Download Extended surgery and pelvic exenteration for locally advanced rectal

UDK 616.36-006.04-089.844
DOI:10.2298/ACI1003023S
/STRU^NI RAD
Extended Surgery and Pelvic Exenteration for Locally
Advanced Rectal Cancer What are the Limits?
........
.................................
rezime
J. D. Smith, P. B. Paty,
Department of Surgery Memorial Sloan Kettering Cancer
Center New York, New York
Historically, locally advanced rectal cancers with
invasion of tumor into adjacent organs (T4 N1,2
tumors) have been considered poor prognosis cancers treated with palliative intent. However with
the advent of multi-modality therapy and improvement in surgical reconstructive techniques, extended resections for rectal tumors are possible
with acceptable patient morbidity and excellent oncological outcomes.
Key words: locally advanced rectal cancer, resection
INTRODUCTION
C
olorectal cancer is the 4th most prevalent cancer in
the US with 39,670 new case of rectal cancer estimated to be diagnosed in 2010. Of the 51,000 anticipated
colorectal cancer deaths in 2010, at least one third of
those will be due to rectal cancer and 10% of diagnosed
rectal cancers will be from locally advanced or T4 disease.1 Historically T4 or rectal cancers locally invading into
adjacent organs was considered inoperable disease. Unfortunately this led to the terminal symptoms of rectal cancer such as multiple fistulas, defecation difficulties and intractable pain due to the involvement of pelvic nerves,
which are extremely debilitating and can be particularly
challenging to palliate. Significant improvements in the
treatment of rectal cancer have occurred in the last 20 years to reduce the incidence of local recurrence of rectal cancer following surgery, the most significant being development of effective neo-adjuvant chemo-radiotherapy and
the widespread use of Total Mesorectal Excision (TME)
of the rectum during rectal cancer surgery.2,3
The most challenging situation arises when the tumor
has extended beyond the mesorectal plain and or invades
into adjacent organs representing a locally advanced, T4
tumor. These tumors pose a significant therapeutic dilemma for both patient and physician combined in the attempt for cure and palliation of symptoms. Treatment options must be discussed with a multimodality team with
input from colorectal surgeons, medical and radiation oncologists, in consultation with gynecologists, orthopaedic
surgeons and plastic and reconstructive surgeons where
appropriate. Once the tumor has spread beyond the mesorectal plain it frequently spreads to adjacent organs; the
sacrum and sacral nerves posteriorly; the vagina, uterus,
seminal vesicles, prostate and bladder anteriorly; and the
ureters, autonomic plexus and internal ileac lymph nodes
and vessels laterally.
The aims of surgery are to obtain a complete resection
of the tumor without residual microscopic disease, termed
an R0 resection. To do this the adjacent organs can be resected, while simultaneously trying to preserve as much
functional anatomy as is possible, such as sphincters nerves and bladder. The consequences for the patient of obtaining an R0 resection versus an R1 or 2 resection (microscopic or macroscopic tumor at the margin) are significant
with 5 year overall survival reducing from 50-60% with
R0 resections to 0-15% with R1 or 2 resections.4,5 The concept of extensive resection of multiple pelvic organs to
resect pelvis tumors was first described by Dr Brunschwig, a gynecologist working at Memorial Hospital in
New York in the 1940’s. While the morbidity and mortality rates he reported were extremely high subsequent improvements in reconstructive techniques and peri-operative management have made extended resections and exenterations for pelvic malignancies a much more palatable
treatment option.
In this paper we shall review the perioperative treatment, surgical technique, and clinical outcomes of patients with locally advanced rectal cancer.
