The American Journal of Surgery (2013) 206, 739-747
Clinical Science
Ileal or ileocecal resection for chronic radiation enteritis
with small bowel obstruction: outcome and risk factors
Ning Li, M.D., Weiming Zhu, M.D., Jianfeng Gong, M.D., Yi Li, M.D., Wenkui Yu, M.D.,
Qiyi Chen, M.D., Ling Ni, M.D., Liang Zhang, M.D., Lili Gu, M.D.,
Jieshou Li, M.D., Ph.D.*
Department of General Surgery, Jinling Hospital, Medical School of Nanjing University, Nanjing, 210002, PR, China
KEYWORDS:
Radiation enteritis;
Intestinal failure;
Risk factors;
Surgery;
Intestinal resection;
Postoperative
complications
Abstract
BACKGROUND: The choice of the optimum surgical procedure for chronic radiation enteritis (CRE)
has not reached a consensus over the years. This study aimed to evaluate the outcomes in patients undergoing ileal or ileocecal resection for CRE and to identify predictive risk factors for postoperative
complications.
METHODS: Univariate and multivariate analyses of a retrospectively gathered database (2001 to
2011) were performed on a cohort of patients (N 5 158) undergoing ileal or ileocecal resection for
CRE obstruction at a single institution.
RESULTS: Overall and major morbidity rates were 57.0% (90 patients) and 28.5% (45 patients), respectively. Surgical complications occurred in 20 patients (12.7%) and postoperative permanent parenteral nutrition dependence was 12.1% (12 of 99 patients). Multivariate analysis determined that an
American Association of Anesthesiologists’ score of III or higher, anemia, low platelet level, intraoperative transfusion, presence of radiation uropathy, and experience of surgeons were independent risk
factors for Clavien-Dindo grades III to V morbidity.
CONCLUSIONS: Ileal or ileocecal resection for CRE has an acceptable risk of permanent intestinal
failure and surgical complications. This study also provides the 1st evidence of predictive risk factors
for postoperative morbidity of ileal or ileocecal resection for CRE.
Ó 2013 Elsevier Inc. All rights reserved.
Chronic radiation enteritis (CRE) is a rare complication
of radiation therapy for pelvic malignancy, mainly rectal,
gynecological, and prostate cancers. Small intestinal obstruction due to radiation injury can occur with rates from
.8% to 13% depending on the tumor and radiotherapy
The authors declare no conflicts of interest.
This study was Funded by Jiangsu Provincial Special Program of
Medical science (BL2012006) and National Natural Science Foundation
of China (Grant No. 81270006).
* Corresponding author. Tel.: 186-25-80860037; fax: 186-25-80860220.
E-mail address: lijieshourigs@aliyun.com
Manuscript received October 4, 2012; revised manuscript January 5,
2013
0002-9610/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved.
http://dx.doi.org/10.1016/j.amjsurg.2013.01.045
characteristics.1–3 Traditionally, home parenteral nutrition
(PN) has been recommended as the primary therapy for
CRE with obstruction because of the high rates of surgical
complications.4 However, because of the progress in operative techniques and perioperative management, surgery has
gained popularity as the 1st choice for patients with CRE recently. Around one third of patients with CRE will require
surgery for intestinal obstruction secondary to strictures or
adhesions or as therapy for intestinal fistulae or perforation.5
Until now, there has been a lack of consensus about the
optimum surgical procedure for intestinal obstruction due
to CRE. Some advocate either a conservative approach
with adhesiolysis, bypass surgery, or creation of diverting
740
The American Journal of Surgery, Vol 206, No 5, November 2013
stomas without resection of the primary lesion or a more
radical operation with resection of the diseased segment of
the bowel. Although resectional surgery has been shown
to cause a higher incidence of leakage and mortality than
bypass, diseased bowel left behind can cause bleeding and
can result in perforation and fistulization, and, therefore, a
need for reoperation. Several studies have suggested
liberal resection of the affected bowel as the preferable
therapy.5–7 According to a recent article by Lefevre et al,8
ileocecal resection is the only factor that protected against
reoperation for recurrent CRE, which demonstrates the
importance of resecting all damaged tissue in patients
with CRE. An early study suggested that resectional surgery had a similar mortality but decreased reoperation
rates and the ultimate need for long-term PN compared
with a nonresection group.9 Perrakis et al10 also reported
a favorable outcome without disease recurrence of 17 patients treated by resection of the diseased bowel segment.
