Current Status of Laparoscopy for Colon and Rectal Cancer Steven D Wexner, MD, FACS, FRCS, FRCS (Ed) Chairman, Department of Colorectal Surgery 21st Century Oncology Chair in Colorectal Surgery Chief of Staff Cleveland Clinic Florida Professor of Surgery, Ohio State University Health Sciences Center at the Cleveland Clinic Foundation Clinical Professor of Surgery, University of South Florida College of Medicine Clinical Professor of Biomedical Science Department of Biomedical Science Florida Atlantic University College of Medicine Dan Enger Ruiz, MD David Vivas, MD Clinical Research Fellows

Laparoscopy: Colorectal cancer Short term benefits Bowel function recovery Quality of life (including pain) Hospital stay Costs Long term benefits Recurrence Survival

Laparoscopy: Colorectal cancer Bowel Function Recovery Randomized Author Year N of patients Bowel function (mean/median n of days) Lap Open Milsom 1998 54 53 3 4 Curet 2000 18 2.7 4.4 Lacy 2002 111 108 1.5 2.3 Hasegawa 2003 29 30 2 3.3 Kaiser 2004 20 p<0.05

Laparoscopy: Colorectal cancer Bowel Function Recovery The evidence that laparoscopy offers faster bowel function recovery than the traditional open approach may be considered high (Level I)

Laparoscopy: Colorectal cancer Quality of Life - Pain Randomized Author Year N of patients Less pain/analgesic requirement (days)? Lap Open p value Stage 1997 15 14 Yes < 0.05 Schwenk 1998 30 < 0.01 Milsom 54 53 0.02 Weeks 2002 168 221 0.03 Hasegawa 2003 29 0.002 Kaiser 2004 29 20 Yes < 0.05 Nelson 435 425 <0.001

Laparoscopy: Colorectal cancer Quality of life Randomized trial (COST trial) 449 patients 228 Laparoscopy (Lap) , 221Open Pain, hospital stay Quality of life (2 days, 2 weeks, 2 months) Symptom distress scale Quality of life index Global rating scale (1-100) Weeks, JAMA 2002

Results Lap n = 228 Open n = 221 Age (years) 68.2 69.4 Gender M:F 108:120 108:113 Tumor stage I II III IV 88 77 57 5 69 78 62 11 ASA classification I or II 198 32 189 P = N.S. Weeks, JAMA 2002

Results Oral analgesics 1.9 2.2 0.03 IV narcotics/analgesics 3.2 4.0 Lap (n = 228) Open (n = 221) P value Oral analgesics 1.9 2.2 0.03 IV narcotics/analgesics 3.2 4.0 <0.001 Hospital stay 5.6 6.4 Values are means Patients in the Lap group had only greater mean global rate scores at 2 weeks after surgery (76.9 vs. 74.4; p=.0009) No other differences in quality of life Weeks, JAMA 2002

Laparoscopy: Colorectal cancer The superiority of laparoscopy in reducing pain during the same length of the postoperative period seems evident (Level I) Other aspects of quality of life warrant further investigation

Laparoscopy: Colorectal cancer Hospital Stay Randomized Author Year N of patients Hospital Stay (days) Lap Open Stage 1997 15 14 5 8 Schwenk 1998 30 10.1 11.6 Milsom 54 53 6 7 Curet 2000 18 5.2 7.3 Lacy 2002 111 108 7.9 Weeks 168 221 5.6 6.4 Hasegawa 2003 29 7.1 12.7 Kaiser 2004 20 Nelson 435 425 p<0.05

Laparoscopy: Colorectal cancer Hospital stay There is high evidence (Level I) that laparoscopy for malignancy is associated with an earlier discharge compared to laparotomy

Laparoscopy: Colorectal cancer Cost Randomized, prospective trial Subset of patients from the Swedish COLOR trial Study period – 12 weeks after surgery Analysis of direct medical cost (hospital and outpatient) and indirect cost (loss of productivity) Janson, BJS 2004

