1. Ultra-Low Sphincter Saving Procedures -
Re-defining the inferior resection limit
4th East – West
Colorectal Days
Hungary
Oct , 2008
W. Douglas Wong, M.D.
Chief,Colorectal Service
Memorial Sloan Kettering Cancer Center
Professor of Surgery
Cornell University Medical School

2. Sphincter preserving surgery should be considered the standard for the majority of low rectal cancers

3. How much distal margin do you need?
5 cm rule*
2 cm rule**
“end of the 2 cm rule”
*Williams et al. Reappraisal of the 5cm rule of distal excision for carcinoma of the rectum. Br. J Surg ;70:
**Pollett et al. The relationship between the extent of distal clearance and survival and local recurrence rates after curative anterior resection for carcinoma of the rectum. Ann Surg ;198:

4. What is an adequate distal margin for sphincter sparing rectal resection?
MSKCC Studies
Whole Mount Pathologic Analysis ( Annals of Surgery 2007)
Distal Margin Analysis Study ( Unpublished 2008 )
Coloanal / Intersphincteric Study ( Submitted )
1) Good afternoon and thank you to the Society for the opportunity to present this work on the management of stage IV rectal cancer.
2) The question that I would like to ask is when is rectal resection justified.

5. Annals of Surgery 2007;245(1):88-93
Study # 1
A Prospective Pathologic Analysis Using Whole-Mount Sections of Rectal Cancer Following Preoperative Combined Modality Therapy Implications for Sphincter Preservation
Jose Guillem, David Chessin, Jinru Shia, Arief Suriawinata, Elyn Riedel, Harvey Moore,
Bruce Minsky, and W. Douglas Wong
Annals of Surgery 2007;245(1):88-93

6. Aims of the Study
To use whole mount pathologic analysis to characterize microscopic patterns of residual disease
Circumferential margins
Distal resection margins
To identify clinicopathologic factors associated with residual disease

7. Methodology
109 patients prospectively accrued with ERUS staged locally advanced rectal cancer (T2-T4 and /or N1)
Median distance of 7 cm. from anal verge
Preoperative chemoradiation followed by TME based resection
Comprehensive whole mount pathologic analysis was performed

8. Results
Sphincter preserving resection was feasible in 87 patients (80%)
Distal margins negative in all 109 pts
Median 2.1 cm; range 0.4 – 10 cm
Intramural extension beyond gross mucosal edge of residual tumor was only in 2 patients (1.8 %)
Both < .95 cm
No positive circumferential margins although 6 were less that 1 mm
Median 10 mm; range mm
On multivariate analysis, residual disease was observed more frequently in distally located tumors < 5 cm from the anal verge (p=.03)

9. Impact of distal margin
Distal Margin Rectal Cancer
Impact of distal margin
MSK1: Whole mount analysis of 87 locally advanced RC after neoadjuvant CMT and LAR
No positive margins
2.2% had intramural extension
beyond mucosal edge of tumor
9.5mm
1) There are three local treatment options: rectal resection, pelvic radiation, and combination therapy.
2) None will control the metastatic disease.
3) However, rectal resection has the shortest delay to systemic chemotherapy and does not compromise the patient’s ability to tolerate chemotherapy by suppressing the bone marrow.
4) So, we wished to quantify the morbidity of surgery and see how effective it can be without the benefit of radiation in patients with advanced disease.
3mm
1. Guillem JG, Ann Surg Jan;245(1):88-93

10. Conclusions
Following preoperative chemoradiation and TME, distal margins of 1 cm seems adequate
Occult tumor beneath the mucosal edge was rare and when present was limited to less that 1 cm
These results extend the indications for sphincter preservation as distal resection margins of only 1 cm may be acceptable for locally advanced rectal cancer treated with preoperative chemoradiation

11. Distal Margin Analysis
Study # 2
Distal Margin Analysis
Nash G, Paty P, Guillem J, Temple L, Weiser M, and Wong D
( Unpublished Data 2008 )
1) Good afternoon and thank you to the Society for the opportunity to present this work on the management of stage IV rectal cancer.
2) The question that I would like to ask is when is rectal resection justified.

12. Distal margin rectal cancer
Study Hypotheses
Margin of less than 8mm is associated with higher risk of local recurrence (LR)
Mucosal recurrence (MR) is the mechanism of higher LR
1) We performed a retrospective
2) To answer the following questions . . .

13. Study Cohort 627 patients with primary rectal cancer
Distal margin rectal cancer
Study Cohort
627 patients with primary rectal cancer
Study period:
Curative resection
No involvement of adjacent organs
Low anterior resection
Stapled anastomosis
Hand-sewn coloanal anastomosis (HSCAA)
Median follow up 5.8 years
1) This study cohort is comprised of stage IV patients who underwent resection of rectal primary between 1991 and 2000 without perioperative radiotherapy.
2) Their metastatic disease was documented by biopsy and/or imaging and their charts were available for review.
3) The median age of the group of 80 patients, was 63 years with 48 men and 32 women. .

