Carcinoma anal canal

CARCINOMA ANAL CANAL
PRESENTOR:-
DR ABHISHEK KUMAR
2ND YEAR PG
CHAIR PERSON:-
DR RAMESH HOSMANI
ASSOCIATE PROFESSOR
DEPT OF GENERAL SURGERY
KIMS HUBLI

• The line of fusion of the
endodermal and
ectodermal parts of
anal canal is marked by
a line called pectinate
line that lies below the
anal columns.
• This line marks the
transition of anal canal
lining from simple
columnar to stratified
squamous epithelium.

Definition
• Surgical :
 The anal canal is the terminal
portion of the intestinal tract it
begins at the anorectal junction
(the point passing through the
levator ani muscles), is about 4
cm long, and terminates at the
anal verge.
• Anatomical :
 that extends from the dentate
line to the anal verge.

Anal canal
• Begins at ano-rectal junction
• Rectal ampulla narrows at
ano-rectal junction
• From ano-rectal junction
canal passes Downwards &
Backwards through Pelvic
diaphragm
• Opens at anal orifice
situated in gluteal cleft 4
cms below & in front of tip
of coccyx.

Relations
• Anterior : Perineal body
In male – bulb of penis & urethra
In female – Lower part of post. wall of vagina
• Posterior: Ano-coccygeal raphe
Fibro-fatty tissue between peri-anal skin & raphe
• Lateral: Ischio-rectal fossa and its contents (inferior rectal vessels an
pudendal nerve.

Interior of Anal canal
• Divided into 3 areas
• 1 Anorectal Ring
Upper (15 mm)
• 2 Dentate line
Intermediate (15 mm)
• 3. White line of Hilton
Lower (8 mm)
• 4.Anal verge

Hilton’s line
• It is a contrast between bluish
pink area above and black skin
below
• The line is represented by inter-
sphincteric groove at the lower
end of the internal sphincter
• Indicates lower end of internal
sphincter
• Anal intermuscular septum is
attached carrying the fibres of
levator ani and longitudinal
muscle of rectum

Sphincters of anal canal- Internal
sphincter
• Involuntary sphincter
• Thickening of circular muscle of
lower part of rectum
• Surrounds upper 3/4th of anal canal
• Lower end corresponds with Hilton’s
line
• Middle corresponds with pectinate
line
• Externally separated from ext. sphin.
Muscle by Conjoint sheath derived
from levator ani and longitudinal
muscles of rectum
• Nerve supply: Sup.Hypogastric &
pelvic splanchnic

External Sphincter
• Triple-loop system of Shafik.
The top loop arises and inserts on
the pubis and is made up of the
deep external sphincter and
puborectalis.
The middle loop attaches to the
coccyx (superficial external
sphincter).
The lower loop inserts in the
anterior perianal skin (subcutaneous
external sphincter).
• Nerve supply:Inf. Rectal br. Of
pudendal n, Perineal br. of 4th sacral
n.

•Upper anal canal
Via channels around rectum
into pelvic and pre aortic
nodes
•Lower anal canal
Below dentate line
Inguinal nodes

Nerve supply
Somatic innervation
•Pudendal nerve(S2–S4)
•Inferior rectal n: sensory
&motor to muscles &
mucosa below dentate
line
•Perineal n: sensory &
motor to perineal region

Autonomic innervation
•Sympathetics from thoraco-lumbar segments
via sup. hypo-gastric plexus& hypogastric nn.
•Parasympathetics from S2–S4 (nervi erigentes)
•Unite in inf. hypogastric plexus
•Distributed to pelvic viscera & sexual organs

Nerve supply.
• Internal sphincter
sympathetic (L-5) &
parasympathetic nerves (S-2, S-3, and S-4)
• External sphincter
inferior rectal branch of the pudendal nerve (S-2
,S-3)
the perineal branch of S-4
• Levator ani
sacral roots on its pelvic surface (S-2, S-3, and S-4)
perineal branch of the pudendal nerve

Supporting structures in continence.

Epidemiology
How Common Is This Cancer?

