Journal of Cancer Therapy, 2013, 4, 1228-1235
http://dx.doi.org/10.4236/jct.2013.47143 Published Online September 2013 (http://www.scirp.org/journal/jct)
Sphincter Saving Surgeries for Locally Advanced Low
Rectal Cancer after Neoadjuvant Chemoradiation
Mohamed A. E. Salem1*, Hamza A. Hamza2, Gamal Amira3, Abeer E. Ibrahium4, Ahmed A. S. Salem1
1Surgical Oncology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt; 2Radiation Oncology Department,
South Egypt Cancer Institute, Assiut University, Assiut, Egypt; 3Surgical Oncology Department, National Cancer Institute, Cairo
University, Cairo, Egypt; 4Medical Oncology Department, South Egypt Cancer Institute, Assiut University, Assiut, Egypt.
Email: *salem641972@hotmail.com
Received May 28th, 2013; revised June 28th, 2013; accepted July 2nd, 2013
Copyright © 2013 Mohamed A. E. Salem et al. This is an open access article distributed under the Creative Commons Attribution
License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
ABSTRACT
Background: Rectal cancer accounts for the largest distribution within one anatomical region of the large bowel, with
approximately one third of all CRC located within the rectum. The Golden standard treatment of primary rectal cancer
is curative surgical resection; however, affine balance remains between disease cure and restoration of gastrointestinal
continuity. Combined modality has proven efficacy in many malignant tumors with advantage of organ preservation.
Methods: Forty nine (49) patients with low rectal carcinoma were included in a prospective study, between Jan 2007
and Jan 2012. Preoperative chemoradiation was administrated to all patients and subjected to different techniques of
sphincter saving surgery. Stage I and Stage IV disease at diagnosis were excluded from the study. Results: Forty nine
patients were included in the study. 27 (55%) patients were male and 22 (45%) were female; the age ranges from 23
years to 70 years with the median age 46 years. The main presenting symptoms were bleeding per rectum and tenesmus,
Stage II 18 patients (36.7%), stage III 31 patients (63.3%). Complete clinical and pathological response in 3 patients
(6%), and complete clinical response with only microscopically residual carcinoma in 20 patients (41%), partial re-
sponse in 18 patients (36.7%), and no significant response in 8 patients (16%) 7 from 8 were mucoid carcinoma. Low
anterior resection (LAR) in 22 patients (44.9%), Hartman’s procedure in 4 patients (8.1%), Coloanal pull-through (COP)
was done in 19 patients (38.9%) and perineal colostomy in 4 patients (8.1%). For patients with colo-anal pull-through
technique complete dehiscent and retraction observed in 2 cases, Major leakage in one case, stenosis in 4 cases. Con-
clusion: There is tendency of colorectal cancers to affect younger groups. Most patients presented in advanced stage.
Neadjuvant chemo radiation is an excellent tool in sphincter saving surgery. Coloanal pull-through technique is not a
widely spread technique for low rectal cancer with good oncological safety and acceptable functional outcome.
Keywords: Coloanal Pull-Through; Colo Rectal Cancer; Neoadjuvant Chemoradiation; Low Anterior Resection
1. Introduction
Rectal cancer accounts for the largest distribution within
one anatomical region of the large bowel, with approxi-
mately one third of all CRC located within the rectum.
The Golden standard treatment of primary rectal cancer
is curative surgical resection; however, a fine balance
remains between disease cure and restoration of gastro-
intestinal continuity. Combined modality has proven ef-
ficacy in many malignant tumors with advantage of or-
gan preservation.
Cancers of the distal rectum pose the double problem
of local tumor control and sphincter preservation. Ab-
dominoperineal resection (APR), long considered as the
standard treatment of tumors with a distal edge located
up to 6 cm from the anal verge, provides local control in
a substantial majority of cases, but the resulting loss of
sphincter function represents a psychological burden for
many patients [1,2]
Surgery alone has been the standard treatment for pa-
tients with adenocarcinoma of the cancer rectum. Despite
advances in surgical technique, local recurrence is still a
considerable problem [3]. At time of initial presentation,
approximately 15% of the patients diagnosed with rectal
cancer have locally advanced unresectable disease [4,5].
A more precise understanding of failure patterns,
leading to the acceptance of distal margins of less than 2
cm, and the recent progress in bowel stapling techniques
have made coloanal anastomoses feasible after low rectal
*Corresponding author.
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Sphincter Saving Surgeries for Locally Advanced Low Rectal Cancer after Neoadjuvant Chemoradiation 1229
excision. This latter approach is often associated with
preoperative radiotherapy (RT), which may be consid-
ered to compensate for the limitations of the surgical
technique resulting from narrow radial and distal surgical
margins [6-8].
