1. Feza H. Remzi MD, FACS, FASCRS
Laparoscopy in Colorectal cancer: Where are we now?
Feza H. Remzi MD, FACS, FASCRS
Digestive Disease Center Department of Colorectal Surgery Cleveland Clinic

2. Conclusions Safe for colon cancer Return of earlier bowel function
Less postoperative pain
Better pulmonary postoperative function
Shorter hospital stay
Smaller incision
Its application in rectal cancer needs to be determined

3. Conclusions Selection Early conversion
Do not compromise for the sake smaller incision
No short cuts and do not change your routine
Patients come first

4. Issues and Questions
Does the method of access (LAP vs. Open) in the resection of colon CA affect outcome?
Short term recovery
Long term oncologic outcome
Is there enough data say LAP is safe?
What will be the role of laparoscopy in the treatment of colorectal CA in 2007?

5. Colon

6. History First reports of LAP for colon CA in 1990
Technically difficult and challenging
Time consuming
Short-term benefits (pain, ileus, hospitalization) have not been pronounced compared to open surgery
Has led to resistance among surgeons to learn the technique

7. Port Site Recurrence
Recurrence of tumor in a trocar wound without advanced abdominal disease
First report in 1993
Initially reported rates: %*
NOT necessarily with advanced cancer
Cast a dark shadow over laparoscopic surgery for malignancy
*Berends, Lancet 1994

8. Port Site Recurrence Proposed Mechanisms
Direct seeding of exfoliated cells at port sites
Aerosolized cancer cells with pneumoperitoneum
CO2 enhances tumor growth*
Local conditions at port sites favor implantation
Poor surgical technique
(spillage of tumor cells at operation)
Jones et al. Dis Colon Rectum 1995;38:
Wu JS. Surgery 1997;122: Jacobi et al. Surgery 1997;121: Bouvy et al. Annal Surg 1996;224: Nduka et al. Surg Endosc 1998;12:515. Mathew et al. Br J Surg. 1996;83: Watson et al. Arch Surg. 1997;132: Neuhaus et al. Surg Endosc 1998;12(5):516.
Nduka et al. Surg Endosc 1998;12(5): Jacobi et al. Surg Endosc 1998;12(5):513. *

9. Port Site Recurrence Rates Mid 1990’s
Study Year Recurrences Operations Percent
Ramos
Jacquet
Lumley
Kwok
Fleshman
Franklin
Vukasin
Huscher
Total %
*Series greater than 100 patients
Hughes ’83, Reilley ’96 : Incisional recurrence 0.6 – 0.8 % in open surgery

10. Port Site Recurrence Rates Recent Series
Study
Year
Operations
Recurrences
Percent
Milsom
1998 55
Schiedec
1999
399 1
0.25
Regadas
470 2
0.4
Lechaux
2002
206
0.5
Lumley
181
0.6
Lacy
106
0.1
COST
2004
435
Total
1852 8
0.4%

11. Port Site Recurrence
In experienced hands, the rates of PSR are acceptable
High rates of PSR in earlier reports must have been due to poor surgical technique
Animal models suggesting increased tumor growth with CO2 pneumo did not replicate “real-life” conditions

12. Background: LAP for Colon CA
Our team started in 1991:
Animals
Cadavers
Limited benign diseases
Indications expanded in 1993:
Malignancies

13. Background: Feasibility Studies
Phase I Studies – Cadavers
Rt. Hemicolectomy
(Bohm et. al)
Proctosigmoidectomy
(Milsom et. al)
Abdominoperineal Resection
(Decanini et. al)

14. LAP Surgery for Colorectal CA Early Large Prospective Series
Franklin et al (‘96): 191 LAP / 224 OPEN
At 3 yrs: No disadvantages, no port site mets, faster recovery
COST Group (‘96): 372 pts LAP
No early mets, no port site mets
Poulin et al (‘99): 117 pts LAP
54% survival in stage III at 48 months
*No obvious early disadvantages

15. Adequacy of Resection Randomized Colectomy Trials
Study LAP vs. Open
Nelson* NSD +
Milsom ** NSD
Lacy*** NSD
*N.C.I. / C.O.S.T. Trial, 1996
** Cleveland Clinic Trial, 1996
*** Barcelona Trial, 1995
+ NSD= no significant difference
Bowel margins, # of lymph nodes similar

16. First Randomized Colectomy Trial Preliminary Report
Cleveland Clinic Foundation
n=109 (55 LAP vs. 54 Open)
Median FU: 17 months (range 1.5 –46)
No port site recurrences
Similar number of cancer-related deaths
*Milsom, JACS 1998

