Clinical And Basic Study On Post-chemotherapy Intestinal Dysfunction

ObjectiveTo study the intestinal motility and sensation of post-chemotherapy cancer patients and to explore the relation between chemotherapy and intestinal dysfunction. Further study to the change of histology, inflammatory marker, intestinal barrier and enteric nervous system after 5-Fu intravenous injection to rats and analyze the possible mechanism.Methods1. Clinic study on post-chemotherapy intestinal dysfunction1.1 A total of 46 post-chemotherapy non-gastrointestinal cancer patients were divided into 2 subgroups according to the dominating clinical symptoms. Healthy subjects served as control. Thus 3 subgroups were set up, including the diarrhea group 26 cases), the constipation group(20 cases) and the control group(12 cases). The 3 subgroups were involved in the transit test and the anorectal manometry.1.2 The colon transit time, right hemicolonic transit time, left hemicolonic transit timeand rectosigmoid transit time of the transit test were measured to evaluate the colonic motility. The rectal resting pressure, anal resting pressure, maximal squeezing pressure and relaxing pressure of the anorectal manometry were measured to evaluate the anorectal motility. The first sensation volume, defecating sensation volume, painful sensation volume and the minimal volume to evoke the rectoanal inhibitory reflex of the anorectal manometry were measured to evaluate the anorectal sensation.2. Basic study on post-chemotherapy rats with intestinal dysfunction2.1 Preparation of models:A total of 120 rats were divided into 6 subgroups. Subgroup A, B, C with each of 10 rats served as control. Subgroup D, E, F with each of 30 rats served as chemotherapy goup. Each of the chemotherapy goup was intravenous injected with fluorouracil (20mg/kg) through caudal vein while the control was treated with normal saline. Each rat of subgroup A and D was killed on the 7th day to get their colon. Subgoup B and E were treated in the same way on the 21 st day and subgroup C and F on the 42nd day respectively.2.2 Oberservation indexes:2.2.1 Recorded the general conditions including ingestion, defecation and performance etc.2.2.2 Measured the weight on the 1st,7th,21st,42nd day.2.2.3 Macroscopic oberserved the inflammatory colon segments and scored them.2.2.4 Microscopic oberserved the inflammatory colon specimens and measured the mucosal thickness.2.2.5 The MPO of colon specimns were determined by spectrophotometry.2.2.6 The contents of SP and VIP in the colonic mucus were determined by radioimmunoassay to imply the impairment of ENS.2.2.7 The permeability of colon capillaries were determined by modified EB method.Results1. Clinic study on post-chemotherapy intestinal dysfunction1.1 The CTT and RCTT, LCTT, SRTT of the diarrhea group were significantly shorter than the control group, while the constipation group was longer. All of the diarrhea patients discharged 80% of the markers in 48hrs, all of the controls discharged 80% of the markers in 72hrs,2 cases(10%) of the constipation patients had normal 72hCTT.1.2 The RRP, ARP, MSP and relaxing pressure were similar to the control group no matter in the diarrhea or constipation group. The FSV, DSV, PSV and the minimal volume to evoke the RAIR of the diarrhea group were significantly higher than the control group while the constipation group was lower.2. Basic study on post-chemotherapy rat with intestinal dysfunction2.1 General conditions:The rats of chemotherapy goups performed decreasing food consumption and activity, abnormal defection, dispirited and weakness. The controls did not perform any abnormality.2.2 Weight:On the 7th day, the weight of rats of chemotherapy groups became lower; on the 21st day, the weight was still lower but started to recover; on the 42nd day, the weight had been similar to the controls.2.3 On the 7th day, we could observed significant acute inflammation with high score in the colonic segments of the chemotherapy groups; on the 21st day, the inflammation started to subsidise with decreasing score; on the 42nd day, the inflammation totally subsidized with normal score.2.4 On the 7th day, focal inflammation with a lot of neutrophile granulocytes infiltration occurred in the colonic mucous of the chemotherapy groups, mucosal thickness were less than the controls; on the 21st day, the mucosal inflammation started to subsidized with less neutrophile granulocytes and some lymphocytes and plasma cells, mucosal thickness started to recover; on the 42nd day, the mucosal inflammation had subsidized only with some lymphocytes and plasma cells, mucosal thickness had been similar to the controls.2.5 The determination of MPO:On the 7th day, the activity of MPO in the colonic specimen of the chemotherapy groups was obviously increased; on the 21 st day, the activity of MPO started to fall; on the 42nd day, the activity of MPO had been similar to the controls.2.6 The determination of SP and VIP:On the 7th day, the contents of SP and VIP in the colonic mucous of the chemotherapy groups were significantly higher than those in the controls; on the 21st day, the contents of SP and VIP started to decrease; on the 42nd day, the contents of SP and VIP had been a little higher than the controls. 2.7 The determination of capillaries'permeability:On the 7th day, the content of EB in the colonic wall of the chemotherapy groups was obviously higher than the controls; on the 21st day, the content of EB started to decrease; on the 42nd day, the content of EB had been a little higher than the controls.Conclusions1. Clinic study implied that post-chemotherapy non-gastrointestinal cancer patients definitely had intestinal motility disturbance and visceral hypersensitivity. The intestinal dysfunction was related to chemotharapy. Furthermore, visceral hypersensitivity played a more important role in pathogenesis of post-chemotherapy intestinal dysfunction.2. Basic study implied that after the acute inflammation subsidized in the post-chemotherapy rats, the high contents of SP and VIP in colonic mucous and the high permeability of colonic capillaries could be determined. These demonstrated the persistant damage of nerve-immunity-endocrine net and intestinal barrier. Maybe these cause and keep the persistent low-grade inflammation which resulted in the post-chemotherapy intestinal dysfunction.3. Both infective and non-infective factors could cause persistent low-grade inflammation after the acute inflammation subsidized. This persistent low-grade inflammation may be an important reason of intestinal dysfuction.