Laparoscopy: Colorectal cancer Cost Prospective, Randomized - COLOR LCR (n=98) OCR (n=112) Differ OR time (min) 155 122 33 Length of stay (days) 9.0 9.1 - Conversion 14% Total cost first admission 6931 5375 1556 Total cost of care after discharge (readmissions/reoperations) 2548 1860 688 Total cost excluding productivity lost 9479 7237 2244 Productivity loss 2181 2579 -398 Total cost 11660 9814 1846 All costs in Euros Janson, BJS 2004

Laparoscopy: Colorectal cancer Cost Prospective, Randomized - COLOR LCR (n=98) OCR (n=112) First admission Complications 21% 16% Reoperations 8% 4% After discharge 12% 7% 6% 3% Janson, BJS 2004

Laparoscopy: Colorectal cancer Cost Total cost to society similar in both groups Direct costs to healthcare system much higher for LCR Higher OR cost Cost of complications and reoperation which happened more often in LCR Same length of stay in both (9 days) Faster recovery and return to work offset higher healthcare system cost Janson, BJS 2004

Laparoscopy: Colorectal cancer Costs The data available do not provide adequate evidence on whether total costs significantly differ between laparoscopy and laparotomy in the treatment of malignancy. Costs may significantly vary depending on the healthcare system

Laparoscopy: Colorectal cancer Randomized Controlled Trial 111 Laparoscopy vs. 106 Laparotomy Non metastatic colon cancer Median follow-up time: 43 (27-85) months Postoperative chemotherapy for all suitable patients with Stage II or III rectal cancer Intention-to-treat analysis Lacy et al, The Lancet 2002

Laparoscopy: Colorectal cancer Recurrence Open (n=102) Hazard Ratio (95% CI) P value Tumor recurrence 18 (17%) 28 (27%) 0.72 (0.49-1.06) 0.07 Type of recurrence Distant metastasis Locoregional relapse Peritoneal seeding Port-site metastasis 7 3 1 9 14 5 -- 0.57 Time to recurrence (months) 15 (14) 17 (12) 0.66 Surgical treatment of recurrence with curative intention 6 (33%) 9 (32%) 1.00 Lacy et al, The Lancet 2002

Laparoscopy: Colorectal cancer Survival Open (n=102) Hazard ratio (95% CI) P value Overall mortality 19 (18%) 27 (26%) 0.77 (0.53-1.12) 1.04 Cancer-related mortality 10 (9%) 21 (21%) 0.68 (0.50-0.90) 0.03 Causes of death Perioperative mortality Tumor progression Others 1 9 3 18 6 -- 0.19 Lacy et al, The Lancet 2002

Laparoscopy: Colorectal cancer Predictive factors Hazard ratio (95% CI) P value Probability of being free of recurrence Lymph node metastasis (presence or absence) Surgical procedure (Open vs. Lap) Preoperative serum CEA (> ng/ml vs. < 4 ng/ml) 0.31 (0.16-0.60) 0.39 (0.19-0.82) 0.43 (0.22-0.87) 0.0006 0.012 0.018 Overall survival Surgical procedure (open vs. Lap) Lymph-node metastasis (presence vs. absence) 0.48 (0.23-1.01) 0.49 (0.25-0.98) 0.052 0.044 Cancer-related survival 0.29 (0.12-0.67) 0.38 (0.16-0.91) 0.004 0.029 Cox’s regression model Lacy et al, The Lancet 2002

Laparoscopy: Colorectal cancer Overall survival Lacy et al, The Lancet 2002

Laparoscopy: Colorectal cancer Cancer-related survival Lacy et al, The Lancet 2002

Laparoscopy: Colorectal cancer Recurrence free – by Stage Lacy et al, The Lancet 2002

Laparoscopic Colectomy: Cancer Laparoscopic resection of colorectal malignancies a systematic review English language Randomized controlled trials Controlled clinical trials Case series/reports Chapman et al. Ann Surg 2001

Laparoscopic Colectomy : Cancer 52 papers met inclusion criteria “Little high level evidence was available” “The evidence base for laparoscopic-assisted reection of colorectal malignancies is inadequate to determine the procedures safety and efficacy” Chapman et al. Ann Surg 2001