However, the early and long-term outcomes, postoperative
complications, and risk factors for early postoperative
complications of ileal or ileocecal resection for CRE are
unknown in large cohort studies.
In our department, resection of the irradiated small
bowel lesion causing obstruction is the primary surgical
option for CRE with intestinal obstruction. The aim of the
current study was to evaluate the early postoperative and
long-term outcomes in patients with ileal or ileocecal
resection for diseased intestinal segments of radiation
enteritis, and we analyzed the risk factors for postoperative
complications.
Methods
Patients
Adult patients who had undergone ileum or ileocecal
resection for CRE with intestinal obstruction from January 2001 to December 2011 were retrospectively analyzed. Clinical data were collected from medical case
records. All patients had postoperative pathologic diagnosis of CRE. CRE patients with uncured malignancy (n
5 50), conservative treatment but not surgery (n 5 44),
isolated colorectal lesions (n 5 39), intestinal fistula (n 5
82), or patients undergoing bypass (n 5 6) and stoma
surgery without resection (n 5 2) were not included for
analysis.
Patients’ demographic and clinical data include previous
malignancy, type of tumor surgery, total dosage and type of
radiotherapy, concomitant chemotherapy, and surgical parameters. History of smoking, diabetes, and previous
abdominal surgery were also considered as demographic
data. Postoperative hospital stay was also recorded. For
nutritional risk screening, recent weight loss (compared to
preillness),11 body mass index (BMI), and serum albumin
level were used. Approval of the study was obtained from
the ethics committee of Jinling Hospital.
Risk factors
With reference to the studies by Lefevre et al,8 Chen
et al,12 and Regimbeau et al,5 34 demographic and clinical
variables accounting for possible influence on the perioperative period were recorded: age (660 years); sex (male/female); presence of acute radiation enteritis (grade I to
III)13; radiation dosage (cumulative dosage of external and
endocavitary radiation, .50 Gy vs %50 Gy); concomitant
chemotherapy; intraperitoneal chemotherapy; latency of disease (%6 m vs .6 m); time from disease onset to surgery
(%5 m vs .5 m); BMI (,17.5 kg/m2); significant weight
loss (defined as a 10% decrease in weight upon comparison
of the patient’s preillness); low BMI and significant weight
loss (BMI , 17.5 kg/m2 and weight loss R 10%); American
Association of Anesthesiologists (ASA) classification score
III to IV; gynecologic malignancy; abdominoperineal resection; history of smoking, diabetes mellitus, hypertension, and
abdominal surgery prior to radiation; presence of radiation
uropathy (ureter obstruction, radiation cystitis Rgrade II according to the scale devised by the Radiation Therapy Oncology Group,14,15 history of ileal neobladder and renal
insufficiency with serum creatine [SCr . 110 umol/L]);
the presence of radiation proctitis16; history of surgery aiming at solving CRE; intraoperative blood transfusion R400
mL; preoperative albumin (Alb , 35 g/L vs Alb R 35 g/L);
preoperative white blood cell count (R10,000/mm3, R3,500
,10,000/mm3, or ,3,500/mm3); preoperative platelet count
(R100 ! 109/L vs ,100 ! 109/L); preoperative anemia
(,12 g/dL in males and ,11 g/dL in females); preoperative
total PN dependence; preoperative intestinal decompression
(with nasointestinal tube, long-intestinal tube, or percutaneous endoscopic gastrotomy with jejunal extension); anastomosis fashion (stapled side-to-side vs stapled end-to-side);
site of resection and anastomosis (ileocecal vs ileal); length
of operation (.3 hours vs %3 hours); and surgeons’ experience (,40 cases vs R40 cases). A fast track recovery (FCS)
protocol was employed in 2007, and we also included the
time of surgery (before and after 2007) for risk factor
analysis.
Postoperative complications
Postoperative morbidity was graded according to the
Clavien-Dindo classification, as described by Lefevre et al.8
For patients undergoing a staged operation (ie, stoma in the
1st operation and stoma reversal in the 2nd operation), the
complication rate was calculated as the total events encountered in 2 operations, but length of postoperative stay was
recorded only for the 1st operation. Dependence on total
PN postoperatively for over 2 weeks was considered as
postoperative morbidity according to the upgraded
Clavien-Dindo classification in 2004.17 Postoperative short
bowel syndrome was defined as a remnant small bowel
length of 180 cm or less with associated malabsorption, according to Boland et al.18
N. Li et al.
Ileal/ileocecal resection for CRE
Surgical complications include anastomotic leakage,
intra-abdominal abscess, postoperative peritonitis, wound
dehiscence, and intra-abdominal hemorrhage. Incomplete
resection of the lesions causing postoperative obstruction
was also considered a surgical complication.
