This document discusses cancer of the anal canal. It compares mitomycin vs cisplatin for treating anal canal cancer and finds that mitomycin, 5-FU and radiation led to significantly lower rates of colostomy at 5 years compared to cisplatin. It recommends the combination of 5-FU, mitomycin and radiation as the standard of care. The combination was associated with 5-year survival rates of 80% for small cancers down to 45-55% for larger or more invasive cancers, with overall survival of 65-75%.

1. Cancer of the Anal Canal

2. U.S. GI Intergroup
 Compared mitomycin vs cisplatin
 The rate of colostomy at 5 years was
significantly lower in the mitomycin, 5-FU,
radiation arm (10 vs. 19%; P = .04).
 Disease-free and overall survival rates were
similar in each group.
 Grade 3-4 hematologic toxicity was higher in
those who received mitomycin (60% vs.
42%) but other acute toxicity levels were
similar.
 The combination of 5-FU, mitomycin, and
radiation was recommended as the
preferred standard of care.

3. The combination of radiation, 5-
FU, and mitomycin
5-year survival rates local control rates
 80% for (T1)
 70% for (T2)
 45% to 55% for larger or
deeply invasive cancers
(T3 or T4)
 65% to 75% overall
 90% to 100% - (T1)
 65% to 75% - (T2)
 40% to 55% - (T3 or
T4)
 60% overall.
 Up to 5% of patients
overall lost anorectal
function because of
treatment-related
morbidity

4. Timing of delivery of
chemotherapy
 The importance of timing relative to
radiation each day is not known.
 Mainly by analogy with the results of
trials already completed in more
common cancers, and by general
usage, the delivery of 96- to 120-hour
infusions of 5-FU, together with bolus
injections of cisplatin or mitomycin on
the first or second day of the 5-FU
infusion, is the schedule used most
widely.

5. Increasing the total radiation dose and
shortening the overall duration of the radiation
schedules
 When combined with 5-FU and mitomycin –
- 30 Gy in 3 weeks eradicate up to about
90% ( < 3 cm in size).
- Higher doses, from 45 Gy in 5 weeks to 54
Gy in 6 weeks, sometimes supplemented by
additional radiation after an interval of 6 to 8
weeks - controlled 65% to 75% larger than
4 cm.70
 Improved tumor control was observed .
 Although the patients also received higher
total doses of chemotherapy, increase in
radiation dose was the more significant
factor.

6. INTRODUCTION
 Cancer of the anal canal is an uncommon malignancy,
accounting for approximately 1.5% to 2% of all cancers
of the lower alimentary tract in the United States.
 The risk of anal canal cancer has increased over the past
30 years with its association with HPV and HIV.

7. ANATOMY
 The anal canal is a 4-cm-long structure that passes downward and
backward from the rectal ampulla (level of pelvic floor) to the anus (anal
verge).
 The proximal border of the anal canal clinically corresponds to the anal
sphincter at the level of the puborectalis muscle (palpable as the anorectal
ring on digital rectal examination). This is where the rectum enters the
puborectalis sling, made by fibers from both sides.
 The distal end of the anal canal is at the level of the anal verge, where the
groove between the internal sphincter and the subcutaneous part of the
external sphincter is palpable.
 This also is the level of the squamous-mucocutaneous junction and the
perianal skin.

9.  It follows that two distinct categories of tumors arise in
the anal region.
 Tumors that develop from mucosa (columnar,
transitional, or squamous) are true anal canal cancers
tumors
 that arise from skin at or distal to the squamous-
mucocutaneous junction are termed anal margin
tumors

11. definitions
 Anal Canal= 4 cm mucosa
lined region from junction of the
puborectalis portion of the
levator ani muscle and the
external anal sphincter, and
extends distally to the anal
verge
 Transitional zone- from
glandular (columnar) to
squamous mucosa- at dentate
line
 Anal Margin- begins at the
anal verge. It represents the
transition from the squamous
mucosa to the epidermis-lined
perianal skin.
Rectal
glandular
mucosa
Transitional
Squamous
True Epidermis

12. epidemiology
 Relatively uncommon.
 Seen in middle age- median age at
diagnosis 61 years.
 Slight female preponderance
 Incidence is increasing possibly due to
association with hpv.
 More common in men having anal
receptive intercourse and hiv +.

