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Anal cancer 2008

Anal cancer 2008. John Northover St Mark’s Hospital M62 course, 2008. The disease. Rare - 1% of bowel cancers First GI tumour to become ‘non-surgical’ II. Peak of development activity - 1990s. Viral aetiology and treatment. The development of therapy. Surgery alone Radiotherapy alone

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Anal cancer 2008

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  1. Anal cancer2008 John Northover St Mark’s Hospital M62 course, 2008

  2. The disease • Rare - 1% of bowel cancers • First GI tumour to become ‘non-surgical’ II

  3. Peak of development activity - 1990s Viral aetiology and treatment

  4. The development of therapy • Surgery alone • Radiotherapy alone • Combined modality therapy

  5. Surgical results, St Mark’s Abdominoperineal excision: • Margin, 72 cases, 5YS = 55% • Canal, 123 cases, 5YS = 58% Pinna-Pintor et al, 1989

  6. Radiotherapy results • 72 patients: • 67% 5 year survival • 75% anal function retained Papillon et al, 1985

  7. The coming of combined therapy • Nigro began in 1974 • Three inoperable cases • Complete remissions

  8. Optimum non-surgical therapy? RADIOTHERAPY ALONE or CHEMO plus RADIOTHERAPY

  9. ACT I trial - patient entry Randomised 577 patients 331 surgeons, 162 radiotherapists

  10. UKCCCR trial - side effects Radiotherapy alone Chemoradiotherapy 62% 65%

  11. ACT I - Local treatment failure 111/285 125/283 P<0.001, RR=0.57 (0.45, 0.73)

  12. ACT I - Deaths from anal cancer 77/285 105/283 P=0.02, RR=0.71 (0.53, 0.95)

  13. ACT I - Disease at death RT CM Locoregional only 48 38 Distant ± LR 48 29 Other 7 4 TOTAL 105 77

  14. Surgical salvage ACT I

  15. Surgical salvage ACT I • 265/577 (46%) local failures • 143/265 (54%) radical surgery • 10/143 (7%) no cancer in specimen

  16. Surgical salvage ACT I • 67/133 (50%) alive at 2.1 years • 58/133 (44%) further pelvic rec. • Perineal wound healing -median 2 m.

  17. Surgical salvage ACT I - ARE 22/40 51/89 P>0.5 , RR=0.89 (0.54, 1.47)

  18. Lessons from ACT I • CMT established • High local failure rate (33%) • Less distant spread with CMT • Surgical salvage disappointing

  19. ACT II - the questions • Better primary chemotherapy? • 5FU + MMC • 5FU + CDDP • “Adjuvant” therapy?

  20. ACT II Trial - Protocol

  21. Intra-epithelial neoplasia Normal AIN I AIN II AIN III

  22. The main target AIN III

  23. AIN - why does it matter? • Premalignant • Multifocal • High risk groups • Increasing incidence • Anal ca. incidence rising

  24. Aetiology of AIN • HPV infection • Mainly types 16, 18, 32, 33 • Integrates into genome • Genetic instability

  25. High risk groups • Immune deficiency • Pathological - HIV • Therapeutic - transplant recipients • MSM

  26. Relative prevalence of AIN • ‘Normal’ haemorrhoidectomy: • 3 in 8153 specimens (0.04%) Lemarchand 2004 • HIV+ men: • 20 in 103 men (19.4%) Kreuter 2005 x500 INCIDENCE

  27. ± universal HPV infection (95%) • Majority have AIN (81%) • HAART does not protect Palefsky 2005

  28. Risks in other groups MSW MSS WSN

  29. Men who have Sex with Women

  30. Men who have Sex with Sheep

  31. Women who have Sex with Nobody

  32. Symptoms • None • Pruritus • Bleeding

  33. Anoscopy

  34. Aceto-white lesions

  35. Diagnosis of AIN III Corkscrew vessels (AIN III)

  36. Risk of progression Nottingham study • 35 patients AIN III • FU 63m (14-120) • 28 immune competent - no Ca • 6 immune deficient - 3 (50%) Ca Scholefield et al 2005

  37. Surveillance - in known cases? • AIN I/II • None in immune competent • 6-12m in immune deficient? • AIN III • 6-12m in all - or immune def. only?

  38. Should there be screening? • High risk groups • MSM, HIV+ ?? • What marker lesion? • HPV type, AIN stage? • What tests? • Anoscopy, HPV type, histology? • What intervention?

  39. Should there be screening? • x20 anal cancer in MSM • AIN highly prevalent • ? Natural history • ? Improved outcomes • Rx morbidity and recurrence CASE NOT MADE

  40. Medical management Surgery: • may be difficult (cf cervix) • high recurrence rate Medical: • Imiquimod • Vaccination

  41. Medical management Imiquimod • Introduced 1997 • Cytokine induction • Stimulates cellular immunity • Approved for anogenital warts • ? Role in neoplasia (VIN)

  42. Surgical options • LE ± graft ± faecal diversion

  43. Surgical options • LE ± graft ± faecal diversion • Recurrence rates • Surgical morbidity

  44. Excision and Thiersch graft

  45. Excision and Thiersch graft

  46. Excision and Thiersch graft

  47. Excision and advancement flaps

  48. Anal cancer2008 John Northover St Mark’s Hospital M62 course, 2008

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