Primary end points of this study to:
1) Assess the pathological response after CT based de-
lineation 3DCRT concurrently with fluorouracil;
2) Feasibility of sphenteric preservation after neoad-
juvant chemoradiation;
3) Quality of life after different surgical techniques af-
ter chemoradiation to preserve anal sphincter.
Secondary end point is disease free survival and OAS.
2. Patients and Methods
From Jan 2007 to Jan 2012, 49 consecutive patients with
primary cancers involving the distal rectum (up to 6 cm
or less from the anal verge) were treated by preoperative
RT, with concomitant chemotherapy, at the South Egypt
Cancer Institute, Assiut University, Assiut, Egypt.
The aim of the preoperative chemo-radiation was es-
sentially to achieve down-staging in T2 tumors, while for
T3 tumors the aim was both improvement of local con-
trol and down-staging.
2.1. Inclusion Criteria
Patients had to present histologically confirmed adenoca-
rinoma of the rectum without evidence of distant metas-
tases, and the inferior edge of the tumor had to be located
not further than 6 cm from the anal verge. Only Interna-
tional Union Against Cancer (UICC) T2-T4, N0 or N1
tumors staged were included. The tumor should not in-
volve more than two-thirds of the rectal circumference to
be accessible to CXR therapy. Patients with a perform-
ance status 2 according to the Eastern Cooperative On-
cology Group (ECOG) system.
2.2. Exclusion Criteria
Previous pelvic irradiation therapy; Previous history of
malignant disease; Any other serious illness and/or major
organ dys-function; Pregnancy or lactation.
Pretreatment evaluation included physical examination,
proctoscopy and/or colonoscopy, abdominal/pelvic com-
puterized tomography (CT) and/or MRI, chest X-ray and
serum carcinoembryonic antigen (CEA).
The distance between anal verge and the caudal edge
of the tumor was assessed by proctoscopy and/or digital
examination.
The preoperative tumor classification was determined
using information from the digital examination (includ-
ing assessment of mobility), CT and/or MRI scan and/or
trans-rectal ultrasound, when available. Pretreatment pa-
tient characteristics are displayed in Table 1.
Table 1. pretreatment patient characteristics.
Age range (mean) 23 - 70 Ys (46 Ys)
Male/female 27/22
Distance from anal verge to the
lower tumor edge (cm)
Mean
2 - 6 cm
4 cm
Stage
Stage II (T3-T4,N0)
Stage III ( T2-T4,N1) only
18 (36.7%)
31 (63.3%)
2.3. Preoperative Therapy
On conventional simulator using prone position with full
bladder which provide maximal displacement of small
bowel out of the pelvis. We use lasyer for patient posi-
tioning and immobilization. We use CT and at the same
isocenteric position, multiple CT cuts at 0.5 cm interval
throughout the entire volume. CT data then transferred to
the computer planning system (Version Xio-Release 4.2).
At each CT slice, we delineates our target volumes
(CTV1, CTV2, CTV3, PTV) CTV1 (peri-rectal, presac-
ral, internal iliac regions) the caudal extent of this elec-
tive target volume should be a minimum of 2 cm caudal
to gross disease, including coverage of the entire meso-
rectum to the pelvic floor. Unless there is radiographic
evidence of extension into the ischiorectal fossa, exten-
sion of: CTV1 does not need to go more than a 5 milli-
meters beyond the levator muscles. For very advanced
rectal cancers, extending through the mesorectum or the
levators, we add 2 cm margin up to bone wherever the
cancer extends beyond the usual compartments.
CTV2: if there is any extension into gynecologic, geni-
tourinary structures or anal canal, the external iliac re-
gion should be added. We added 7 - 8 mm margin in soft
tissue around the external iliac vessels, but one should
consider a larger 10+ mm margin anterolaterally espe-
cially if small vessels or nodes are identified in this area.
CTV3: boost clinical target volume extend to entire
mesorectum and presacral region at involved levels, in-
cluding 2 cm cephalic and caudal in the mesorectum and
2 cm on gross tumor within the anorectum.
PTV margin of 0.7 cm around CTV, except at skin re-
sulting in PTV1, PTV2 and PTV3 around CTV1, CTV2
and CTV3 respectively.
A complete 3D plan done with tissue inhomogeneity
correction taking inconsid-eration normal tissue toller-
ance as the femoral head and neck, and intestine.
We delivered 4500 cGy in 25 fractions to PTV1 and
PTV2 then boost 540 cGy in 3 fractions to PTV3.