Laparoscopic Colectomy : Cancer Disadvantages vs. Open Colectomy Significantly longer operative times Possibly more expensive Possibly worse short term immune effects Chapman et al. Ann Surg 2001

Laparoscopic Colectomy : Cancer “Laparoscopic resection of colorectal malignancy was more expensive and time-consuming” The new procedure’s advantages revolve around early recovery from surgery and reduced pain” Chapman et al. Ann Surg 2001

Laparoscopic Colectomy : Cancer Advantages vs. Open Colectomy Improved cosmesis (no data but appears uncontentious) Quicker hospital discharge Less narcotic use, though possibly larger benefits for certain types of colectomy (low colonic) Possibly less pain at rest, at least for patients who have uncovered procedures Possibly earlier return of bowel function and resumption of normal diet Chapman et al. Ann Surg 2001

Laparoscopic Colectomy : Cancer Short term Quality-of-Life outcomes Following Laparoscopic-Assisted Colectomy vs Open Colectomy for Colon Cancer (COST Study) AIMS Are disease free and overall survival equivalent ? Is laparoscopic approach associated with better QOL ? Weeks et al. JAMA 2002

Laparoscopic Colectomy : Cancer Randomized control trial 449 patients Adenocarcinoma of single segment of colon Excluded: Acute presentation, rectal and transverse colon cancers, advanced local disease, those lesions with evidence of metastatic disease, ASA IV or V Quality of surgery: All surgeons with > 20 cases; Random audit of cases Weeks et al. JAMA 2002

Laparoscopic Colectomy : Cancer Outcomes: Survival: still pending QOL at 2days, 2 weeks and 2 months using: Symptom Distress Scale, Global QOL Scale, QOL index Results: Intention to Treat Analysis Shorter use of narcotics Shorter length of stay by 0.8 days (p<0.01) Quality of life: no difference Weeks et al. JAMA 2002

Laparoscopic Colectomy : Cancer Conclusions “The modest benefits in short term QOL measures we observed are not sufficient to justify the use of this procedure in the routine care setting” Unresolved Issues: Blunting of QOL differences via analgesic use QOL differences between POD 2 and POD 14 Recurrence and survival outcomes Incidence of small bowel obstruction Weeks et al. JAMA 2002

Laparoscopic Colectomy : Prospective, Randomized, Controlled 48 institutions, 872 patients Prospective, randomized Follow-up 4.4 years Conversion 21% End point was time to tumor recurrence Nelson, NEJM 2004

Prospective, Randomized, Controlled Laparoscopic (n=435) Open (n=425) Age 70 69 Female 212 220 Location Right Left Sigmoid 237 32 166 232 164 TNM Stage 1 2 3 4 Unknown 20 153 136 112 10 33 146 121 16 Nelson, NEJM 2004

Prospective, Randomized, Controlled: Outcome at Surgery Laparoscopic (n=435) Open (n=425) P value Bowel margins (cm) 10-13 11-12 0.4-0.9 Lymph nodes 12 1.0 Surgery time (min) 150 90 <0.001 Conversion - Intraoperative complications 8 15 NS Length of incision (cm) 6 18 Nelson, NEJM 2004

Prospective, Randomized, Controlled: Post-operative Laparoscopic (n=435) Open (n=425) P value IV narcotics (days) 3 4 <0.001 PO narcotics (days) 1 2 0.02 Length of Stay 5 6 30-day mortality NS Complications 92 85 Rates of readmission 10 12 Rates of reoperation <2% Nelson, NEJM 2004

Prospective, Randomized, Controlled: Outcome Laparoscopic (n=435) Open (n=425) P value Recurrence* (4.4yrs) 76 84 0.83 Wound recurrence 1% P=0.50 NS 3-yr survival 86% 85% P=0.51 NS *Laparoscopic procedure not significantly inferior to Open Procedure. Nelson, NEJM 2004