Risk Factors for Anal Cancer
Strong Evidence1
• History of receptive anal intercourse
• HPV Infection (anogenital warts)
• History of cervical, vulvar, or vaginal cancer
• More than 10 sexual partners
• History of STD
• Immunosuppression after solid-organ
transplantation
Moderately strong
evidence1
• Cigarette smoking
• Long-term use of corticosteroids
• HIV infection
 Populations in which risk factors are more prevalent have higher
incidences of anal cancer.2
 Anal intercourse is a risk factor but is not required for anal HPV
infection or cancer development in men or women.3
1. Ryan DP NEJM 2000; 342(11):792-800. 2. Daling JR et al. Cancer 2004;101(2):270-280. 3. Goodman MT JID
2010;201:(9)1331-1339.

HPV
1.Villiers Virology 2004;324:17-27.
Most common among HIV+ Men: 6, 16, 18, 31
Vandersnoek et al., 2005 n=286 HIV+ Men
HIGH-RISK: 16, 18, 26, 31, 45, 54, 55, 56, 64
INTERMEDIATE-RISK: 33, 35, 39, 52, 58
LOW-RISK: 6, 11, 42, 43, 44

HPV Infection
• High-risk HPV type-16 detected in almost 80-90% cases of SCC
anus. (to a lesser extent, types 18, 31, 33, 35, and others.)
• 80% of anal cancers demonstrated more than one HPV genotype.
• Incidence 15 times higher in homosexual men.
• Mostly sexually transmitted, and cancer risk increased in women
with history of receptive anal intercourse.
• Women with high-grade cervical or vulvar dysplasia are more
susceptible to develop anal cancer, as cervical or vulvar HPV
infection escalates anal HPV infection risk.
Grulich AE, Poynten IM, Machalek DA, et al. The epidemiology of anal cancer. Sex Health 2012;9:504–508.
Machalek DA, Poynten M, Jin F, et al. : a systematic review and meta-analysis. Lancet Oncol 2012;13:487–500.

HIV Infection
• Anal cancer incidence in HIV patients is estimated to be twice that
of HIV-negative patients.
• HIV-positive patients with anal cancer tended to develop earlier
recurrences than HIV-negative patients by 20 months, although the
median survival ( 34 vs 39 months ) were similar (CHAMP
Study).
• Highly active antiretroviral therapy (HAART) has resulted in
patients with HIV living longer and the development of related
malignancies.
• In contrast to other HIV-associated malignancies, the incidence of
anal cancer has actually risen following implementation of
HAART.

• According to NCI, rise in anal cancer incidence during 1980 to
2005 was predominantly seen in males with HIV, relative to
their female counterparts
• Among men, incidence rates increased by 3.4% annually
overall and by 1.7% annually in men without HIV infection
• Among women, anal cancer increased 3.3% annually overall
and by 3.3% annually in those without HIV infection.
North American AIDS Cohort Collaboration on Research
and Design (NA-ACCORD), 1996-2007
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;104:1591–1598.

• In a meta analysis of 53 studies, prevalence of both high risk
anal HPV subtypes (74 versus 34 percent) and anal cancer
(45.9 versus 5.1 per 100,000 men) was significantly higher
among HIV positive compared with HIV negative MSM.*
• Without controlling for receptive anal intercourse and prior
HPV infection, it is difficult to discern the true effect of HIV
on the incidence of anal cancer.
• It is possible that HIV infection interacts with HPV to
predispose to anal cancer(significant immunosuppression
(CD4 count below 200/microL)-- increased HPV replication &
Infection with more than one type of HPV).
*Machalek DA, Poynten M, Jin F, et al. Anal human papillomavirus infection and associated neoplastic
lesions in men who have sex with men: a systematic review and metaanalysis. Lancet Oncol 2012; 13:487.

Treatment Points Specific to HIV+
• Pre-treatment CD4 count predicts outcome & tolerance of
chemoradiation1
– CD4 >200 similar to general pop
– CD4 <200 sig more toxicity from Tx…closer monitoring
• HAART  better tolerance of chemoradiation2
 improved local tumour control2
1. Hoffman et al. Significance of pretreatment CD4 count on outcome and treatment tolerance of HIV-positive
patients with anal cancer. Int J Rad Oncol Biol Phys 1999;44:127-31.
2. Place et al. Outcome analysis of HIV patients with anal squamous cell carcinoma. Dis Colon Rectum
2001;44:506-12.

