1. A. MONTORI M.D. F.A.C.S. PROFESSOR OF SURGERY UNIVERSITY OF ROME “LA SAPIENZA” President of EAcSS HOW TO AVOID MAJOR SURGERY IN RECTAL CANCER MSO-MTCC PG TRIPOLI October 1 ST 2010

2. LOCAL EXCISION FOR RECTAL NEOPLASMS THE LOCAL EXCISION OF RECTAL NEOPLASMS STILL REPRESENTS A VERY CONTROVERSIAL ISSUE: The nature of the lesion (benign or malignant) The nature of the lesion (benign or malignant) The location (distance from anal verge) The location (distance from anal verge) The metodology to be used The metodology to be used The progress of technology The progress of technology The different approach (Surgical or Endoscopic) The different approach (Surgical or Endoscopic) The results obtained The results obtained The radicality of the intervention (Long-Term survival - QoL) The radicality of the intervention (Long-Term survival - QoL)

3. LOCAL EXCISION FOR RECTAL CANCER LOCAL EXCISION OF RECTAL CANCER IN LOW-RISK PATIENTS IS APPEALING BUT IT PROVIDES LIMITED CONTROL OF THE DISEASE (LACK OF “N” STAGING). NEVERTHELESS IN THE RECENT YEARS IT IS POSSIBLE TO ACHIEVE A CORRECT PREOPERATIVE TUMOR AND NODE STAGING DUE TO THE SIGNIFICANT IMPROVEMENT OF THE TRANSANAL ULTRASOUND, MRI, LYNPHOSCINTIGRAFY, ELICOIDAL CT SCAN IMAGING. (LACK OF “N” STAGING). NEVERTHELESS IN THE RECENT YEARS IT IS POSSIBLE TO ACHIEVE A CORRECT PREOPERATIVE TUMOR AND NODE STAGING DUE TO THE SIGNIFICANT IMPROVEMENT OF THE TRANSANAL ULTRASOUND, MRI, LYNPHOSCINTIGRAFY, ELICOIDAL CT SCAN IMAGING.

4. NORMAL ( FIVE LAYERS NORMAL ( FIVE LAYERS ) T 1 T 1 T 3 N 1 T 3 N 1 TRANSRECTAL US

5. LOCAL EXCISION FOR RECTAL CANCER

6. VIRTUAL ENDOSCOPY

7. LOCAL EXCISION FOR RECTAL CANCER DIGIT EXPLORATION DIGIT EXPLORATION TUMOR MARKERS TUMOR MARKERS RETTOSIGMOIDOSCOPY RETTOSIGMOIDOSCOPY (BIOPSY: microbiopsies for grading - TATOO: defining the excisional line ) ENDOSCOPIC LYMPHOSCINTIGRAPHY ENDOSCOPIC LYMPHOSCINTIGRAPHY TRANSRECTAL US (T-n) TRANSRECTAL US (T-n) TC SCAN (Spiral TC Scan and Virtual Endoscopy (T-n) TC SCAN (Spiral TC Scan and Virtual Endoscopy (T-n) MRI (T-n) MRI (T-n) BONESCAN BONESCAN FLEXIBLE(colonoscopy)RIGID

8. ENDOSCOPY: 10-15 mm normal mucosa biopsies & tatoo Defined excinal line on hystol. ass normal mucosa Eval. post RxTerapy response Follow up Macrobiopsies for grading

9. ENDOSCOPIC LYNPHOSCINTIGRAFY 1.0 ml colloidal rhenium sulfide marked with 99m TC

10. TRANSRECTAL US (N 1 )

11. LOCAL EXCISION FOR RECTAL CANCER TRANSANAL APPROACH: TRANSANAL APPROACH: PAPILLON: Parachute Technique PAPILLON: Parachute Technique PARKS PARKS MAEDA 2004: Minimally Invasive Transanal Surgery - MITAS ) MAEDA 2004: Minimally Invasive Transanal Surgery - MITAS ) INTERSPHINTERIC EXCISION (MASON) INTERSPHINTERIC EXCISION (MASON) TRANS-SACRAL APPROACH (KRASKE) TRANS-SACRAL APPROACH (KRASKE) TRANSANAL ENDOSCOPIC MICROSURGERY TEM (BUESS 1984) TRANSANAL ENDOSCOPIC MICROSURGERY TEM (BUESS 1984) (ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION FOR ADENOMA) (ENDOSCOPIC MUCOSAL RESECTION AND SUBMUCOSAL DISSECTION FOR ADENOMA) SURGICAL APPROACH ENDOSCOPIC APPROACH

12. TRANSANAL APPROACH (PAPILLON: Parachute Technique) LOCAL EXCISION FOR RECTAL CANCER

13. TRANSANAL APPROACH (PARKS) TRANSANAL APPROACH (PARKS)

14. Minimally Invasive Transanal Surgery - MITAS MAEDA et al. 2004 LOCAL EXCISION FOR RECTAL CANCER

15. INTERSPHINTERIC EXCISION (MASON) LOCAL EXCISION FOR RECTAL CANCER

16. TRANS-SACRAL APPROACH (KRASKE) TRANS-SACRAL APPROACH (KRASKE)

17. LOCAL EXCISION FOR RECTAL ADENOMA & CANCER TRANSANAL ENDOSCOPIC MICROSURGERY (TEM) - G. BUESS 1984 (ADENOMA) - E.LEZOCHE 1996 (CANCER) G. BUESS