17. Cleveland Clinic Trial
Short term advantages to LAP
Less narcotic use *
Earlier return of flatus
(3.0 vs. 4.0 days) *
Earlier return of FEV1 and FVC to 80% of pre-op (3.0 vs. 6.0 days) *
* p < 0.05

18. The Barcelona Trial Lacy et al, 1993 – 1998
Single institution, two surgeons
All non-metastatic colon cancer
n=219 (111 LAP vs. 108 Open)
Intention to treat analysis
Median FU: 43 months (range )

19. Tumor Recurrence and Mortality
LAP
Open
Tumor recurrence
Time to recurrence (mo)
Overall mortality
Cancer-related mortality *
18 (17%)
15 (14)
19 (18%)
10 (9%)
28 (27%)
17 (12)
27 (26%)
21 (21%)
: p < 0.05 *
Lacy AM, Lancet 2002

20. COST* Study Group Randomized Prospective Study
Nelson, et al.
Non-inferiority randomized trial
48 institutions, USA and Canada
n=872 (1994 – 2001)
Median FU: 4.4 years
Primary endpoint: Time to tumor recurrence
*Clinical Outcomes of Surgical Therapy Study Group
Nelson, NEJM, May 2004

21. Inclusion Criteria Exclusion Criteria > Age 18
Adenocarcinoma of the colon
Exclusion Criteria
Prohibitive abdominal incisions
Advanced or metastatic disease
Transverse colon or rectal cancer
Acute obstruction or perforation
Severe medical illness

22. Credentialing 66 surgeons at 48 institutions > 20 LAP colectomies
Video to review oncologic technique
Random audit of videotapes*
Assessment of bowel margins*
* Reviewed by external monitoring committee

23. Randomization Stratification variables Tumor site ASA classification
Right, left, sigmoid
ASA classification
I, II, or III
Surgeon

24. Survival and Recurrence Cost Trial
LAP (n=435)
Open (n=428)
P value
Tumor recurrence
76 (17 %)
84 (19 %)
NS*
Overall survival
79%
78%
Disease-free survival
73%
Time to recurrence
Wound recurrences
2 (0.5 %)
1 (0.2 %) NS
* True for any stage

25. Short Term Results Cost Trial
LAP
Open
P value
Hospital stay (days) 5 6
<0.001
IV narcotics (days) 3 4
Oral narcotics (days) 1 2
OR time (min)
150 95
Incision length (cm) 18
Overall complications (%)
92 (21)
85 (20)
0.64
Intraop complications (%)
16 (4)
8 (2)
0.10
Surgical margins, # of LN’s similar

26. COST Trial Conclusions
LAP is not oncologically inferior to Open
Marginal short term benefits seen with LAP in post-operative recovery
Similar complications rates (LAP vs. Open)
“… it is safe to proceed with laparoscopically assisted colectomy in patients with cancer.”

27. However…
Study was not powered to detect whether LAP was oncologically superior
Conversion rate 21% (n=90) excessive
LAP (n=435) / 48 institutions / 7 years
Only 1.3 laparoscopic cases / institution / year!!!

28. Results COST trial results substantiate results found in other trials
LAP for colon CA is oncologically safe
Small benefits are seen in post-operative recovery with LAP
With good surgical technique, the rate of port site recurrences is minimal

29. Summary
Whether LAP is oncologically superior to open surgery is still controversial…
In 2007: LAP is here to stay
Patients will demand it..
Anticipate more and more cases of colon CA will be resected laparoscopically

30. Cleveland Clinic Trial
Longterm Results
It is the only prospectively randomized study with 10 year or more follow -up
There were no differences between the Lap versus open groups stage by stage in cancer specific survival or recurrence
Geissler ASCRS Seattle 2006

31. COLOR Trial 1997-2003, 29 centers in Europe
Over 600 patients in each group
Less pain, blood loss, earlier recovery of bowel function and shorter hospital stay in Lx group
17 % conversion rates
Equivalent morbidity and mortality
Lancet 2005

32. CLASICC Trial 1996-2002, 27 UK centers 794 patients
Less pain and shorter hospital stay in Lx group
29 % conversion rates
Equivalent morbidity and mortality
Increase positive radial margins in LX group
Converted patients had raised complication rates
Lancet 2005

33. Summary
Surgeons participating in the COST study were experienced in LAP colectomies
The results of the COST trial is not a license to start LAP colectomies for malignancy
“Proceed with caution…”
We owe it to our patients to exercise good oncologic technique and COMMON SENSE to avoid unwanted results!!!