13. ETIOLOGY AND RISK
FACTORS
 HPV infection
 Immunosuppression- transplant
patients and those with HIV.
 Cigarrete smoking- 5 FOLD increased
risk

14.  Benign anal conditions -- fistulae,
fissures, and hemorrhoids -- do not
appear to predispose to cancer .
 Fissures may facilitate the access of
high-risk HPV to basal epithelial cell
layers.
 Any increased risk of cancer from
chronic IBD -
? Discontinued ( danish population
based study )

15. AIN
 Presence of cellular and nuclear
abnormalities in the perianal and anal
epithelium without a breach of the
epithelial basement membrane.
 Precursor to scc of anal canal.

16.  Parallel observations in the cervix in
which HPV infection causes the
development of CIN, the precursor lesion
to invasive cervical cancer.
AIN = squamous intraepithelial lesion
(SIL)
Also called carcinoma in situ and
Bowen’s dz
AIN 1 = LSIL
AIN 2&3 = HSIL

17. AIN & HIV
 Limited data for HIV negatve pts
AIN 1 (LSIL)
- LSIL progresses to HSIL in more than 50
percent of HIV-positive homosexual males
within two years.
AIN 2&3 (HSIL)
- risk for progression to invasive cancer
ranges from 10 to 50 percent among HIV
positive patients
Among HPV-infected individuals, the
prevalence of HSIL and anal carcinoma is
higher in those with concomitant HIV infection
compared to those who are HIV-negative.

18. HPV and AIN
 HPV causes anal intraepithelial
neoplasia(AIN) which progresses from
low grade to high grade dysplasia and
ultimately to invasive cancer.
 Hpv 16 & 18 are strongly implicated.
 As anal lesions progress there is also
accumulation of mutant p53
expressions.

19.  The high-risk HPV E6 and E7 proteins
are thought to contribute to the
induction of anogenital cancers by
interacting with and degrading the
function of p53 and pRb, respectively.
 HPV DNA integration is needed for
transition from low- to high-grade AIN.
 Loss of heterozygosity at 11q23 is the
most consistent event, and appears to
be independent of human
immunodeficiency virus (HIV) status.

20.  Anal pap smears – sensitiivity 69 to
93% and specificity ranges from 32 to
59%.
 Anoscopy, anal cytology, and high-
resolution anal colposcopy each play
a role in the assessment of AIN.
 High-grade AIN recurs or persists after
treatment in less than 25% of those
who are HIV-negative, but in up to
80% of HIV-positive patients.

21. Management of AIN
 Excision is for clinically definable lesions.
WLE guided by frozen sections.
1 cm margins
Large defects closed with local flaps
WLE is associated with high rates of disease recurrence
and anal incontinence/stenosis
 Targeted destruction guided by high-resolution anoscopy
Decreased morbidity compared to WLE
High risk for persistent or recurrent disease among HIV+
Surveillance examinations performed at six-month
intervals as long as dysplasia is present
 Treatment with imiquimod or 5-fluorouracil has initial 50-
90% response rates.
Recurrence limited with long duration therapy
Compliance limited by significant skin irritation

22.  Photodynamic therapy.
 Some authors recommend
observation only for wide-field low
grade AIN, and even for high-grade
AIN when there are no signs of
invasive cancer, if the risk of functional
damage due to ablative treatment is
considered too great.

23. WHO Classification of Anal
Cancer
Anal canal
 Squamous cell carcinoma
- Keratinizing (below dentate)
- Nonkeratinizing (above dentate)
- Basaloid (transitional)
 Adenocarcinoma
- Rectal type
- Of anal glands
- Within anorectal fistula
 Small cell carcinoma
 Undifferentiated
“Anal Cancer” = squamous cell
cancer arising in the mucosa of
the anal canal
Anal margin
 Squamous cell carcinoma
 Giant condyloma
 Basal cell carcinoma
 Others (Melanoma)
 Bowen's disease (SCC in situ)
 Paget's disease (Intraepithelial
adenocarcinoma)
Classification of tumor is
determined by the
pathology/histology of the
tumor not the anatomic
location as determined by the
surgeon or endoscopist.

