Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_894_Библиотеки_им_академика_М_И_Перельмана.pdf
340
followed by reconstruction for perianal Paget’s
disease, a number of non-invasive treatments,
such as topical imiquimod, radiotherapy, and
photodynamic therapy, have been utilized with
varying degrees of success [84–89]. Nonetheless,
surgical excision remains the treatment of choice,
when feasible; chemoradiotherapy has a role in
the presence of concomitant anorectal adenocarcinoma and may also be used in conjunction with
surgical excision when invasive perianal Paget’s
disease is present.
High-Grade Squamous Intraepithelial Lesion
High-grade squamous intraepithial lesion (HSIL)
is a non-keratinizing intraepithelial squamous
cell carcinoma rst described by John Bowen in
1912 [90], and rst reported in the perianal region
by Vickers in 1939 [91]. Previously referred to as
perianal Bowen’s disease, HSIL is often considered in some ways to be analogous to HPVmediated AIN, though the two entities have very
different clinical characteristics. While HSIL is
more common in females in the fth decade of
life, AIN is more commonly seen in males, especially those with HIV infection and an immunocompromised state. The natural history of HSIL
is generally benign, with less than 5% progressing to invasive carcinoma [92]; the risk of AIN
progressing to invasive cancer is still being
dened, but it is generally accepted as being
much higher than this.
As with perianal Paget’s disease, perianal
HSIL typically presents with non-specic complaints, such as anal itching, burning, seepage,
and pain with defecation. Up to 30% may present
with a palpable mass lesion [93]. Physical examination reveals raised, irregular, scaly, brownishred plaques with eczematoid features (Fig.19.8).
The plaques may have a “crust” or may weep
serous uid. Clinically, HSIL is often mistaken
for other dermatologic conditions, such as leukoplakia, eczema, psoriasis, and Paget’s disease.
Suspicious lesions should be biopsied in a
full-thickness fashion; this can often be done in
the ofce setting using a punch biopsy.
B. R. Kann
Fig. 19.8 High-grade squamous intraepitheal lesion
(Perianal Bowen’s disease)
Histologically, HSIL demonstrates disordered
epidermal hyperplasia with parakeratosis and
hyperkeratosis in the supercial surface layers,
and mitotic gures in all layers (Fig. 19.9).
“Bowenoid” cells, large atypical cells with haloed
large hyperchromatic nuclei, are typically
present.
Unlike Paget’s disease, the presence of other
concomitant malignancies or progression of the
index lesion to malignancy is quite rare in the
setting of perianal HSIL.The standard of care is
wide surgical excision. Because microscopic
disease often extends beyond grossly visible
disease, a systematic 4-quadrant biopsy
technique, including intra-anal biopsies, to map
the extent of disease has previously been
advocated [94, 95]. However, as is the case with
perianal Paget’s disease, given the low risk of
progression to invasive cancer, high rates of postoperative recurrence, large skin defects requiring
advancement aps, and potential functional
issues, the utility of this has come into question.
Outcomes data is limited to small retrospective
series and case reports, given the rarity of perianal
HSIL.Beck etal. reported a series of 33 patients
from the Cleveland Clinic, 27 of whom were
managed with wide local excision or simple
excision; only 1 patient developed a new invasive
skin cancer during a mean follow-up of 3.7years
[94]. A later series from the same institution found
local recurrence rates to be 23.1% after wide local
excision, 53.3% after simple local excision, and
80% after CO
vaporization; recurrence rates
2
estimated by Kaplan–Meier analysis were
19 Anal Neoplasms
Fig. 19.9 High-grade
squamous intraepitheal
lesion (Perianal Bowen’s
disease)
341
signicantly lower comparing radically treated
patients (abdominoperineal resection and wide
local excision) and conservatively treated patients
(simple excision and vaporization). Three of 47
patients developed an invasive cancer in the
post-op period—all had been initially treated
conservatively. The median time to recurrence
was 38.5months after conservative treatment and
41.5months after radical treatment, highlighting
the need for long-term follow-up [95].
Sarmiento et al also reported a 31% 5-year
recurrence rate for patients with perianal HSIL
managed with local excision; all but 1 recurrence
was managed with wider local excision. Fiveyear survival was 75%, lower than an agematched population, though only 1 death was
attributable to HSIL [96]. In contrast,
Margenthaler et al found a much lower recurrence rate in a series of 25 patients with perianal
HSIL.Twenty-three patients in this report underwent wide local excision, 19 of which underwent
formal mapping. Only three recurrences were
seen, 2 of which had positive margins after wide
local excision (one with mapping) and the third
of which had clear margins after mapping [93].
When wide surgical excision is not feasible or
refused by the patient, other treatment options
exist. Topical 5-uorouracil (5-FU) has been
reported as an effective means of managing perineal HSIL. Graham etal reported a series of 11
patients, 8 of which were treated with topical
5-FU (5%) for 16weeks. One patient required 8
additional weeks for incomplete resolution, but
one year after completion of therapy, all but 1
patient, who was HIV positive, were free of HSIL
[97]; others have reported similar experiences
[98]. The use of radiotherapy and photodynamic
therapy has also been reported to produce favorable results. This subject is discussed in greater
detail in Chap. 20.