Follow-up
All patients were followed for over 3 months. Obstruction recurrence and reoperation for CRE were recorded.
Patients’ tumor status, BMI, body weight change, dependence on PN, enteral nutrition, and usage of antidiarrhea
agents were also documented. Survival status was evaluated
by review from the medical database and by telephone
follow-up of all patients who had no regular postoperative
outpatient visits for more than 3 months.
Statistical analysis
All analyses were performed with the Statistical Package
for Social Sciences version 13.0 software (SPSS, Chicago,
IL). Consecutive data were presented as mean with standard
deviation or median (range). Statistical analysis was performed by the Mann–Whitney U test or Student’s t test for
continuous variables and Pearson’s chi-square test for categorical variables as appropriate. Potential risk factors for
postoperative complications were evaluated by univariate
analysis, and risk factors with a univariate probability of
less than .1 were included in the multivariate analysis using
multivariate logistic regression analysis. A probability value
of less than .05 was accepted as statistically significant.
Results
Clinical data
A cohort of 158 consecutive patients (32 males and 126
females) was included in the study from January 2001 to
December 2011. Patients’ characteristics are listed in
Table 1.The main primary malignancy was gynecological
(112 patients, 70.9%) and rectal cancers (37 patients,
23.4%). Patients’ median age on surgery was 51.0 (23 to
82) years and the mean preoperative BMI was 18.08 6 2.86
(12.1 to 29.4) kg/m2. The mean radiation dosage was 55.97
6 15.93 (20 to 128) Gy. The majority of the patients
(n 5 136, 86.1%) had a postoperative radiation therapy. Prior
to surgery, 60 patients (38.0%) were dependent on total PN.
Surgical procedures
The surgical procedures were performed a median of 5
(1 to 157) months after the 1st onset of symptoms for CRE.
The majority of the patients were classified as American
Society of Anesthesiologists’ (ASA) grade II (n 5 91,
57.6%) or III (n 5 48, 30.4%).
741
Table 1 Demographics of 158 patients receiving ileal or
ileocecal resection for chronic radiation enteritis obstruction
Patients’ demographics
Median age (years, range)
Gender (male/female)
Type of primary malignancy, n (%)
Rectal carcinoma/lymphoma
Cervical carcinoma
Ovary cancer
Endometrial cancer
Tubal cancer
Ovary and endometrial cancer
Cervical and rectal cancer
Ovary and rectal cancer
Seminoma
Others
Radiation therapy, n (%)
Radical irradiation (cervical cancer/
rectal lymphoma)
Preoperative
Postoperative
Pre- and postoperative
Radical irradiation and postoperative
Cumulative delivered dosage of RT, Gy,
mean, SD (range)*
Presence of acute radiation enteritis, n (%)
Median latency period (months, range)†
BMI (kg/m2) prior to surgery, n (%)
,17.5
17.5–22
R22
Body weight loss compared to
preillness, n (%)
.10%
%10%
Unknown
Concomitant radiation uropathy, n (%)
Radiation proctitis, n (%)
Previous surgery aiming at CRE with
obstruction, n (%)
Associated risk factors for CRE, n (%)
Diabetes mellitus
Smoking
Hypertension
Previous abdominal surgery
51.0 (23–82)
32/126
36/1 (22.8/.6)
79 (50.0)
7 (4.4)
24 (15.2)
1 (.6)
1 (.6)
1 (.6)
1 (.6)
4 (2.5)
3 (1.9)
14/1 (8.9/.6)
4 (2.5)
136 (86.1)
2 (1.3)
1 (.6)
55.97 6 15.93
(20–128)
64 (40.5)
6 (2–276)
73 (46.2)
73 (46.2)
12 (7.6)
89
56
13
16
20
25
(56.3)
(33.5)
(10.1)
(10.1)
(12.7)
(15.8)
4
16
8
47
(2.5)
(10.1)
(5.1)
(29.7)
BMI 5 body mass index; CRE 5 chronic radiation enteritis;
RT 5 radiation therapy; SD 5 standard deviation.
*Radiation dosage unclear in 26 cases.
†
Five patients presents with symptoms of CRE in 2 months.
Details of the surgical procedure are shown in Table 2.
All patients received open surgery; 143 (90.5%) had a 1stage operation, while staged operation was adopted in 15
(9.5%) patients. The overall (P 5 .844) and major (grade
III to V) (P 5 .863) morbidity did not differ between the
2 groups.