INCIDENCE
Approximately 40,000 patients are diagnosed each year
with rectal cancer in the USA and of those approximately
25% will succumb to their disease. Ten percent of those
pati-ents with rectal cancer will present with locally advance or T4 disease in the absence of distant metastatic
24
J.D. Smith et al
ACI Vol. LVII
TABLE 1
OUTCOMES FOLLOWING TOTAL PELVIC EXENTERATION FOR LOCALLY ADVANCED RECTAL
CANCER
No of patients
Operative deaths
Local recurrence
5 year survival
Hong Kong, 2000
15
0
ns
64%
Taivan, 2001
50
1
ns
49%
Yokohama, 2003
71
0
ns
54%
Netherlands, 2007
32
1
22%
52%
Tokyo, 2009
91
0
9%
52%
TABLE 2
OUTCOMES FOLLOWING SACRAL RESECTION FOR LOCALLY ADVANCEC RECTAL CANCERS
No of pts
Operative deaths
Local recurrence
5 year survival
8
0
22%
56%
Poland, 2009
158
0
4.4%
68%
Japan, 2003
20
0
ns
47%
Netherlands, 2009
dise-ase.6 With appropriate multimodality treatment the
mortality rates at 5 years can be as low as 40%.7 With the
advent of effective neo-adjuvant chemotherapy and radiotherapy up to 60% of locally advanced and specifically
55% of T4 tumors can be downstaged.8 This may enable a
TME resection to be preformed. Even if down staging to
T3 disease is not possible, tumor shrinkage in response to
the neoadjuvant treatment may help to facilitate preservation of adjacent organs at surgery.
IMAGING/STAGING
Pre-operative imaging is essential to identify the extent
to the tumor invades into adjacent organs. As mentioned
before the most important factor to reduce the incidence
of local recurrence is obtaining an R0 resection with no
residual microscopic disease left. Tumor invasion into the
high sacrum (involvement of S2), encasement of the sciatic nerve or common ileac vessels, extensive retroperitoneal metastatic lymph nodes and unresectable distant
metastatic disease all make it impossible to obtain an R0
resection. These patients are therefore co-nsidered inoperable.
High quality pre-operative imaging is essential for appropriate patient selection. It also gives the surgeon an idea
of the extent of resection necessary and which organs
needed to be resected, i.e. need for sacrectomy or prostatectomy. High resolution pelvic MRI with or without gadolinium contrast is currently the best radiological test for
determining local tumor spread in the pelvis, however
endo- anal ultrasound is also a useful adjunct. Although
the overall accuracy of MRI to detect tumor adjacent organ spread and lymph node involvement is reduced in the
irradiated pelvis from 92% to 66%, it still offers the best
imaging for pre-operative planning of the appropriate surgical procedure.9
This is because sensitivity and specificity of endo-anal
ultrasound following neo-adjuvant treatment is inferior to
that of MRI, 77.8% and 37.5% respectively compared to
75% and 88% with MRI.10,11 EUS however can still have
a role in identifying pelvic lymphadenopathy.10 PET scanning may also be used to out rule or clarify suspected distant metastatic disease but has limited role in staging of
pelvic disease either pre or post neo-adjuvant treatment.
PREOPERATIVE CHEMORADIATION
Neo-adjuvant radiotherapy has been standard of care for
locally advanced rectal cancer (T3 and T4 tumors). Numerous studies have demonstrated a reduction in local recurrence of rectal cancer compared to surgery alone.
A meta analysis published in 2000 by Camma et al of14
randomized control trials comparing pre-op radiotherapy
and surgery to surgery alone demonstrated an improved
overall survival for RT and surgery with and odds ratio of
0.84 and a p-value of 0.04.12 Pre-operative RT can be given either as short course radiation with large fractions (5
x 5 Gy) for 1 week, followed by immediate surgery or as
long course, 5 – 6 weeks of conventional fractionation
(1.8 – 2.0 Gy) and surgery 4 – 6 weeks later. No trial has
shown differences between the two approaches. However
with the advent of adding chemotherapy to neo-adjuvant
treatment long course treatment has become more popular.