Screening & Prevention
• No published guidelines that recommend screening of the general
population
• There are high-risk groups that may benefit from such, most
prominently patients infected with HIV
Rationale for screening for SIL
 High incidence of the anal cancer within the proposed screening population
(i.e., HIV-positive patients)
 available screening tests are effective and cost-efficient
 early detection can change the outcome of the disease. The availability of
effective treatments that can ablate HSIL
 significant morbidity and mortality associated with anal cancer if it is not
prevented by effective screening and treatment.
Gimenez F, Costa-e-Silva IT, Daumas A, et al. Arq Gastroenterol 2011;48:136–145.

• The initial recommended screening test is an “anal Pap
smear” that evaluates cells in the anal canal for
abnormal cytology through swabbing.
• Patients with abnormal cytology should then be
evaluated by high-resolution anoscopy, which facilitates
the visualization of abnormal lesions, allowing biopsy
and/or removal.

HRA images
• A. Normal
• B. high-grade dysplasia;
i)fine irregular
punctation
ii)coarse irregular
punctuation
iii)prominent and
dilated linear vessels
• C. mosaic pattern with
punctuation.
• D. AIN with ulcer. Biopsy
showed AIN 3.

High-Resolution Anoscopy
• Because AIN shares many of the pathogenic features of
cervical CIN, a technique similar to colposcopy has been
successfully transferred to the anus as high-resolution
anoscopy (HRA).
• This technique is based on the principle that with the
application of acetic acid to dysplastic tissue exhibits distinct
changes and patterns in the anal mucosa similar to the
changes seen with cervical CIN.
• After application of 3% acetic acid to the anal canal and
perianal skin, tissues that harbor AIN turn acetowhite.
• Acetic acid sets the background upon we can identify the
characteristic vascular changes of LGAIN and HGAIN. HGAIN,
in addition to being acetowhite, tend to be flat and exhibit
vascular punctation and mosaicism, whereas LSILs are
generally raised lesions that have warty vessels.

• Lugol's solution may be applied in areas of
diagnostic uncertainty. Areas that do not take up
Lugol's are considered at high risk for harboring
HSIL.
• HRA-directed biopsies of lesions can be performed
in the office or operation theatre.
• HRA directed ablative procedures can be performed
for HGAINs.

Anal Intraepithelial Neoplasia (AIN)
• Anal and cervical canal share embryologic, histologic, and
pathologic characteristics
• Both develop from embryonic cloacal membrane, and are
sites of fusions of endodermal and ectodermal tissue to
form squamocolumnar epithelial junction
• Both display metaplastic and dysplastic changes related to
HPV infection

AIN-multifocal process associated with HPV, analogous
to cervical dysplasia
Scholefield JH, Castle MT, Watson NF. Malignant transformation of high-grade anal intraepithelial neoplasia. Br J
Surg 2005;92:1133–1136.

• Once disease has reached grade III AIN, it rarely regresses.
• Its estimated that approximately 1% of AIN III patients progress to
invasive malignancy, annually.
• Incidence of progression of AIN III is substantially increased in
patients who are immunocompromised.
• Prevalence of AIN among HIV-negative homosexual men is high
(>36%), and almost universal among HIV-positive homosexual men.
Perez,Principles and Practices of Radiation Oncology,6th edition

HG‐AIN
• histologic grades AIN 2 and 3
• abnormal basaloid cells, characterized by an
increased nuclear to cytoplasmic ratio, replace more
than one‐half of the epithelium
• true precursor of invasive anal squamous cell
carcinoma
LG‐AIN
• histologic grade AIN 1
• 20 to 25 percent of the epithelium is replaced by
abnormal cells
• may spontaneously regress

As a result, four distinct categories of tumors arise in the
anal region:
• Tumors that develop from any of three types of mucosa
lining anal canal are termed anal canal cancers.
• Tumors arising in transitional or squamous mucosa are
SCCs and behave similarly (most series reporting
outcomes of “anal cancer” refer exclusively to these
tumors).
• Adenocarcinomas arising from glandular elements are rare
but share similar natural history to rectal
adenocarcinomas; they are treated similarly.

• Tumors arising within hair bearing skin at or distal to
mucocutaneous junction are referred as anal margin
cancers. However, preferred term is perianal skin
cancers.
• Primary rectal SCCs(very rare), can be difficult to
distinguish from anal cancers, and should be treated as
anal cancer.
• Determination of site of origin that overlap anorectal
junction can be problematic. For staging purposes, such
tumors are classified as rectal cancers if their epicenter
is located >2 cm proximal to dentate line, and as anal
canal cancers if <2 cm from the dentate line.