Anal Margin Squamous Cell Cancer
The anal margin extends from the junction of
non-hair-bearing and hair-bearing squamous epithelium outwards onto the perianal skin for a distance of 5-cm. Squamous cell cancers of this
region exhibit behavior similar to other cutaneous squamous cell cancer, draining into regional
lymph node basins. They typically present
between the ages of 65 and 75.
Diagnosis is often delayed due to mistaking
lesions for hemorrhoidal disease. Symptoms
include a painful perianal mass, bleeding, pruritis,
and drainage/discharge. Suspicious lesions should
be biopsied, and a CT of the chest, abdomen, and
pelvis should be performed to exclude metastatic
disease. Staging is similar to that of anal canal
squamous cell cancer. Careful palpation of the
inguinal lymph nodes should be done to evaluate
for nodal extension. While the risk of nodal
342
involvement is low with T1 lesions, up to 24% of
T2 lesions and 67% of T3 lesions will have nodal
metastases at the time of diagnosis [99].
In addition to tumor staging, the involvement
and proximity of the anal sphincter to the site of
the tumor is essential in guiding management.
Treatment for smaller (T1, T2) lesions without
nodal metastasis is surgical excision with a 1cm
margin, if possible without compromising
sphincter function. Wound closure may necessitate a rotational or pedicle skin ap. Surgical
excision of larger lesions may result in a signicant soft tissue defect or necessitate excision of a
portion of the sphincter complex to achieve negative margins. Management of these larger lesions
that closely oppose the sphincter complex, as
well as those with metastatic lymph node involvement, should be with CMT, given in a similar
manner as for anal canal squamous cell cancer.
B. R. Kann
Anal Margin Basal Cell Cancer
Basal cell cancers of the anal margin are rare,
accounting for 0.2% of anorectal neoplasms and
0.27% of all cutaneous basal cell cancers [11].
They more frequently are seen in men, and typically occur in the sixth decade of life. They are
frequently associated with other skin lesions, and
the diagnosis of an anal basal cell cancer should
trigger a thorough dermatologic examination.
Anal basal cell cancers appear similar to other
cutaneous basal cell cancers, typically as a mass
with central ulceration and a raised pearly border
(Fig. 19.10). Complaints are non-specic and
may include bleeding, pain with sitting, and pruritis. These lesions tend to be very slow growing
and very rarely metastasize. Treatment is usually
via wide local excision, if feasible without compromising sphincter function. Skin grafting or
advancement aps may be necessary for wound
closure. In rare instances, APR may be necessary
to achieve negative margins. Positive surgical
margins are associated with a 29% local recurrence rate [100].
Paterson el al reported a series of 21 cases of
anal basal cell cancer; 33% had multiple basal
cell cancers at other sites. Most were treated with
local excision and there were no local recurrences
Fig. 19.10 Anal margin basal cell carcinoma
[101]. Gibson etal reported a series of 51 basal
cell cancers of the perianal and genital regions,
15 of which were classied as perianal; again, the
majority were treated with local excision [102].
The cancer-specic survival rate in both series
was 100%.
Conclusion
While neoplasms of the anal canal and anal
margin are relatively rare, a thorough knowledge of the variety of lesions seen in this
anatomic region is essential. Presenting
symptoms tend to be vague and non-specic;
a thorough history and physical exam and a
high index of suspicion are often necessary
to achieve an accurate diagnosis and institute appropriate treatment in a timely fashion.
Squamous cell carcinoma of the anal canal is
commonly seen in association HPV and HIV
infection, and is typically managed with combined modality chemoradiation with excellent
oncologic results, and reasonable functional
results. Less common malignancies of the
anal canal, including anal adenocarcinoma
and melanoma, have much poorer prognoses.
19 Anal Neoplasms
343
Squamous cell and basal cell carcinomas of
the anal margin can typically be managed with
local excision in the absence of metastatic
disease. Pre-malignant conditions of the anal
margin, including Paget’s disease and HSIL
are rare but should be included in the differ-
ential diagnosis of patients with complaints of
anal discomfort or itching that do not improve
with usual measures.
References
1. Simpson JAD, Scholeeld JH.Diagnosis and man-
agement of anal intraepithelial neoplasia and anal
cancer. BMJ. 2011;343:d6818.
2. Siegel RL, Miller KD, Jemal A. Cancer statistics,
2017. CA Cancer J Clin. 2017;67:7–30.
3. Pineda CE, Welton ML.Management of anal squa-
mous intraepithelial lesions. Clin Colon Rectal Surg.
2009;22:94–101.
4. Chin JY, Hong TS, Wo JY. Anal cancer: current
and future treatment strategies. Gastrointest Cancer
Targets Ther. 2013;3:19–27.
5. Shridhar R, Shibata D, Chan E, Thomas CR. Anal
cancer: current standards in care and recent changes
in practice. CA Cancer J Clin. 2015;65:139–62.