Br. 3
Extended surgery and pelvic exenteration for locally
advanced rectal cancer
The rational for adding chemotherapy to a neo-adjuvant
regime is compelling. Chemotherapy acts as a sensitising
agent for radiotherapy, improving its efficacy. It allows
for down staging of tumors to facilitate sphincter preserving surgery or in the case of T4 tumors, preservation of
more organs at surgery and also allows for ealier systemic
treatment of micrometastaitc disease. Complete remission
rates of up to 30 % have been demonstrated following
neo-adjuvant chemo radiotherapy compared to 10% with
radiotherapy alone.8,13 Adding infusional 5-FU to pre-op
RT reduced rates of local recurrence and increases rates of
both tumor regression and complete remission of the tumour.14,15
Recently capcitabine has also been substituted as a radio
sensitising chemotherapeutic agent with similar resul-ts16
Addition of post operative chemotherapy, particularly if a
clinical response to pre-operative treatment has been seen
is also advocated.17,18
TYPES OF OPERATION
The type of the operation preformed depends on the distance of the tumor from the anal sphincters, and the extent
of spread into the adjacent organs. The operation can be
divided into 2 distinct phases, the first being the resection
phase and the second being the reconstructive phase. The
types of resections are categorized by the organs resected
in continuity with the rectum.
The most common operations include total exenteration
for large bulky rectal tumors invading bladder or prostate;
posterior exenteration for women with tumors invading
the uterus; anterior exenteration for sigmoid cancers invading posterior wall of bladder and anterior wall of uterus;
extended resections for cancers focally invading pelvic
structures (seminal vesicle, vagina, bladder, ureter, autonomic plexus) or metastatic to lymph nodes in pelvic side
wall. Less commonly performed are sacral resections for
tumors that invade or densely adhere to sacrum or coccyx:
APR with sacrectomy or sacropelvic exenteration.
The reconstructive portion depends on the extent of the
resection. The colon can be re-anastomosed to the rectum
or the anal canal if the external sphincters are intact.
When the bladder has been removed, urinary diversion is
required, either by ileal conduit or by continent diversion.
Dead space in the pelvis can lead to abscess formation
and, when possible, should be filled with omentum. Large
defects in the perineal skin or vagina may need to be filled
with rectus or gracilis myocutaneous flaps
METHODS OF RESECTION
Patients are given a bowel preparation the day before
surgery and prophylactic antibiotics at induction of anesthesia. Depending on the type of resection the operation is
either in one or two stages. Initially the patient is place in
the lithotomy position to allow access to the pelvis anteriorly and the perineum.
If sacral resection is planned a second stage is necessary
and the patient is turned prone for the second part of the
operation. Pre-operative ureteric stenting can help protect
and identify ureters intraoperatively during mobilization
25
and for APR’s, suturing of the anus also helps reduce fecal contamination. As a general rule adherence to adjacent
structures must be assumed to be invasion of tumor into
the adjacent viscus and all or part of needs to be resected
with the tumor en bloc. Total exenteration A total pelvic
exenteration is the removal or the rectum, bladder; with
the vagina, uterus, cervix and parametrium in the female
and prostate and seminal vesicles in the male.
The first step is to inspect the abdomen looking for disseminated peritoneal disease or small liver metastases not
picked up on pre-op imaging which would change management. The origin of the inferior mesenteric artery at the
aorta is then dissected. Retroperitoneal lymph nodes are
inspected for metastatic disease, which might indicate unresectable disease if not easily removed. The ureters are
identified and preserved. They are not transected until resectability is confirmed, thus also allow for monitoring of
urine output. The inferior mesenteric artery are then ligated and transected. The recto-sigmoid colon is then transected approx 10cms proximal to the tumor.
The rectum is then dissected posteriorly down to the levator ani muscle. Care should be taken to avoid the pelvic
nerves if possible. At this point the bladder is mobilized
from the retropubic space and the lateral bladder pillars
attached to the lateral pubic rami are ligated and transected. If the patient is female the cardinal ligaments which
support the vagina and cervix are transected and ligated at
the pelvic sidewall. In a male patient the dissection is continued anteriorly to include the prostate gland. At this point a decision is made whether a low anterior resection is
possible or an APR in necessary. If an APR is necessary
the dissection continues below the lavatory ani muscles.
