out-patient and telephone follow-up. The Wexer constipation scale (WCS), the Wexer incontinence scale (WCS), the Wexer incontinence scale (SF-36) and the SF-36 health questionnaire were grouped according to the time at the time of the post-operation follow-up. 10 of the patients were willing to perform the immunohistochemical study on the postoperative anastomotic stoma on the premise of informed consent, and we took the pre-operative transrectal mucosa specimen and the submucosal biopsy in the vicinity of the post-operative anastomotic stoma for 5-HT and TRPA1 immunohistochemical staining, and analyzed the positive expression of the immunohistochemistry by using the image analysis software. The pre-examination subjects signed the informed consent form, and the study was approved by the Ethics Committee of the Field Surgery Research Institute of Daping Hospital of the Third Military Medical University. II. Test indicator 1. Quality of life of the patient after rectocele resection: including the gastrointestinal life quality score, the Wexner incontinence score, the Wexer Constipation score, and the SF-36 life quality score (including: physiological function, body pain, social function, general health, mental health, physiological function, energy, 8 dimensions, such as emotional functions, also include another health indicator: health change). Expression of the submucosal TRPA1 receptor in the vicinity of the rectal anastomosis. The expression of 5-hydroxytryptamine in the adjacent mucosa of the rectum. As a result. The quality of life of patients after ARS was 1. Gastrointestinal life quality score: compared with the score of 0-6 months after operation, there was a significant improvement in the quality of gastrointestinal life in the 7-24 month post-operation group (P0.05). 2. Wexer Constipation Score: There was a significant decrease in the constipation score in the 7-24-month group after the operation (P0.05). There was a significant decrease in the incontinence score in the 7-24-month group after the operation (P0.05). 4. SF-36 Life Health Questionnaire: the physiological function, physical function, energy, social function, physical pain, emotional function, general health status of the patient's SF-36 score after rectocele, compared with the score of the 0-6 month post-operation group. The 8 sub-items and the healthy changes of mental health were significantly improved in the postoperative period from 0 to 6 months after operation (P0.05). II. The expression of TRPA1 receptor in the subrectal mucosa was compared with the immunohistochemical positive expression of TRPA1 in the region of the rectal mucosa. Compared with the pre-operative group, the positive expression of TRPA1 in the upper group of the patients with postoperative ARS was significantly lower (P0.05), while the positive expression of TRPA1 in the lower group of the anastomotic stoma was significantly lower (P0.05); and the expression of TRPA1 between the upper and lower groups of the anastomotic stoma was not found to be significant (P0.05). III. The expression of 5-HT in the subrectal mucosa was compared with the 5-HT immunohistochemical positive expression in the region of the rectal mucosa. Compared with the pre-operative group, the positive expression of 5-HT in the upper group of the patients with the postoperative ARS was significantly lower (P0.05), and the expression of 5-HT in the lower group of the anastomotic stoma was significantly lower (P0.05); and the expression of 5-HT between the upper and lower groups of the anastomotic stoma was not found to be significantly different (P0.05). Conclusion Through this study, we find that the patients with pre-rectal excision have a significant improvement over time, the quality of gastrointestinal life, constipation, fecal incontinence, and the health status of the patients. The disorder of the defecation function after the rectocele resection may be down-regulated with the expression of TRPA1 in the rectal mucosa, and the expression of 5-HT is down-regulated. The mechanism of the abnormal signal of the sensory signal of the intestinal mucosa in the pathogenesis of ARS is worth further study.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R657.1
[Abstract]:Objective The anterior resection syndrome (ARS) is a general term of a wide bowel movement disorder in the patients with rectal cancer after the operation of the sphincter of rectal cancer. The incidence rate is up to 90%. The common symptoms include acute and frequent urination, increased defecation frequency, insatiety of defecation, and incontinent. and the like. ARS has a serious effect on the quality of life after operation, and the exact definition of ARS has not been established at present, and there is a lack of unified symptom assessment criteria, and the pathogenesis of ARS is not clear. It is suggested that the reduction of the capacity of the new rectum, the injury of the nervous system, the autonomic nerve injury, etc. are the causes of the ARS. The recent study found that the sensory signal of the intestinal mucosa plays an important role in the pathogenesis of the intestinal motility disorder. After the pre-resection, the patients had the symptoms of frequent occurrence, inexhaustible defecation, and the like, and the sensory function of the colorectal mucosa was abnormal. It was found that the transient receptor potential channel-ankyrin subfamily member 1 (TRPA1) of the transient receptor potential channel family of