Cumulative Incidence of Recurrence at Any Satge

Overall Survival at Any Stage

Prospective, Randomized, Controlled: Conclusions No difference between: Time to recurrence Disease-free survival Overall survival Oncologic outcome of laparoscopic resection is similar to that of open resection Laparoscopic approach is associated with less pain and a shorter hospital stay than conventional surgery Nelson, NEJM 2004

Laparoscopic Colectomy : CLASICC Trial Colon and Rectal Cancer 27 UK institutions, 794 patients Prospective, randomized, controlled Follow-up at 1 and 3 months 29% conversion rate Guillou, Lancet 2005

Laparoscopic Colectomy CLASICC Trial Colon and Rectal Cancer Positivity rates of circumferential and longitudinal resection margins Proportion of Dukes’ C2 tumors In-Hospital mortality Primary Endpoints Complication rates Quality of life Transfusion requirments Secondary Endpoints Guillou, Lancet 2005

CLASICC Trial Profile Guillou, Lancet 2005

Prospective, Randomized, Controlled Open (n=276) Laparoscopic (n=345) Conversion (n=143) Age 69 68 Female 121 (44%) 167 (48%) 49 (34%) Colon Rectum 144 (52%) 132 (48%) 185 (52%) 160 (46%) 61 (43%) 82 (18%) TNM Stage T 0 T 1 T 2 T 3 T 4 -- 9 (4%) 36 (16%) 141 (64%) 33 (15%) 17 (6%) 48 (17%) 175 (63%) 36 (13%) 4 (3%) 16 (13%) 71 (60%) 28 (24%) N0 N1 N2 Not Investigated 130 (59%) 51 (23%) 38 (17%) 159 (58%) 70 (25%) 46 (17%) 1 63 (53%) 33 (28%) 21 (18%) 2 (2%) M0 M1 Not investigated Missing 96 (44%) 8 (4%) 107(49%) 98 (36%) 4 (1%) 15 (5%) 57 (48%) 7 (6%) 52 (44%) 3 (3%) Guillou, Lancet 2005

CLASICC: Outcome at Surgery Open (n=276) Laparoscopic (n=345) Conversion (n=143) Time to first bowel movement (days) 6 (4.5-7) colon 6 (4-7) rectum 5 (4-6.5) colon 5 (3-7) rectum 6 (4-8) rectum Time to normal diet 6 (5-8) colon 7 (5-8) rectum 5 (4-7) colon 6 (5-7) rectum 7 (5-9) rectum Anaesthetic time (min) 135 (100-175) 180 (140-220) 180 (135-223) Length of incision (mm) 228 (180-300) 70 (55-100) 200 (150-285) All data are median Guillou, Lancet 2005

CLASICC: Pathology Laparoscopic Open Converted Lymph-node Duke’s C2 12 ( 8-17) 34 (6%) 13.5 (8-19 18 (7%) -- 16 (12%) Colon Distance from tumor to mesenteric resection margin Circumferential resection margin + 8cm (6.5-10) 16 (7%) 9cm (7-11) 6 (5%) Rectum 30 (16%) 14 (14%) P>0.05 Guillou, Lancet 2005

CLASICC: Complications Intraoperative complications Laparoscopic (intention to treat) Open General 54 (10%) 27 (10%) (Colon) Haemorrhage Cardiac/Pulmonary Bowel Injury Ureteric Injury Other 2 (1%) 10 (4%) 6 ( 2%) 5 (4%) 4 (3%) -- (Rectum) Haemorrhage 17 (7%) 11 (4%) 3 ( 1%) 9 (4%) 7 (5%) 1 (1%) 2 (2%) P > 0.05 Guillou, Lancet 2005

CLASICC: Complications 30 days post op Laparoscopic Open Converted Total Complications 133 (39%) 115 (42%) 99 (69%) (Colon) wound infection chest infection anastomotic dehiscence DVT Other 8 (4%) 10 (5%) 7 (4%) 5 (3%) 32 (17%) 7 (5%) -- 31 (22%) 5 (8%) 6 (10%) 1 (2%) 11 (18%) (Rectum) wound infection 16 (10%) 12 (8%) 13 (8%) 30 (19%) 16 (12%) 6 (5%) 10 (7%) 2 (2%) 33 (25%) 16 (20%) 12 (15%) 1 (1%) 35 (43%) Death 16 (1%) 15 (5%) 13 (9%) P>0.05 Guillou, Lancet 2005

