Fast-Track Surgery Improves Postoperative Clinical Recovery and Immunity After Elective Surgery for Colorectal Carcinoma:Randomized Controlled Clinical Trial
Dongjie Yang •Weiling He •Sheng Zhang •Huayun Chen •Changhua Zhang •Yulong He
Published online:24April 2012
ÓThe Author(s)2012.This article is published with open access
Abstract
Background Few clinical studies or randomized clinical trial results have reported the impact of fast-track surgery on human immunity.This study aimed to investigate the clinical and immune impact of fast-track surgery in colo-rectal cancer patients undergoing elective open surgery.Methods A controlled randomized clinical trial was conducted from November 2008to January 2009with a 1-month postdischarge follow-up.A total of 70patients with colorectal carcinoma requiring colorectal rection were randomized into two groups:a fast-track group (35cas)and a conventional care group (35cas).All included patients underwent elective open colorectal rection with combined tracheal intubation and general anesthesia.Clinical parameters and markers of immune function were evaluated
in both groups postoperatively.Results In all,62patients completed the study:32in the fast-track group and 30in the conventional care group.Our findings revealed a significantly shorter postoperative hospital stay and faster return of gastrointestinal function in patients undergoing fast-track rehabilitation.In addition,we found a quicker respon of white blood cells in the fast-track group than in the conventional care group.We also found that blood levels of globulin,immunoglobulin G,and complement 4on postoperative day 3were higher in the fast-track group than in the conventional care group.
Conclusions Fast-track surgery accelerates clinical recovery and improves postoperative immunity after elec-tive open surgery for colorectal carcinoma.
Introduction
Fast-track surgery (FTS)is a promising comprehensive program for surgical patients.It aims to decrea the per-ioperative stress respon to the surgical trauma,thereby leading to a decrea in complication rates after elective surgery [1,2].Numerous clinical trials have provided positive evidence of the benefits of utilizing FTS,including improving postoperative recovery,shortening the hospital stay,accelerating the return of gastrointestinal function,and reducing morbidity and mortality
rates [3–6].Some rearchers believe that FTS also has positive effects on the human immune system,which may result in quicker recovery of postoperative immune function [7].Neverthe-less,few clinical studies or randomized clinical trial (RCT)results have reported the impact of FTS on human immu-nity.Therefore,bad on the hypothesis and prent evi-dence of the benefits of FTS,this prospective,randomized comparative study investigated the effects of FTS on postoperative clinical recovery and immunity in patients with colorectal carcinoma undergoing elective open surgery.
Materials and methods Participants
This study was conducted in the Department of Gastroin-testinal and Pancreatic Surgery,First Affiliated Hospital of
Dongjie Yang and Weiling He contributed equally to this study.D.Yang ÁW.He ÁS.Zhang ÁH.Chen ÁC.Zhang ÁY.He (&)Department of Gastrointestinal and Pancreatic Surgery,The First Affiliated Hospital of Sun Yat-n University,58Zhongshan Rd II,Guangzhou 510080,China e-mail:
World J Surg (2012)36:1874–1880DOI
10.1007/s00268-012-1606-0
Sun Yat-n University from November2008to January 2009.The surgical procedures were performed by experi-enced surgeons(they had performed at least200colorectal procedures before participating in the study).Seventy patients who were clinically diagnod as having colorectal carcinoma were assigned randomly to two groups com-prising35patients each:FTS group and conventional care group.Inclusion criteria included:age C18and B80years, no preoperative chemotherapy or radiotherapy,American Society of Anesthesiologists(ASA)grade I/II,body mass index(BMI)17.5–27.5kg/m2,preoperative rum albumin C30g/l.All of the patients underwent elective open colorectal rection with combined tracheal intubation and general anesthesia.Exclusion criteria included immune-related dia;primary diabetes mellitus or impaired gluco tolerance;hiatus hernia;gastroesophageal reflux dia(GERD);pregnancy;bowel obstruction;patients with difficult airway access(difficult to intubate);and drug intake,which might affect bowel movement and function. Patients also would be excluded if the following circum-stances occurred:failure of thoracic epidural catheter inrtion;intraoperative blood transfusion;patients who r
equired a stoma;unrectable carcinoma.