Chemotherapy
Laboratory studies: CBC, serum albumin, bilirubin, AST,
ALT, ALP, urea, creatinin and CEA before chemother-
apy.
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Sphincter Saving Surgeries for Locally Advanced Low Rectal Cancer after Neoadjuvant Chemoradiation
1230
Chemotherapy regimen: 5-flourouracil 400 mg/m2 +
leucovorin 20 mg/m2 D1-4 of first and fifth week of ra-
diation
2.4. Surgery
Surgery was performed at a median interval of 25 days
(range 20 - 40 days) from completion of chemo radiation.
Low anterior resection was done in 22 (44.9%) patients
(9 with coloanal and 13 with colorectal anastomoses), 4
(8.1%) patients under continent perineal colostomy, 4
(8.1%) patients under Hartman’s procedures and subse-
quent continuity using surgical stapler and coloanal pull
through was done in 19 (38.9%) patients (34.7%) for
those patients where low anterior resection is not on-
cologically save and the only alternative is APR. A tem-
porary transverse colostomy was performed in 10 pa-
tients and temporary ileostomy in 5 patients.
2.4.1. Techniques of Transanal Pull-Through
The idea for transanal pull through was taken from man-
agement of Hirschsprung’s Disease. In patients undergo-
ing transanal pull through with coloanal anastomosis, the
technique was standardized according to the following
steps: The left colon with the splenic flexure was mobi-
lized after ligature and section of the inferior mesenteric
vein and artery. The mesosigmoid was then mobilized
and the plane of the mesorectum was entered in continu-
ity as the dissection proceeded distally (Figure 1). This
plane was followed down to the level of the pelvic floor
when a total mesorectal excision (TME) was performed
[9]. The dissection of the rectum and mesorectum was
performed applying slight lateral traction to open the
cleavage plane between the mesorectum and the lateral
wall of the pelvis. This allowed clear visualization and
preservation of the pelvic autonomic nerves. Transaction
of rectum at least 2 cm below tumor growth with presser-
vation of anal sphincter, Mucosectomy of any remaining
rectal mucosa, telescoping of colon (Figure 2) or ileal
loop (Figure 3) through the anus, the colo-anal anasto-
mosis was done from below between colon and the anal
canal with 2/0 absorbable sutures, the distal stump leave
to be ischemic and trimming done after 7 - 10 days post-
operative. Oral feeding started after regain bowel move-
ment.
2.4.2. Techniques of Continent Perineal Colostomy
After performing abdominoperineal resection, a 7 - 8 cm
smooth muscle colonic cuff was prepared from resected
segment of the sigmoid colon. Mesenteric fat and epip-
loic appendages were removed. The colonic tube was
then inverted and the mucosa was sharply dissected from
the sub mucosa. After a longitudinal incision along tinea
coli, a flap 3 to 4 cm wide and 7 cm long was created.
The neosphincter was created by first securing the flap to
Figure 1. Mesorectum dissection.
Figure 2. Coloanal pull through.
anti mesenteric portion of colon with interrupted 3 - 0
absorbable sutures. This was subsequently wrapped three
quarter turns through the rest 3 cm proximal to terminal
colon. The pull-through colon was matured at the skin
using interrupted 3 - 0 absorbable sutures in tension free
fashion.
3. Result
Forty nine (49) patients were included in the study. 27
(55%) patients were male and 22 (45%) were female, the
age range from 23 years to 70 years with the median age
46 years. The main presenting symptoms were bleeding
per rectum and Tenesmus. Stage II eighteen patients
(36.7%) and Stage III thirty one patients (63.3%).
All patients had a pretreatment biopsy diagnosis of
adenocarcinoma (11 well-differentiated, 18 moderately
differentiated, 7 poorly differentiated and 13 (26.5%)
mucoid carcinoma). Most cases of mucoid carcinoma (10
cases) were in young age under 40 years.
Neoadjuvant chemoradiation was administrated for all
patients. pathological evaluation of the resected specimen
show all circumferential resection margins were clear by
at least 1 cm , complete clinical and pathological response
in 3 patients (6%), and complete clinical response with
only microscopically residual carcinoma in 20 patients
(41%), partial response in 18 patients (36.7%), no sig-
nificant response in 8 patients (16%) 7 from 8 were
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Sphincter Saving Surgeries for Locally Advanced Low Rectal Cancer after Neoadjuvant Chemoradiation 1231
Figure 3. Total colectomy with ileoanal pull through.
mucoid carcinoma.
