Jonathan E. Efron, MD, FACS, FASCRS The Mark M Ravitch, MD Endowed Professorship in Surgery Chief of the Ravitch Division Associate Professor of Surgery Johns Hopkins University

Innovative Surgical Management in the Treatment of Rectal Cancer: MIS, Robotic, and Beyond

Disclosures

• None

Overview • Current Standard of Care

– Staging – Neoadjuvant Therapy – Technique

• MIS techniques • TEM/TAMMIS • Robotic Approach • Watch and Wait

Staging Determine extent of local

disease • History and physical exam

– pain • Digital rectal examination • Vaginal examination • Endoscopy • Imaging Studies

Imaging of Body

• CT Abdomen/Pelvis/Chest • CXR • MRI • US • ? PET scan

Current Neoadjuvant Recommendations in United States

• T3, NO or any T, N1 or 2 • Middle or Distal Rectum • Circumferential Margin • Long Course Therapy • Surgery 8-10 weeks

– Possibly 12 weeks

TME Radial Margin

TME Anatomy

Total Mesorectal Excision (TME)

TME: Heald’s Data

Outcome 5 year 10 year All Patients(519) Cancer Specific Survival 68% 66% Local Recurrence 6% 8% Curative Only(405) Local Recurrence 3% 4% Disease Free Survival 80% 78%

(Heald et al, Arch Surg 1998)

Open TME Series: Local Recurrence

Author # series # patients Local recurrence rates

Wibe et al (NCR*) N/A 3516 6.4%LAR; 8.2% APR Ridgeway/Darzi 13 6058 6.6% Colquoun et al. 7 5%-9%

* Norwegian Cancer Registry (Gordon and Nivatvongs. Principles and Practice of Surgery for the Colon, Rectum, and Anus 3rd ed. 2007: 695.)

Definitions: MIS Surgery • Laparoscopic assisted proctectomy with TME

– Laparoscopic colonic mobilization with open proctectomy

– Laparoscopic colonic and rectal resection with laparoscopic TME and double stapled coloanal

– Laparoscopic colonic and rectal resection with TME and intersphincteric dissection and hand sewn coloanal anastamosis.

– Laparoscopic Abdominoperineal resection – SILS – Robotic

• Hand assisted proctectomy with TME

Measures of Quality and Outcome

• Short Term Complications – Mortality – Morbidity

• Pathological Assessment – TME specimen, circumferential margins – Lymph nodes

• Long Term Complications • Recurrence • Survival

Laparoscopic Colon Cancer Prospective Trials

Group Technique Convert Morbidity Mortality Rec Year n % % % % Lacey Lap 105 11 12 1 17 (2002) Open 101 31 1 27 COST Lap 435 21 21 <1 16 (2004) Open 428 20 1 18 COLOR Lap 536 17 21 1 N/A (2005) Open 546 20 2 N/A CLASSIC Lap 484 29 10 5 N/A (2005) Open 253 10 4 N/A

S/P Resection

MIS Surgery for Rectal Cancer

• Is MIS Total Mesorectal Excision possible? • How does the physiology of

pnuemoperitoneum and laparoscopic surgery effect the tumor biology? – It Doesn’t

CLASSIC TRIAL: Rectal Data Variable Open Laparoscopic Intention to treat 128 253 Actual treatment 132 160 Conversion rate N/A 82 (57%) Complications 18 (14%) 45 (18%) + CRM* for AR** 14 (14%) 30 (16%) + CRM* for APR 7 (26%) 10 (20%) *Circumferential Resection Margin; **Anterior Resection (Guillou et al. Lancet 2005;365:1718-26)

CLASSIC Trial: Long Term Outcomes

• 3 year results • 794 patients (526 laparoscopic; 268 open) • NO difference in 3 year survival • Differences in Survival

– Overall survival: 1.8% – Disease free Survival: -1.4% – Local recurrence: -0.8%

(Jayne et al. J Clin Oncol 2007;25(21):3061-8)

Randomized trial comparing lap and open surgery in patients with Rectal cancer

• 204 patients – Mid and low rectal cancers – Stage II and III – 103 laparoscopic – 101 open

• Blood loss: – > for open surgery

• Return of GI function and discharge: • Quicker in lap group • Complications and circumferential margins:

– no difference • Number of lymph nodes

– > in lap group • NO difference:

– Local recurrence – Overall survival – Disease free survival

(Valero et al. Br J Surg 2009;96(9): 982-9)

Cochrane Review: Laparoscopic versus open total mesorectal excision for rectal cancer

• Search from Jan 1990-Dec 2005 • 80 studies total; 48 included • 4224 patients • 3 grade 1b studies (individual randomized trials) • 12 grade 2b studies (individual cohort studies) • 5 grade 3b studies (case control studies) • 28 grade 4 studies (case series) • Only one randomized control trial with 3 and 5

year follow up. (Breukink et al Cochrane Database System Rev. 2006 (4):CD005200)

Laparoscopic Resection of Rectosigmoid Cancer

• Prospective randomized study • 1993-2002 • 5 year follow up • 403 patients randomized • Conversion rate 23.2%

(Leung et al. Lancet 2004;363:1187-92)

Laparoscopic Resection of Rectosigmoid Cancer Laparoscopic Open Patients, n 203 200 Direct Cost ($) 9297 7148 Lymph nodes (#) 11.1 12.1 Distal Margin (cm) 4.5 4.5 OP time (min) 189.9 144.2 EBL (cc) 169 238 Complications, n 40 45 Incisional hernia, n 8 4

(Leung et al. Lancet 2004;363:1187-92)

Laparoscopic Resection of Rectosigmoid Cancer

Laparoscopic Open Patients, n 203 200 5 year survival 76.1% 72.9% 5 year disease free 75.3% 78.3%

(Leung et al. Lancet 2004;363:1187-92)

Cochrane Review: Laparoscopic versus open total mesorectal excision for rectal cancer

• Three and five year survival (17 studies): – No difference (5 year survival: 63% to 92.1%)

• Local recurrence (31 studies): – No difference (3.75% to 6.8%)

• Mortality (37 studies):No difference (0-2%) • Morbidity (36 studies):No difference (6-37.6%) • Anastomotic leak:No difference (0.5-37%)

(Breukink et al Cochrane Database System Rev. 2006 (4):CD005200)

Cochrane Review: Laparoscopic versus open total mesorectal excision for rectal cancer

• Laparoscopic TME had significant benefit in: – Blood loss – GI recovery rate – Post operative pain score – Postoperative analgesia – Immunological response – Length of stay

(Breukink et al Cochrane Database System Rev. 2006 (4):CD005200)

Cochrane Review: Laparoscopic versus open total mesorectal excision for rectal cancer

• Open TME had significant benefit in: – Duration of surgery – Cost (only one study)

(Breukink et al Cochrane Database System Rev. 2006 (4):CD005200)

Port Placement

Evisceration and resection

Lap TME Specimen

Questions • How do we deal with the distal and mid

rectum? • Is it safe to leave the mesorectum?

Laparoscopic TATA: Laparoscopic Transanal Transabdominal Approach

• 79/102 patients • 1998-2008 • Excluded:

– Stage IV – Tumors 3 cm from the anorectal ring – No neoadjuvant therapy

• Mean follow up: 34.2 months • Conversion rateL: 2.5% • Morbidity:

– Major: 11% – Minor:19%

• Local Recurrence: 2.5% • Distant Recurrence: 10.1%

(Marks J et al. Surg Endosc 2010 Nov 24(11):2700-7)

Transanal Endoscopic Microsurgery/TAMIS

• Trans anal excision – TEM superior to standard – ? TAMIS Equivalent

• Risk of lymph node metastasis – Recurrence

• T stage – T1 lesions – T2 lesions – T2 after neoadjuvant therapy

Transanal Endoscopic Microsurgery vs. Laparoscopic Total Mesorectal Excision for T2N0 Rectal Cancer.

• 78 patients – T2N0 tumors – Median follow up 70 months

• Morbidity less in TEM (p=0.001 TEM TEM+RT Laparoscopic n 32 11 35 Recurrence 26% 0% 9%

( Allax ME et al. J Gastrointest Surg 2012 Oct 16 epub)

TAMIS: Feasibility of transanal minimally invasive surgery for mid-rectal lesions.