24. NATURAL HISTORY
 Anal cancer is predominantly a locoregional disease, with possible
direct extension to surrounding tissues and lymphatic dissemination
to inguinal and pelvic nodes; hematogenous distant metastasis is a
relatively rarer occurrence.
 Anal canal cancers constitute 75% of all lesions, and only 25% are
anal margin tumors.
 Local spread may be present in approximately 50% of cancers at
diagnosis with involvement of the anal sphincter or surrounding soft
tissues.
 Extension to the rectum and perianal skin also may occur.
 Invasion of the vaginal septum is more common than invasion of
the prostate gland because of the presence of Denonvillier’s fascia
in men, which acts as a barrier

25.  Lymphatic drainage is dependent on the anatomic location of the primary
tumor.
 Tumors that arise distal to the dentate line drain to inguinal lymph nodes
(superficial and deep), and those above the dentate line spread primarily to
the internal iliac system, and with more proximal lesions, spread occurs to
the inferior mesenteric group.
 The regional nodes are considered to be inguinal (superficial and deep
femoral), internal iliac, and perirectal (anorectal, perirectal, and lateral
sacral). All other nodal groups represent sites of distant disease.
 The incidence of involvement of inguinal nodes is directly proportional to
the size and extent of the primary tumor. Overall, this risk may be
approximately 10% at diagnosis but may increase to 20% for tumors larger
than 4 cm, and with T4 disease, this may be as high as 60%.

26.  Distant metastasis may occur to any organ, but the liver and
lungs are most frequently involved. Overall, distant
metastases are relatively rare.
 At diagnosis, only 5% to 10% of patients will be found to
have distant disease.
 After curative treatment, the risk of distant disease varies,
ranging between 10% and 30%, and depends on the initial
tumor (T) stage.
 The risk of distant metastasis also increases with the number
of regional nodes involved

27. CLINICAL PRESENTATION
AND DIAGNOSIS
 Most patients with anal cancer are first seen with rectal bleeding.
This occurs in approximately 50% of patients;
 30% experience pain or the sensation of a rectal mass.
 Pruritus in 30%
 Altered bowel habbits -rare
 A common concern with most anal neoplasms is the frequent delay
in diagnosis resulting from confusion with more common, benign
conditions. Thus, the clinician must maintain a high index of
suspicion when evaluating lesions of the anal canal and margin.
 An interval of 4 to 6 months may ensue between onset of symptoms
and diagnosis in up to 50% of patients.

28. WORK UP
 Physical examination
1. Regional lymph nodes
2. Adjacent organs for direct invasion
3. Anogenital areas for concurrent malignancies
 Proctoscopy &Biopsy of primary tumor
 Fine-needle aspiration biopsy or simple excision of enlarged
inguinal nodes
 Chest radiograph
 CT/MRI of abdomen and pelvis( mri preferrd as delineates soft
tissue planes better and also better to detect involvement of urethra
or vagina)
 HIV antibody assay, if risk factors are present

29.  EUS to evaluate for sphincter
involvement and perianal lymph
nodes.
 Consider PET scan since 25% of
patients have metastatic disease by
PET not seen on CT and 20% of
inguinal nodes negative by CT are
PET positive.

30. STAGING
 PRIMARY TUMOR (T)
 TX Primary tumor cannot be assessed
 T0 No evidence of primary tumor
 Tis Carcinoma in situ
 T1 Tumor =2 cm in greatest dimension
 T2 Tumor >2 cm but =5 cm in greatest dimension
 T3 Tumor >5 cm in greatest dimension
 T4 Tumor of any size 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

31.  REGIONAL LYMPH NODES (N)
 NX Regional lymph nodes cannot be assessed
 N0 No regional lymph node metastasis
 N1 Metastasis in perirectal lymph node(s)
 N2 Metastasis in unilateral internal iliac and/or inguinal lymph
node(s)
 N3 Metastasis in perirectal and inguinal lymph nodes and/or
bilateral internal iliac and/or inguinal lymph node

32. AJCC stage groups
 Stage I T1 N0 M0
 Stage II T2 N0 M0
T3 N0 M0
 Stage IIIA T1 N1 M0
T2 N1 M0
T3 N1 M0
T4 N0 M0
 Stage IIIB T4 N1 M0
Any T N3 M0
Any T N2 M0
 Stage IV Any T Any N M1

36. PROGNOSIS
 5 y survival-
T1 — 86 percent
T2 — 86 percent
T3 — 60 percent
T4 — 45 percent
N0 — 76 percent
N+ — 54 percent

37. Molecular prognostic factors
 High expression of p53 associated
with decreased DFS.
 Also local control rates are lower with
increased p53 expression.
 High level of Ki 67 – longer DFS.

