Analysis Of Anorectal Function In Patients Of Cervical Cancer With Chronic Pelvic Radiation Disease

1.BACKGROUD Organs in pelvis like rectum,colon,uterus and prostate are with high incidence of carcinomas.Pelvic radiotherapy is an important part of comprehensive therapy of pelvic organs' cancers.The indications of pelvic radiotherapy include carcinomas of cervix,prostate,colon,rectum and skin.As is estimated that there are almost 300000 patients received radiotherapy,in which pelvic radiotherapy account for majority.Despite pelvic radiotherapy can well control deterioration of tumor,even though can cure some carcinomas,complications of radiotherapy which is difficult to deal with bite doctors' nails.Patients' quality of life is severely affected after radiotherapy.New types of radiotherapy can partly reduce complications of radiotherapy,but due to the radioactive rays penetrating tissues straightly,tissues around the target organs cannot be completely avoided being irradiated.Because of the accumulation effect,doctors can not recognize chronic radiation injury in early phase results in the prevention and treatment cannot be applied effectively.Anorectum is susceptible to carcinomas,plans of anorectal adjuvant therapy include pelvic radiotherapy.Fixed and closed to uterus,vagina,prostate and bladder,anorectum cannot be protected when irradiating these target organs.Thus,anorectum is the most susceptible area to radiation.There is almost 50% patients suffer from rectal stimulation symptoms which includes hematochezia,stools frequency increase,fecal urgency,pain,tenesmus,mucous stool and even fecal incontinence.These symptoms were denominated as “radiation proctitis”.Nowadays,it is gradually reaching consensus that “pelvic radiation disease” is a more accurate nomenclature.Injury areas of pelvic radiation disease contain digestive system,urinary system,reproduction system,skin,bones,nerves and lymph vessels.There are two valves in alimentary tract,one of which is ileocecal valve,the other one is anorectum.The most part resected of alimentary tract is ileocecal valve whose main function is to delay the time of food transmitted to cecum.After resection of ileocecal valve,food can rapidly transfer into colon results in malabsorption of nutrition.So,anorectal function is especially important to PRD patients.Nevertheless,there is no study concerns to PRD patients' anorectal function since the definition of PRD was conveyed.With the follow up of PRD patients,it is obvious that many PRD patients suffer from rectal simulation symptoms,some of them even complaint of fecal incontinence.These PRD patients have to change their life style lead to their social activity be restricted.There are four Mechanisms of rectal symptoms researched in former studies.The first one is that radiation intestinal crypt stem cells injury induce up-regulation of P53 gene while down-regulation of Bcl-2 gene,that cause cells apoptosis and intestinal mucosal barrier damaged,then lead to bacteria translocation.Secondly,radiation ray injury Na+-K+ pump in epithelium cells lead to malabsorption of Na+ and Cl-.Another mechanism is that bacteria over growth caused by bowel dyskinesia.The last one is microvascularjavascript:void(0);endothelium injury lead to thrombomodulin decrease caused thrombophilic endothelium cell increased that result in endarteritis obliterans which is the main reason of tissue ischemia.TGF-? up-regulated respond to ischemia increase the production of CTGF.CTGF induces submucosa fibrosis which is the main feature of chronic radiation injury.Therapies to radiation anorectal injury conclude medication,endoscopy,hyperbaric oxygen(HBO)and surgery.Agents with mechanism of anti-inflammatory,anti-bacteria overgrowth,protect intestinal epithelium,antioxidant and promote epithelium cell nutrition metabolism also Chinese traditional medicine have little effect.Defecation is intimately relevant to nerve and muscles around anorectum which are also irradiated,this may be the main reason of PRD patients' symptoms.Therefore,this study mainly research the change of PRD patients.2.OBJECTIVE(1)To demonstrate the changes of chronic PRD patients' anorectal function compared with healthy individuals.(2)To research the differences of chronic PRD patients' anorectal function between pre and post resection of intestine or lieocecal junction with serious lesions.To seek for better surgery plans for chronic PRD patients through assessing anorectal functions in order to enhance the quality of their lives.3.MATERIALS & METHODS Twenty cervical cancer with chronic PRD patients and healthy individuals were recruited as PRD group and control group separately.The two group subjects were matched according to age.Inclusion criteria of PRD group: 1.Pelvic radiotherapy had completed more than 6 months.2.Primary tumor was cervical carcinoma.3.There werebowel lesions need to be resected but the lesions were not in colon and anorectum.4.Defecation function was normal before pelvic radiotherapy.Exclusion criteria of PRD group: 1.Previous history contained anorectal area surgery.2.Anorectal stricture.3.Patients suffered from constipation,unrelaxed pelvic floor syndrome,hypertension,diabetes,cerebral apoplexy and peripheral neuropathy before pelvic radiotherapy.4.Recurrence or metastasis is diagnosed through serum tests or image examination.Control group subjects were mainly from out-patient department for health examination.Exclusion criteria of control group contains: 1.Individuals suffered from constipation,unrelaxed pelvic floor syndrome,hypertension,diabetes,cerebral apoplexy and peripheral neuropathy.2.There were anorectal disease like tumor,stenosis and obstruction.The two groups subjects' general information were inquired after recruited.General information contains: age,job,native place,height,weight,body mass index,blood pressure,heart and rate.PRD group patients were additional recorded: current diagnosis,staging of cervical carcinoma,operative approach of cervical carcinoma,methods and doses of pelvic radiotherapy,end time of radiotherapy and operation history.Blood