3. Anatomy and histology of the anal canal
• Definition - the ‘‘surgical’’ anal canal from the anorectal ring (upper portion of the
puborectalis/levator complex) at the floor of the pelvis
to the anal verge. Appx 4 cm in length
The anal verge is the point at which modified squamous
epithelium (anoderm) of the anal canal meets hairbearing perianal skin.
4. Anatomy and histology of the anal canal
• The lining of the anal canal is divided into three
zones:
• Colorectal zone - proximally
• Anal transitional zone (ATZ, extending approx. 1
cm upward from dentate line)
• Squamous zone (extending distally from the
dentate line to the anal verge.
5. • The colorectal zone - columnar mucosa identical to the distal
rectal mucosa.
• The ATZ
- many epithelial variants, including squamous & colorectal
type mucosa
- ‘‘ATZ epithelium,’’- 4-9 cell layers including basal, columnar,
& cuboidal cells.
- Melanocytes and endocrine cells are also occasionally
found.
• The squamous zone - unkeratinized squamous mucosa without skin appendages.
- Melanocytes may also be present.
6. Anal verge
• The perianal skin contains sweat, sebaceous &
apocrine glands & is keratinized
• The anal margin - perianal skin extending
approx. 5- 6cm from the anal verge.
• All skin cancers can affect the anal margin .
9. Epidemology – Anal cancer
• Anal cancers are about one-tenth as common
as cancers of the rectum.
• Cancers arise in the canal 3 to 4 times more
frequently than in the perianal skin.
• In North America and Western Europe
squamous cell cancers - 80% of anal cancers
• In Japan only 20% are squamous.
10. Risk factors of anal cancer
Old age
Common in female - 1:1.5 – 2
Cigarette smoking – fourfold increase of risk
A history of anal intercourse
sexually transmitted disease
11. • HPV infection.
• Human immunodefi ciency virus (HIV)
• Immunosuppression - tenfold risk is seen in
immunosuppressed
• Cancer of the cervix, vagina, or vulva
• Benign lesions of the anus (such as chronic
anal–rectal inflammation)
15. Routes of spread – LOCAL EXTENSION
• Sphincter muscles
• Perianal connective
tissues
• Rectum
• Perineum
• Prostate
•
•
•
•
•
Perineal fossa
Perianal skin
Pelvic wall
Vaginal septum
Anal-vaginal fistula is
seen in <5% of cases
16. Lymphatic spread
• May occur early in disease
• Overall lymph node spread is seen in 25% of
cases at diagnosis
• Delayed inguinal lymph node metastasis is
seen in approximately 10–25% of patients
17. • Distant metastasis is relatively rare, and extra
pelvic metastasis is seen in <10% of patients
before treatment
Common sites of metastasis include
• Liver
• Lungs
• Extrapelvic lymph nodes
18.
19.
20.
21.
22.
23. Prognostic factors
•
•
•
•
•
•
•
Advanced stage at diagnosis
Male gender
Age ≥65 years
Hemoglobin levels ≤10 g/l at presentation
Nodal metastasis at presentation
Poor performance status
Presence of HIV infection or AIDS
24. Management – Anal Canal Carcinoma
• For a long time APR remained the standard of
care for anal cancer.
Papillon et al
• In the early 1960s
• Introduced the concept - long-term local
control with definitive radiation therapy.
25. Chemo radiotherapy
• Nigro et al. In 1974
• First demonstrated complete pathologic
responses to concurrent
5-fluorouracil, Mitomycin C, and Radiation
therapy.
26.
27. Surgery - Indications
• Has limited role in the primary treatment of anal
cancer
• Local excision can be considered only for selected
patients with well differentiated early-stage
(T1N0M0)
• SCC that is <40% circumferential involvement
• No sphincter involvement
• Abdominal peritoneal resection (APR) is reserved
for salvage after primary chemoradiotherapy
failure
28. Radiation therapy - Indications
• EBRT with concurrent chemotherapy is the
mainstay treatment for localized anal cancer
• RT alone can be reserved for stage T1N0M0
disease
• Palliation to primary or metastatic foci
Techniques
• EBRT using three-dimensional conformational
RT(3D-CRT) or IMRT
• Brachytherapy has no role in the treatment and is
associated with high incidence of anal necrosis
29.
30. UKCCCR Trial
• Randomized 585 patients to either radiation
therapy (RT)alone or concurrent
chemoradiation therapy (CRT)
• RT alone used 45 Gy in 20 or 25 fractions over
4–5 weeks
31. UKCCCR Trial
• 5-FU - 1,000 mg/m2, days 1–4 or
750 mg/m2 days 1–5
continuous infusion
• Mitomycin C - 12 mg/m2 bolus on day 1
• During the first and last week of Radiotherapy
33. UKCCCR Trial
• 3-Year local control rates (61 versus 36%, p <
0.001)
• Addition of chemotherapy produced a
reduction of 46% in local failure (p < 0.0001)
• No benefit of OS observed with CRT
36. Radiation Therapy Techniques
• Radiation fields should encompass
1. Tumor bed
2. Regional lymph node areas (including inguinal
nodes) for locoregional control
• The patient should be placed in the supine
position
• Full bladder
• A radio-opaque marker at the anal verge of the
edge of the tumor
37. • 3dCRT - planning using CT simulation with
small bowel contrast is highly recommended.