Prophylactic stoma was preformed in 6 patients in
CAP and 9 patients of LAR. A closure of the diverting
stoma could be performed, on average, 18 weeks after
surgery. The closure rates were significantly lower in pa-
tients with anastomotic leakage. In one patient with clo-
sure of the colostomy and weak functional results, and in
one patient with recto-vaginal fistula, a permanent colo-
stomy was again performed after previous closure.
Major leakage occurs in 2 case of colo-anal pull through
due to ischemia of rectal stump and complete retraction
of the stump requiring refashioning in one case and re-
anastomosis in the other case and covering ileostomy.
One case of minor leakage managed conservatively.
For low anterior resection 1 case of major leakage man-
aged by covering ileostomy and 3 cases of minor leakage
managed conservatively.
Only one case with covering stoma develop minor
leakage which managed conservatively all case of conti-
nent perineal colostomy developed sever stenosis and fi-
brosis with poor continence requiring reconstruction of
terminal colostomy.
With a median follow-up of 26 months (range 4 - 72
months) from the start of RT, 10 (20.4%) patients have
died from their disease 4 in colo-anal pullthrough group
4 in low anterior resection group and 2 in continent per-
ineal colostomy. thirteen (26.5%) of 49 patients exhibited
tumor progression. Nine (18.3%) developed local recur-
rence; 4 in CAP group 4 in LAR group and 1 in CPC
group. Four patients had progress of disease without lo-
cal recurrence 2 in CAP patients 1 LAR and 1 in CPC.
Tumor progression was diagnosed at an average of 20
months (4 - 60 months).
The 4-year actuarial survival for all patients was 69%.
The 2-year actuarial locoregional control rates were
76.5% for all patients, 86% for the 14 patients with
marked pathological tumour response to chemoradiation.
No significant difference in disease-free survival was
observed between patients operated by LAR, Continent
perineal colostomy or by Trans anal pull through surgery.
The characteristics surgical types, surgical complica-
tion and functional outcome of patients (Table 2).
4. Disscussion
Historically, patients with mid to distal rectal cancers had
to undergo abdominoperineal resection to achieve ade-
quate oncological clearance. However, with better equip-
ment and improved surgical techniques, low anterior re-
section with a low colorectal or coloanal anastomosis has
become the technique of choice [10]. Two major issues
encountered in the surgical resection of low rectal can-
cers (tumor located <6 cm from anal verge) are tumor-
free surgical resection margin and adequate fields of
colo-anal pull-through anastomosis [11].
The beneficial effect of preoperative pelvic irradiation
as an adjuvant treatment has been confirmed in several
studies [12,13].
Preoperative radiochemotherapy decreases the tumor
volume, induces downstaging, and facilitates surgical re-
section. In addition, it transforms the vegetative compo-
nent of the tumor into an ulcerative scar, and this may
decrease intraoperative tumor seeding [14]. We observed
significant tumor regression 47%, This high rate of tu-
mor regression, compared with the 18% to 26% reported
after preoperative radiotherapy
alone [15,16],
is similar
to the 53% to 64% observed after preoperative radio-
therapy potentiated by che
motherapy [17-19].
Adding chemotherapy to preoperative radiotherapy
improve both local control and distal disease [14].
The
median age of our study is 46 years which younger
than age reported in other studies, where they reported
median age range from 59 - 70 years the exact cause
cannot be explained but may be due to genetic back-
ground or exposure to carcinogenic materials.
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Sphincter Saving Surgeries for Locally Advanced Low Rectal Cancer after Neoadjuvant Chemoradiation
Copyright © 2013 SciRes. JCT
1232
Table 2. Sphincter-saving procedur e , surgical complication and functional outcome.
Colo anal pull through (COP) LAR (low anterior
resection) Continent perineal
colostomy
Gender
Male
Female
12 (63.1%)
7 (36.9%)
11 (50%)
11 (50%)
4 (100%)
0
Age range
median age
23 - 62 years
42 years
31 - 70 years
48 years
35 - 55 years
43 years
Procedure Colo-anal pull through 18
Ileo-anal pull through 1
Stapler 9
Hand swing 13
Leakage
Major
Minor
2 (complete detachment & retracted
intra-abdominally)
1
1
3
No
Prophylactic stoma
Colostomy
Ileostomy
6
5
1
9
5
4
No
Postoperative stenosi s 5 (26%) 4 (18%) 4 (100%)
Urologic Complication 3 (15.8%) 1 (4.5%) No
Disease progression
Local recurrence
Distance metastasis
Local and distance metastasis
3 (15.8%)
1 (5.3%)
1 (5.3%)
2 (9%)
3 (13.6%)
1 (4.5%)
0
1
0
Functional outcome
Continence for solid & liquid
stool & flatus
Continence for solid stool & occasional
incontinence for liquid stool
Soiling at night
Frequent episodes of incontinence
for liquid stool
8 (42.1%)
5 (26.3%)
2 (10.6%)
2 (10.6%)
15 (68.2%)
5 (22.7%)
1 (4.5%)
1 (4.5%)
0
1
2
1
Most patients with rectal carcinoma can now be treat-
ed by sphincter-saving surgery, but many pay a price for
restoration of continuity. The “anterior resection syn-
drome” of faecal leakage and urgency of defaecation
may afflict up to 50 per cent of patients after low anterior
resection and is more common after very low colorectal
or coloanal anastomosis [20].
