AIN III and Perianal skin intraepithelial neoplasia

1. AIN III and Perianal skin intraepithelial neoplasia

2. SSC of Anus • CRT for SCC of Anus studies have shown that the use of combined chemoradiation therapy results in local failure rates between 14 to 37%, 5-year overall survival rates of 72 to 89% and 5-year colostomy-free survival rates of 70 to 86% • The ACT II study showed that the outcomes and non hematologic toxicities with cisplatin were equivalent to mitomycin while resulting in significantly lower hematologic toxicity. Taken together, the data suggest that 5-FU plus mitomycin remains the standard of care, but that 5-FU and cisplatin could be considered a reasonable approach as well. • The relevance of maintenance (adjuvant) chemotherapy was addressed in the ACT II study. Patients were randomized to an arm receiving two cycles of cisplatin plus 5-FU (maintenance) or to a “no maintenance arm” following completion of chemoradiation. The 3-year disease-free and overall survival rates were 75% and 85% on the maintenance arm versus 75% and 84% on the no maintenance arm. The lack of a clinical benefit for induction or maintenance chemotherapy does not support the implementation of these strategies.

3. SCC • SALVAGE THERAPY Salvage therapy may be indicated for patients with persistent or recurrent disease after completion of primary chemoradiotherapy. The preferred treatment for persistent or recurrent disease following combined modality therapy is APR. • Complications from salvage APR appear to be greater in patients undergoing this procedure after primary chemoradiotherapy. In a retrospective study of 35 patients who underwent salvage APR for persistent and/or recurrent disease, 13 patients experienced perineal wound infection necessitation reoperation and delayed healing occurred in 23 patients. Fifteen patients, 12 of whom underwent salvage APR for persistent disease, experienced secondary failure. • The median survival duration after secondary failure was 19 (range, 1–78) months.135 • In the UKCCCR trial, there was a relapse rate of 40% in 29 patients who underwent salvage therapy for persistent disease.

4. AIN III

5. Trends in the Occurrence of High-Grade Anal Intraepithelial Neoplasia in San Francisco: 2000–2009 • Although screening of human immunodeficiency virus (HIV)-positive individuals for anal intraepithelial neoplasia (AIN; a precursor of anal cancer) has been practiced in San Francisco among HIV health care providers since the early 1990s, to the authors’ knowledge no study to date has focused on evaluating recent AIN trends. • During 2000 through 2009, the majority of AIN 3 cases occurred among men (1152 of 1320 men; 87.3%). Rates of AIN 3 during the corresponding period increased by 11.48% per year (P <.05) among men and were stable among women. Comparing rates among men during 2000 to 2004 with those during 2005 to 2009, the largest increases were noted among those aged 50 years to 64 years (RR, 2.47; 95% CI, 1.93–3.17) and among black individuals (RR, 3.49; 95% CI, 2.14–5.85). During the same period, anal cancer rates were stable among men and women. • Rates of AIN 3 increased in San Francisco during 2000 through 2009, in conjunction with an anal cytology screening program for high-risk groups, whereas rates of invasive anal cancer were unchanged. Continued surveillance is necessary to evaluate the impact of screening and human papillomavirus vaccination on the prevention of human papillomavirus-related AIN and anal cancer.

6. Surgery for AIN • Brown et al reported 34 patients with HGAIN who were treated surgically and followed for a median of 41 months from a single hospital in the UK. • Patients with lesions smaller than 1 cm (15 of 34) treated with simple excision had no disturbance of anal function. HGAIN extended to the margins in 19 of 34 specimens. • Macroscopic recurrences occurred in 14 of 34 patients, and 12 of these recurrences were at the resection margin and four of 14 patients required more than one excision for macroscopic disease. • Five of 19 patients with more extensive disease had postoperative disturbance of anal function. • The authors commented that three patients whose initial histology showed HGAIN were found to have clinically unsuspected invasive anal cancer in the excised specimen. • None of the patients with excisions progressed to invasive anal squamous carcinoma. This patient cohort included patients with extensive disease that were treated aggressively with excisions. While no patient developed cancer, approximately 25% of patients with extensive disease had anal function defects postoperatively.

7. Surgery in AIN III • Scholefield et al reported on their experience caring for a patient population that included 35 patients with perineal or perianal AIN-3 who were followed for a median of 63 months.26 • Only patients who had AIN-3 limited to less than 30% of anal circumference were offered excision. None of the patients in their cohort was known to be HIV-infected, but six of 35 were being treated in the long term with immunosuppressants. • In 12 of 28 patients with localized disease treated by excision, at least one margin was not clear. • Macroscopic recurrence of AIN-3 occurred in four patients. • All six patients with known immunosuppression had multifocal AIN-3. Three of these six patients developed invasive anal squamous cell carcinoma during follow-up. • None of the 28 patients with focal disease treated with excision developed anal squamous cell carcinoma or were reported to have postoperative disturbances of anal function. • The three patients who developed anal squamous cell carcinoma all had multifocal AIN-3 and were not offered excision. • These data indicate that limiting surgery to patients with less extensive disease reduces disturbances in anal function that seriously affect quality of life. • The data also imply that not treating immunosuppressed patients with extensive disease puts them at high risk for progression to anal squamous cell carcinoma.

8. Surgery for AIN III • Watson et al from New Zealand reported the outcome of 72 patients with AIN who were observed for a median follow-up of 60 months. • Approximately 30% of the patients were immunosuppressed, with 17 receiving immunosuppressants and five being HIV-positive. • Postoperative disturbances of anal function were common, and nine patients developed faecal incontinence; of these, four required colostomy. • Despite this aggressive treatment, eight of 72 patients (11%) progressed to invasive anal squamous cell carcinoma. • These studies, when taken together, have changed the view of excision therapy for HGAIN. • It is now considered by many not to be an ideal treatment for patients with extensive or multifocal HGAIN. • The findings leading to this change include incomplete excisions that leave clinically in apparent HGAIN at surgical margins that subsequently recur, frequent HGAIN recurrences even in patients whose surgical sites indicate that the HGAIN has been completely excised, and patients who have excisions for more than minimal disease often haveclinically important post-procedure morbidity.

9. Peri-anal Skin Cancer SSC of the skin around the anus appears to be a different condition It appears we can treat this as Skin cancer and therefore allows excision of perianal skin and local reconstruction with a rotation flap Defunction patients and do with a plastic surgeon

10. AIN at the BRI • Dedicated Anal neoplasia clinic • 2 dedicated Anal cancer surgeons • Histopathology by an expert • Same person seeing the patient on almost every visit • Poorly attended by Senior Trainees !! • AIN I-II 6/12 month OPD visit no intervention if no change or new disease. • AIN III 3/12 review in OPD if worried urgent EUA and either excision biopsy or incision biopsy • Support by plastic surgeon and dermatologist • Support by 2 ½ CNS

11. AIN at the BRI • Aspirations; • See all the histology of new cases • Ask Enthusiastic colleagues to help expand the service • Increase the use of local plastic surgical intervention