• 16 patients – 3 T1 – 8 S/P neoadjuvant therapy – 4 neuroendocrine – 1 mucocele

• TAMIS technique • 7.5 cm from the anal verge (4-10cm) • No morbidity or mortality • LOS: 3 days

(Lim SB et al. Surg Endosc Nov 2012;26(11):3127-32)

Robots

=

Positioning, Tucking, Securing

Port Placement

5-12 mm lap port

8 mm robot port

5 mm lap port

Port Placement

Feet

Head

Short term Outcomes: Proctectomy • Retrospective study 2004-2007 • 39 patients robotic proctectomy • Low and Mid rectal cancer except T4 - 22 LAR - 11 inter-sphincteric - 6 APR • Complications - 0% mortality - 12.8% morbidity - 12.1 % anastomotic leak • Median OR time 285 minutes • Conversion rate 2.6 % • Median hospital stay 4 days • All negative circumferential margin • Median 13 LN removed • No local recurrence: median follow-up 13 months

(Pigazzi et al. Ann Surg Oncology 2007.)

Robotic Proctectomy: 3 Year Follow Up • 64 patients (Stage l – lll) • Mean OR time: 270 min • Conversion rate: 9.4% • Anastamotic leak: 4/52 (7.7%) • Median lymph nodes: 14.5 • Median distal margin: 3.4 cm • Circumferential margins: - • Recurrence:

– Local: 2/64 (3%) – Overall: 6/64 (9%) – 3 year overall survival: 96.2% – 3 year disease free survival: 73.7%

(Baek et al. Ann Surg 2010 May: 251(5):882-6)

Robot-Assisted Laparoscopic Surgery of the Colon and Rectum • Review of Literature for Robotic colon and

rectal surgery • 39 studies

– 13 ileocecal resections – 220 right colectomies – 190 left colectomies/sigmoid resection – 440 anterior resections – 149 APR/intersphincteric resections – 11 subtotal colectomies

(Stavros et al. Surg Endosc 2012 26:1-11)

New da Vinci Technology for Colorectal Surgery

Seal & cut up to 7mm diameter vessels

Compact snake-wrist architecture

Full control from the surgeon console

Articulation: 60º pitch, 25ºyaw

45mm jaw (white, green & blue re-loads)

13mm diameter instrument

Full control from the surgeon console

EndoWrist® One™ Vessel Sealer

EndoWrist® Stapler*

* 510K application is pending

EndoWrist® Suction Irrigator

Multi-purpose instrument:

-Suction, Irrigation, - Ideal 3rd arm

instrument Articulating tip Full control from the

surgeon console or bedside assistant

Firefly™ Fluorescence

Imaging

Intra-operative fluorescence visualization

Indocyanine green

Vasculature identification and soft tissue perfusion

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Robotic Rectal Publications

Population Complication Rate

Conversion Rate

LOS (days)

CRM Positive Margin

Baik SH (2009) 56 5.4% 0.0% 5.7 7.1% Bianchi (2010) 25 16.0% 0.0% 6.5 0.0% Park (2010) 52 19.2% 0.0% 10.4 1.9% Patriti (2009) 29 30.6% 0.0% 11.9 0.0% Pigazzi (2010) 41 22.0% 7.3% 6.5 2.4% Choi GS (2010) 41 29.3% 0.0% 9.9 4.9% Pigazzi (2007) 39 12.8% 2.6% 4.0 0.0% Pigazzi, Luca (2010) 143 24.0% 4.9% 8.3 0.7% Kim SH (2009) 50 18.0% 0.0% 9.2 2.0% Prasad LM (2010) 51 22.0% 3.9% 6.5 0.0%

Robotic (weighted average)

527 20.2% 2.5% 7.9 1.9%

Population Complication Rate

Conversion Rate

LOS (days)

CRM Positive Margin

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Robot-Assisted Laparoscopic Surgery of the Colon and Rectum

Conversion rate Morbidity Right 1.1% 13.4% Left 3.8% 15.1% Anterior resection 0.4% 9.7%

(Stavros et al. Surg Endosc 2012 26:1-11)