The study protocol was approved by the Rearch Ethics Committee of the First Affiliated Hospital of Sun Yat-n University(Guangzhou,China).Written informed connts were obtained from the patients and their families.This study was registered under chictr,identifier number ChiCTR-TRC-00000157.
Interventions
The intervention protocols of the FTS group were as follows: normal he day before surgery;drink 250ml of5%carbohydrate2h before surgery[8];no routine nasogastric tube drainage;early as possible removal of urine and venous catheters(urinary catheter:removed when the patient became conscious and could be mobilized out of bed;deep venous catheter:removed when vital signs were stable);oral feeding started6–12h after surgery,fol-lowing a stepwi plan from oral liquid nutrition to normal diet.Ensure(400g;Abbott,Chicago,IL,USA)was applied as oral nutrition and was mixed with water for1Kcal/ml. The oral feeding plan was as follows:6–12h after surgery, Ensure mixture,30–50ml every1–2h;postoperative day (POD)2and afterward,Ensure mixture,100–200ml every 2–3h,plus mi-fluids according to the patient’s tolerance. Mobilization was encouraged
from the night of the opera-tion.Patients were encouraged to meet predefined mobility targets over the postoperative days.
The intervention protocols of the conventional group were as follows:normal he day before surgery,routine u of nasogastric tube drainage,and oral intake initiated on return to normal gastrointestinal func-tion(bowel sounds orflatus)following a stepwi plan from oral liquid nutrition(Ensure400g)to a normal diet. Patients were sat up and assisted to mobilize on POD1,but they were not aggressively mobilized until discontinuation of the thoracic epidural.Urinary catheters were removed following epidural catheter removal.
The same interventions were applied in both groups: Routine bowel preparation was done with gentamicin and metronidazole.Polyethylene glycol electrolyte powder (HYGECON,Jiangxi,China)was ud as a laxative.Other measures included prophylactic u of antibiotics;avoid-ance of long-acting opioids;intraoperative maintenance of normothermia with an upper-body forced-air heating cover;a midline incision of minimal length;intraoperative and postoperativefluid restriction;no routine u of abdominal drains;the combination of continuous epidural mid-thoracic local anesthetics plus nonsteroidal antiin-flammatory drugs(NSAIDs)to control postoperative pain. Postoperative blood gluco was controlled with the fasting blood gluco(FBG)l
evel maintained at\12mmol/l. Administration of any blood product was unacceptable,as was giving any agent that could affect immunity.Total postoperative calorie administration was controlled in the range of25–30Kcal/kg per24h in both groups.
Discharge criteria included the following:normal body temperature;independently mobile;return to normal gas-trointestinal function(defecation at least once);normal oral diet,no need for parenteral nutrition;controllable pain with oral analgesia;willing to go home.Patients were read-mitted at the request of the primary care physician or if the patient made direct contact with the hospital describing deteriorating health at home.Patients were followed up within1month after discharge(follow-up by telephone every3days during thefirst2weeks,once a week during the last2weeks).The patient was told that the rearcher should be informed promptly if the patient had any discomfort.
Both groups were protocol-driven,with checklists for patients,nursing staff,and surgical staff to help maintain compliance.Teaching ssions and dummy runs were held before trial commencement to clarify potential points of confusion and reduce protocol violations.Patients were admitted to one of two nursing areas depending on the results of randomization.Although the interventions were protocol-driven,a geographically parate location was considered desirable to minimize protocol co
ntamination.