CLASICC: Conversions Conversion Rate (Colon) 61 (25%) -Tumor fixity -Uncertainty of tumor clearance -Obesity 37 (61%) 13 (21%) 5 (8%) Conversion Rate (Rectum) 82 (34%) -Tumor fixity/Uncertainty of tumor clearance -Anatomical uncertainty -Inaccessibility of tumor 34 (41%) 21 (26%) 17 (21%) 16 (20%) Guillou, Lancet 2005

Laparoscopic Colectomy : Prospective, Randomized, Controlled Outcome at 3 years Open N=20 Converted N=13 Laparoscopic N=15 Recurrence % 5 23 Survival Status Alive without disease % 90 62 93 Alive with disease % Died, Disease-related % 8 7 Died, non-disease related % Equivalent in terms of recurrence and survival Kaiser, J Lap and Advanced Surg Tech 2004

Laparoscopy vs. Open: Colon Cancer Meta-analysis of 12 randomized controlled trials (2512 patients) Year Patients Lacy 2002 219 COST 428 COLOR Neudecker 30 Braga 269 Singapore 2001 236 Schwenk 2000 60 Leung 34 Curet 73 Hewitt 1998 25 Milsom 113 Stage 1997 29 Abraham, BJS 2004

Laparoscopy vs Open: Colon Cancer Meta-analysis of 12 randomized controlled trials (2512 patients) Odds Ratio P value Mortality 0.85 NS Morbidity 0.62 <0.003 All complications 0.60 <0.001 Local Complications 0.51 All wound complications 0.47 0.003 All leakage 0.84 Hemorrhage 0.71 Reoperation 0.70 Systemic, Cardiac, Respiratory, DVT 0.65-0.81 Abraham, BJS 2004

Laparoscopy vs Open: Colon Cancer Meta-analysis of 12 randomized controlled trials (2512 patients) Patients Improvement First Flatus 476 33.5% Tolerating Solid Diet 406 23.9% 80% Recovery of Peak Expiratory Flow 94 44.3% Pain 6-8hr postop At rest During coughing 173 34.8% 33.9% Narcotic Analgesia (first 48hrs) 269 36.9% Length of Hospital Stay 1237 20.6% Abraham, BJS 2004

Laparoscopy: Colon Cancer Conclusion Laparoscopy for colon cancer has shown to be potentially superior to laparotomy in regard to short-term benefits and equivalent with regard to long term benefits Available data appear to support that laparoscopic colectomy and conventional open colectomy have either similar or superior long-term outcomes (Level 1 evidence) Surgeons with sufficient expertise and ongoing peer-reviewed data collection may offer this therapy to appropriately selected patients

Laparoscopy vs. Open Colectomy in Cancer Patients Randomized Trial Variable Laparoscopy (n = 190) Open (n = 201) Age (yr) 65 (13) 67 (11) Male/female ratio 115/75 121/80 ASA score 1.9 (0.6) 2.0 (0.7) Hemoglobin (g/l) 126 (19) 124 (22) Obesity 17 (8.9) 12 (6) Undernutrition 22 (11.6) 24 (11.9) Albumin (g/l) 36.9 (5.3) 36.2 (6.5) Braga, DCR 2005

Laparoscopy vs. Open Colectomy in Cancer Patients: Long-Term Complications P Value Overall 13 (6.8) 30 (14.9) 0.02 Incisional hernia 9 (4.7) 18 (8.9) NS Intestinal obstruction 3 (1.6) 6 (3) Abdominal abscess 0 (0) 1 (0.5) Urinary dysfunction 3 (1.5) Peristomal abscess Anastomosis stenosis Braga, DCR 2005

Laparoscopy vs. Open Colectomy in Cancer Patients Quality of Life Braga, DCR 2005

Laparoscopy vs. Open Colectomy in Cancer Patients Five-Year Survival by Cancer Stage Braga, DCR 2005