• The vast majority of anal canal tumors are classified as SCC ( 85-90
%)
• It encompasses tumors previously described as
– Basaloid
– Cloacogenic
– transitional
– mucoepidermoid
– verrucous mucoepidermoid varieties
• From treatment standpoint, these all approached as SCC.
• Majority of are nonkeratinizing, tumors arising below dentate line
often display keratinizing properties.
• 10% to 15% are adenocarcinomas, most of which arise from anal
glands or within anal fistulae.

• Bowen's disease (SCC in situ) can occur within perianal skin
as in other areas of non sun exposed skin.
• Paget disease of the anus(intraepithelial adenocarcinoma) can
be of two types:
1. primary cutaneous malignancy with sweat gland
differentiation
2. lesion with adjacent squamous epithelium involvement by
lateral intramucosal spread from underlying adenocarcinoma of
rectum or perianal glands.
• Anal Melanomas should be treated according to same
principles commonly applied to this tumor at other sites.

Clinical Presentation
• Most common presentation - bleeding from the anus.
• Symptoms of anal cancer can be diverse and include
– Pain
– sensation of a mass
– itching
– anal discharge
– Tenesmus
– sense of fullness
– lump in the anal canal.
• Extensive lesions may present with incontinence, passage
of gas or stool from vagina, or significant change in
bowel habits.
• 20% of patients are initially asymptomatic.
• Any mass should be biopsied for a diagnosis.

Clinical staging is performed by a combination
of clinical, endoscopic, and radiographic
examinations
• Detailed history including an assessment of anal sphincter function
as well as HIV risk factors.
• Digital rectal examination to identify
– Tumor location & extent
– fixation to sphincter complex or
– adjacent organs such as vagina and prostate.
• Anoscopy provides
– information about extent of mucosal spread, including relationship to the dentate line,
and
– facilitates biopsy

• It may be necessary to examine patients under anesthesia secondary to
pain and sphincter muscle spasms.
• Female patients should undergo a gynecologic examination to
determine vaginal involvement and to exclude other HPV-associated
cancers.
Examination of Inguinal nodes
• Of all patients presenting with palpable inguinal lymph nodes, only
50% are malignant; therefore, fine-needle aspiration is often
recommended in suspected cases, and a positive result may guide
radiation field design and dose.
• Complete blood counts with serum biochemistry including HIV/CD-4
levels in the presence of risk factors

Imaging
• MRI (external phased-array coils on high-magnetic-field
scanners) - imaging modality of choice
Significant advantages
I. Native multiplanar capability
II. Superior soft-tissue differentiation
III. Biological noninvasiveness
IV. Optimal safety profile of gadolinium based contrast
agents.

For evaluation of primary
• Display low-to intermediate T1 signal intensity and
positive enhancement after intravenous gadolinium
contrast.
• Display intermediate T2signal intensity, lower to that
of normal ischioanal fat and almost always superior to
internal reference standard represented by uninvolved
anal sphincters and gluteal muscles
• Sensitivity of MRI (& EAUS) approach 90– 100 %,
with high concordance regarding tumour size.

For nodal evaluation
• Short-axis threshold values of 8 mm, 5 mm and 10 mm
have been suggested for pelvic, perirectal and inguinal
lymph nodes, respectively
• Additional features include loss of normal bean-shape
and fatty hilum, internal T1 and T2 signal heterogeneity
with central necrosis, and inhomogeneous enhancement
• In 2010 ESMO recommended MRI as primary imaging
modality to accurately stage SCAC, taking into account
maximum tumour diameter, possible invasion of
adjacent organs and nodal involvement

Endoanal ultrasound: Endosonography of anal
canal
• Diagnostic test of choice for evaluation of anal sphincter
anatomy and identification of sphincter defects associated with
fecal incontinence
• EAUS is used to stage and follow up anal neoplasms.
• Endoanal ultrasound has been used to assess tumor depth and
sphincter involvement, but has not affected treatment plans
and, thus, presently, ultrasound staging is not routinely
recommended.
• Anatomy of anal canal is imaged sonographically at three
levels (upper, mid, and distal anal canal).