38. SURGICAL
MANAGEMENT

39. Surgery
 Surgical treatment was the primary therapy 20 to 35 years ago, but
it has been replaced by sphincter-sparing therapy with combination
chemoradiotherapy.
 Surgical therapy is now used most often as a method of salvage.
 Surgical treatment, when it was used as a primary therapy, required
an abdominoperineal resection (APR).
 This consisted of wide local excision of the anus, to include the
levator ani muscles and contents of the ischiorectal fossa.
 The operation results in a permanent colostomy, as well as loss of
sexual function, in most patients.
 Overall, 5-year survival rates were approximately 50-70% in
different serieses.

43. Radical resection
 For intermediate-stage primary anal canal
cancer who -
- Cannot tolerate radiation therapy or
chemoradiation
- Incontinent because of irreversible damage of
the sphincters
- Anovaginal fistula
- Prior pelvic radiation treatment (most
frequently for carcinoma of the cervix)
- Active inflammatory bowel disease affecting
the rectum or anal region
- Failure of chemoradiation or radiation and less
frequently, complications of the initial treatment.

44. Residual cancer
 Suspected residual cancer should be confirmed
by biopsy.
 Random biopsies from the site of the primary
cancer in the absence of clinical features .
 Residual masses after radiation or
chemoradiation may take several months to
regress fully.
 Frequent examination by an experienced
observer is desirable, including, if necessary,
examination under anesthesia.
 C/F - hard-edged ulcer
- an enlarging mass
- increasing pain

45. SALVAGE SURGERY
 Locoregional failure in 30%
½ recurrence, ½ progression
Salvage APR is associated with five-
year survival rates from 24 to 58%
 Salvage Surge
APR = abdominoperineal resection
Pelvic exenteration = multiviseral
resection
 Urinary and fecal diversion

46. RECURRENCES
 Strictly, all local recurrences are due to
residual cancer.
 Salvage surgery offers a potential for
long-term local control and survival in
roughly one third to one half of the
patients fit for surgery who do not have
clearly unresectable cancer or known
extrapelvic disease.
 Need reconstructive surgery to close
defects in irradiated pelvic tissues should
be considered.

47. Prognostic variables
 Node positivity
 Size of the resected tumor
 Status of resection margins
 An analysis of the pathologic data from
patients in the UKCCCR trial showed –
lateral excision margin free of
cancer
> 1 mm - recurrence occurred in
25%
< 1mm - recurrence occurred in

48. Problems in Surgery
 Perineal wound healing  skin
breakdown
 fistula
formation,
 Malnutrition
 Debility due to pain
 Flap reconstruction should be
considered

49. TREATMENT OF
LYMPHATICS
 Lymphatic Drainage
Lymphatic drainage of anal cancers
depends on the location of the tumor in
relation to the dentate line.
Tumors below the dentate line drain to
the inguinal and femoral nodes.
Tumors above the dentate line drain to
the perirectal and paravertebral nodes, a
pattern similar to that seen with rectal
cancers.
Tumors in the most proximal portion of
the canal drain to the nodes of the inferior
mesenteric system.

50. Lymph Node Management
 Chemoradiation is the treatment of choice for inguinal lymph
node disease
Cure rates approach 90 percent for synchronous disease
Bilateral groins should be incorporated into the radiation
fields with the addition of a boost for clinically positive lymph
nodes.
Metachronous lymph nodes + in 10 to 20%
Usually appearing w/in six months after treatment
Respond well to CRT
 Formal node dissection is reserved for metastases residual
or recurrent after radiation-based treatment.