Laparoscopy vs. Open Colectomy in Cancer Patients Five-year Disease-Free Survival Braga, DCR 2005

Laparoscopy vs. Open Colectomy in Cancer Patients Conclusion Laparoscopic colorectal resection reduced longterm complication rate, improved quality of life in the first postoperative year, and did not adversely affect survival in cancer patients Braga, DCR 2005

Laparoscopy for Rectal Cancer

Laparoscopy: Rectal Cancer Total Mesorectal Excision Advantages Amplification of planes of mesorectum and pelvic fascia 30 degree laparoscope better visibility in narrow pelvis Easier identification of pelvic autonomic nerve plexus Disadvantages Technically demanding Absence of tactile sensation Difficulty in assessing surgical margins Difficulty in ultralow cross-clamping Learning curve

Laparoscopy: Total Mesorectal Excision (TME) Prospective review – 58 months Control group – open rectal resections Second consultant Same unit (21 vs. 22) Hartley et al. DCR 2001

Laparoscopy: Total Mesorectal Excision (TME) 42 Attempted Laparoscopic Rectal Mobilizations 14 Early Conversions 28 Laparoscopic Rectal Dissections 7 AP Resections 21 Anterior Resections 1 Non Curative Resection 6 Partial Open Dissection 6 Total Laparoscopic AP 15 Total Laparoscopic AR 21 Laparoscopic TME – Study Group Hartley et al. DCR 2001

Laparoscopy: Total Mesorectal Excision (TME) Completed Laparoscopic (n=21) Open (n=22) Laparoscopic Conversions* (n=21) Mean age (range) 66 (37-82) 65 (47-79) 72 (58-90) Male:female 15:6 15:7 13:8 Dukes’ Stage A 5 4 B 10 8 C 6 13 D 1 Tumor height ([number] cm above anal verge, mean (range)) Anterior resection [15] 6.2 (4-9) [16] 6.4 (4-10) [16] 7 (5-10) Abdominoperineal resctn. [6] 2 (0-5) [6] 1.66 (0-5) [1] 1 Unresectable [0] [2] 6 (4-8) Hartmann’s resection [2] 9 (6-12) * Includes the one palliative lap. APR Hartley et al. DCR 2001

Laparoscopy: Total Mesorectal Excision (TME) Reason for Conversion Number Fixed tumor 2 Doubtful resectability 4 Gross obesity 2 Dense adhesions 2 Obstructed sigmoid 1 Ureter not identified 2 Camera failure 1 TOTAL 14 (33%) Hartley et al. DCR 2001

Laparoscopy: Total Mesorectal Excision (TME) Group Specimen Length (cm) Longitudinal Margin (cm) Radial Margin (cm) No. Positive Margins Lymph Node Yield Laparoscopic (n=21) 27.5 (24-30) 4* (3.5-5) 0.65 (0.33-1.5) 6 (3.25-9.5) Open (n=22) 26.5 (23.75-32) 2.5 (1.05-3.5) 0.8 (0.225-1.2) 7.0 (4.5-10.5) Converted laparoscopic (n=19) † 28 (24-32) 2 (1.5-3.5) 0.6 (0.35-1) 2 ‡ 7 (6-10) Values are medians (interquartile ranges) * p=0.02, Mann-Whitney test for nonparametric data vs. open group † n=19 because two patients not resected;includes the one palliative lap. APR ‡ Both known palliative Hartley et al. DCR 2001

Laparoscopy: Total Mesorectal Excision (TME) Group Operating Time (min) Duration of Ileus (days) Analgesia Requirements (days) Hospital Stay (days) Laparoscopic (n=21) 180* (168-218) 3.0 (3.0-4.0) 4.0 (3.0-6.0) 13.5 (10.25-27.0) Open (n=22) 125 (104-144) 4.0 (3.0-5.0) 15.0 (11.75-28.5) Converted laparoscopic (n=21)† 146 (136.5-179.5) 4 (3.5-7) 5 (3.5-7) 16 (11.5 – 33) Values are medians (interquartile ranges) * p=0.003, Mann-Whitney test for nonparametric data vs. open cases † Includes the one palliative lap. APR Hartley et al. DCR 2001