Measurements
Patients’preoperative lf-feelings were evaluated before anesthesia ,thirsty,hungry).Anesthe-sia-related complications were measured.Intraoperative
measurements were carefully recorded in detail,including surgical procedures,blood loss,fluid transfusion,and blood transfusion,among others.The return of normal gastroin-testinal function(time tofirst bowel sounds/flatus,defeca-tion,initiation of soft diet),hospital stay,and complications were recorded postoperatively.Blood tests[white blood cell (WBC)count,liver function tests(LFTs),rum biochem-istry,humoral immunologic index]were performed on appointed days.The humoral immunologic factors tested in our study included rum globulin,immunoglobulin G (IgG),immunoglobulin M(IgM),immunoglobulin A(IgA), complement3(C3),and complement4(C4).
购物中心英文Experimental blood tests were performed on the morn-ing of the operation and on PODs1,3,and7.All blood samples were taken from peripheral ,before breakfast.We also took blood samples to test the WBC count at the end of surgery.英语口语视频
Sample size,randomization,and implementation
The intention of our study was to detect possible changes of human immunity on the basis of clinical benefits.Like many other clinical studies,we lected the length of hospital stay(LOS)as the main endpoint.On the basis of previous data for postoperative LOS,(10.38days on average)for patients undergoing major colonic surgery at our institution,we calculated that35patients in each group would be required to detect a30%reduction in postop-erative LOS with an a level of0.05and a b level of0.01.
Patients were informed about the aims and details of this study.Patients signed connt forms after the study was explained.Block randomization was computer-generated. Eligible patients were randomly assigned in a1:1ratio.The investigators who designed the study prepared the enve-lopes and assigned participants to their groups but had no contact with the patients throughout the study.The inves-tigator recruiting the patients,administering the interven-tions,and evaluating the outcomes had no role in the randomization process.
Statistical analys
Data were analyzed using SPSS for Windows13.0(SPSS, Chicago,IL,USA).Numerical variables were expresd as the mean±SD unless otherwi stated.Categoric vari-ables were expresd by a
黄薇薇constituent ratio or rate.Dif-ferences between the two groups were tested using a two-tailed Student’s t test for normally distributed data and the Wilcoxon test for noncontinuous variables.The v2test and Fisher’s exact test were ud to compare discrete variables.
A value of p\0.05was considered statistically significant.
Compared with our primary protocol,we made a mod-ification to the enrollment of participants before trial commencement,which initially intended to enroll patients with gastrointestinal tumors other than colorectal cancer. The aim was to control the homogeneity of the patients and thus control bias.The sample size decread from60to35 accordingly.The Rearch Ethics Committee of the First Affiliated Hospital of Sun Yat-n University(Guangzhou, China)approved all the changes.
Results
In all,62patientsfinished the study,including32patients in the FTS group and30in the conventional care group. Three patients were excluded from the FTS group andfive patients from the conventional care group.(Fig.1)Patients in the two groups had comparable preoperative baline characteristics,including x,age,rum hemoglobin and albumin levels,and body mass index(Table1).
No statistically significant differences were detected between the two groups regarding the operating time,blood loss orfluid transfusion during the operation,surgical procedure,or tumor staging.However,patients in the FTS group did experience significantly less discomfort in terms of hunger and thirst(Table1).
Postoperative clinical parameters
Patients in the FTS group showed significantly accelerated recovery of gastrointestinal function compared to that of the conventional care group in terms of time tofirst bowel sounds/flatus(2±1vs.4±2days,p\0.05),defecation (3.84±1.63vs.6.44±2.53days,p\0.05),and initia-tion of soft diet(4.0±2.0vs.8.2±2.16days,p\0.05). Postoperative hospital stay was significantly shorter in the FTS group than in the conventional care group(6.0±1.0 vs.11.7±3.82days,p\0.05).