Ileocecal resection or anastomosis was performed in 75
(47.5%) patients, while ileum resection or anastomosis was
performed in 60 (38.0%) patients; 4 (2.5%) had combined
742
The American Journal of Surgery, Vol 206, No 5, November 2013
Table 2 Surgical parameters of ileal or ileocecal resection for
chronic radiation enteritis with obstruction
Table 3 Postoperative morbidity according to Clavien-Dindo
classification
Surgical parameters
Clavien-Dindo classification
No. of patients
Grade I
Ileus
Delayed gastric emptying
Diarrhea
Incisional infection
Grade II
Total parenteral nutrition for over
2 weeks
Catheter infection
Early postoperative obstruction
Grade III
Cholestasis and biliary drainage
Pleural effusion and drainage
Intra-abdominal/pelvic abscess
Anastomotic leak
Intra-abdominal hemorrhage
Gastrointestinal hemorrhage
Would infection/bleeding/dehiscence
Pneumothorax and chest drainage
Incomplete resection and reoperation
Early postoperative obstruction
Ureter obstruction and J-tube placement
Deep vein thrombosis
Grade IV
Respiratory failure
Intra-abdominal hemorrhage and
respiratory failure
Pelvic abscess and renal failure
Anastomotic leak and renal failure
Heart failure
Circulation collapse needing vasoactive
drugs and ICU
Grade V
25 (15.82%)
2
1
16
6
20 (12.66%)
12
Preoperative ASA grade, n (%)
ASA II
ASA III
ASA IV
Mean operation time (minutes),
mean 6 SD (range)
Surgical procedure, n (%)
Ileocecal resection/anastomosis
Ileal resection/anastomosis
Ileal and ileocecal resection/anastomosis
Resection with permanent ileostomy
Ileal/ileocecal resection/anastomosis and
colonic stoma, n (%)
Operative strategy, n (%)
One-stage operation
Two-stage operation
Median postoperative hospital stay
(days, range)
Postoperative short bowel, n (%)
120–180 cm
60–120 cm
%60 cm
No. of patients
91 (57.6)
48 (30.4)
8 (5.1)
164.5 6 40.6
(105–300)
75
60
4
19
16
(47.5)
(38.0)
(2.5)
(12.0)
(10.1)
143 (90.5)
15 (9.5)
13 (4–110)
13 (8.2)
8 (5.1)
2 (1.3)
ASA 5 American Association of Anesthesiologists; SD 5 standard
deviation.
ileum and ileocecal resection, and the remaining 19
(12.0%) patients had diseased lesion resection and permanent ileostomy. Patients who had a permanent ileostomy
had an increased but not significant percentage of ASA
grades III and IV patients (10 of 19 vs 93 of 45/138; P 5
.086), but no difference in overall (P 5 .583) and major
morbidity (P 5 .809) compared with those with anastomosis. Sixteen (10.1%) patients needed concomitant colonic
stoma for sigmoid-rectal stenosis (n 5 12), severe radiation
proctitis (n 5 3), and rectovaginal fistula (n 5 1).
Surgical outcomes
The median postoperative stay was 13 (4 to 110) days.
Since 2007, a fast track recovery (FCS) protocol has been
adopted, which significantly reduced the length of postoperative hospital days (24.07 6 16.59 [6 to 80] days before
2007 vs 16.59 6 14.02 [4 to 110] days after 2007; P 5.013).
Sixty-eight (43.0%) experienced no adverse events and
recovered uneventfully; 184 episodes of postoperative
complications occurred in 90 patients (57.0%). The overall
and major (grades III to V) postoperative morbidity were
57.0% (n 5 90) and 28.5% (n 5 45), respectively.
Postoperative morbidity according to Clavien-Dindo classification is listed in Table 3. Postoperative mortality occurred in 3 patients (1.9%): 1 patient from uncontrolled
intra-abdominal hemorrhage, and the other 2 died of severe
intra-abdominal sepsis and pulmonary fungal infection,
respectively.
7
1
33 (20.89%)
3
4
5
3
2
2
7
1
2
2
1
1
9 (6.70%)
3
1
1
1
1
2
3 (1.89%)
Anastomotic leak, intra-abdominal abscess, intestinal
fistula or postoperative peritonitis, wound dehiscence, and
intra-abdominal hemorrhage were observed in 19 episodes
in 17 patients (10.8%). Incomplete resection causing postoperative intestinal obstruction was observed in 3 patients
(1.9%). The overall surgical complication was 12.7% (20
patients). Thirteen patients (8.2%) required relaparotomy
for postoperative complications.