The perineal dissection then begins and anal canal and lower rectum are dissected out through the ischiorectal fossa and the urogenital diaphragm. In an extensive tumor
removal of vagina, vulva and urethra the may be necessary. The specimen can then be removed abdominal or perineal incision. The reconstructive phase now begins.
POSTERIOR EXENTERATION
A posterior exenteration may be performed in a female
if the bladder is not involved in the tumor. The vagina, cervix, uterus and adnexa are removed along with the rectum. The procedure is similar to a total exenteration, except instead of dissecting anterior to the bladder in the retropubic space, the peritoneum over the bladder is incised
and the bladder is sharply dissected off the anterior surface of the cervix and vagina down to or beyond the lavatory ani muscle depending on the level of the tumor. The
ureters must be dissected free distally from the anterior
parametria over the ureteral tunnel as it runs along with
the uterine artery. APR and sacrectomy The operation begins in the same fashion as a total exenteration.
The anterior dissection is developed in the ventral plane
preserving the female reproductive organs, prostate and
bladder if possible. The dorsal and dorsolateral dissection
follows the transsacral plane down to the level of the transaction of the sacrum. If the tumor extends up to the level
of S2 the cancer is deemed unresectable.
26
J.D. Smith et al
At this stage the level of sacral transaction is marked using K-wire through the sacrum or a deep cut of the osteotome. A gauze can be placed in the presacral space to reduce bleeding while the patient is turned into the prone
position. When the patient is in the prone position a dorsal
longitudinal incision is made from L5 down to and incorporating the anal canal.
The gluteus maximus and minimus muscles are then
dissected off the sacrum as flaps are raised bilaterally. The
sacrotuberous and sacrospinous ligaments are transected
at the sacrum which facilitates access to the pelvic floor
muscles, and the infra piriformis opening. Medially to the
infra piriformis a finger can be introduced into the presacral space to identify the level of the sacral resection. The
sacrum is then resected with care taken not to damage the
sacral roots. Then sacrum, the lateral pelvis walls and the
rectum are then removed en bloc. If there are any concerns about inadequate tumor margins the area should be irradiated with intra-operative radiotherapy (IOERT) if it is
available. Sacropelvic Exenteration. Sacropelvic exenteration combines the posterior dissection of the APR sacrectomy and the anterior dissection a pelvic exenteration.
This is reserved for patients with bulky rectal tumor extending into the sacrum posteriorly and the female reproductive organs or bladder and prostate. The rectum is remover en-bloc with the sacrum and resected visceral organs following division of the sacrum in the prone position
Again IOERT can be used if there is any doubt about an
RO resection APR/LAR with partial cystectomy of vaginectomy If the rectal tumor does not extend too aggressively into the bladder or specifically the trigone of the bladder, a partial cystectomy may be performed.
If necessary the ureters can be reimplanted using a
psoas hitch recons-truction. Similarly if part of the vagina
is involved a local resection of part of the vagina may be
undertaken. If the vaginal defect is too large to be closed
primarily a myocutaneous rectus abdominus flap may be
used to reconstruct the vaginal defect.
PELVIC AND PERINEAL RECONSTRUCTION
The organs and areas which may need reconstruction include the bowel, bladder, vagina, and large perineal defects. If the external anal sphincters were able to be preserved a colorectal or coloanal anastomosis with or without a
j-pouch or coloplasty may be performed. A covering defunctioning ileostomy would always be recommended due
to the increase probability of an anastomotic leek due to
the extensive surgery and neo-adjuvant treatment. If an
APR is performed an end colostomy must be constructed.