of PRD group was collected for routine test,hepatorenal function test and tumor markers test.PRD patients all received total parenteral nutrition(TPN)due to malnutrition and diseases that cannot take in food orally in almost the PRD patients.Formula of TPN is consisted of glucose 3g/kg·d,amino acid 1.5g/kg·d,and structured triglyceride 1g/kg·d.Control group intake ordinary diet.Enema Solution consisted of 25% Magnesium sulfate,glycerinum enema 60 ml and water 90 ml was applied 3 times before rectoscopy for mechanical bowel preparation with saline 500 ml to PRD group.Administration time were 19:00 and 23:00 the day before rectoscopy and 5:00 the same day of rectoscopy examination.Monosodium phosphate 45 ml and 750 ml water were took orally to control group 19:00 the day before rectoscopy and 5:00 the day of rectoscopy.Rectal mucosa situation of 0-15 cm away from anal verge was recorded and classified with Vienna rectoscopy score.All subjects were told to stop taking in gastrointestinal dynamic medicine for 3 days.Twenty milliliters of glycerine enema is used in all subjects to defecate remains stool of rectum at 8:00 three days after rectoscopy when anorectal manometry examination is administrated.Anorectal manometry examination is administrated at 11:00,the record contained anal resting pressure,maximum squeezing pressure,anal distension pressure,rectal defecation pressure,maximal tolerated rectal volume,length of functional sphincters,rectum initial threshold and rectal defecation threshold.Anorectal manometry data is inputted into SPSS21.0software for analysis,the two groups were analyzed with paired-samples T test.PRD patients were divided into two subgroups according to VRS score.Mild subgroup referred to 0-2 scores,severe subgroup referred to 3-5 group.Restricted by the sample size,the two subgroups were analyzed with Mann-Whitney U test.Operation approaches and remain small bowel length were recorded.PRD patients were followed-up 3 months,6 months and 1 year after the surgery was completed.Follow up contents include: weight,blood pressure,heart rate,BMI,shape of stool,defecation times everyday,food intake,dosage of enteral nutrition and whether need parenteral nutrition support.Whether there were rectum stimulation symptoms like hematochezia,increased stool frequency,pain in rectum and perineum,tenesmus,fecal incontinence or mucous stool was also recorded.PRD patients received anorectal manometry.Data of anorectal manometry was analyzed in SPSS21.0.Follow-up data and preoperative data were analyzed with paired-samples T test.4.RESULTS Indications of surgery for PRD patients contain:1.Intestinal obstruction;2.Intestinal perforation;3.Intestinal fistula.PRD patients were commonly existing malnutrition before operation.The PRD group is significantly lower in BMI when compared with control group.Rectoscopic results showed that appearance of telangiectasis,massive ulcers and deep ulcers commonly existed in PRD patients' rectum.Only 3 patients' VRS score is 0.Compared with control group,anal resting pressures,anal distension pressure,maximum anal squeezing pressure,rectal defecation pressure and maximum tolerated rectal volume was significantly lower in PRD group.The results reminded that functions of internal anal sphincter(IAS)and external anal sphincter(EAS)were severely injured.Also the rectal distension function and compliance were decreased.That the rectal initial threshold and the rectal defecation threshhold were no significantly different between PRD group and control group showed that PRD patient' sensation function is maintained normal.The PRD patients' abnormal defecation is possibly related to anorectal muscles injury and rectal tolerate volume decrease.The data of the two subgroups showed that there were no significantly different between the two subgroups.It implied that mucosa and anorectal muscles injured irrelevantly.PRD patients with normal rectoscopic appearance may also have abnormal defecation,and normal defecation can happen in anorectal mucosa heavily injured PRD patients.It's necessary for PRD patients especially who need their lesion bowel resected receiving anorectal function assessed detailedly in order to make a better plan to enhance PRD patients' quality of life.The 3 month,6 months and 1year follow-up data showed: 1.ARP,AMSR,ADP,RDP,RDT and RMTV significantly increased,while RIT decreased in 3 months.2.In 6 months,compared with 3 months,ARP,AMSR,ADP,RDP,RDT and RMTV also increased but the range is less than data in 3 months compared with preoperative data.There was no significant change between 1 year and 6months.A large proportion of PRD patients complained about fecal frequency increase,tenesmus and anal pain.There were a small proportion of PRD patients' complaints about bloody stool and fecal incontinence,this situation is obvious in 3 months after surgery.In 6 months,these symptoms alleviated.But the symptoms had no change in 1 year compared with 6 months if symptoms lasted more than 6 months.5.CONCLUSIONS Cervical carcinoma patients with PRD were commonly company with anorectal dysfunction that mainly manifests decreasing in ARP,AMSR,ADP,RDP,RDT and RMTV.Rectal mucosa injury is common in PRD patients,even serious injury was found.Manifestations like stool frequency increase and tenesmus are possibly the result of combined effect of mucosa and muscle injury.Anorectal function of cervical carcinoma patients with PRD improved greatly 3 months after intestine with lesions was resected.Six months' data was not as evident as 3 months.The mechanism may be the complicated pathophysiologic changes such as malnutrition,bowel obstruction,disuse of anorectum,infection and adhesion of bowel.The manometry data improved 3 months after surgery may be resulted from the solution of intestinal obstruction,recovery of malnutrition,removed infection,restored defecation and defecation exercise.Anorectal manometry data in six months and 1 year after PRD patients received surgery seemed stable may be caused by constant radiation injury.That is why medication have little effect in PRD patients.