6. Daling JR, Madeleine MM, Johnson LG, et al.
Human papilloma virus, smoking, and sexual
practices in the etiology of anal cancer. Cancer.
2004;101:270–80.
7. Shiels MS, Pfeiffer RM, Chaturvedi AK, et al.
Impact of the HIV epidemic on the incidence rates
of anal cancer in the United States. J Natl Cancer
Inst. 2012;104:1591–8.
8. Ryan DP, Compton CC, Mayer RJ.Carcinoma of the
anal canal. N Engl J Med. 2000;342:782–800.
9. Osborne MC, Maykel J, Johnson EK, Steele
SR. Anal squamous cell carcinoma: an evolution
in disease and management. World J Gastroenterol.
2014;20:13052–9.
10. Tanum G, Tveit K, Karlsen KO.Diagnosis of anal
carcinoma– doctor’s nger still the best. Oncology.
1991;48:383–6.
11. Samdani T, Nash GM.Anal cancer. In: Steele SR,
Hull TL, Read TE, etal., editors. The ASCRS textbook of colon and rectal surgery. 3rd ed. Cham:
Springer; 2016. p.357–71.
12. Billingham R.Neoplasms of the anus and the peri-
anal skin. In: Mazier WP, Levien DH, Luchtefeld
MA, Senegore AJ, editors. Surgery of the colon,
rectum, and anus. Philadelphia: WB Saunders; 1995.
p.205–28.
13. NCCN clinical practice guidelines in oncology –
anal carcinoma (version 1.2017 – November 23,
2016). Available from: https://www.nccn.org/profes-
sionals/physician_gls/pdf/anal.pdf. Accessed March
23, 2017.
14. Bilimoria KY, Bentrem DJ, Rock CE, et al.
Outcomes and prognostic factors for squamous-cell
carcinoma of the anal canal: analysis of patients
from the National Cancer Data Base. Dis Colon
Rectum. 2009;52:624–31.
15. Kolev NY, Tonev AY, Ignatov VL, etal. The role of
3-D endorectal ultrasound in rectal cancer: our experience. Int Surg. 2014;99:106–11.
16. Granata V, Fusco R, Reginelli A, etal. Radiological
assessment of anal cancer: an overview and update.
Infect Agent Cancer. 2016;11:52.
17. Granata V, Fusco R, Catalano O, et al. Early
assessment of colorectal cancer patients with
liver metastases treated with antiangiogenic
drugs: the role of intravoxel incoherent motion
in diffusion-weighted imaging. PLoS ONE.
2015;10:e0142876.
18. Cotter SE, Grigsby PW, Siegel BA, etal. FDG-PET/
CT in the evaluation of anal carcinoma. Int J Radiat
Oncol Biol Phys. 2006;65:720–5.
19. Ed W, Heriot AG, Ng M, etal. The impact of 18-uorodeoxyglucose positron emission tomography on
the staging, management and outcome of anal cancer. Br J Cancer. 2009;100:693–700.
20. Bhuva NJ, Glynne-Jones R, Sonoda L, etal. To PET
or not to PET? That is the question. Staging in anal
cancer. Ann Oncol. 2012;23:2078–82.
21. Caldarella C, Annunziata S, Treglia G, et al.
Diagnostic performance of positron emission tomography /computed tomography using uorine-18
uorodeoxyglucose in detecting locoregional nodal
involvement in patients with anal cancer: a systematic review and meta-analysis. Sci World J.
2014;2014:196068.
22. Mistrangelo M, Pelosi E, Bellò M, etal. Role of positron emission tomography-computed tomography
in the management of anal cancer. Int J Radiat Oncol
Biol Phys. 2012;84:66–72.
23. Wells IT, Fox BM. PET/CT in anal cancer – is it
worth doing? Clin Radiol. 2012;67:535–40.
24. Jones M, Hruby G, Solomon M, et al. The role of
FDG-PET in the initial staging and response assessment of anal cancer: a systematic review and metaanalysis. Ann Surg Oncol. 2015;22:3574–81.
25. Nigro ND, Vaitkevicius VK, Considine B Jr.
Combined therapy for cancer of the anal canal: a preliminary report. Dis Colon Rectum. 1974;17:310–2.
26. Buroker TR, Nigro NM, Bradley G, etal. Combined
therapy for cancer of the anal canal: a follow-up
report. Dis Colon Rectum. 1977;20:677–8.
27. Nigro ND, Seydel HG, Considine B, etal. Combined
preoperative radiation and chemotherapy for squamous cell carcinoma of the anal canal. Cancer.
1983;51:1826–9.
28. Nigro ND.Multidisciplinary management of cancer
of the anus. World J Surg. 1987;11:446–51.
29. UKCCCR Anal Cancer Trial Working Party.
Epidermoid anal cancer: results from the UKCCCR
randomized trial of radiotherapy alone versus radiotherapy, 5-uorouracil, and mitomycin. UKCCCR
Anal Cancer Trial Working Party. UK Coordinating
344
B. R. Kann
Committee on Cancer Research. Lancet.