34. Rectum

35. Laparoscopic Learning Curve
461 cases among 3 surgeons
Operative time evaluated
Conclusion:
30 case learning curve
Schlachta – DC&R 2001

36. Learning Curve of Laparoscopic Resection for Rectal Cancer Li-China
105 cases
Divided into 3 groups by time
Learning curve for experienced laparoscopic surgeons is 35 cases doing 2.1 cases a month

37. How Much Colorectal Surgery to General Surgeons Do? Hyman-JACS 2002
ABS recertification database
2434 general surgeons (’95-97)
Mean 33 colon cases
75% do less than 17 cases per year
Mean 12.3 anal cases
75% do less than 16 cases per year

38. Minilap vs. Laparoscopy
52 patients
173 minutes
Discharge=6d
BM=3.9 d
Incision 8 cm
Minilap
35 patients
69 minutes
Discharge=6.9d
BM = 4 d
Incision 12 cm
Fleshman, Fry – DC&R 1997

39. Surgeon - Technique Heald 4% local recurrence - 87% survival
Quirke - Lancet 1986
positive margines in 14/52 specimens
positive correlation with recurrence

40. Discussion Biases of self-designated interests Better technique
Better approach to patients
Better follow-up
Superior psychological support

41. Surgeon Procedure Volume and Outcome
2815 rectal cancers
30 day mortality not influenced by doing more that 21 cases
2 year mortality was very significantly influenced (34 vs 24% mortality)
Schrag-Ann Surg 2002

42. Influence of Hospital and Surgeon Volume on In-Hospital mortality Hannan, Brennan-Surgery 2002
NY Statewide database
Top quartile and bottom quartile differ by 50% (overall mortality 3.5%)

43. Conclusion Patients operated upon by members of ASCRS have 13% decreased death rate with a minimum of 3 years follow-up

44. Conclusion The surgeon is the most significant variable we can influence in the treatment of patients with colorectal cancer

45. Surgeon’s Influence
The surgeon is the most significant variable we can influence in the treatment of patients with colorectal cancer
Breast
Cardiac
Pancreas
Esophagus
? Lung

46. We must accept the fact that surgical technique is important to outcome and that change in technique cannot be accepted without validation.

47. CLASICC Trial Guillou Lancet 2005
LAR Radial Margin Positive
Open = 4/64 (6%)
Laparoscopic = 16/129 (12%) NS
Converted = 29%
Increased TME achieved with laparoscopy
Concern raised about the risk of increased local recurrence

48. Laparoscopic vs Open Surgery for Rectal Cancer: a meta-analysis
20 studies
2071 patients; 909 LX, versus 1162 open
Short term outcomes may be improved
Laparoscopic rectal cancer surgery results in an earlier postoperative recovery and a resected specimen that is oncologically comparable to open surgery
Aziz 2006 Ann Surg Oncol

49. Stage I, II similar 3 yr survival
Laparoscopic and Open Anterior Resection for Upper and Mid Rectal Cancer
265 patients
Stage I, II similar 3 yr survival
Open = 89.8%
Lap = 88.6%
Stage III 3 yr survival of concern
Open = 65.6%
Lap = 55.5%
Law-DC&R 2006

50. There is no short term advantage that can outweigh increased long term cancer recurrence

51. Laparoscopic vs. Open total Mesorectal Excision for Rectal Cancer Cochrane Database 2006
80 studies identified
48 met inclusion, 4224 patients
Methodological quality of most of the included studies was poor.
There is evidence that LX TME results in less blood loss, quicker return to normal diet, less pain, less narcotic use and less immune response. It seems likely that LX TME is associated with longer operative time and higher costs. No results of quality of life were reported.

52. Ethical Issues
Offering experimental ? surgery outside of a research environment
A Marketing tool

53. Conclusion Surgical technique is important
New techniques must be validated
Laparoscopic LAR has increased CRM
Laparoscopic proctectomy remains unproven and certainly not the standard

54. With the ethical values we have in the United States, how can a surgeon even consider performing a laparoscopic proctectomy outside of a study environment?

55. Conclusions Safe Return of early bowel function
Less postoperative pain
Better pulmonary postoperative function
Shorter hospital stay
Smaller incision
Its application in rectal cancer needs to be determined

56. Conclusions Selection Early conversion
Do not compromise for the sake smaller incision
No short cuts and do not change your routine
Patients come first

57. Preoperative Rectal Cancer Staging