18. FULL THIKNESS + “local perirectal fat “ EXCISION” SHAPE OF THE SPECIMEN IS LIKE A TRUNCATED PYRAMID

19. WE START TO THINK THAT RECTAL CANCER COULD BE TREATED WITH LOCAL EXCISION NEARLY 25 YEARS AGO! Int J Colorect Dis (1986) 1:208-211 Surg Endosc (1987) 1:113-117

20. NEED FOR ADJUVANT THERAPY RADIOTHERAPY (Full Dose: 5,040 cGy - 4 weeks) RADIOTHERAPY (Full Dose: 5,040 cGy - 4 weeks) CHEMOTHERAPY (5 fu cont. infusion 200mg/m2/day for 2 weeks) CHEMOTHERAPY (5 fu cont. infusion 200mg/m2/day for 2 weeks) (IMMUNOTHERAPY) (IMMUNOTHERAPY) LOCAL EXCISION FOR RECTAL CANCER

21. OUR EXPERIENCE 1987-1992: XRT OUR EXPERIENCE 1987-1992: XRT (FULL DOSE) (26 Pts) LOCAL EXCISION FOR RECTAL CANCER LOCAL RECURRENCES 3 Pts (mean follow up 30 months) T1 5 T2 12 T2 12 T3 9 T0 3 T1 14 T1 14 T2 7 T3 2 DOWNSTAGING LOCAL EXCISION PREPOST

22. OUR EXPERIENCE 1992 - 2001: XRT+CHT (11 Pts) LOCAL EXCISION FOR RECTAL CANCER LOCAL RECURRENCES 1 Pts (mean follow up 30 months) T1 4 T2 4 T3 3 T0 5 T0 5 T1 4 T1 4 T2 2 T2 2 T3 0 T3 0 DOWNSTAGING LOCAL EXCISION PREPOST

23. LOCAL EXCISION FOR RECTAL CANCER WE CAN CONCLUDE THAT IN OUR EXPERIENCE, NEOADJUVANT XRT+CHT GIVE A BETTER RESPONSE AS FAR AS LOCAL EXCISION FOR RECTAL CANCER IS CONCERNED. Angelita Habr-Gama Dis Colon Rectum 1998 ACCORDING TO A.HABR-GAMA 30.5% OF Pts WITH DOWNSTAGING (T0) DO NOT NEED SURGERY.

24. LOCAL EXCISION FOR RECTAL CANCERS IS ASSOCIATED WITH A LOW MORBIDITY AND PROVIDES SATISFACTORY LOCAL CONTROL AND DISEASE-FREE SURVIVAL RATES FOR T1 RECTAL CANCER. THERE WAS, HOWEVER, A NEED FOR A RANDOMIZED, CONTROLLED TRIAL FOR T2 CANCERS, COMPARING LOCAL EXCISION (FULL THICKNESS ABLATION WITH RDT-CHT) TO RADICAL RESECTION. LOCAL EXCISION FOR RECTAL CANCER

25. INCLUSION CRITERIA Patients staged as T 2 N 0 G 1-2 : tumour diameter lower than 3 cm tumour diameter lower than 3 cm within 6 cm from the anal verge within 6 cm from the anal verge TEM VS LAPAROSCOPIC RESECTION Lezoche & coll. Surg. Endoscopy 2005

26. AIM OF THE STUDY To compare the results of two minimally invasive procedure (TEM vs Laparoscopic Low Anterior Resection or Laparoscopic Abdominal Perineal Resection) in the treatment of low rectal cancer. TEM VS LAPAROSCOPIC RESECTION INFACT IT IS WELL KNOWN THAT LAP COLORECTAL RESECTION IS LESS IMMUNOSUPPRESIVE THAN THE OPEN APPROACH

27. EXCLUSION CRITERIA Evidence of local or distance metastases Evidence of local or distance metastases Other malignancies in history Other malignancies in history TEM VS LAPAROSCOPIC RESECTION Exclusion criteria for radiotherapy: severe diverticular disease or previusly radiotherapy severe diverticular disease or previusly radiotherapy Exclusion criteria for chemotherapy: patients older than 70 years and/or with compromised general patients older than 70 years and/or with compromised general conditions conditions Lezoche & coll. Surg. Endoscopy 2005

28. Prospective randomized trial 40 patients T 2 N 0 G 1-2 40 patients T 2 N 0 G 1-2 with 3 year follow-up were randomized to: 20 patients to TEM 20 patients to Lap. Resect. (arm A) (arm B) TEM VS LAPAROSCOPIC RESECTION