The recurrence rate in our study is 18.3% of the cura-
tively operated patients is in accordance with other studies
of this surgical procedure, where rates range from 0 to
30% [21-25].
The method of anastomosis (hand-sewn vs. stapled)
does not seem to influence recurrence rates [26].
Problems concerning the anastomosis, mostly insuffi-
ciencies, present the most common and widely discussed
complications in rectal surgery. The depth of the anas-
tomosis and the aim of a tension-free anastomosis in the
pull-through operation make high demands on the blood
supply of the colon. Most likely, the blood supply suffers
from the mobilization and the skeletonization of the
mesocolon.
Suture insufficiency plays a key role in postoperative
morbidity. The rate of this complication after CAA is
generally reported to be comparable with previous study
[21-23,27]. The correlation of this complication and neo-
adjuvant radiation (most likely by causing obliterating
endarteritis) was significant.
Stricture formation, a common problem at the site of
the anastomosis, occurred in 13 patients 26.5%, (five in
CAP and 4 of LAR and in 4 patients of CPC) in the pa-
tients in this study. This rate does not clearly differ from
the rates after deep anterior resection, although not much
Sphincter Saving Surgeries for Locally Advanced Low Rectal Cancer after Neoadjuvant Chemoradiation 1233
data exists for comparison. In general, this complication
is considered to be higher in stapled anastomosis [28].
The fistula formation was encountered in 1 (2%) pa-
tient developed rectovaginal fistula after LAR using sta-
pler techniques.
After deep anterior resection with stapled anastomosis,
the rate of fistula formation was approximately 2% [29].
In addition to rectal and gynecological surgery, radiation
and chemotherapy can typically lead to fistula formation
[30,31].
Acceptable anorectal continence after rectal resection
and hand-sewn anastomosis is widely described in the
literature [21,23,32-37].
In most of these studies the majority of patient conti-
nence was described as low grade (Grade I or II accord-
ing to Kirwan). The overall disillusioning results in this
study in comparison to other studies have to be analyzed
critically, as a uniform classification was not used in
every study, and all patients in this study had reduced
sphincter function caused by treatments prior to surgery.
Generally, a hand-sewn suture facilitates nerve growth
through the anastomosis, which is more likely to be im-
paired by stapled anastomosis, and can lead to better dis-
crimination and a better recovery of the anal inhibitory
reflex [38]. Presurgical radiotherapy of the rectum or its
neighboring organs further influences anorectal conti-
nence [27]. However the neoadjuvany therapy downstage
the locally advanced low rectal cancer and change the
decision option from abdomenoperineal to sphincter sav-
ing procedures in many cases.
5. Conclusions
There is a tendency of rectal cancers to affect younger
groups. Most patients presented advanced stage and ag-
gressive histopathology.
Using a multimodal approach, conservative treatment
was possible in patients with locally advanced carcino-
mas of the lower third of the rectum that would have re-
quired APR in most instances. Preoperative radiochemo-
therapy was associated with a low rate of complications
and induced significant down staging, Coloanal pull-
through technique is not a widely spread technique for
low rectal cancer with good oncological safety and ac-
ceptable functional outcome however large numbers of
patients have to study.
6. Acknowledgements
The authors received no financial or other support for the
research reported in manuscript.
Contributions: M.A.S. participate in collection of pa-
tient’s data, patient diagnoses and surgical evaluation and
surgical resection of patient subjected to surgery, general
coordination, drafting of manuscript and writing final
manuscript.
H.A. Carried out collection of patient’s data, patient
diagnoses, radiotherapy administration, follow up. A.I.
carried out collection of patient’s data, patient diagnoses,
chemotherapy administration and follow up. G.A. And
A.W. participate in surgical evaluation and management
of patients subjected to surgery. All authors have read
and approved manuscript.
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