Although no statistically significant differences were found for the surgical site infection(SSI)rate(2/30vs. 1/32,p=0.6066),pneumonia(1/30vs.0/32,p=0.4839), and intestinal dysbiosis(5/30vs.1/32,p=0.0986) between conventional care and FTS groups,patients in the FTS group had a significantly lower rate of total infectious complications than did the conventional group(8/30vs. 2/32,p\0.05).No statistically significant differences were found for noninfectious compli
cations between the conventional care and FTS groups(4/30vs.4/32,p= 1.0000),including vomiting(1/30vs.3/32,p=0.6132), stress ulcer(1/30vs.0/32,p=0.4839),arrhythmia(1/30 vs.0/32,p=0.4839),and urine distension(1/30vs.1/32, p=1.0000).No anastomotic leakage,anastomotic bleed-ing,abdominal infection,anesthesia-related complications, or hospital readmissions due to complications were detec-ted in either group.
White blood cell count
效益英文
A statistically significant difference was found regarding the WBC count at the end of surgery,with a higher WBC count found in the FTS group than in the conventional care group (Table 2).No statistically significant difference was detected in levels of WBC count on the morning of the day of the operation.The tendencies for WBC count change were different in the two groups.In the FTS group,the WBC count ro quickly to the highest point at the end of surgery and then dropped gradually to a normal level on POD 7.In conventional group,the WBC count quickly ro to a high level at the end of surgery and fluctuated at that high level until POD 7(Table 2).Thus,the FTS group had a quicker WBC respon,including rising and drop-ping counts,than the conventional care group.
Humoral immunologic parameters
No statistically significant differences were detected in preoperative levels of rum globulin,IgG,IgM,IgA,C3,or C4between the two groups.On POD 3,statistically significant differences were found in levels of rum globulin,IgG,and C4,with the FTS group having higher levels than in the conventional group (Table 3).
No statistically significant differences were detected in the postoperative levels of rum IgM,IgA,or C3between the two groups (Table 3).There were also no statistically significant differences in the recovery rates of all factors (Table 4).
Discussion
Numerous clinical trials have provided positive evidence of the benefits of utilizing FTS [3–6].However,most of the FTS studies or reviews/meta-analysis intended only to determine the clinical impact of FTS [3–6,9–12],with only a few studies evaluating the impact of FTS on human immunity.The aim of the prent RCT was to evaluate prospectively the clinical and immunologic results of fast-track colorectal surgery.Interpretation
In this study,the principal differences between the two arms concern a shorter period of preoperative starvation,early removal of catheters,early oral feeding,and earlier mobili-zation.Our findings indicate
that FTS leads to a significantly faster recovery of gastrointestinal function,as indicated by time to first flatus,bowel movements,and initiation of a soft diet.In addition,patients in the FTS group suffered signifi-cantly fewer infectious complications without increasing noninfectious ones.In agreement with the clinical advan-tages,we obrved a significant decrea in the postoperative length of hospital stay in fast-track patients.
As far as the immunologic effects are concerned,one study demonstrated that,compared to carbohydrate intake before surgery,fasting may abate the expression of monocyte HLA-DR postoperatively [13].Another study showed that the u of FTS perioperatively enhanced the human body’s cellular immunologic ability [i.e.,T cells,Th cells,natural killer (NK)cells][7].In this clinical
trial,
Fig.1Patient flow throughout the study.FTS fast-track surgery
we found that the FTS group had a higher WBC count than did the conventional care group at the end of surgery.In addition,the FTS group had a quicker WBC respon,including rising and dropping counts,than the conventional care group.Although we did not test the differences in the WBC subgroups,the changes that were en reprented some degree of cell-mediated immunity difference between the two groups.
Until now,no studies have reported the effect of FTS on human humoral immunity.Our results indicated that FTS accelerated the recovery of rum globulin.As we know,immunoglobulin and complement are two vital elements of globulin [14,15].Our findings showed that FTS group had significantly higher levels of rum IgG and C4on POD 3.With its high affinity and wide distribution,IgG is the most abundant immunoglobulin in the blood and extracellular fluid,playing a major role in the immune respon to fight
Table 1Patients’preoperative/intraoperative characteristics Characteristic FTS Conventional (n =32)(n =30)Age (years)57.2±11.7059.5±12.10Sex (no.)Male 20(62.5%)22(73.3%)Female
12(37.5%)8(26.7%)Body mass index (kg/m 2)22.25±2.4521.69±2.48Hemoglobin (g/l)125.8±18.8129.