29. ANAGRAPHIC DATA TEM VS LAPAROSCOPIC RESECTION TEM n=20 TEM n=20 LR n=20 Gender, male [n, (%)] 12 (60) 13(65) p n.s.* Age (years) [median, (25 th p-75 th p)] 68(64-70) 67(62-68) n.s. # Range (years) 34-74 48-78 * Chi-Square Test # Wilcoxon Test Lezoche & coll. Surg. Endoscopy 2005

30. RADIOTHERAPY DOWNSTAGE TEM VS LAPAROSCOPIC RESECTION TEM n=20 TEM n=20 LR n=20 Radiotherapy downstage 7 p T0 6 p T1 7 p T0 4 p T1 p n.s * Reduction > 50% 4 6 n.s * n.s * No significative effect 3 3 n.s.* n.s.* * Chi-Square Test Lezoche & coll. Surg. Endoscopy 2005

31. INTRAOPERATIVE COMPLICATIONS TEM VS LAPAROSCOPIC RESECTION TEM n=20 TEM n=20 LR n=20 Conversions: - to open - lap. LAR to lap. APR - lap. LAR to lap. APR 0022 p 0.05 Operative time (minutes) 110 (45-210) 196 (150-300)* 172(130-210)** 0.001# Blood loss (ml) 45250(100-700) 0.001 # Transfusions (n. of patients) -4 0.053 ^ * Laparoscopic low anterior resection **Laparoscopic Miles procedure # Wilcoxon Test ^Fisher Exact Test

32. STOMA TEM VS LAPAROSCOPIC RESECTION TEM n=20 TEM n=20 LR n=20 No Stoma 20 (100 %) 12 (60 %) p 0.016^ temporary ileostomy temporary ileostomy 0 4 (20 %) definitive colostomy definitive colostomy0 4 (20 %) 4 (20 %) ^Fisher Exact Test ^Fisher Exact Test

33. INTRAOPERATIVE COMPLICATIONS TEM VS LAPAROSCOPIC RESECTION TEM n=20 TEM n=20 LR n=20 Analgesic (n. of pts) 220 p 0.001* Hospital Stay (days) 4.5 (3-6) 7.5 (6 –10) 0.001# No p.o. Complicat. MinorMajor 17 (85%) 2 (10%) 1 (temp. ileostomy) 17 ( 85 %) 2 (10 %) 1 (temp. ileostomy) n.s ^ n.s ^ n.s ^ * Chi-Square Test # Wilcoxon Test ^Fisher Exact Test

34. FOLLOW-UP 48 months (36-76) TEM VS LAPAROSCOPIC RESECTION TEM n=20 TEM n=20 LR n=20 Local recurrence 1 ( at 6 mo., APR 15 mo. disease free ) 1 (dead) 1 (dead) Distant metastases 1 (dead after hepatic resection) Disease free survival rate 85% 80% 1 (dead) * Chi-Square Test # Wilcoxon Test ^Fisher Exact Test

35. CONCLUSIONS 1 TEM VS LAPAROSCOPIC RESECTION According to the study design in our experience TEM versus LR with preoperative chemoradiotherapy has achieved no significant difference in terms of: probability of local recurrence or distant metastases (5%) probability of local recurrence or distant metastases (5%) disease free survival rate (85% in arm A and 80% and B ) disease free survival rate (85% in arm A and 80% and B ) post operative complications post operative complications

36. CONCLUSIONS 2 TEM VS LAPAROSCOPIC RESECTION According to the study design in our experience TEM versus LR with preoperative chemoradiotherapy has achieved significative better results in terms of: n. of temporary & definitive stoma (p 0.016) n. of temporary & definitive stoma (p 0.016) convertion rate (p 0.05) convertion rate (p 0.05) operative time (p 0.001) operative time (p 0.001) blood loss (p 0.001) and necessity of trasfusions blood loss (p 0.001) and necessity of trasfusions use of analgesic (p 0.001) use of analgesic (p 0.001) hospital stay (p 0.001) hospital stay (p 0.001)

37. CONCLUSIONS 3 ADVANTAGES OF TEM TEM VS LAPAROSCOPIC RESECTION low operative trauma low operative trauma more rapid return to more rapid return to - normal respiratory functions - normal respiratory functions - quick ambulation - quick ambulation - normal activities better cosmetic results better cosmetic results

38. THE LOCAL EXCISION OF THE RECTAL CANCER STILL REPRESENTS TODAY A VERY CONTROVERSIAL ISSUE, HOWEVER THE ROLE OF NEOADJUVANT THERAPY SEEMS TO BE BENEFICIAL. THEREFORE PRIOR TO PROCEEDING FOR EXCISION OF RECTAL CANCER A MULTIDISCIPLINARY APPROACH AMONG SURGEON, ONCOLOGIST, RADIOLOGIST AND PATHOLOGIST IS NEEDED IN ORDER TO SELECT THE Pts AND CONSIDER THE RISK OF LOCAL RECURRENCES. CONCLUSION 4 LOCAL EXCISION FOR RECTAL CANCER