HYBRID LAPAROSCOPIC

ROBOTIC PROCTOCOLECTOMY

SILS

• Minimal data • Retrospective small series and case reports • No definitive benefit over other MIS

techniques • Most data on Right colectomies for colon

cancer

© 2012 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

TABLE 1 Feasibility and Safety of Single-Incision Laparoscopic Colectomy: A Systematic Review. Makino, Tomoki; MD, PhD; Milsom, Jeffrey; Lee, Sang Annals of Surgery. 255(4):667-676, April 2012. DOI: 10.1097/SLA.0b013e31823fbae7

TABLE 1 -a. Perioperative Parameters of Single-Incision Laparoscopic Colorectal Surgery: Included Studies

© 2012 Lippincott Williams & Wilkins, Inc. Published by Lippincott Williams & Wilkins, Inc. 2

TABLE 3

Feasibility and Safety of Single-Incision Laparoscopic Colectomy: A Systematic Review. Makino, Tomoki; MD, PhD; Milsom, Jeffrey; Lee, Sang Annals of Surgery. 255(4):667-676, April 2012. DOI: 10.1097/SLA.0b013e31823fbae7

TABLE 3 . Postoperative Recovery of Single-Incision Laparoscopic Colectomy

The Future “To boldly go where no man has gone before”

Captain James T. Kirk

“Steel isn’t the answer to a systemic biological disease”

Gershon Efron MD

NOTES:Mini-laparoscopy-assisted transrectal low anterior resection (LAR): a preliminary study.

• 3 patients • One 10 mm port, one 5 mm port, one 2mm

port • Transanal TME • Double purse string stapled anastamosis. • LOS: 5 days • 1 patient readmitted for dehydration

(Lacy A et al. Surg Endosc 2012 Jul 18, E pub)

Incisionless: No Surgery • Predictors of complete response

– Tumor markers – Inflammatory markers – Treatment regimine

• Adequate post treatment assessment: determine cpr – MRI – PET/CT – Endoscopy

Watch and Wait: Habr-Gama Evaluation and

Treatment • T2/T3 lesions • Chemo Radiation

therapy • 12 week observation • Assessment of cCR

– Physical Exam – Endoscopy – CEA – CT scan – Excisional Biospy – MRI

Follow up

• Every month – Rigid proctoscopy – Digital exam – CEA – CT scan

• Every 6 weeks to 6 Months – PET/CT – MRI

Watch and Wait: Habr-Gama

Year n T2 FU months Chem cCR LR 1998 118 yes 36 FU/FA 30.5% 27% 2004 265 15 57.3 FU/FA 26.8% 3% 2005 260 20 57 FU/FA 27.3% 3% 2006 361 14 60 FU/FA 27.4% 5% 2011 173 16 65 5-FU based 38.7% 4.6%

(Glynne-Jones R et al. BJS 2012;99:897-909)

Watch and Wait: Others Author, year n Radiation Chem cCR LR Rossi, 1998 16 50.4 Gy FU/FA 38% 83% Nagakawa, 2002 52 45-50.4 Gy FU/FA 19% NS Lim, 2007 48 50 Gy 5-FU 56% 23% Hughes, 2010 58 45 Gy FU/FA 17% 60% Seshadri, 2011 23 45 Gy 5-FU/mmc - 43% Dalton, 2012 49 45 Gy Capecit 24% 50% Yu, 2011 22 54 Gy Capecit None 41% Maas, 2011 21 50.4 Gy Capecit 10.9% 5% Total 289 33.8%

(Glynne-Jones R et al. BJS 2012;99:897-909)

Where we stand • Some evidence to suggest similar oncological

results when comparing MIS to open TME. • Evidence to show benefits seen with other MIS

colectomy procedures. • Guidelines for laparoscopic colectomies for cancer

should be extrapolated • Possibly avoid in obese patients or those with

large bulky tumors. • Requires advance laparoscopic and colorectal

experience • Preliminary Data on Watch and Wait

– Needs Replication

Where are we going? • Need randomized trials to confirm suspicions. • Japan: JCOG 0404

– Randomized trial comparing lap and open colon and rectal cancer

• Color II – International randomized trial comparing lap and open

rectal cancer • US ACOSOG funded trial

– 500 patient randomized trial comparing lap and open rectal resections

• Multicenter Prospective Data Base on Watch and Wait Patients

• Robotic Prospective Trials – International/Korea

December 19, 2012 57

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