Risk factors for postoperative complications
Table 4 shows the perioperative factors analyzed in a
univariate way to detect their influence on postoperative
morbidity.
On univariate analysis, an ASA score of III or IV (P 5
.001), intraoperative transfusion 400 mL or more (P 5
.011), and preoperative platelet count less than 100 !
109/L (P 5 .009) had a significant contribution in overall
postoperative morbidity. Compared with other tumors,
CRE surgery after gynecologic malignancy had less
N. Li et al.
Table 4
Ileal/ileocecal resection for CRE
743
Univariate analysis of factors associated with postoperative complications
Variables
No. of patients
Overall morbidity
P
Grade III–V
P
Age (years)
Sex
Acute radiation enteritis
Radiation dosage (Gy)*
Concomitant chemotherapy
Intraperitoneal chemotherapy
Latency period (months)
Symptom onset to referral (months)
BMI (kg/m2)
Weight loss compared to preillness
BMI , 17.5 kg/m2 and weight loss R 10%
ASA score
Gynecological malignancy†
APR
Previous abdominal surgery
Smoking history
Diabetes mellitus
Hypertension
Radiation uropathy (include SCr .110 umol/L)
Radiation proctitis
Previous surgery for CRE
Intraoperative transfusion
Preoperative albumin
Preoperative WBC count (!109/L)
Preoperative WBC count (!109/L)
Preoperative platelet count (!109/L)
Preoperative anemia (,11 (female)/12
(male) g/dL)
Preoperative TPN dependence
Preoperative intestinal decompression
Anastomotic fashion
Resection and anastomosis site‡
Operation time (hours)
Surgery before 2007
Experience of the surgeon (cases)
,60/R60 (127/31)
Male/female (32/126)
Yes/No (64/94)
%50/.50 (77/55)
Yes/No (91/67)
Yes/No (6/152)
%6/.6 (79/79)
%5/.5 (80/78)
,17.5/R17.5 (73/85)
R10%/,10% (89/56)
Yes/No (49/96)
III–IV/I–II (56/102)
Yes/No (112/44)
Yes/No (23/135)
Yes/No (47/111)
Yes/No (12/146)
Yes/No (4/154)
Yes/No (8/150)
Yes/No (16/142)
Yes/No (20/138)
Yes/No (25/133)
R400 mL/,400 mL (10/148)
,35 g/L/R35 g/L (41/117)
,3.5/R3.5, ,10 (57/95)
R10/R3.5, ,10 (6/95)
,100/R100 (16/142)
Yes/No (96/62)
71/19
20/0
42/48
41/36
51/39
1/89
48/42
41/49
45/45
54/30
32/52
42/48
57/31
17/73
30/60
8/82
2/88
5/85
12/78
14/76
20/70
9/81
28/62
29/56
5/56
15/75
56/34
.587
.479
.070
.161
.786
.042
.335
.177
.977
.339
.199
.001
.027
.076
.257
.480
.766
.745
.124
.208
.011
.029
.099
.322
.236
.009
.665
34/11
9/36
19/26
21/17
26/19
0/45
21/24
20/25
23/22
24/17
15/27
27/18
27/16
10/35
12/33
5/40
2/43
3/42
11/34
13/32
11/34
8/37
14/31
17/25
3/25
11/34
33/12
.335
.940
.782
.649
.977
.115
.484
.326
.435
.659
.755
.000
.123
.085
.593
.292
.334
.562
.000
.000
.061
.000
.366
.529
.209
.000
.041
Yes/No (60/94)
Yes/No (59/95)
Stapled SSA/ESA (82/57)
Ileal/ileocecal (60/75)
%3/.3 (129/29)
Yes/No (29/129)
,40/R40 (75/83)
36/54
33/57
44/34
33/42
69/21
21/69
53/37
.754
.619
.484
.908
.063
.063
.000
20/25
20/25
24/16
14/19
31/14
11/34
27/18
.370
.244
.878
.788
.009
.212
.047
APR 5 abdominoperineal resection; ASA 5 American Association of Anesthesiologists; BMI 5 body mass index; CRE 5 chronic radiation enteritis;
ESA 5 end-to-side anastomosis; SCr 5 serum creatine; SSA 5 side-to-side anastomosis; TNP 5 total parenteral nutrition; WBC 5 white blood cells.
*Radiation dosage unknown in 26 patients.
†
Two patients had combined gynecological and rectal cancer were not included for analysis.