• Lesions of anal canal appear as hypoechoic areas on EAUS, and size and
extent can be detailed.
• Effective in initial evaluation
• EAUS staging (uTNM) of anal canal cancers corresponds to TNM staging
• EAUS is useful in detecting residual tumor as well as early local recurrence after
treatment.
• Currently,EAUS is part of most surveillance programs for anal cancer.

Modified endoscopic staging system
• Tarantino and Bernstein
• Emphasized depth of penetration over tumor size
• used to distinguish early lesions amenable to less aggressive
treatment.
• shown in a prospective, multicenter study to be superior to clinical
staging in predicting local recurrence

• CECT -used to evaluate distant disease and inguinal adenopathy
• FDG-PET/CT -can address all three staging criteria(Grigsby et
al):demonstrate the extent of the primary tumor; detect lymph node
metastases; and reveal any sites of distant metastases
• NCCN guidelines recommend PET/CT as a part of standard pre-
treatment workup, but PET-CT does not replace a diagnostic CT
scan

• Pre-treatment PET/CT upstaged 9-37.5% and down staged 0-25% of
patients with anal cancer
• Can be used for radiation planning as it clearly defines sites of
metabolically active tumor. Radiation treatment fields changed in
3.7-33.3% of patients.
• Sensitivity of CT for nodal metastases in pelvic and inguinal region
is 40-68%. By contrast, PET/CT showed higher specificity (80-
90%) and sensitivity (70-90%) in detection of nodal and distant
metastases

• Post-treatment PET/CT is indicated to determine response to therapy
and it is highly predictive of long-term clinical outcomes
• Recently considered for follow-up after radio- and chemo‐ therapy
• Finally, PET-CT scans have prognostic value as well, with significant
correlation between metabolic response posttreatment and
progression-free as well as OS

AJCC Staging – Anal Canal & Anal
margin Cancers
• The definitions of TNM and the stage groupings have not
changed from the sixth edition.
• The classification applies to carcinomas only; melanomas,
carcinoid tumours, and sarcomas are not included.
American Joint Committee on Cancer • 2010 , AJCC 7th edition

T Staging
• T X : Primary tumour cant be assessed
• T 0 : No evidence of primary tumour
• Tis : Carcinoma in situ (Bowen's disease, high-grade squamous
and anal intraepithelial lesions)
• T 1 : Tumor 2 cm or less in greatest dimension
• T 2 : Tumor more than 2 cm but not more than 5 cm in greatest
dimension
T1 T2
2-5 cm

• T 3 : Tumor more than 5 cm in greatest dimension
ANAL CANAL
• T 4 : Tumor of any size that invades adjacent organ(s); e.g., vagina, urethra,
bladder*
• *Direct invasion of the rectal wall, perirectal skin, subcutaneous tissue, or the
sphincter muscle(s) is not classified as T4
ANAL MARGIN
• T 4 : Tumour invades deep extradermal structures ( i.e, cartilage, skeletal
muscle or bone)
>5 cm

LN Staging
• N X : regional lymph nodes cannot be assessed
• N 0 : no regional lymph node metastasis
ANAL CANAL
• N 1 : metastasis in perirectal lymph node(s)
• N 2 : metastasis in unilateral internal iliac and/or inguinal
lymph node(s)

• N 3 : metastasis in perirectal and inguinal lymph nodes and/or
bilateral internal iliac and/or inguinal lymph nodes
ANAL MARGIN
• N 1 : metastasis in perirectal lymph node(s)
• M Staging
• M X : Distant metastasis cant be assessed
• M 0 : No distant metastasis
• M 1 : Distant metastasis

LN Involvement
• Lymphatic drainage and nodal involvement of anal cancers depend on the
location of the primary tumor.
• Tumors above the dentate line spread primarily to the anorectal, perirectal, and
paravertebral nodes
• Tumors below the dentate line spread primarily to the superficial inguinal
nodes.
• The regional lymph nodes are as follows
Perirectal
– Anorectal
– Perirectal
– Lateral sacral
Internal iliac (hypogastric)
Inguinal
– Superficial
• All other nodal groups represent sites of distant metastasis.