14. Patient and Tumor Characteristics - LAR
Distal margin rectal cancer
Patient and Tumor Characteristics - LAR
Group 1 2 3
P value
Distal margin
<8mm
8-19mm
20-60mm n
103
230
294
Age ≤60 years
59%
53%
47%
0.07
Female
46%
39%
40%
0.40
2-6cm from AV
81%
57%
17%
<0.001
pT3/4
16%
34%
54%
pN1/2
23%
29%
25%
0.48 M1 1% 2% 3%
0.47
LVI 9%
10%
0.97
Preop CMT
58%
61%
60%
0.87
Any adjuvant rx
72%
76%
74%
0.73
DSS at 6 years
90%
87%
0.76
OS at 6 years
84%
85%
83%
0.67
1) And we found that most of these variables were significant predictors of survival.
2) However, many of these variables are overlapping.
3) So to determine which variables were most important, a multivariate analysis was applied.

15. Local recurrence Distal margin <8mm 8-19mm 20-60mm P-value
Distal margin rectal cancer
Local recurrence
Distal margin
<8mm
8-19mm
20-60mm
P-value
LR events
13/103
13/230
15/294
Absolute LR
12.6%
5.7%
5.1%
0.006
DM = 20-60mm
DM = 8-19mm
DM < 8mm *
1) And we found that most of these variables were significant predictors of survival.
2) However, many of these variables are overlapping.
3) So to determine which variables were most important, a multivariate analysis was applied.
* P = 0.008

16. Mucosal recurrence Distal margin <8mm 8-19mm 20-60mm P value
Distal margin rectal cancer
Mucosal recurrence
Distal margin
<8mm
8-19mm
20-60mm
P value
MR events
8/103
4/230
4/294
Absolute MR
7.8%
1.7%
1.4%
<0.001
DM = 20-60mm
DM = 8-19mm
DM < 8mm *
1) And we found that most of these variables were significant predictors of survival.
2) However, many of these variables are overlapping.
3) So to determine which variables were most important, a multivariate analysis was applied.
* P = 0.001

17. Pelvic recurrence (excludes iMR)
Distal margin rectal cancer
Pelvic recurrence (excludes iMR)
Distal margin
<8mm
8-19mm
20-60mm
P value
PR events
7/103
11/230
13/294
Absolute PR
6.8%
4.8%
4.4%
0.63
DM = 20-60mm
DM = 8-19mm
DM < 8mm
1) And we found that most of these variables were significant predictors of survival.
2) However, many of these variables are overlapping.
3) So to determine which variables were most important, a multivariate analysis was applied.
P = 0.62

18. Changes over time: 1991-1997 and 1998-2004
Distal margin rectal cancer
Changes over time:
and
1) And we found that most of these variables were significant predictors of survival.
2) However, many of these variables are overlapping.
3) So to determine which variables were most important, a multivariate analysis was applied.

19. Variation of LR n 1991-97 98-2004 P value <8 mm 41 22% 62 6.5% 0.02
Distal margin rectal cancer
Variation of LR n
P value
<8 mm 41
22% 62
6.5%
0.02
8-19 mm 74
6.8%
156
5.1%
0.62
20-60 mm
127
7.9%
167
3.0%
0.06
All patients
242
9.9%
385
4.4%
0.007
1) And we found that most of these variables were significant predictors of survival.
2) However, many of these variables are overlapping.
3) So to determine which variables were most important, a multivariate analysis was applied.

20. Use of adjuvant therapy
Distal margin rectal cancer
Variation of LR n
P value
<8 mm 41
22% 62
6.5%
0.02
8-19 mm 74
6.8%
156
5.1%
0.62
20-60 mm
127
7.9%
167
3.0%
0.06
All patients
242
9.9%
385
4.4%
0.007
Use of adjuvant therapy
1) And we found that most of these variables were significant predictors of survival.
2) However, many of these variables are overlapping.
3) So to determine which variables were most important, a multivariate analysis was applied. n
1991-7
P value
Preop CMT
286
46%
462
67%
<0.001
Any adjuvant
65%
78%

21. Distal margin rectal cancer
Conclusions
Sphincter sparing techniques do not compromise local control or survival
Careful surveillance for MR is warranted in patients with close DM
Salvage is feasible for most MR
In conclusion, Despite a growing body of evidence suggesting poorer cancer outcome following TAE, the prevalence of TAE of rectal cancer has not decreased between 1998 and 2004 Furthermore, there is no trend towards greater selectivity in the use of TAE

22. Rationale for ultralow LAR/CAA

23. Ultralow LAR/CAA with Intersphincteric Dissection
We need less distal margin than we once thought
Internal sphincter is an extension of the rectal wall
Weiser et al. Adenocarcinoma of the Colon and Rectum. In Shackelford’s Surgery
of the Alimentary Tract6th ed, 2007