Laparoscopy: Total Mesorectal Excision (TME) Complication Laparoscopic (n=21) Open (n=22) Converted Laparoscopic (n=21)† Wound infection 1 2 Respiratory tract infection Wound hematoma Clinical anastomotic leakage 4* Bowel obstruction * P = 0.329 Fisher’s exact test vs. open group † Includes the one palliative lap. APR Hartley et al. DCR 2001

Laparoscopy: Total Mesorectal Excision (TME) Follow-up for Patients Having Curative Laparoscopic and Open Resections For Rectal Cancer, Including Complete Mesorectal Excision Laparoscopic (n=21) Open (n=22) Local recurrence 1 (5%) 1 (4.5%)* Death (all causes) 6 (29%) 5 (23%)† * Median follow-up was 38 (range, 6-53) months † p=1 and † P=0.736, Fisher’s exact test Hartley et al. DCR 2001

Laparoscopy: Total Mesorectal Excision (TME) Feasible in 50% of patients where possible Yields histologic and early survival and recurrence figures comparable to open surgery Hartley et al. DCR 2001

Laparoscopy: Total Mesorectal Excision (TME) case control study VARIABLE/GROUP LAPAROSCOPIC OPEN P value OPERATIVE TIME(min) 200 180 0.06 BLOOD LOSS(ml) 250 1000 <0.001 >1000 ml FLUID INTAKE 3 6 0.002 SOLID DIET (days) 4 7 0.046 HOSPITALIZATION (days) 12 19 0.007 MORBIDITY 37% 51% N/A ANASTOMOTIC LEAK (n) 2 MORTALITY(n) 1 Breukink, Int J Colorectal Dis 2005

Laparoscopy: Rectal Cancer Case controlled series for LAR N Conversion OR Time (mins) Anastomotic Technique Goh, 97 OLAR LLAR 20 - 0% 73 90 Partial TME with double staple Leung, 97 50 16% 150 196 Schwander, 99 OLA/pr LLA/pr 32 NS 209 281 LAR 19 Lap 19 Open, APR 13 Lap 13 Open Hartley, 01 22 42 50% 125 180 LAR, APR, Hartmann Anthuber, 03 334 101 11% 219 218 TME with colonic J if <6cm Breukink, 05 LAR APR 10 31 195 225 Double stapled anastomosis

Laparoscopy: Total Mesorectal Excision (TME) case control study VARIABLE/GROUP LAPAROSCOPIC OPEN CIRCUMFERENTIAL MARGIN(mm) 3 (2-31) 5 (2-31) DISTAL MARGIN mm 35 (10-100) 10 (1-30) NUMBER OF NODES 8 (1-25) 8 (2-20) FOLLOW UP (months) 14 (2-31) 19 (2-31) LOCAL RECURRENCE DISTANT METASTASIS 5 Breukink, Int J Colorectal Dis 2005

Laparoscopy: Rectal Cancer Case controlled series for LAR Length of Stay LRM DRM Morbidity Leak Goh, 97 OLAR LLAR 5.5 5 clear 4 4.5 5% 20% NS Leung, 97 8 6 30% 26% 6% 2% 0% Schwander, 99 OLA/pr LLA/pr 21 15 31% 3% Hartley, 01* OTME LTME 13.5 0.8 0.65 2.5 18% 1 Anthuber, 03 19 14 DN 54% 1% 7% 9% Breukink, 05 LAR APR 11 3.5 37%

Laparoscopy: Rectal Cancer Case controlled series for APR N Conversion OR Time (mins) Anastomotic Technique Seow-Chen, 97 OAPR LAPR 11 16 - NS 100 110 TME Ramos, 97 18 10% 208 229 Fleshman, 99 42 152 21% 209 234 Lap APR with TME Leung, 00 34 25 166 216 Baker, 02 61 28 25% ?TME