Changes in staging AJCC 8th edn
• Tumours of anal margin and perianal skin defined as
within 5cm of the anal margin are now classified with
carcinomas of the anal canal
• T categories are unchanged
• N0 No regional lymph node metastasis
• N1 Metastasis in regional lymph node(s)
• N1a Metastases in inguinal, mesorectal,and/or
internal iliac nodes
• N1b Metastases in external iliac nodes
• N1c Metastases in external iliac and in
inguinal, mesorectal and/or internal iliac nodes
• M categories are unchanged

• Lymphatic invasion occurs relatively early.
• Overall risk of regional nodal involvement at diagnosis - about
25%.
• Pelvic lymph node metastases found in as many as 30% of
patients treated by abdominoperineal resection.
• Inguinal metastases were detected clinically in up to
approximately 20% of patients at initial diagnosis and were
present subclinically in further 10% to 20%.
• Nodal metastases were associated with 30% of cancers confined
to the sphincter muscles.
• Ortholan C, Resbeut M, Hannoun-Levi JM, et al. Anal canal cancer: management of inguinal nodes and benefit of prophylactic inguinal irradiation (CORS-03 study). Int J Radiat Oncol
Biol Phys 2012;82(5):1988–1995.
• 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;52:624–631.

Anal melanoma staging
• Staged on a clinical basis, focusing on loco-regional and
distant spread
• Stage I is local disease only, Stage II is a local disease with
increased thickness and ulcerations, Stage III is local disease
with involvement of regional lymph nodes, and Stage IV
shows distant metastatic disease

Prognostic Factors
1.Tumour factors
• T and N stages are most important prognostic factors
• 5-year OS for stage I, II, IIIA, IIIB, and IV are 69.5%, 68.1%,
45.6%, 39.6%, and 15.3%, respectively
RTOG 98-11 study- tumor size (>5 cm), involved lymph nodes (N+),
and male sex were associated with worse 5-yr DFS and OS
EORTC 22861 study- skin ulceration, lymph node involvement, and
male sex were independent variables associated with LRF and OS
• histologic subtypes have not been shown as substantial prognostic
factors.(study by Schlienger et al - no significant difference in
survival among cloacogenic, well-differentiated, and moderately or
poorly differentiated anal carcinomas.

2.Patient factors
• Performance status
• Gender
• Patients who continue to smoke tobacco- greater risk of
local relapse.
• HIV-positive patients- impaired tolerance of RT and
chemotherapy.
– high viral load
– low lymphocyte CD4-positive counts.

3.Biochemical & Molecular factors
p53
• overexpressed with a range of 34% to 100%.
• Wong et al. described that increased p53 expression was
associated with worse local–regional control and DFS
p21
• lack of p21 expression is associated with poor prognosis in
SCCA.
• Holm et al. reported that lack of p21 expression was
associated with reduced OS
• Nilsson et al. reported that absence p21 expression was
responsible for increased LRF.
• Ki-67, nuclear factor kappa B, SHH, and Gli-1 are
associated with DFS

Treatment
Topical therapy
• For small lesions (<1 cm at base)
• Bichloroacetic or Trichloroacetic acid
• topical 5‐fluorouracil
Immune modulation
• Imiquimod (ALDARA) ‐ can result in pathological resolution
of AIN in HIV positive MSM on HAART
Infrared coagulation
• For lesions that are too large for TCA
• direct application of a 1.5 second pulse of irradiation in the
infrared range to dysplastic anal epithelium
• results in tissue destruction to depth of approximately 1.5 mm

Imiquimod
• A topical immunomodulator, acts on the Toll-like receptor 7 of
the humoral immune system resulting in the secretion of
various proinflammatory cytokines and activation of both
humoral and cell-mediated immunity.
• In a series by Wieland U et al 28 HIV-positive men with high-
risk HPV types who were treated with imiquimod 3 times a
week for 16 weeks, 17 showed a complete clinical and
pathologic response. Of the patients with HGAIN, 78% had a
complete response, with a concomitant decrease in HPV DNA.
Two with LGAIN progressed to HGAIN.

• Imiquimod may be safely recommended for
treatment of patients with LGAIN and HGAIN
with higher CD-4 lymphocyte counts.
• Close follow-up is required given the high
recurrence rate.