‡
Nineteen patients had permanent ileostoma, and 4 patients had combined ileal and ileocecal resection (2 anastomosis). They are excluded for
analysis.
postoperative morbidities (39.28% vs 54.39%, P 5 .027).
Patients who had previously undergone surgery for CRE
also had a significant increased risk for postoperative morbidity (80.00% vs 52.63%, P 5 .011). Among surgeons, the
experienced surgeons (R40 cases) had significantly fewer
postoperative complications (44.58% vs 70.67%, P ,
.001) compared with the less-experienced group.
Significant predictive factors for major (grades III to V)
postoperative morbidity include an ASA score of III or IV
(P , .001), concomitant radiation uropathy (including SCr
.110 umol/L, P , .001), radiation proctitis (P , .001), preoperative platelet count less than 100 ! 109/L (P , .001),
preoperative anemia (,110 g/L in females and ,120 g/L
in males, P 5 .041), intraoperative transfusion 400 mL or
more (P , .001), operation time longer than 3 hours (P 5
.009), and less-experienced surgeons (P 5 .047).
After univariate analysis, variables with a probability
value less than .1 were selected for multivariate analysis
using a multivariate logistic regression model. Table 5 summarizes the results of multivariate analysis. An ASA score
of III or IV, previous surgery for CRE, and lack of surgical
experience were predictive of overall morbidity in ileal or
ileocecal resection for CRE. Additionally, an ASA score
of III or IV, the presence of radiation uropathy, intraoperative transfusion, decreased platelet count, preoperative anemia, and less-experienced surgeons were independent
predictors for developing major (grades III to V) postoperative complications.
744
Table 5
The American Journal of Surgery, Vol 206, No 5, November 2013
Multivariate analysis of factors associated with postoperative complications
Overall morbidity
Variables
P
Acute radiation enteritis
ASA score
Gynecological malignancy
APR
Radiation uropathy
Radiation proctitis
Previous surgery for CRE
Intraoperative transfusion
Preoperative albumin
Preoperative platelet count
Preoperative anemia
Operation time (hours)
Surgery before 2007
Experience of the surgeon
.126
.037
.235
.827
.043
.056
.351
.142
.895
.239
.001
Grades III–V morbidity
OR (95% CI)
P
2.46 (1.06–5.74)
.010
3.54 (1.04–12.09)
.917
.002
.639
.613
.014
.011
.030
.372
.26 (.11–.57)
.018
OR (95% CI)
3.34 (1.34–8.35)
10.97 (2.39–50.26)
11.70 (1.63–83.76)
6.46 (1.54–27.14)
3.38 (1.13–10.16)
.30 (.11–.81)
APR 5 abdominoperineal resection; ASA 5 American Association of Anesthesiologists; CI 5 confidence interval; CRE 5 chronic radiation enteritis;
OR 5 odds ratio.
Follow-up
Of the 155 patients discharged, 119 (74.8%) were on
follow-up. Nineteen patients (12.3%) died of tumor recurrence during follow-up. One patient who could not wean off
PN died of PN-related complications 6 years after discharge.
The median follow-up was 20.0 (3 to 128) months for the
remaining 99 patients (with 2 tumor recurrence).
Postoperative short bowel, defined as residual small
bowel length 180 cm or less, was observed in 23 patients
(14.6%). Among them, 2 patients had remnant small bowel
length 60 cm or less. At the end of follow-up, 12 patients
(12.12%) were permanently dependent on PN. Twenty
patients (20.2%) used antidiarrhea agents intermittently and
17 patients (17.17%) were supplemented with enteral
nutrition. Patients’ BMIs were 20.17 6 3.01 (12.33 to
27.94) kg/m2 on last follow-up vs 17.61 6 2.96 (12.11 to
29.41) kg/m2 prior to surgery (paired t test, P , .01).
Six patients (6.1%) had recurrent intestinal obstruction
after surgery; 1 (1.0%) patient developed radiation cystitis
2 years after discharge.
Comments
In this cohort study, we retrospectively analyzed the
clinical outcomes and risk factors of ileal or ileocecal
resection for patients with CRE in a specialized and highvolume gastrointestinal surgery center. The study had a
median follow-up of 20 months and revealed that the
aggressive resection for CRE with intestinal obstruction
could be adopted with an acceptable incidence of postoperative permanent intestinal failure (12.12%) and surgical
complications (12.7%). The cohort in this study is a rather
homogenous group with patients with only intestinal
obstruction and surgical resection included. This is the
1st study specially exploring the clinical outcome and risk
factors of resectional surgery for CRE obstruction.
