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Anal Intra-Epithelial Neoplasia(AIN)

Anal Intra-Epithelial Neoplasia(AIN). Dr Catherine Cheng Tuen Mun Hospital. Case. Male, 77 years old Chairbound, lives with family Medical History NPC completed RT in 2001 with bilateral vocal cord palsy and recurrent aspirations, on PEG feeding and has a tracheostomy

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Anal Intra-Epithelial Neoplasia(AIN)

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  1. Anal Intra-Epithelial Neoplasia(AIN) Dr Catherine Cheng Tuen Mun Hospital

  2. Case • Male, 77 years old • Chairbound, lives with family • Medical History • NPC completed RT in 2001 with bilateral vocal cord palsy and recurrent aspirations, on PEG feeding and has a tracheostomy • Laparoscopic Cholecystectomy for cholecystitis 2012

  3. Case • Bleeding anal polyp with excision done June 2017 • PathologyAIN 3 with areas of SCC, AIN extends to resected margin, invasive foci negative at margin • What would you do now?

  4. Options • 1) Discuss for re-excision of lesion • 2) Consult oncology for radiotherapy • 3) Observe, watchful waiting • 4) Upfront local treatment with 5-FU or Electrocautery

  5. Case • Multidisciplinary Meeting - Managed conservatively in view of poor premorbid • Admitted to medical end of November 2017 with pneumonia • Found to have persistent PR bleeding and anal mass. Hb 9.5

  6. Wide Local Excision with Advancement Skin Flap performed on 23rd January 2018

  7. Pathology • Moderately differentiated SCC • Invasive foci not present in margin • 12 o’clock margin showed AIN 3

  8. Definition https://www.cancer.org/cancer/anal-cancer/about/what-is-anal-cancer.html • Pre-malignant lesion of the anal mucosa • Anal canal 2 – 4cm in length • A precursor to Anal Cancer • Can progress to Anal Cancer (SCC) from AIN I/II/III Joseph R Roberts. World J GastrointestOncol. 2017; 9(2): 50–61

  9. Presentations • Anal/Pelvic Pain • Per Rectal Bleeding • Rectal Mass • Tissue Prolapse • Local soiling • Incontinence to flatus or stool • Constipation Common Less common

  10. Incidence • ~8600 cases of anal cancer per year in USA • Incidence on rising trend Siegel RL. et al. CA cancer J Clin. 2018; 68 (1): 7

  11. Risk factors • HIV • Men having sex with men (MSM) • HPV infection • History of Cervical CA/Gynaecological CA • Smoking • Post-transplant/Inflammatory Bowel Disease/Immunosuppressed individuals

  12. LAST Criteria • Low Anogenital Squamous Terminology - 2012 • LSIL – AIN 1, Condyloma, ASCUS • HSIL – AIN 2, AIN 3, Bowen’s disease, SCC in-situ • (CIN, VaIN, VIN, PeIN) • SISCCA (Superficial invasive squamous cell carcinoma) – Anus/Vulva/Vagina/Cervix/Penis Darragh TM. et. al. Arch Patho Lab Med. 2012; 136(10):1266-97

  13. HSIL to SCC up to 19.6% <=LSIL <=LSIL: low grade squamous intraepithelial lesion Berry J M. et al. Int J Cancer. 2014; 1;134(5):1147-55 William C. Mathews et. al. Plosone. 2014. 0104116

  14. Screening methods • PR examination • Anal cytology +/- DNA detection • Swab stick, Papanicolaou stain (Pap Smear), +/- PCR • High resolution anoscopy (HRA) +/- biopsy • Acetic acid, ‘acetowhite lesions’ (acetowhite epithelium - AWE), Lugol’s Iodine • Wolf forceps • 4 quadrant biopsy

  15. Siekas LL et. al, AIDS Read. 2009;19:178–186

  16. Recommendation - Palefsky and Rubin (2009) Palefsky JM et al. ObstetGynecolClin North Am. 2009;36:187–200

  17. How risky are high risk patients? • High risk AIN patients  Anal Cancer VS General population  Colon CA = x1.2 higher Joseph R Roberts. World J GastrointestOncol. 2017; 9(2): 50–61

  18. SPANC Trial • Study of the Prevention of Anal Cancer • Epidemiology of anal HPV in homosexual men aged 35 and older • Prospective longitudinal cohort study • Community based study • Sydney, Australia • Started in September 2010 and will concluded in mid-2015 • Follow-up continuing to 2018 • 5 study visits over 3 years • By July 2013, approximately 404 men had been assessed for inclusion and over 350 men have been recruited into the study

  19. Treatment Options • Trichloroacetic acid (TCA) • 5-flurouracil • Imiquimod Cream • RFA • Electrocautery (diathermy) • Infra red coagulation • Surgical treatment Topical therapy Ablative therapy Operative treatment

  20. Considerations • Size • Number • Location • Grade of lesions • Duration of treatment • Side effect profile • Patient compliance rate

  21. Stephen E Weis. OncoTargetesTher 2013. 6: 651–665.

  22. Stephen E Weis. OncoTargetesTher 2013. 6: 651–665.

  23. Stephen E Weis. OncoTargetesTher 2013. 6: 651–665.

  24. Role of Radiotherapy • No evidence to support to use of radiotherapy in AIN • ?Role in recurrent AIN Filip Troicki et. al. J Med Case Reports. 2010; 4: 67.

  25. Recommendation • LSIL: observation • Treatment only to reduce symptoms (not risk of CA) • HSIL: recommended for treatment • Periodic HRA for early detection of Anal SCC (earlier SCC staging  better prognosis) for those choosing not to have treatment • Exception – poor pre-morbid with short survival predicted (little benefit from treatment) Palefsky JM et al. ObstetGynecolClin North Am. 2009;36:187–200

  26. ANCHOR TRIAL • Anal Cancer HSIL Outcomes Research • 12 United States sites • Aims to determine whether screening and treatment of HSIL is effective in reducing subsequent anal cancer in high risk groups (i.e. HIV positive)

  27. Summary • Clinical case • Definition, risk factors, treatment options • Management recommendations • Upcoming trials

  28. References • AIN: a review of diagnosis and management - https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5314201/ • Progression rates of AIN to anal cancer, HRA examples - World J Gastrointest Oncol. 2017 Feb 15; 9(2): 50–61. • Diagnosis / Treatment / Surveillance Algorithm - Palefsky JM, Rubin M. The epidemiology of anal human papillomavirus and related neoplasia. Obstet Gynecol Clin North Am. 2009;36:187–200 • HPV Vaccine against Anal HPV Infection and Anal Intraepithelial Neoplasia – NEJM Med 2011; 365:1576-85 • Comparison of imiquimod, topical fluorouracil, and electrocautery for the treatment of anal intraepithelial neoplasia in HIV-positive men who have sex with men: an open-label randomised controlled trial – The Lancet Oncology. April 2013, Volume 14, Issue 4: 346 – 353 • Evaluation and Management of Anal Intraepithelial Neoplasia in HIV-Negative and HIV-Positive Men Who Have Sex with Men – Current Infectious Disease Reports March 2010, Volume 12, Issue 2, p126-133 • LAST Criteria – Archives of Pathology Lab Med. 2012;136:1266–1297 • Onco Targets Ther. 2013; 6: 651–665. • Filip Troicki et. al. Radiation therapy of recurrent anal squamous cell carcinoma in-situ: a case report. J Med Case Reports. 2010; 4: 67.

  29. Questions

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