TCA and BCA
• Topical 85% trichloroacetic acid (TCA) or
bichloroacetic acid are directly cytotoxic therapies
that destroy tissue by chemical coagulation of
proteins.
• There has been a single report by Singh JC et al of
TCA treatment in 54 patients with AIN.
• The study included a mixture of
immunosuppressed patients, 65% of whom were
HIV-infected. Patients were treated with topical
TCA at intervals of 1–2 months for up to four
applications

• A median of two treatments was required for
patients who had no evidence of AIN at follow-up
HRA examination
• When analyzed on a per lesion basis, 73% of AIN-1
patients and 71% of AIN-2/3 patients had no
evidence of AIN on follow-up HRA examination.
• The authors concluded that TCA, because of its
ease of use, low cost, and good safety profile, was
a reasonable first-line therapy for patients with
two or fewer AIN lesions.

Topical 5 FU
• In a prospective trial (Richel O et al )from
Europe, 46 HIV-infected MSM were enrolled,
approximately 75% of whom had multifocal
HGAIN.
• The purpose of this pilot study was to evaluate
the safety and efficacy of treatment with 5% 5-
FU for all grades of AIN.
• 18 participants (39%) had complete clearance of
AIN and 8 (17%) had a partial response. 17
participants (37%) did not respond.

• These data taken together demonstrate the
efficacy of 5-FU, but the optimal dose, frequency
of administration, and duration of treatment are
uncertain.
• Authors concluded that 5-FU works well, but only
for patients who are motivated enough to tolerate
the side effects for treatment of extensive and
often severely symptomatic AIN.

Anoscopy directed lesion ablation
• Large or circumferential lesions
• Electrocautery ablation
• The use of high‐resolution anoscopy may minimize
complications
• High rate of local recurrence, even with complete ablation,
mandates careful surveillance

HRA directed Infrared Coagulation
• Goldstone recognized that the standard surgical
techniques had excessive morbidity and were
unsuitable for treating multifocal disease, which is
increasingly being identified in immunosuppressed
patients.
• Infrared coagulation, which has been used successfully
for treatment of internal hemorrhoids and condyloma,
was offered for treating AIN.
• Infrared coagulation ablation offers important
advantages for patients being treated for AIN. Infrared
coagulation requires no anorectal preparation, and is
performed as an outpatient procedure under local
anesthesia.

HRA guided electrocautery ablation
• HRA-guided electrocautery was initially described as an
operating room technique for extensive HGAIN disease.
• There is only one study by Goldstone et al, wherein 232
patients were treated with HRA guided Electrocautery
ablation. At final evaluation 83% of HIV-negative
patients and 69% of HIV-positive patients were free of
HGAIN
• Goldstone et al compared his results using HRA-guided
electrocautery ablation with infrared coagulation of
HRA, and concluded that the outcome of
electrocautery ablation was similar to infrared
coagulation.

Treatment
• Until the late 1970s, the conventional treatment for
anal canal cancer was an APR.
• Nigro et al. challenged this practice with a report of
3 patients with squamous cell cancer of the anal
cancer who following preoperative treatment with
30 Gy plus concurrent fluorouracil (5-FU) and
mitomycin-C were found to have a pathologic
complete response at the time of surgery.

Role of surgery
• Surgery for the initial diagnosis and staging of anal
canal tumors should be limited to a biopsy of the
primary tumor and evaluation of the inguinal lymph
nodes.
• Clinically enlarged inguinal lymph nodes should be
aspirated. If the cytology is nondiagnostic or
demonstrates only benign disease, an open excisional
biopsy of 1 or 2 lymph nodes is recommended.
• Under no circumstances should a formal lymph node
dissection be performed for the initial evaluation of
suspicious nodes, as it can increase the morbidity of
radiation and has no therapeutic value.

EVOLUTION OF TREATMENT
MODALITIES
• Local and locally advanced AC
• Initially, non-metastatic tumors of the anal canal
were treated with abdominoperineal resection
(APR) and permanent colostomy, with a five-year
survival of 40% to 70% and a perioperative
mortality of 3%. In 1974, Nigro et al achieved
complete pathological response in 3 patients using
a combination of radiation therapy (30 Gy) and
chemotherapy that included mitomycin C (MMC)
and 5-fluorouracil (5-FU).

Role of Sentinal lymph node biopsy
• Some authors have suggested a routine SLN evaluation as a staging technique.
• A systematic review of 16 published series evaluating outcome of SLN biopsy of
inguinal nodes included 323 patients, and success in identifying SLN was 86%.