51. CLINICALLY NORMAL NODES
 If dissected - significant postoperative wound healing
problems or chronic lymphedema.
 Rate of late failure in clinically normal inguinal nodes not
treated prophylactically ranges from about 10% to 25%.
 May prove uncontrollable in up to one half of the patients.
 Because of the morbidity - elective lymphadenectomy of
clinically normal inguinal nodes is not recommended.
 Elective irradiation of clinically normal inguinal node areas
- little morbidity
- reduces the risk of late node failure in the volume
irradiated to less than 5%

52. Sentinel Lymph Node Bx
 SLNB identifies inguinal metastases in
10–40% of anal cancer patients with
limited morbidity ranging between 3%
and 7%.
The clinical impact of this procedure
on the therapeutic approach is
unclear as long as the inguinal nodes
are included in the radiation field.

53. APR

54. The Technique
Pre-operative
 Consent
 Bowel preparation
 Stomal therapy and siting for
stoma
 DVT prophylaxis
 Antibiotics
 Urinary catheter

55. The Technique
Set-up
 Extended Lloyd-Davies position
 Good assistance
 Long midline incision
 Wide retraction
 Small bowel packed out of the way
 Full laparotomy (liver etc)

56. Operative Position

57. TME
Principle is that the sharp
dissection(diathermy/ scissors) should
only proceed in the areolar tissue
plane(holy plane) within and thus
sparing the autonomic nerve plexuses,
the non visceral presacral fat pad, the
parietal sidewall fascia of the pelvis, the
hypogastric plexus, vesicles and
prostate in males and vagina in
females.

59.  The sigmoid is grasped with toothed
forceps and reflected medially The
adjacent adhesive bands are divided
with long curves scissors, and the
peritoneal reflection is retracted
laterally with forceps. Following this
procedure, the sigmoid is usually
mobilized easily toward the midline.
The peritoneal surface on the left
side of the colon is picked up with
forceps and divided with long,
curved, blunt-nosed Metzenbaum
scissors, which are gently
introduced downward beneath the
peritoneum to separate the
underlying structures, such as the
left spermatic, or ovarian, vessels or
ureter, from the peritoneum to avoid
their accidental injury. The
peritoneum is incised down to the
cul-de-sac on the left side

62. APR

63.  The inferior mesenteric vein is often
divided above the left colic branch and
a mobilization of the splenic flexure is
performed so as to allow creation of
the descending colostomy without
tension. The blood supply to the
descending colon is now derived from
the middle colic artery via the marginal
artery of Drummond.

64. Ligation Inferior Mesenteric Vein

65.  Although involved lymph nodes may not be
evident in the mesentery over the bifurcation
of the aorta, it is desirable to ligate the inferior
mesenteric artery just distal to the origin of
the left colic artery . The contents of the
proximal clamps are tied, and the ligation is
reinforced by a transfixing suture.
 Some prefer to ligate the inferior mesenteric
artery as near its point of origin from the aorta
as possible. Usually, this level is near the
ligament of Treitz. The blood supply to the
sigmoid to be used as a colostomy is now
derived from the middle artery through the
marginal artery of Drummond.

66. High Ligation Inferior
Mesenteric Artery

68.  The peritoneum
along the right side
of the rectosigmoid
junction is incised
lateral to the
inferior mesenteric
and superior
hemorrhoidal
vessels .

69.  This incision extends down to the
pouch of Douglas. The right ureter is
identified beneath the residual
peritoneum, and its course over the
iliac vessels is exposed with blunt
gauze dissection. The proximal
bowel is retracted anteriorly and
laterally. The superior hypogastric
nerves are visualized just below the
iliac vessels and the ureters. The
dissection proceeds behind the
superior hemorrhoidal vessels
toward the entrance of the presacral
space behind the sacral promontory.
Division of the retrosacral fascia or
ligament just below the sacral
curvature at about S2 is done
sharply in the midline with scissors
or electrocautery.

70.  The peritoneal reflection in
the pouch of Douglas is
incised about 1 cm up its
anterior reflection over the
bladder in men (shown in
this illustration) or behind
the uterus in women. The
bladder or uterus is
retracted anteriorly using a
fiberoptic lighted deep
pelvic retractor. The sharp
dissection proceeds
anterior to Denonvilliers'
fascia until the prostate and
seminal vessels or the
rectovaginal septum is
seen.