A main concern for primary ileal or ileocecal resection
in CRE is the high morbidity rate. Earlier literature reported
that postoperative complications, particularly anastomotic
leaks, can occur in up to 30%, and 40% to 60% of patients
will require more than 1 laparotomy.19 In another large cohort study (77 resections in 107 patients) by Lefevre et al,8
the overall morbidity, mortality, and surgical postoperative
morbidity rates from 1980 to 2009 were 74.8%, .9%, and
28.0%, respectively. Reappraisal of the surgical treatment
of CRE in 48 patients (37 resections) by Onodera et al7
from 1975 to 2003 reported a morbidity of 21.7% and mortality of 4.1%. A similar finding of 5% mortality and 29%
morbidity was also reported by Regimbeau et al5 after 65
bowel resections for radiation enteritis from 1984 to
1994. In the present study, with postoperative total PN dependence longer than 2 weeks included, postoperative morbidity was observed in 56.96% of the patients, with major
(grade III or IV) morbidity in 28.48% and overall mortality
1.89%, indicating that ileal or ileocecal resection for CRE
is still an operation with a high morbidity rate. Surgical
rate of complications in the current study is 12.7% (including 3 incomplete resections), which is lower than the results
of previous studies. Because the majority of the data in previous studies were either obtained before 2003 or over a
long period of time (30 years by Lefevre et al8) and the surgical techniques and perioperative care have evolved dramatically in recent years, this might explain the decreased
postoperative complication rate in the current cohort. Actually, morbidity rates have decreased in our department since
2007, although not statistically significantly (P 5 .063).
Also, we believed that a specialized high-volume center
(average more than 15 patients per year in our hospital)
might be helpful in reducing complications after such a
high-risk surgery.20
N. Li et al.
Ileal/ileocecal resection for CRE
Incidence of intestinal failure after surgical intervention
for radiation-induced bowel injury varies among studies.
According to Regimbeau et al,5 PN dependence was observed in 32% of patients who underwent resection surgery
compared with 38% in the conservative group, after a
follow-up of a median of 40 months. In another retrospective study by Gavazzi et al,21 10 of 17 patients (58.8%) who
underwent surgery eventually developed intestinal failure,
but the type of the operation was not mentioned in their article. In a large cohort by Lefevre et al,8 the incidence of
permanent home PN is 49.5% in 104 patients. The incidence of short bowel after surgery is 14.56% and permanent intestinal failure is 12.12% in the current cohort,
which are both lower than in previous studies. However,
this was at the cost of an incomplete resection in 3 cases
(1.9%), but fortunately not increased anastomosis leakage.
As preoperative enteroclysis is carried out in our department, it is useful for evaluation of obstruction site and
length of remaining healthy small bowel, which might
help to avoid excessive resection and maximally preserve
the small bowel length. Another explanation for the reduced intestinal failure rate might be the advancement of
irradiation techniques in recent years, such as intensitymodulated radiotherapy, which can decrease the small
bowel dosage and chronic gastrointestinal toxicity and
thereby the extent of injured bowel for resection.22
Identifying risk factors that may influence the patient’s
outcome may be helpful for the success of ileal or ileocecal
resection for CRE. However, until now no such study has
been conducted. In this current study, we analyzed 34
possible factors that may influence outcome for CRE ileal
or ileocecal resection. Consistent with previous studies in
surgery, our results revealed that a preoperative ASA score
of III or higher and intraoperative transfusion are associated with increased overall and major complications.
Preoperative anemia also contributed to increased risk
(OR 3.38) for major morbidity. Therefore, preoperative
anemia should be corrected, and diagnosis and improvement of decompensated comorbidities should also be
properly adjusted before CRE ileal or ileocecal resection
to minimize the risk.
The history of previous surgery aimed at solving CRE
obstruction as an independent factor (OR 3.54) emphasized
the importance of referring CRE patients to a specialized
center for initial surgical treatment. The impact of the
surgeon’s experience on surgical outcome has been well
recognized in various procedures.23,24 As ileal or ileocecal
resection is technically demanding, with high morbidity
rates, we examined whether surgical experience is required
to achieve optimum proficiency in CRE resection surgery.
The 6 surgeons in this study major in gastrointestinal surgery, and 2 were in the high-experience group (R40 cases).