1996;348:1049–54.
30. Northover J, Glynne-Jones R, Sebag-Monteore
D, et al. Chemoradiation for the treatment of epidermoid anal cancer: 13-year follow-up of the rst
randomised UKCCCR Anal Cancer Trial (ACT I).
Br J Cancer. 2010;102:1123–8.
31. Bartelink H, Roelofsen F, Eschwege F, et al.
Concomitant radiotherapy and chemotherapy is
superior to radiotherapy alone in the treatment of
locally advanced anal cancer: results of a phase III
randomized trial of the European Organization for
Research and Treatment of Cancer Radiotherapy and
Gastrointestinal Cooperative Groups. J Clin Oncol.
1997;15:2040–9.
32. Flam M, John M, Pajak TF, etal. Role of mitomycin
in combination with uorouracil and radiotherapy,
and of salvage chemoradiation in the denitive nonsurgical treatment of epidermoid carcinoma of the
anal canal: results of a phase III randomized intergroup study. J Clin Oncol. 1996;14:2527–39.
33. Ajani JA, Winter KA, Gunderson LL, et al.
Fluorouracil, mitomycin, and radiotherapy vs uorouracil, cisplatin, and radiotherapy for carcinoma of
the anal canal: a randomized controlled trial. JAMA.
2008;299:1914–21.
34. James RD, Glynne-Jones R, Meadows HM, et al.
Mitomycin or cisplatin chemoradiation for treatment
of squamous-cell carcinoma of the anus (ACT II):
randomised, phase 3, open-label, 2 x 2 factorial trial.
Lancet Oncol. 2013;14:516–24.
35. Peiffert D, Tournier-Rangeard L, Gerard JP, et al.
Induction chemotherapy and dose intensication of the radiation boost in locally advanced
anal carcinoma: nal analysis of the randomised
UNICANCER ACCORD 03 trial. J Clin Oncol.
2012;30:1941–8.
36. Rothenstein DA, Dasgupta T, Chou JF, et al.
Comparison of outcomes of intensity-modulated
radiotherapy and 3-D conformal radiotherapy for
anal squamous cell carcinoma using a propensity
score analysis. J Clin Oncol. 2011;29:2011.
37. Yates A, Carroll S, Kneebone A, etal. Implementing
intensity-modulated radiotherapy with simultaneous
integrated boost for anal cancer: 3 year outcomes at
two Sydney institutions. Clin Oncol. 2015;27:700–7.
38. Van Damme N, Deron P, Van Roy N, etal. Epidermal
growth factor receptor and K-RAS status in two
cohorts of squamous cell carcinomas. BMC Cancer.
2010;10:189.
39. Deutsch E, Lemanski C, Pignon JP, etal. Unexpected
toxicity of cetuximab combined with conventional
chemoradiotherapy in patients with locally advanced
anal cancer: results of the UNICANCER ACCORD
16 phase II trial. Ann Oncol. 2013;24:2834–8.
40. Kochhar R, Renehan AG, Mullan D, et al. The
assessment of local response using magnetic resonance imaging at 3- and 6-month post chemoradiotherapy in patients with anal cancer. Eur Radiol.
2017;27:607–17.
41. Vercellino L, Montravers F, de Parades V, et al.
Impact of FDG PET/CT in the staging and the
follow-up of anal carcinoma. Int J Color Dis.
2011;26:201–10.
42. Teagle AR, Gilbert DC, Jones JR, et al. Negative
18F-FDG-PET-CT may exclude residual or recurrent disease in anal cancer. Nucl Med Commun.
2016;37:1038–45.
43. Papaconstantinou HT, Bullard KM, Rothenberger
DA, Madoff RD.Salvage abdominoperineal resection after failed Nigro protocol: modest success,
major morbidity. Color Dis. 2006;8:124–9.
44. Van der Wal BC, Cleffken BI, Gulec B, etal. Results
of salvage abdominoperineal resection for recurrent
anal carcinoma following combined chemoradiation
therapy. J Gastrointest Surg. 2001;5:383–7.
45. Ghouti L, Houvenaeghel G, Moutardier V, et al.
Salvage abdominoperineal resection after failure of
conservative treatment in anal epidermoid cancer.
Dis Colon Rectum. 2005;48:16–22.
46. Butler CE, Gündeslioglu AO, Rodriguez-Bigas
MA. Outcomes of immediate rectus abdominus
myocutaneous ap for reconstruction for irradiated
abdominoperineal resection defects. J Am Coll Surg.
2008;206:694–703.
47. Hinojosa MW, Parikh DA, Menon R, etal. Recent
experience with abdominal perineal resection
with vertical rectus abdominus myocutaneous ap
reconstruction after preoperative pelvic radiation.
Am Surg. 2009;75:995–9.
48. Chessin DB, Hartley J, Cohen AM, etal. Rectus ap
reconstruction decreases perineal wound complications after pelvic chemoradiation and surgery: a
cohort study. Ann Surg Oncol. 2005;12:104–10.
