- Severe anal pain.
- Palpable mass usually present on perineal or digital rectal
- Systemic sepsis.
Perirectal abscess and fistulous disease not associated with
a specific systemic disease is most commonly cryptoglandular in
origin. The anal canal has 6–14 glands that lie in or near
the plane between the internal and external sphincters. Projections
from the glands pass through the internal sphincters and drain into
the crypts at the dentate line. Glands may become infected when
a crypt is occluded, trapping stool and bacteria within the gland.
Occlusion may follow impaction of vegetable matter or edema from
trauma (firm stool or foreign body) or as a result of an adjacent inflammatory
process. If the crypt does not decompress into the anal canal, an abscess
may develop in the intersphincteric plane. The abscess may track
within or across the intersphincteric plane. Abscesses are classified
according to the space they invade (Figure 31–5).
The most difficult to treat occurs when the abscess tracks proximally
or circumferentially within the intersphincteric plane or within
the ischiorectal fossa and deep postanal space. Regardless of location,
the extent of an abscess may be difficult to determine without examination
Composite diagram of acute anorectal abscesses and spaces.
(a) Pelvirectal (supralevator) space. (b) Ischiorectal space. (c)
Perianal (subcutaneous) space. (d) Marginal (mucocutaneous) space.
(e) Submucous space. (f) Intermuscular space.
Antibiotics given while allowing the abscess to mature are not
helpful. Early surgical operative drainage is the best way to avoid
the potentially disastrous complications of undrained perineal sepsis.
When the abscesses are drained, either surgically or spontaneously,
50% have persistent communication with the crypt, creating
a fistula from the anus to the perianal skin (fistula-in-ano). A
fistula-in-ano is not a surgical emergency.
An anorectal abscess typically causes severe and continuous throbbing
pain that may worsen with ambulation and straining. Swelling and
discharge are noted less frequently. Patients may present with fever,
malaise, urinary retention, and life-threatening sepsis. People
with diabetes mellitus or immune compromise are most vulnerable.
A patient with fistula-in-ano may report a history of severe pain,
bloody purulent drainage associated with resolution of the pain,
and subsequent chronic mucopurulent discharge.
Physical examination reveals a tender perianal or rectal mass.
The size is often difficult to assess until the patient is anesthetized.
An apparently small abscess may extend high into the ischiorectal
or supralevator space. A fistula is present when internal and external openings
are identified. A firm connecting tract is often palpable.
and Imaging Studies
No imaging studies are necessary in uncomplicated abscess fistulous
disease. Sinograms, transrectal ultrasound, CT, and MRI may be useful
in the evaluation of complex or recurrent disease. Transrectal ultrasound
can identify branching of fistulous tracts, persistent undrained
sepsis, and extent of sphincter involvement. Hydrogen peroxide injection
of the tract may improve sensitivity of the ultrasound. CT scan
may be helpful in finding an undiagnosed supralevator abscess. MRI
and MRI with endorectal coil may be of use in identifying and classifying
Abscess and fistula disease of cryptoglandular origin must be
differentiated from complications of Crohn disease, pilonidal disease,
hidradenitis suppurativa, tuberculosis, actinomycosis, trauma, fissures,
carcinoma, radiation injury, chlamydiosis, local dermal processes,
retrorectal tumors, diverticulitis, and urethral injuries.
About 10% of patients with Crohn disease present with
anorectal abscess fistulous disease with no antecedent history of
inflammatory bowel disease. Tuberculosis may cause indolent, pale, granulomatous
perianal disease, but there is usually a known history of tuberculosis.
Hidradenitis suppurativa gives multiple chronic, draining fistulas,
as might be seen with undiagnosed horseshoe abscess fistula disease.
Pilonidal disease may extend toward the perineum; it is distinguished
from cryptoglandular disease by the presence of inspissated hairs,
the direction of the tract, and the presence of other openings in
the sacrococcygeal area. A colonic source may be suspected in a
patient with known inflammatory bowel disease or diverticular disease.
Other less common causes include tumors, radiation, infections,
and urologic injuries.
The complications of an undrained anorectal abscess may be severe. Unless
drained, the infection may spread rapidly and result in extensive
tissue loss, sphincter injury, and even death. In contrast, a fistula-in-ano,
which develops when the abscess is drained, is not a surgical emergency.
A chronic fistula may be associated with recurring perianal abscess
formation and, rarely, with cancer of the fistulous tract.
Abscesses should be drained surgically. It is best done in the
operating room, where anesthesia allows adequate evaluation of the
extent of disease. Abscesses thought to be superficial in the office
may be found to extend above the levators. Intersphincteric abscesses are
treated by an internal sphincterotomy that drains the abscess and
destroys the crypt. Perirectal and ischiorectal abscesses should
be drained by a catheter or with adequate excision of skin to prevent
premature closure and reaccumulation of the abscess. If the internal opening
of the fistula is identified and external sphincter involvement
is minimal, a fistulotomy may be performed when the abscess is drained.
However, the internal opening is often hard to find because of the
inflammation, and drainage is all that can be achieved. In this instance,
catheter drainage is preferred to skin excision because the catheter (1) establishes
drainage with minimal disruption of normal perianal skin, (2) facilitates
identification of the internal opening at subsequent evaluation,
and (3) facilitates patient compliance by eliminating the need for
packing or leaving the wound open.