This study shows that patients whose surgeons had performed over 40 operations had a risk of overall complication .26 times and a risk of major complications .30
times, lower than patients whose surgeon’s experience did
not exceed this threshold. Therefore, surgeons who have
745
limited experience in ileal or ileocecal resection for CRE
must carefully select their patients through thorough preoperative evaluation and should give more attention to the occurrence of postoperative complications.
Myelosuppression is a common complication after
chemoradiotherapy, and its influence on surgical outcomes
is largely unknown.25 In the current study, we addressed the
effect of preoperative leukocytopenia and thrombocytopenia as possible risk factors for surgical outcome. Consistent
with the results by Reim et al,26 preoperative clinically unapparent leukocytopenia is not a risk factor for postoperative complications. However, a preoperative platelet count
less than 100 ! 109/L was independently correlated with
major postoperative morbidity. This finding is supported
by previous studies. In a review of 536 patients by Sullivan
et al,27 patients who had undergone recent radiotherapy had
increased complications in emergency surgery, and thrombocytopenia is an independent risk factor for postoperative
death. Patients with complications after pancreatoduodenal
area resection also had significantly lower preoperative
platelet count compared with those without.28 Yang
et al29 also showed that preoperative low platelet count is
an independent risk factor of postoperative morbidity in
major hepatic resection of hepatocellular carcinoma for patients with underlying liver diseases. In another study for
resection of hepatocellular carcinoma, low platelet count
was independently associated with increased major complications.30 Hence, CRE patients with a low platelet count
might benefit from more conservative surgical procedures,
such as bypass or stoma, especially for inexperienced
surgeons.
Literature has shown that ileocecal resection not only
decreased the risk of repeated surgery for CRE but also the
risk of anastomotic leakage.5 Galland and Spencer19 suggested using the ileum and transverse colon for anastomosis
to reduce anastomotic leakage. However, we did not observe a difference of postoperative morbidity between ileocolic and ileoileal anastomosis. Theoretically, the irradiated
bowel has weakened blood supply due to obliterative vasculitis,31 and side-to-side anastomosis can preserve better
blood supply of the anastomosis and therefore decrease
the incidence of anastomotic leakage compared with
end-to-side anastomosis.32 Unfortunately, we did not find
a difference of postoperative morbidity between the 2 anastomotic fashions.
A substantial percentage of CRE patients had more than
1 radiotherapy-associated lesion, commonly ileum with
rectum or ileum with urinary tract. Kimose et al33 found a
combination of radiotherapy injuries affecting the colon,
rectum, small bowel, or the urinary tract in 62% of 182 patients. Turina et al13 demonstrated that two thirds of their
patients developed 2 or more complications from radiotherapy. The incidence rates of colorectal lesions (34 of 158),
radiation proctitis (20 of 158), and radiation uropathy (16
of 158) in the current cohort are 21.5% and 10.1% (both injuries, 9 of 158, 5.7%), respectively. Therefore, we suggest
preoperative colonoscopy or contrast enema examinations
746
The American Journal of Surgery, Vol 206, No 5, November 2013
routinely be performed in patients with CRE obstruction.
Concomitant radiation uropathy may be an indicator of
the severity of radiation injury and the vulnerability of patients to radiation injury, and Chen et al12,34 showed that it
was an independent predictive factor for the need of surgery
and poor overall survival after surgery. Consistent with this,
we also identified it as an independent risk factor for postoperative major morbidity.
Fast track surgery (FCS) has gained wide popularity in
gastrointestinal surgery in recent years.35,36 It aims at reducing surgical stress response, organ dysfunction, and
morbidity, thereby promoting a faster recovery after surgery. Since 2007, a fast track perioperative care protocol
was adopted for our CRE surgery patients, which included
thoracic epidural analgesia, perioperative fluid restriction,37
early ambulance and oral intake, early removal of the gastrointestinal tube, suprapubic urine catheter, and no standard use of abdominal drains. Our results revealed the
FCS did not significantly reduce overall morbidity (P 5
.063), however, it shortens the postoperative hospital stay
(16.6 vs 24.1 days). This indicates that the fast track methodology could be more widely adopted in ileal or ileocecal
resection for CRE.
Conclusions
Our experience has demonstrated that the acceptable
incidence of permanent intestinal failure and surgical
complications justified the application of resection surgery
in CRE with intestinal obstruction. Besides an ASA score
of III or higher and intraoperative transfusion, factors such
as preoperative anemia, thrombocytopenia, inexperienced
surgeons, and presence of radiation uropathy contribute
significantly to postoperative major morbidity. Applying
the principles of fast track surgery in this procedure may
reduce the length of postoperative hospital stay.
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