49. Devulapalli C, Jia Wei AT, DiBiagio JR, etal. Primary
versus ap closure of perineal defects following
oncologic resection: a systematic review and metaanalysis. Plast Reconstr Surg. 2016;137:1602–13.
50. Singh M, Kinsley S, Huang A, et al. Gracilis ap
reconstruction of the perineum: an outcomes analysis. J Am Coll Surg. 2016;223:602–10.
51. Das P, Cantor SB, Parker CL, etal. Long-term quality of life after radiotherapy for the treatment of anal
cancer. Cancer. 2010;116:822–9.
52. Joseph K, Vos LJ, Warkentin H, et al. Patient
reported quality of life after helical IMRT based
concurrent chemoradiation of locally advanced anal
cancer. Radiother Oncol. 2016;120:228–33.
53. Sunesen KG, Nørgaard M, Lundby L, et al. Longterm anorectal, urinary and sexual dysfunction
causing distress after radiotherapy for anal cancer:
a Danish multicenter cross-sectional questionnaire
study. Color Dis. 2015;17:O230–9.
54. Bentzen AG, Balteskard L, Wanderàs EH, et al.
Impaired health-related quality of life after
chemoradiotherapy for anal cancer: late effects
in a national cohort of 128 survivors. Acta Oncol.
2013;52:736–44.
55. Frisch M, Biggar RJ, Goedert JJ.Human papillomavirus-associated cancers in patients with human
19 Anal Neoplasms
345
immunodeciency virus infection and acquired
immunodeciency syndrome. J Natl Cancer Inst.
2000;92:1500–10.
56. Machalek DA, Poynten M, Jin F, etal. Anal human
papillomavirus infection and associated neoplastic lesions in men who have sex with men: a systemic review and meta-analysis. Lancet Oncol.
2012;13:487–500.
57. Chang GJ, Gonzales RJ, Skibber JM, etal. A twentyyear experience with adenocarcinoma of the anal
canal. Dis Colon Rectum. 2009;52:1375–80.
58. Bertelson N, Blumetti J, Cintron J, etal. Anal adenocarcinoma: outcomes in an uncommon malignancy.
Am Surg. 2015;81:1114–7.
59. Chang AE, Kernell LH, Menck HR. The National
Cancer Data Base report on cutaneous and noncutaneous melanoma: a summary of 84,836 cases from
the past decade. The American College of Surgeons
Commission on Cancer and the American Cancer
Society. Cancer. 1998;83:1664–78.
60. Parra RS, de Almeida ALNR, Badiale GB,
et al. Melanoma of the anal canal. Clinics.
2010;65:1063–5.
61. Zhong J, Zhou JN, Xu FP, Shang JQ. Diagnosis
and treatment of anorectal malignant melanoma: a
report of 22 cases with literature review. Ai Zheng.
2006;25:619–24.
62. Garrett K, Kalady MF.Anal neoplasms. Surg Clin
North Am. 2010;90:147–61.
63. Chen H, Cai Y, Liu Y, etal. Incidence, surgical treatment, and prognosis of anorectal melanoma from
1973 to 2011: a population-based SEER analysis.
Medicine. 2016;95:e2770.
64. Brady MS, Kavolius JP, Quan SH. Anorectal melanoma. A 64 year experience at Memorial Sloan
Kettering Cancer Center. Dis Colon Rectum.
1995;38:146–51.
65. Podnos YD, Tsai NC, Smith D, Ellenhorn JD.
Factors affecting survival in patients with anal melanoma. Am Surg. 2006;72:917–20.
66. Kiran RP, Rottoli M, Pokala N, Fazio VW. Longterm outcomes after local excision and radical surgery for anal melanoma: data from a
population database. Dis Colon Rectum. 2010;53:
402–8.
67. Metildi C, McLemore EC, Tran T, etal. Incidence
and survival patterns of rare anal canal neoplasms
using the surveillance epidemiology and end results
registry. Am Surg. 2013;79:1068–74.
68. Fletcher CD, Berman JJ, Corless C, etal. Diagnosis
of gastrointestinal stromal tumors: a consensus
approach. Int J Surg Pathol. 2002;10:81–9.
69. Darier J, Coulillaud P.Concerning a case of Paget
disease of the perineal and scrotal area. Ann
Dermatol Syphiligr. 1893;4:25–33.
70. Kyriazanos ID, Stamos NP, Miliadis L, et al.
Extra-mammary Paget’s disease of the perianal
region: a review of the literature emphasizing the
operative management technique. Surg Oncol.
2011;20:e61–71.
71. Berardi RS, Lee S, Chen HP. Perianal extramammary Paget’s disease. Surg Gynecol Obstet.
1988;167:359–66.
72. Banerjee S, Chatterjee M, Chand K.Extramammary
Paget’s disease. Indian J Dermatol Venereol Leprol.
2005;71:417–20.
73. Sahai A, Kodner IJ. Premalignant neoplasms and
squamous cell carcinoma of the anal margin. Clin
Colon Rectal Surg. 2006;19:88–93.
74. Beck DE, Fazio VW. Perianal Paget’s disease. Dis
Colon Rectum. 1987;30:263–6.