The bladder if completely resected can be reconstructed
using a variety of different techniques using colon or ileum leaving patients with continent (Indiana pouch, Mainz pouch, Florida pouch or Miami pouch) or incontinent
(Ileal conduit, colonic conduit or ureterocolostomy) urinary diversions. The decision whether to use reconstructive
flaps in closure of the perineal defect or to close primarily
depends on the side of the defect left in the perineal wound. Should the vagina need reconstructing or the sacral
rese-ction performed then a myocutaneous flap, either
ACI Vol. LVII
with the rectus muscle of the gracilis muscle would be advisable to facilitate wound healing.
Omental patches and prosthetic and biological meshes
or grafts have also been advocated to fill the pelvic dead
space following extensive pelvic exenterations.
OUTCOME
The single most important factor influencing both local
recurrence rates and overall survival is the ability to obtain a complete microscopic or R0 resection. Other factors
affecting survival include the presence positive lymph nodes, lymphovascular invasion, and a lack of response in
CEA level post-operatively.19,20 Overall survival rates for
locally invasive rectal cancers are relatively good with 5
year survival rates ranging fro 49% to 64% following pelvic exenteration and 47% to 68% following abdomino-sacral resections. (Tables 1 & 2)
SUMMARY
Patients with rectal tumors extending into adjacent organs now have potentially curative treatment options.
Multi-modality treatment is the optimal therapy with neoadjuvant radiotherapy and chemotherapy facilitating down
staging of tumors, enabling less aggressive resecti-ons.
Good pre-operative imaging with a high resolution MRI
scan can allow planning of the appropriate surgical procedure and organ resection. Treatment options must be
made in the setting of a multidisciplinary team including
not only colorectal surgeons but gynecologists, orthopaedic surgeons, plastic and reconstructive surgeons, radiation oncologist and oncologists. Patients need to be psychologically prepared for extensive resections, prolonged hospital stays and high incidences of morbidity. Input from
stoma therapy nurses, dietetics and pre-operative counseling is crucial to prepare patents for the rigor of treatment.
Following tumor resection and recovery, adjuvant chemotherapy is advisable to reduce the risk of local and distant
recurrence. In conclusion, following multimodality treatment and extended surgical resection, 5 year survival of
up to 60% can be achieved with acceptable patient morbidity.
SUMMARY
EKSTENZIVNA HIRURGIJA I PELVI^NA EGZENTEREZA KOD LOKALNO UZNAPREDOVALOG KARCINOMA REKTUMA. GDE SU GRANICE?
Istorijski, lokalno uznapredovalim karcinomima rektuma sa tumorskom invazijom u okolne organe (T4 N1,2
stadijum tumora) davana je loa{a prognoza i tretirani su
sa palijativnom namerom. Medjutim, uz napredak multi - modalne terapije, kao i hirur{kih rekonstruktivnih
tehnika, ekstenzivne resekcije kod karcinoma rektuma sa
prihvatljivim morbiditetom i odli~nim onkolo{kim rezult
atima .
Klju~ne re~i: lokalno uznapredovali karcinom, rektum,
resekcija
Br. 3
Extended surgery and pelvic exenteration for locally
advanced rectal cancer
REFERENCES
1. Gunderson, L.L., et al., Revised tumor and node categorization for rectal cancer based on surveillance,
epidemiology, and end results and rectal pooled analysis
outcomes. J Clin Oncol, 2010. 28(2): p. 256-63.
2. Cecil, T.D., et al., Total mesorectal excision results in
low local recurrence rates in lymph node-positive rectal
cancer. Dis Colon Rectum, 2004. 47(7): p. 1145-9; discussion 1149-50.
3. Hosein, P.J. and C.M. Rocha-Lima, Role of combined-modality therapy in the management of locally advanced rectal cancer. Clin Colorectal Cancer, 2008. 7(6): p.
369-75.
4. Vermaas, M., et al., Total pelvic exenteration for primary locally advanced and locally recurrent rectal cancer.
Eur J Surg Oncol, 2007. 33(4): p. 452-8.
5. Ferenschild, F.T., et al., Abdominosacral resection for
locally advanced and recurrent rectal cancer. Br J Surg,
2009. 96(11): p. 1341-7.