71.  The paths of the
anterior and
posterior
dissections (Figure
9) show the close
adherence to the
presacral fascia
posteriorly and to
the actual prostate
and seminal
vesicles anteriorly.

72.  The two lateral dissections in the TME are time-
consuming, as the surgeon carefully proceeds to
expose the parietal fascia over the lateral pelvic wall
structures.
 The fiberoptic lighted deep pelvic retractors are
essential for clear visualization during lateral retraction
of the rectum and anterior elevation of the bladder or
the uterus and vagina.
 The preservation of the pelvic autonomic nerve plexus
and the anterior roots of sacral nerves S2, S3, and S4
is essential for anal continence and sexual function. The
plexus is seen as a dense plaque of nerve tissue that
comes close to the rectum at the level of the prostate or
upper vagina

73.  . The TME does not encounter "lateral
suspensory ligaments" but rather a fusion of
the lateral mesorectum with tissue that may
contain the middle hemorrhoidal arteries as
the dissection heads toward the autonomic
nerve plexus.
 This tissue is divided with electrocautery, and
the middle hemorrhoidal vessels may require
a ligature. The course of the ureters and the
autonomic plexus is noted as the dissection
is carried down to the levators

76. The Technique
Preparation Proximal Bowel

77. The Technique
Preparation Proximal Bowel

78. The Technique
Preparation Proximal Bowel

86. PERINEAL PART

88.  The skin in the
region of the anal
orifice is seized
with several Allis
forceps, and the
incision is made
through the skin
and subcutaneous
tissue at least 2 cm
away from the
closed anal orifice

89.  All blood vessels
are clamped and
tied to prevent
further loss of
blood as the
operation
progresses

90.  he posterior portion of
the incision is extended
backward over the
coccyx, and the anus is
tipped upward to enable
its attachments to the
coccyx to be severed
more readily. After the
anococcygeal raphe is
severed and the
presacral space is
entered, the
accumulated blood from
above is suctioned out.

91.  The levator muscle is
exposed on one side
and, with the finger held
beneath it, is divided
between paired clamps
as far from the rectum
as possible.Following
the ligation of all
bleeding points on one
side, a similar division of
the levator ani muscles
is carried out on the
opposite side.
Alternatively, the levator
muscles may be
transected with
electrocautery.

92.  Palpation of the inlying
urethral catheter will
facilitate the procedure by
localizing the urethra and
preventing accidental injury
to the prostate, urethra.
The skin and subcutaneous
tissue of the perineum are
retracted upward, while the
anus is pulled downward
and backward to assist in
the exposure. The rectum
is pulled down, the
remaining attachments of
the levator ani muscles and
transversus perinea are
divided, and all bleeding
points are ligated

93.  . In the female the
dissection between the
rectum and vagina is
more easily
accomplished if
counterresistance is
applied to the posterior
vaginal wall by the
surgeon's fingers. In the
presence of extensive
infiltrating growths it may
be necessary to excise
the perineal body as well
as a portion of the
posterior vaginal wall.

97. Resected Specimen
Abdominoperineal resection

98. Anal Margin Cancers
 Anal margin -distal end of the anal canal to a 5-
cm margin surrounding the verge.
 Treat similar to skin cancer.
 WLE for T1 and early T2 lesions that can be
excised with a 1-cm margin.
 Larger T2 cancers -add prophylactic radiation to
the inguinal lymph nodes along with radiation or
excision of the primary tumor.
 T3 and T4 lesions- radiation to both inguinal
regions and the pelvis, along with 5-FU and
mitomycin C.
 APR for bulky tumors extending into the
sphincter or surrounding structures.

99.  When possible, initial surgical
management is preferred to radiation-
based treatment of perianal cancers
because of the frequent morbidity from
long-term changes in the perianal skin
after irradiation.

100.  The regional nodes for the perianal skin are the
inguinal nodes.
 Perirectal or pelvic node metastases are very
uncommon.
 The risk of inguinal node metastases is about
10%, associated mainly with category T3 or T4
tumors, or poorly differentiated cancers.
 Elective inguinal nodal irradiation has been
suggested for those categories only.
 The management of abnormal inguinal nodes is
similar to that of anal canal cancer.

101. THANK YOU….