75. Perez DR, Trakarnsanga A, Shia J, etal. Management
and outcome of perianal Paget’s disease: a 6-decade
institutional experience. Dis Colon Rectum.
2014;57:747–51.
76. Murakami K, Tanimura H, Ishimoto K, et al.
Reconstruction with bilateral gluteus maximus rotation ap after wide local excision for perianal extramammary Paget’s disease. Report of two cases. Dis
Colon Rectum. 1996;39:227–31.
77. Gaertner WB, Hagerman GF, Goldberg SM, Finne
CO.Perianal Paget’s disease treated with wide excision and gluteal ap reconstruction: report of a case
and review of the literature. Dis Colon Rectum.
2008;51:1842–5.
78. St Peter SD, Pera M, Smith AA, etal. Wide local
excision and split-thickness skin graft for circumferential Paget’s disease of the anus. Am J Surg.
2004;187:413–6.
79. Marchesa P, Fazio VW, Oliart S, et al. Long-term
outcome of patients with perianal Paget’s disease.
Ann Surg Oncol. 1997;4:475–80.
80. McCarter MD, Quan SH, Busam K, et al. Longterm outcome of perianal Paget’s disease. Dis Colon
Rectum. 2003;46:612–6.
81. Isik O, Aytac E, Brainard J, et al. Perianal Paget’s
disease: three decades experience of a single institution. Int J Color Dis. 2016;31:29–34.
82. Sarmiento JM, Wolff BG, Burgart LJ, et al. Paget’s
disease of the perianal region – an aggressive disease? Dis Colon Rectum. 1997;40:1187–94.
83. Conklin A, Hassan I, Chua HK, etal. Long-term functional and quality of life outcomes of patients after
repair of large perianal skin defects for Paget’s and
Bowen’s disease. J Gastrointest Surg. 2009;13:951–5.
84. Mirer E, El Syaed F, Ammoury A, etal. Treatment
of mammary and extramammary Paget’s skin disease with topical imiquimod. J Dermatolog Treat.
2006;17:167–71.
85. Vereecken P, Awada A, Ghanem G, et al. A
therapeutic approach to perianal Paget’s disease:
topical imiquimod can be useful to prevent or defer
surgery. Med Sci Monit. 2007;13:CS75–7.
86. Velenik V, Segedin B, Anderluh F, etal. Radiotherapy
for perianal Paget’s disease: a case report. Tumori.
2008;94:750–3.
87. Hata M, Omura M, Koike I, et al. Role of radiotherapy as curative treatment of extramammary
Paget’s disease. Int J Radiat Oncol Biol Phys.
2011;80:47–54.
346
B. R. Kann
88. Yasar B, Yasar S, Gunes P. Extramammary Paget’s
disease of the perianal region treated successfully with radiotherapy. Int J Color Dis. 2015;30:
711–2.
89. Runfola MA, Weber TK, Rodriguez-Bigas MA, etal.
Photodynamic therapy for residual neoplasms of the
perianal skin. Dis Colon Rectum. 2000;43:499–502.
90. Bowen JT. Precancerous dermatoses: a study of 2
cases of chronic atypical epithelial proliferation. J
Cutan Dis. 1912;30:241–55.
91. Vickers PM, Jackman RJ, McDonald JR.Anal carcinoma in situ: report of three cases. South Surg.
1939;8:503–7.
92. Cleary RK, Schaldenbrand JD, Fowler JJ, et al.
Perianal Bowen’s disease and anal intraepithelial neoplasia: review of the literature. Dis Colon
Rectum. 1999;42:945–51.
93. Margenthaler JA, Dietz DW, Mutch MG, et al.
Outcomes, risk of other malignancies, and need for
formal mapping procedures in patients with perianal
Bowen’s disease. Dis Colon Rectum. 2004;47:1655–
60. discussion 1660-1
94. Beck DE, Fazio VW, Jagelman DG, Lavery
IC. Perianal Bowen’s disease. Dis Colon Rectum.
1988;31:419–22.
95. Marchesa P, Fazio VW, Oliart S, et al. Perianal
Bowen’s disease: a clinicopathologic study of 47
patients. Dis Colon Rectum. 1997;40:1286–93.
96. Sarmiento JM, Wolff BG, Burgart LJ, etal. Perianal
Bowen’s disease: associated tumors, human papillomavirus, surgery, and other controversies. Dis Colon
Rectum. 1997;40:912–8.
97. Graham BD, Jetmore AB, Foote JE, Arnold
LK. Topical 5-uorouracil in the management
of extensive anal Bowen’s disease: a preferred
approach. Dis Colon Rectum. 2005;48:444–50.
98. Welch ML, Grabski WJ, McCollough ML, et al.
5-uorouracil iontophoretic therapy for Bowen’s disease. J Am Acad Dermatol. 1997;36(6 Pt 1):956–8.
99. Newlin HE, Zlotecki RA, Morris CG, et al.
Squamous cell carcinoma of the anal margin. J Surg
Oncol. 2004;86:55–62.
