Digestive Disease CenterDepartment of Colorectal Surgery

Cleveland Clinic

Feza H. Remzi MD, FACS, FASCRS

Laparoscopy in Colorectal cancer: Where are we now?

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

Conclusions

• Selection

• Early conversion

• Do not compromise for the sake smaller incision

• No short cuts and do not change your routine

• Patients come first

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?

Colon

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

Port Site Recurrence

• Recurrence of tumor in a trocar wound without advanced abdominal disease

• First report in 1993

• Initially reported rates: 0 - 21%*

• NOT necessarily with advanced cancer

• Cast a dark shadow over laparoscopic surgery for malignancy

*Berends, Lancet 1994

Port Site RecurrenceProposed Mechanisms

Direct seeding of exfoliated cells at port sitesAerosolized cancer cells with

pneumoperitoneumCO2 enhances tumor growth*Local conditions at port sites favor implantationPoor surgical technique

(spillage of tumor cells at operation)

Jones et al. Dis Colon Rectum 1995;38:1182-8.

Wu JS. Surgery 1997;122:1-7. Jacobi et al. Surgery 1997;121:72-78. Bouvy et al. Annal Surg 1996;224:694-701. Nduka et al. Surg Endosc 1998;12:515. Mathew et al. Br J Surg. 1996;83:1087-1090. Watson et al. Arch Surg. 1997;132:166-168. Neuhaus et al. Surg Endosc 1998;12(5):516.

Nduka et al. Surg Endosc 1998;12(5):515. Jacobi et al. Surg Endosc 1998;12(5):513.

*

Port Site Recurrence RatesMid 1990’s

Study Year Recurrences Operations PercentRamos 1994 3 208 1.4Jacquet 1995 7 445 1.6Lumley 1996 1 103 1.0Kwok 1996 1 100 1.0Fleshman 1996 4 372 1.1Franklin 1996 0 191 0Vukasin 1996 5 480 1.1Huscher 1996 0 146 0

Total 21 2045 1.0 % *Series greater than 100 patients

Hughes ’83, Reilley ’96 : Incisional recurrence 0.6 – 0.8 % in open surgery

Port Site Recurrence RatesRecent Series

Study YearOperation

sRecurrenc

esPercent

Milsom 1998 55 0 0

Schiedec

1999 399 1 0.25

Regadas 1999 470 2 0.4

Lechaux 2002 206 1 0.5

Lumley 2002 181 1 0.6

Lacy 2002 106 1 0.1

COST 2004 435 2 0.5

Total 1852 8 0.4%

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

Background: LAP for Colon CA

• Our team started in 1991: • Animals• Cadavers• Limited benign diseases

• Indications expanded in 1993: • Malignancies

Background: Feasibility Studies

Phase I Studies – Cadavers• 1993 - Rt. Hemicolectomy

(Bohm et. al)• 1993 - Proctosigmoidectomy

(Milsom et. al)• 1993 - Abdominoperineal Resection

(Decanini et. al)

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

Adequacy of ResectionRandomized 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

First Randomized Colectomy TrialPreliminary 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

Cleveland Clinic Trial

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) *

Short term advantages to LAP

* p < 0.05

The Barcelona Trial

Lacy et al, 1993 – 1998Single institution, two surgeonsAll non-metastatic colon cancern=219 (111 LAP vs. 108 Open)Intention to treat analysisMedian FU: 43 months (range 27 - 85)

Tumor recurrenceTumor recurrence

Time to recurrence (mo)Time to recurrence (mo)

Overall mortalityOverall mortality

Cancer-related mortality Cancer-related mortality **

18 (17%)18 (17%)

15 (14)15 (14)

19 (18%)19 (18%)

10 (9%)10 (9%)

28 (27%)28 (27%)

17 (12)17 (12)

27 (26%)27 (26%)

21 (21%)21 (21%)

LAP LAP OpenOpen

Lacy AM, Lacy AM, Lancet Lancet 20022002

Tumor Recurrence and Mortality

: : pp < 0.05 < 0.05**

COST* Study GroupRandomized 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

Inclusion Criteria> Age 18Adenocarcinoma of the colon

Prohibitive abdominal incisions Advanced or metastatic disease Transverse colon or rectal cancer Acute obstruction or perforation Severe medical illness

Exclusion Criteria

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

Randomization

Stratification variables

• Tumor site– Right, left, sigmoid

• ASA classification– I, II, or III

• Surgeon

Survival and RecurrenceCost Trial

LAP (n=435)Open (n=428)

P value

Tumor recurrence 76 (17 %) 84 (19 %) NS*

Overall survival 79% 78% NS*

Disease-free survival

73% 73% NS*

Time to recurrence NS*

Wound recurrences 2 (0.5 %) 1 (0.2 %) NS

* True for any stage

Short Term ResultsCost Trial

LAP Open P value

Hospital stay (days) 5 6 <0.001

IV narcotics (days) 3 4 <0.001

Oral narcotics (days) 1 2 <0.001

OR time (min) 150 95 <0.001

Incision length (cm) 6 18 <0.001

Overall complications (%) 92 (21) 85 (20) 0.64

Intraop complications (%) 16 (4) 8 (2) 0.10

Surgical margins, # of LN’s similar

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.”

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

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

Cleveland Clinic Trial

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

Longterm Results

Geissler ASCRS Seattle 2006

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 mortalityLancet 2005

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

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!!!

Rectum

Laparoscopic Learning Curve

• 461 cases among 3 surgeons– Operative time evaluated

• Conclusion:– 30 case learning curve

Schlachta – DC&R 2001

Discussion

• Biases of self-designated interests– Better technique– Better approach to patients– Better follow-up– Superior psychological support

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

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

We must accept the fact that surgical technique is important to outcome and that change in technique cannot be accepted

without validation.

CLASICC TrialGuillou 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

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

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

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

recurrence

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.

Ethical Issues

• Offering experimental ? surgery outside of a research environment

• A Marketing tool

Conclusion

• Surgical technique is important• New techniques must be validated• Laparoscopic LAR has increased CRM• Laparoscopic proctectomy remains

unproven and certainly not the standard

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

Conclusions

• Selection

• Early conversion

• Do not compromise for the sake smaller incision

• No short cuts and do not change your routine

• Patients come first

Preoperative Rectal Cancer StagingPreoperative Rectal Cancer Staging