24. Oncologic Outcome of Coloanal Anastomosis
Author
Year n
Follow-up
Local recurrence
Tiret et al
2003 26
39 mo
3.4%
Portier et al
2007
173
67 mo
10.6%
Saito et al
2006
228
41 mo
5.8%
Rullier et al
2005 92
>24 mo
2.0%
Tilney et al*
612
9.5%
*literature review

25. Weiser M, Quah HM, Shia J, Guillem J, Paty P, Temple L, Goodman K,
Study # 3
Sphincter Preservation in low rectal cancer is facilitated by preoperative chemoradiation and intersphincteric dissection
Weiser M, Quah HM, Shia J, Guillem J, Paty P, Temple L, Goodman K,
Minsky B and Wong D
( Submitted paper 2008 )
1) Good afternoon and thank you to the Society for the opportunity to present this work on the management of stage IV rectal cancer.
2) The question that I would like to ask is when is rectal resection justified.

26. Aim of the Study
To evaluate oncologic outcome in patients with locally advanced distal rectal cancer treated with preoperative chemoradiation followed by:
LAR with stapled coloanal anastomosis
LAR with intersphincteric dissection and hand sewn coloanal anastomosis
APR

27. Background Data
From a cohort of 601 consecutive patients from 1998 – 2004 :
148 patients were identified with Stage II and III rectal cancers (ERUS Staged uT3-4 and/or N1) at or below 6 cm from the anal verge
All treated with preoperative long course
chemoradiation and TME

28. Median Distal Margin Median Distal Margin
LAR Stapled Coloanal cm ( 0.9 – 1.3 cm)
LAR Handsewn Intersphincteric cm ( 0.9 – 1.3 cm)
APR cm ( 3.5 – 4.6 cm)

29. Oncologic Outcome (MSKCC data)
LAR
Coloanal
n = 41
Intersphincteric dissection
n = 44
APR
n = 63
p-value
Age 60 54 67
Male
44%
57%
52% ns
Distance from anal verge
6 (3-6)
5 (3-6)
3 (0-6)
0.0001
Pathologic CR
24%
25% 6%
0.018
Poor differentiation 7% 5%
28%
0.003
+ circumferential margin 0%
13%
0.11
MSKCC 2008

30. Oncologic Outcome (MSKCC data)
LAR
Coloanal
n = 41
Intersphincteric dissection
n = 44
APR
n = 63
Crude recurrence rate
6(15%)
7(16%)
26(41%)
Local
1(2%)
0(0)
6(9%)
Distant
5(12%)
22(35%)
5 yr RFS (95% CI)
85%
83%
47%
5 yr DSS (95% CI)
97%
96%
59%
MSKCC 2008

31. Oncologic Outcome of Coloanal Anastomosis
MSKCC 2008

32. Conclusions
In low rectal cancer, sphincter preservation is facilitated by significant response to chemoradiation and intersphincteric dissection without oncologic compromise
APR is more likely required in those patients with lesser response to neoadjuvant therapy and is associated with poorer outcome

33. Functional outcome of ultralow LAR with coloanal anastomosis

34. Functional Outcome after LAR/CAA
81 patients
Median 2 BM / day
Continence
complete 51%
incontinent gas 21%
minor leak 23%
significant leak 5%
56% excellent or good composite function
(continence, evacuation, #BMs)
74% of patients were satisfied
Paty et al. Long-term functional results of coloanal anastomosis for rectal cancer. Am J Surg ;167:90-95.

35. QOL: Anal Sphincter Preservation or Sacrifice
Despite LAR patients suffering defecation problems, they had better QOL than APR patient
Bowel function did not significantly impact on overall QOL
Stoma patients
More limited everyday work and hobby activities (role functioning)
More disrupted social and family life (social functioning)
Less able to get about and look after themselves (physical functioning)
Felt less attractive (body image)
These changes persisted over time (4 years)
LAR scores improved with time while APR did not.
Greatest improvement in QOL was when temporary stomas were reversed.
Engel et al. Quality of life in Rectal Cancer Patients. Ann Surg 2003;238:

36. Quality of Life: Stoma vs Sphincter Preservation
LAR vs APR
Quality of Life: Stoma vs Sphincter Preservation
“Meta-analysis”
Validated instruments
Studies including APR and LAR
Study included data from 11 studies
1443 patients
486 patients with APR
All retrospective
4 SF-36, 7 EORTC 30, 8 EORTC – CRC38
There are several studies evaluating qol that are all variable in their findings. These authors attempted to gather the data from studies that used validated instruments and compared the qol scores in patients who underwent apr or lar. They identified 11 studies that included 1443 patients, 486 with apr. All the studies were retrospective but they used validated instruments.
Cornish et al. Ann Surg Onc, 2007; 14:

37. QOL: SPS vs APR
Overall when comparing APR to LAR, no differences in general QOL were identified
Cornish et al. Ann Surg Onc, 2007; 14:

38. Conclusions
A 1 cm distal margin is acceptable in patients undergoing neoadjuvant tx
Ultra-low LAR/COLOANAL is oncologically sound
Restores body image
Majority of patients are satisfied with their QOL