Adenocarcinoma of Anal canal
• Adenocarcinoma arises from the columnar epithelium
of the anal canal and its incidence is low accounting for
less than 5 % of all anal malignancies.
• Extension of rectal cancer into the anal canal is the
more common presentation. Occasionally,
adenocarcinoma may occur in patients with ulcerative
colitis or Crohn disease who have ileal pouch-anal
anastomosis.
• APR should be offered for early-stage disease.(T1, T2
and N0)
• For locally advanced disease (T3 or any T with N + ), a
multimodality approach should be considered.

Melanoma of Anorectal region
• Anorectal melanoma is rare and accounts for less than
3 % of all malignant melanomas and less than 1 % of all
anal canal tumors.
• The 5 -year OS rate is generally less than 20 % . The
initial stage at presentation largely determines OS.
• Ross et al. from the M. D. Anderson Cancer Center
reviewed a series of 32 patients with melanoma
treated with either APR or local resection.
• Local recurrence was lower in the APR group (29 % for
APR; 5 8 % for local excision) . However, there was no
difference in OS between the two groups ( 19 . 5
months for APR; 18 .9 months for local resection ) .
• Most authors recommend local excision of anorectal
melanoma if adequate margins could be achieved.

Perineal reconstruction- VRAM Flap

Role of Vaccination
• A promising strategy for the prevention of anal dysplasia and
malignancy is HPV vaccination.
• Two vaccines (Cervarix and Gardasil) are now approved by the
U.S. Food and Drug Administration and have been shown to
protect against cervical cancer in women.
• The quadrivalent HPV vaccine Gardasil has demonstrated efficacy
for prevention of HPV 6-, 11-, 16-, and 18-related genital warts
and has been shown to protect against cancers of the anus, vagina,
and vulva.
* Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial
neoplasia. N Engl J Med 2011;365:1576–1585.

• In a large, double blind study, (Palefsky et al)
– 602 healthy homosexual men were randomized to receive the
quadrivalent HPV vaccine versus placebo.
• Significantly reduced rates of (36-month median follow-up)
– high-grade anal dysplasia
– high-risk HPV infection in the vaccinated group.
• With limited availability and suboptimal outcomes of AIN screening
programs, vaccination may reflect the best long-term approach for
reducing anal cancer risk
* Palefsky JM, Giuliano AR, Goldstone S, et al. HPV vaccine against anal HPV infection and anal intraepithelial
neoplasia. N Engl J Med 2011;365:1576–1585

• FDA has approved Gardasil for prevention of HPV-caused cervical, vulvar,
vaginal, and anal cancers; precancerous cervical, vulvar, vaginal, and anal lesions;
and genital warts in males and females ages 9 through 26
• Vaccines are given through a series of three injections into muscle tissue over a 6-
month period(at 0,1 &6 month).
• In October 2016, the FDA approved a 2-dose schedule for boys and girls initiating
vaccination with Gardasil at ages 9 to 14 years (the second dose is to be
administered 6–12 months after the first).
• Those initiating the HPV vaccination series at older ages (including teens who begin
getting vaccinated after they turn 15 years old) or who
are immunocompromised should still be vaccinated according to the 3-dose
schedule.

• CDC & ACIP has developed the following recommendations
regarding HPV vaccination :
 initiation of routine HPV vaccination at age 11 or 12 years (the
vaccination series can be started beginning at age 9 years)
 vaccination of females aged 13 through 26 years and of males aged 13
through 21 years who have not been vaccinated previously or who
have not completed the 3-dose vaccination series. Males aged 22
through 26 years may be vaccinated
 As of October 2016, CDC and ACIP also now recommend that 11-
and 12-year-olds receive two doses of HPV vaccine at least 6 months
apart rather than the previously recommended three doses.

Summary
• Knowledge of Anatomy is essential in treating anorectal
disease especially for treating benign conditions.
• With increase in immunosuppressed population, the
incidence and prevelance of AIN is increasing, the natural
history of which is unknown, diverse treatment options are
available with varying results.
• APR is offered for treating residual and recurrent localised
anal canal squamous cell carcinoma post Chemo-RT.
• T1 N0 WD Anal margin carcinoma can be treated with WLE.
• Adenocarcinoma primarily treated with APR.
• Melanoma primarily treated with wide excision or APR.

Carcinoma anal canal

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