100. Nielsen OV, Jensen SL. Basal cell carcinoma of
the anus – a clinical study of 34 cases. Br J Surg.
1981;68:856–7.
101. Paterson CA, Young-Fadok TM, Dozois RR.Basal
cell carcinoma of the perianal region: 20-year experience. Dis Colon Rectum. 1999;42:1200–2.
102. Gibson GE, Ahmed I.Perianal and genital basal cell
carcinoma: a clinicopathologic review of 51 cases. J
Am Acad Dermatol. 2001;45:68–71.
103. https://www.iarc.fr/en/publications/pdfs-online/pat-
gen/bb2/bb2-chap7.pdf. Accessed 1 April 2017.
104. Edge SB, Byrd DB, Compton CC, etal. AJCC cancer staging manual. 7th ed. New York: Springer;
2010.
Anal Intraepitheial Neoplasia
AmyL.Lightner, CindyJ.Kin, andMarkL.Welton
20
Introduction
Anal squamous cell carcinoma (ASCC) is an
uncommon malignancy caused by infection with
oncogenic strains of Human papilloma virus
(HPV). The precursor lesion, anal intraepithelial
neoplasia III (AIN III) or high-grade squamous
intraepithelial lesion (HSIL), is also caused by
infection with HPV [1–3]. Although these infections are extremely common with a peak incidence
in the third decade of life, they usually resolve
spontaneously by the end of the decade and without detectable virus in immunocompetent patients
[4, 5]. This tends not to be true in high risk
groups—those who practice anoreceptive intercourse and those immunocompromised from
drugs or disease. At particular risk are Human
immunodeciency virus (HIV)-infected men who
have sex with men as patients who are coinfected
A. L. Lightner
Department of Colon and Rectal Surgery,
Cleveland Clinic, Cleveland, OH, USA
e-mail: Lightner.amy@mayo.edu
C. J. Kin
Department of Surgery, Stanford University School
of Medicine, Stanford, CA, USA
e-mail: cindykin@stanford.edu
M. L. Welton (*)
Fairview Health Services, Corporate Department and
Department of Surgery, University of Minnesota,
Minneapolis, MN, USA
e-mail: mwelton1@fairview.org
with HIV and HPV tend to have higher levels of
HPV, and are more likely to have persistent HPV
infection [6–8].
Of particular concern are the specic oncogenic subtypes HPV 16 and 18, which have been
identied as precursors to cervical intraepithelial
neoplasia [9, 10] and anal intraepthithelial neoplasia (AIN) [11]. Although the frequency of progression of high grade AIN, or HSIL, is unknown, data
suggests the long term risk is in the range of 8.5–
13% [2, 3, 12]. Studies have estimated the incidence ranges between is 131 and 137 per 1000,000
men in HIV positive MSM, a population in which
the incidence of anal cancer is on the rise [13, 14].
Colorectal surgeons are often referred patients
with ‘pain down there’, and ‘bump down there’ or
the common diagnosis of hemorrhoids. Frequently,
on exam, there is no hemorrhoidal disease but rather
visible abnormal tissue. Thus, it is important to consider AIN, understand the treatment options and
their varying efcacy, and counsel patients regarding the need for ongoing surveillance. Additional
detailed information is offered in Chap. 19.
Nomenclature andAnatomy
The interchangeable use of AIN and LSIL and
HSIL can create confusion when communicating and reviewing the literature on this topic.
The classification of terminology for HPV
associated lesions of the lower anogenital tract
© Springer International Publishing AG, part of Springer Nature 2019
D. E. Beck et al. (eds.), Fundamentals of Anorectal Surgery,
https://doi.org/10.1007/978-3-319-65966-4_20
347
348
Pe
ing)
A. L. Lightner et al.
(cervix, vulva, anus, perianus, penis, etc), was
recently re-evaluated with consensus regarding nomenclature. A two-tiered nomenclature
with low-grade (LSIL) and high-grade squamous intraepithelial lesions (HSIL) was recommended, with modifiers of AIN II and III
as needed [15]. LSIL corresponds to AIN I
and HSIL corresponds to AIN II and
III. Carcinoma in situ, Bowen’s disease, and
severe dysplasia are all equivalent to HSIL
and those terms should be abandoned. For the
purposes of this chapter, we will use LSIL and
HSIL throughout.
Before diagnosis and treatment patterns can
be articulated, one must have an accurate
depiction of the anatomy and consistent
nomenclature in order to communicate ndings among care providers. In fact, the lack of
clear understanding of the natural history of
HSIL, arguably based on a lack of consistent
anatomic terminology, has been erroneously
used as an argument for the non-treatment of
HSIL [2, 12]. Anal cancer is dened as a squa-
mous cell carcinoma that may not be seen at all
or in its entirety while gentle traction is placed
on the buttocks. In contrast, a perianal cancer
is a squamous cell carcinoma within 5cm of
the anus that is completely visualized while
gentle traction is placed on the buttocks
(Fig.20.1a, b). The term transformation zone
was borrowed from the gynecologic literature
to direct clinicians to a region 0–10cm above
the dentate line where squamous cell carcinomas may occur in the distal rectal mucosa. This
is a region of squamous metaplasia dynamically varying in extent over time. This immature mucosa is at particular risk for HPV
infection [16].