Laparoscopy: Rectal Cancer Case controlled series for APR Length of Stay LRM DRM Morbidity Mortality Seow-Chen, 97 OAPR LAPR 8 6.5 clear 3 2 55% 25% 0% Ramos, 97 12.9 7.4 NS 66% 44% 5.5% Fleshman, 99 12 7 + in 5 + in 19 27% 33% Leung, 00 16 25 1 48% 61% Baker, 02 18 13 + in 1 3.2 4.5 -/3% -/4% 3% 4%

Laparoscopy: Rectal Cancer Prospective, Randomized, Controlled – Short-term outcome of TME with anal sphincter preservation (ASP) Open Laparoscopic Patients 89 82 Mean age (years) 45 44 Dukes’ Stage A B C D 6 8 68 7 5 10 63 4 Zhou, Surg Endosc 2004

Laparoscopy: Rectal Cancer Results of Surgery Open (n=89) Laparoscopic (n=82) Distance of Tumor from Dentate (cm) 1.5-4cm 4.1-7cm 56 33 48 34 Distal Margin 1.5-3.5 1.5-4.0 Sphincter preservation 100% Anastomotic height Low anterior (>2cm from dentate) Ultralow anterior (<2cm from dentate) Coloanal (at or below dentate) 35 27 30 25 Diverting ileostomy Zhou, Surg Endosc 2004

Laparoscopy: Rectal Cancer Open Laparoscopic P value Operative time (min) 106 120 NS Blood loss (ml) 92 20 0.02 Parenteral analgesics (days) 4.1 3.9 Solid intake (days) 4.5 4.3 Hospitalization (days) 13.3 8.1 0.001 Morbidity Anastomotic leak 12.4% 3 6.1% 1 0.016 Mortality Follow-up 1-16 months Port site mets NA 2 Pelvic recurrence Zhou, Surg Endosc 2004

Laparoscopic Sphincter-Preserving TME with Colonic J-Pouch Reconstruction 105 patients Mean follow up time 26.9 (1.3-65.6) months Tsang WWC, Ann Surg 2006

Laparoscopic Sphincter-Preserving TME with Colonic J-Pouch Reconstruction Mean operative time 170.4 min Mean anastomotic distance from anal verge 3.9 cm Mean circumferential margin 17.1 mm Mean distal margin 3.4 cm Tsang WWC, Ann Surg 2006

Laparoscopic Sphincter-Preserving TME with Colonic J-Pouch Reconstruction 5-year cancer-specific survival rate 81.3% Local recurrence rate 8.9% Tsang WWC, Ann Surg 2006

Laparoscopic Sphincter-Preserving TME with Colonic J-Pouch Reconstruction Conclusion Lap TME with colonic J-pouch is a safe procedure with reasonable operating time and does not appear to pose any threat to the oncologic and functional outcomes Tsang WWC, Ann Surg 2006

Laparoscopic vs. Open Surgery for Extraperitoneal Rectal Cancer 191 consecutive patients 98 patients underwent lap resection 93 patients underwent open resection Morino M, Surg Endosc 2005

Laparoscopic vs. Open Surgery for Extraperitoneal Rectal Cancer Mean follow up (months) 46.3 49.7 NS Conversion rate (%) 18.4 Mobilization (days) 1.7 3.3 < 0.001 Flatus (days) 2.6 3.9 Stool (days) 3.8 4.7 < 0.01 Oral intake (days) 3.4 4.8 Hospital stay (days) 11.4 13.0 Morino M, Surg Endosc 2005

Laparoscopic vs. Open Surgery for Extraperitoneal Rectal Cancer Morbidity (%) 24.4 23.6 NS Mortality (%) 1.0 2.2 Anastomotic leakage (%) 13.5 5.1 Reoperation (%) 6.1 3.2 Local recurrence (%) 12.6 < 0.05 Cumulative 5-year survival rate (%) 80.0 68.9 Disease-free 5-year survival rate (%) 65.4 58.9 Morino M, Surg Endosc 2005

Laparoscopic vs. Open Surgery for Extraperitoneal Rectal Cancer Conclusion Laparoscopic resection for low and midrectal cancer is characterized by faster recovery and similar overall morbidity with no adverse oncologic effect Morino M, Surg Endosc 2005