6. Gunderson, L.L., et al., Revised TN categorization for
colon cancer based on national survival outcomes data. J
Clin Oncol, 2010. 28(2): p. 264-71.
7. Bebenek, M., Abdominosacral amputation of the rectum for low rectal cancers: ten years of experience. Ann
Surg Oncol, 2009. 16(8): p. 2211-7.
8. Janjan, N.A., et al., Tumor downstaging and sphincter
preservation with preoperative chemoradiation in locally
advanced rectal cancer: the M. D. Anderson Cancer Center experience. Int J Radiat Oncol Biol Phys, 1999. 44(5):
p. 1027-38.
9. Kim, D.J., et al., Restaging of Rectal Cancer with MR
Imaging after Concurrent Chemotherapy and Radiation
Therapy. Radiographics, 2010. 30(2): p. 503-16.
10. Arbea, L., et al., Patterns of Response After Preoperative INTENSITY-MODULATED RADIATION THERAPY and capecitabine/oxaliplatin in Rectal Cancer: Is
There Still a Place for Ecoendoscopic Ultrasound? Int J
Radiat Oncol Biol Phys, 2010.
11. Kim, S.H., et al., Accuracy of MRI for predicting
the circumferential resection margin, mesorectal fascia invasion, and tumor response to neoadjuvant chemo-radiotherapy for locally advanced rectal cancer. J Magn Reson
Imaging, 2009. 29(5): p. 1093-101.
12. Camma, C., et al., Preoperative radiotherapy for resectable rectal cancer: A meta-analysis. JAMA, 2000.
284(8): p. 1008-15.
13. Veenhof, A.A., et al., Preoperative radiation therapy
for locally advanced rectal cancer: a comparison between
two different time intervals to surgery. Int J Colorectal
Dis, 2007. 22(5): p. 507-13.
14. Krook, J.E., et al., Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med, 1991.
324(11): p. 709-15.
15. Yamada, K., et al., Pelvic exenteration and sacral resection for locally advanced primary and recurrent rectal
cancer. Dis Colon Rectum, 2002. 45(8): p. 1078-84.
16. Carlomagno, C., et al., Neo-adjuvant treatment of
rectal cancer with capecitabine and oxaliplatin in combination with radiotherapy: a phase II study. Ann Oncol,
2009. 20(5): p. 906-12.
27
17. Smalley, S.R., et al., Phase III trial of fluorouracilbased chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol, 2006. 24(22): p. 3542-7.
18. Collette, L., et al., Patients with curative resection of
cT3-4 rectal cancer after preoperative radiotherapy or radiochemotherapy: does anybody benefit from adjuvant
fluorouracil-based chemotherapy? A trial of the European
Organisation for Research and Treatment of Cancer Radiation Oncology Group. J Clin Oncol, 2007. 25(28): p.
4379-86.
19. Derici, H., et al., Multivisceral resections for locally
advanced rectal cancer. Colorectal Dis, 2008. 10(5): p.
453-9.
20. Larsen, S.G., et al., Prognostic factors after preoperative irradiation and surgery for locally advanced rectal
cancer. Eur J Surg Oncol, 2008. 34(4): p. 410-7.
21. Law, W.L., K.W. Chu, and H.K. Choi, Total pelvic
exenteration for locally advanced rectal cancer. J Am Coll
Surg, 2000. 190(1): p. 78-83.
22. Chen, H.S. and S.M. Sheen-Chen, Total pelvic
exenteration for primary local advanced colorectal cancer.
World J Surg, 2001. 25(12): p. 1546-9.
23. Ike, H., et al., Outcome of total pelvic exenteration
for primary rectal cancer. Dis Colon Rectum, 2003. 46(4):
p. 474-80.
24. Ishiguro, S., et al., Pelvic exenteration for clinical
T4 rectal cancer: oncologic outcome in 93 patients at a
single institution over a 30-year period. Surgery, 2009.
145(2): p. 189-95.