新加坡留学8±20.1Albumin (g/l)
40.84±2.9540.67±3.58Preoperative feeling (no.)Thirsty*2(6.3%)23(76.7%)Hungry*
5(15.6%)20(66.7%)Operating time (min)209±40.1196±50.6Blood loss (ml)150±100a 200±100a Fluid transfusion (ml)2800±500a 2925±500a Type of surgery (no.)Right hemicolectomy 6(18.7%)7(23.3%)Left hemicolectomy 2(6.3%)3(10.0%)Sigmoidectomy 6(18.7%)7(23.3%)Dixon operation 18(56.3%)
13(43.3%)
Tumor staging (no.)TNM classification I 5(15.6%)7(23.3%)II 18(56.3%)16(53.3%)III
9(28.1%)7(23.3%)Dukes classification A 5(15.6%)7(23.3%)B 18(56.3%)16(53.3%)C13(9.4%)2(6.7%)C2地址 英文
6(18.7%)
5(16.7%)
FTS fast-track surgery英文求职信范文
Variables were expresd as the median ±quartile
a
Not subject to normal distribution
*p \0.05
Table 2White blood cell count Time FTS Conventional Statistic p (n =32)(n =30)(Z)Before surgery 6.94±2.08 6.21±2.35a -1.52640.1269End of surgery 12.38±3.1610.65±2.58a -2.17850.0294POD 111.84±2.5710.15±2.57a
-1.38380.1664POD 310.45±5.28
a
11.08±2.230.28310.7771POD 7
8.55±5.70apromime
10.25±5.52a
1.3172
0.1878
POD postoperative day
Variables were expresd as the median ±quartile
a
Not subject to normal distribution
Table 3Serum level of humoral immunologic factors
Factor and time FTS Conventional Statistic p
(n =32)(n =30)
Globulin (g/l)Before surgery无论 还是 都什么句型
27.6±4.026.4±4.9T =0.91740.3643POD 121.6±3.419.6±3.5T =1.89230.0657POD 324.1±2.422.1±3.3
T =2.32570.0252POD 727.5±3.726.6±4.5T =0.7210.4753IgG (g/l)Before surgery 13.76±3.3511.81±2.66T =1.980.0559POD 110.35±2.618.99±2.32T =1.64960.1080POD 310.79±2.398.66±2.09T =2.88280.0067POD 713.27±2.8211.29±3.09T =2.01020.0524IgA (g/l)Before surgery 2.51±1.08a 2.44±1.07a Z =–0.33810.7353POD 1 2.03±0.65 1.88±0.59T =0.72130.4754POD 3 2.33±0.66 2.07±1.00a
Z =-1.05250.2926POD 7 2.98±0.96 2.94±1.07T =0.13930.8900IgM (g/l)Before surgery 1.01±0.38 1.04±0.41T =-0.22700.8217POD 10.71±0.290.78±0.27T =-0.68780.496POD 30.78±0.360.75±0.31T =0.26850.7898POD 7 1.09±0.59a
1.52±0.85Z =0.97270.3307C3(g/l)Before surgery
1.08±0.170.99±0.20T =1.50050.142POD 10.82±0.140.76±0.17T =1.26220.215POD 30.82±0.150.73±0.20T =1.59350.1198POD 70.99±0.230.88±0.26T =1.45330.1551C4(g/l)Before surgery 0.29±0.100.26±0.07T =1.230.2274POD 10.21±0.080.19±0.06a Z =-1.07490.2824POD 30.24±0.090.17±0.05a2011中考物理
Z =-2.10990.0349POD 7
0.28±0.12
0.22±0.10
a
Z =-1.7498
0.0801
Ig immunoglobulin,C3,C4complement 3and 4,respectively Variables were expresd as the median ±quartile
a
Not subject to normal distribution