Clinicians are encouraged to denote the location of lesions, whether HSIL, LSIL or Squamous
cell carcinoma, in relation to standard landmarks—anterior/posterior/left/right—and anal or
perianal—rather than using a clock face and the
dentate line. If the clock face is used, 12 o’clock
must be dened because the position of the
patient moves the clock-face.
a
A
Anus, NOS
(C21.0)
rianus
Fig. 20.1 (a, b) Anal
cancer (A–C), perianal
cancer (D), and skin
cancer (E) as visualized
with gentle traction
placed on the buttocks
b
B
C
DE
C
D
Circular muscle
Longitudinal
muscle
Levator ani muscle
(Palpable as the anorectal r
Dentate line
Internal sphincter
muscle
External sphincter
muscle
Intersphincteric groove
E
Muscularis
propria
20 Anal Intraepitheial Neoplasia
349
Prevention
HPV infection is etiologically associated with
90–96% of anal cancers [17, 18], with HPV 16
being the dominant strain, present in 65–89% of the
anal cancers [11, 17, 19], followed by HPV type 18.
With the development of vaccines that target HPV,
the potential to prevent HPV, and ultimately ASCC,
is a reality. The 9-valent HPV (9vHPV) vaccine
is the only HPV vaccine currently used in the
UnitedStates. Three HPV vaccines were licensed
by the U.S. Food and Drug Administration (FDA)
by 2014: bivalent (2vHPV), quadrivalent (4vHPV),
and 9-valent HPV vaccines. Since late 2016, only
9-valent HPV vaccine is available for distribution
in the United States. The 9-valent HPV vaccine
protects against nine HPV types, including seven
types that can cause cancer [20, 21]. A planned
substudy of that trial analyzed the impact of the
HPV vaccine on the development of HSIL in 602
HIV negative MSM [22]. Although none of the 602
healthy men aged 16–26 developed ASCC within
the 3-year follow-up period, there were 5 cases of
grade HSIL in the vaccine arm and 24 cases in the
placebo arm. This is an observed efcacy of
77.5% for HSIL, which suggests the quadrivalent
HPV vaccine may reduce the risk of ASCC in this
patient population. In addition, the incidence of
persistent HPV infection decreased by 95%.
For patients who present with condyloma acuminatum or low-grade squamous intraepithelial
lesion (LSIL), it is important to note these patients
are not approached the same way as HSIL; both
condyloma and LSIL have very low potential for
malignancy [23]. There is no data to support the
direct progression of LSIL to HSIL or ASCC.Rather
LSIL appears to be a marker in certain at risk groups
for presence of HPV.Thus, those patients that are
symptomatic may have their lesions excised or
destroyed for symptomatic control, but not to prevent ASCC.Subsequent follow up of these patients
depends heavily on age, risk factors, underlying disease states, and sexual practice patterns.
Screening
Compared with cervical cancer, anal cancer is
rare. For the year 2016 SEER data for the
United States projects 12,990 women will be
diagnosed with cervical cancer and 4120 will
die of the disease while 8080 patients will be
diagnosed with anal cancer and 1080 will die
of the disease (https://seer.cancer.gov). Since
the introduction of the Papanicolaou (Pap)
testing, the incidence of cervical cancer has
decreased dramatically and the trend continues to be positive. This success with screening
has led to a template for screening for anal
cancer in high risk groups where overall the
trend is heading in a less favorable direction.
The highest risk group for the development of
anal cancer are MSM regardless of HIV status
[14], and among HIV positive MSM, the incidence of anal cancer is 42 to 131 per 100,000,
a rate higher than the 35 per 100,000 of cervical cancer prior to the introduction of the Pap
test [18]. This same population, have higher
rates of HPV and HSIL, both precursors to
ASCC; 72–92% of HIV positive MSM have
detectable HPV and 50% have biopsy proven
HSIL [23, 24]. Despite these statistics universal screening has yet to be adopted due to the
need for more widespread adoption of highresolution anoscopy (HRA), the need for randomized control trial proving the efficacy of
screening, and the lack of national screening
guidelines for anal cancer.
Diagnosis
A thorough history should be conducted including previous known HPV infections or other sexually transmitted diseases, sexual history
specically regarding anoreceptive intercourse,
HIV status and CD4 count, previous anal conditions, local symptoms, and smoking history.
HSIL is typically asymptotic. When symptomatic, patients may complain of local symptoms such as pruritis, bleeding, discharge,
irritation, and tenesmus. Physical exam should
include visual inspection of the perianal skin and
may reveal subtle changes on the skin or more
obvious raised wart-like plaques. Digital rectal
exam and either anoscopy or high resolution
anoscopy (HRA) should be performed as part of
the routine workup. Digital rectal exam may
reveal subtle mucosal/submucosal masses or
quite obvious masses. Anoscopy may conrm