the intestinal mucosa is a receptor molecule present in the enterochromaffin (EC) cell, and can sense the physical and chemical signals in the intestinal cavity, The intestinal motility was regulated by causing a Ca2 + internal flow-mediated EC to release 5-hydroxytryptamine (5-HT). The role of 5-HT and TRPA1 in the occurrence of ARS has not been reported to date. To this end, this topic is a retrospective analysis of the quality of life and the change of the function of defecation in our hospital, and the changes of the expression of the mucosa-related molecules in the rectum near the anastomotic stoma of the patients with prerectal excision were also observed, and the 5-HT was initially discussed. The role of TRPA1 in the pathogenesis of the pre-resection of the patient is to provide the basis for the in-depth study of its pathophysiological mechanism. Method 1. The subject and method of the study retrospectively analyzed the treatment of the gastric junction of the Daping Hospital from November 2012 to October 2014 and the 105 patients who were included in the standard, and completed the post-operative gastrointestinal life of life score (GQLI) through out-patient and telephone follow-up. The Wexer constipation scale (WCS), the Wexer incontinence scale (WCS), the Wexer incontinence scale (SF-36) and the SF-36 health questionnaire were grouped according to the time at the time of the post-operation follow-up. 10 of the patients were willing to perform the immunohistochemical study on the postoperative anastomotic stoma on the premise of informed consent, and we took the pre-operative transrectal mucosa specimen and the submucosal biopsy in the vicinity of the post-operative anastomotic stoma for 5-HT and TRPA1 immunohistochemical staining, and analyzed the positive expression of the immunohistochemistry by using the image analysis software. The pre-examination subjects signed the informed consent form, and the study was approved by the Ethics Committee of the Field Surgery Research Institute of Daping Hospital of the Third Military Medical University. II. Test indicator 1. Quality of life of the patient after rectocele resection: including the gastrointestinal life quality score, the Wexner incontinence score, the Wexer Constipation score, and the SF-36 life quality score (including: physiological function, body pain, social function, general health, mental health, physiological function, energy, 8 dimensions, such as emotional functions, also include another health indicator: health change). Expression of the submucosal TRPA1 receptor in the vicinity of the rectal anastomosis. The expression of 5-hydroxytryptamine in the adjacent mucosa of the rectum. As a result. The quality of life of patients after ARS was 1. Gastrointestinal life quality score: compared with the score of 0-6 months after operation, there was a significant improvement in the quality of gastrointestinal life in the 7-24 month post-operation group (P0.05). 2. Wexer Constipation Score: There was a significant decrease in the constipation score in the 7-24-month group after the operation (P0.05). There was a significant decrease in the incontinence score in the 7-24-month group after the operation (P0.05). 4. SF-36 Life Health Questionnaire: the physiological function, physical function, energy, social function, physical pain, emotional function, general health status of the patient's SF-36 score after rectocele, compared with the score of the 0-6 month post-operation group. The 8 sub-items and the healthy changes of mental health were significantly improved in the postoperative period from 0 to 6 months after operation (P0.05). II. The expression of TRPA1 receptor in the subrectal mucosa was compared with the immunohistochemical positive expression of TRPA1 in the region of the rectal mucosa. Compared with the pre-operative group, the positive expression of TRPA1 in the upper group of the patients with postoperative ARS was significantly lower (P0.05), while the positive expression of TRPA1 in the lower group of the anastomotic stoma was significantly lower (P0.05); and the expression of TRPA1 between the upper and lower groups of the anastomotic stoma was not found to be significant (P0.05). III. The expression of 5-HT in the subrectal mucosa was compared with the 5-HT immunohistochemical positive expression in the region of the rectal mucosa. Compared with the pre-operative group, the positive expression of 5-HT in the upper group of the patients with the postoperative ARS was significantly lower (P0.05), and the expression of 5-HT in the lower group of the anastomotic stoma was significantly lower (P0.05); and the expression of 5-HT between the upper and lower groups of the anastomotic stoma was not found to be significantly different (P0.05). Conclusion Through this study, we find that the patients with pre-rectal excision have a significant improvement over time, the quality of gastrointestinal life, constipation, fecal incontinence, and the health status of the patients. The disorder of the defecation function after the rectocele resection may be down-regulated with the expression of TRPA1 in the rectal mucosa, and the expression of 5-HT is down-regulated. The mechanism of the abnormal signal of the sensory signal of the intestinal mucosa in the pathogenesis of ARS is worth further study.
【學(xué)位授予單位】：第三軍醫(yī)大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2015
【分類號】：R657.1
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