• Radiation therapy can be divided into three
phases
1. Entire pelvic field
2. Cone-down pelvic field
3. Tumor bed only
39. AP/PA field (whole pelvis)
• Superior: Top of S1
• Inferior: The lower of anal verge or tumor with
3 cm margin
• Anterior lateral: To include lateral inguinal
nodes with 1.5 cm margin, determined by
bony landmark or lymphangiogram
• Posterior lateral: 1.5 cm lateral to the widest
bony margin of the true pelvis
41. • Inguinal lymph nodes are a potential site for
metastatic dissemination.
• Inguinal involvement is demonstrated to be a
poor prognostic factor.
• Benefit of prophylactic inguinal irradiation
(PII) remains questionable because of the
potential serious long-term wound and lower
extremity complications.
45. AP/PA field (cone-down pelvis)
• Superior: Inferior border of sacroiliac joint
• Inferior: same as in the whole-pelvis fi eld
• Anterior lateral: same as in the whole-pelvis
field
• Posterior lateral: same as in the whole-pelvis
field
46. Tumor bed boost field(s)
• Primary tumor: gross tumor with 2- to 2.5-cm
margin
• Lymphadenopathy: gross disease with 2-cm
margin
47. Dose and Treatment Delivery
•
•
•
•
Conventional fractionation
30.6 Gy to the entire pelvis
14.4 Gy to the inferior pelvis
Boost to 54–59.4 Gy to gross tumor, with a 2–
2.5 cm margin is recommended for patients
with T3 or T4, N+ patients, or T2 disease with
gross residual after 45 Gy.
48.
49.
50.
51.
52.
53.
54.
55.
56.
57.
58.
59.
60.
61.
62.
63.
64.
65.
66.
67.
68.
69. Anal margin neoplasms
Bowen’s disease
• Intraepidermal squamous cell carcinoma (SCC)
• Represents the extreme end of a spectrum of epithelial
dysplastic changes known as anal intraepithelial
neoplasia (AIN).
• AIN - dysplastic changes of the anal canal epithelium
• BD generally implies involvement of the perianal skin
• Human papillomavirus (HPV) - etiological agent
• HPV 16 found in 60% to 80% of pts with perianal
Bowen’s disease.
70. Anal margin neoplasms
Bowen’s disease
• May progress to invasive SCC in approximately 2% to
5% of cases .
• Presentation
- as an asymptomatic or mildly symptomatic
scaly, erythematous rash of the perianal area.
- Pruritus and burning of the skin are common
complaints
- May be found incidentally on examination of tissue
removed during other anorectal procedures.
.
71. Anal margin neoplasms
Bowen’s disease
• Diagnosis - by biopsy, and must be distinguished from
other conditions of the perianal area, including Paget’s
disease, melanoma,& other dermatoses.
• Histologic appearance –
- atypical epithelial cells involving the full thickness of the
epidermis, producing sharp demarcation with the normal
dermis.
- cells with large haloed hyperchromatic nuclei, so-called
‘‘bowenoid cells,’’
• Rx - cryosurgery, topical 5-fluorouracil (5-FU), argon laser
therapy, CO2 laser ablation, and photodynamic therapy .
• Rx of choice - WLE - negative microscopic margins.
72. Anal margin neoplasms
Bowen’s disease
• Small defects from WLE can be closed primarily or
covered by SSGs.
• Larger defects may require the use of V-Y, S-shaped, or
house-shaped advancement anoplasty .
• Careful clinical follow-up of longer than five years is
required
• Local recurrence has been reported as late as 111
months after surgery
74. Discussion
• Response assesment after
chemoradiotherapy?
• ACT II trail…..inference
• Recent NCCN guidelines….regarding surgwery
after chemo radiation…..
Editor's Notes
before 30 yearsold and multiple sexual partners (>10) are also identified asincreased risks for anal carcinoma
~85% of cases demostrate human papilloma virus, High risk subtypes include type-16, -18, -31,-33, and -35. ,, or HPV infections(patients, particularly in patients whose CD4 count isless than 200, and those on immunosuppression after organ)may lead to immunodeficiency and further increase the risk of anal carcinoma
It is common for patients and their physicians to attribute such symptoms to hemorrhoids for many months preceding the diagnosis, underscoring the importance of performing a simple anorectal examination for patients with such symptoms.
Pattern of lymphatic spread depends on the location of the primary tumors
T4 for anal margin….deep extra dermal structure skeletal muscle or bone
These authors reported the first large experience of
Break during radiation therapy for skin toxicity should not exceed 10 days. Total dose to the supplemental inguinal lymph node region is 36 Gy in clinically N0, and 45 Gy in N+ disease.A split course of radiation therapy is not recommended; although it is associated with lower incidence of severe toxicity, it may increase local failure and colostomy ratesis usually recommended to cover pelvic and inguinal lymph nodes.