Patients with chronic or recurring abscesses after apparent adequate
surgical drainage often have an undrained deep postanal space abscess
that communicates with the ischiorectal fossa via a horseshoe fistula.
Treatment involves opening the deep postanal space and counterdraining
the tract through the ischiorectal external opening. The horseshoe
fistula almost always arises from a posterior midline cryptoglandular
origin. Once the postanal space heals, the counter drain may be
Immunocompromised patients are a particular challenge. With moderate
compromise (eg, diabetes mellitus), urgent drainage in the operating
room is required, as these patients are prone to necrotizing anorectal
infections. With severe compromise (eg, patients receiving chemotherapy),
infection may occur without an abscess due to neutropenia. In these
patients, it is important to attempt to localize the process, establish drainage,
localize the internal opening, and obtain a biopsy for tissue examination
and culture (to rule out leukemia and to select antibiotics).
The treatment of fistulas is dictated by the course of the fistula.
The Salmon-Goodsall rule is of assistance in identifying the direction
of the tract (Figure 31–6). If the
tract passes superficially and does not involve sphincter muscle,
a simple incision of the tract with ablation of the gland and saucerization
of the skin at the external opening is all that is necessary. A
fistula that involves a small amount of sphincter may be treated
similarly. A tract that passes deep or that involves an undetermined
amount of muscle may be initially treated with a collagen fistula
plug, which has a success rate of 70.8% and 35% for
simple and complex fistulas, respectively. Success rates for patients
who have Crohn disease are lower than for those who do not have
Crohn disease (26.6% versus 66.7%, respectively).
If unsuccessful, the fistula is best treated with a mucosal advancement
flap (described in the section on Rectovaginal Fistula) because immediate
or delayed (as with a seton) muscle division is associated with
a risk for incontinence.
Salmon-Goodsall rule. The usual relation of the primary
and secondary openings of fistulas. When there is an anterior and also
a posterior opening of the same fistula, the rule of the posterior
opening applies; the long anterior fistula is an exception to the
The prognosis for cryptoglandular abscess and fistula disease
is excellent once the source of infection is identified. Fistulas
persist when the source has not been identified or adequately drained, when
the diagnosis is incorrect, or when postoperative care is insufficient.
Brook I et al: The aerobic and anaerobic bacteriology
of perirectal abscesses. J Clin Microbiol 1997;35:2974.
Chapple KS et al: Prognostic value of magnetic resonance imaging
in the management of fistula-in-ano. Dis Colon Rectum 2000;43:511.
Cho DY: Endosonographic criteria for an internal opening of
fistula-in-ano. Dis Colon Rectum 1999;42:515.
Cintron JR et al: Repair of fistulas-in-ano using fibrin adhesive:
long-term follow-up. Dis Colon Rectum 2000;43:944.
Garcia-Aguilar J et al: Anal fistula surgery. Factors associated with
recurrence and incontinence. Dis Colon Rectum 1996;39:723.
Ho YH et al: Marsupialization of fistulotomy wounds improves
healing: a randomized controlled trial. Br J Surg 1998;85:105.
Jun SH et al: Anocutaneous advancement flap closure of high
anal fistulas. Br J Surg 1999;86:490.
Knoefel WT et al: The initial approach to anorectal abscesses:
fistulotomy is safe and reduces the chance of recurrences. Dig Surg
Ky AJ et al: Collagen fistula plug for the treatment of anal
fistulas. Dis Colon Rectum 2008;51:838
Miller GV et al: Flap advancement and core fistulectomy for
complex rectal fistula. Br J Surg 1998;85:108.
Nelson RL et al: Dermal island-flap anoplasty for transsphincteric
fistula-in-ano: assessment of treatment failures. Dis Colon Rectum
Park JJ et al: Repair of chronic anorectal fistulae using commercial
fibrin sealant. Arch Surg 2000;135:166.
Practice parameters for treatment of fistula-in-ano—supporting
documentation. The Standards Practice Task Force. The American Society
of Colon and Rectal Surgeons. Dis Colon Rectum 1996;39:1363.
- Passing stool and flatus through the vagina.
Tract generally visible or palpable.
Rectovaginal fistulas occur as a result of obstetric injury,
Crohn disease, diverticulitis, radiation, undrained cryptoglandular disease,
foreign body trauma, surgical extirpation of anterior rectal tumors,
and malignancies of the rectum, cervix, or vagina. The fistulas
are classified as low, middle, or high. The location and cause of
the fistula determine the operative approach.
Passing stool and flatus through the vagina is characteristic
of rectovaginal fistulas. There may be varying degrees of incontinence.
An opening in the vagina or rectum may be seen or felt on physical examination.
and Imaging Studies
A vaginogram or barium enema may identify the fistula. If the fistula
is not demonstrated on radiographic or physical examination, a dilute
methylene blue enema may be administered with a tampon in the vagina.
If a fistula is present, it should be confirmed by methylene blue
staining of the tampon.
The signs and symptoms of a rectovaginal fistula are fairly unmistakable.
The important differential is the cause of the fistula, as this
affects management, as discussed shortly.
The major complications of a rectovaginal fistula are impaired
hygiene and incontinence.
The cause and location of the fistula determine the treatment.
Involvement of surrounding tissue by the disease process that leads
to the fistula may limit the surgical options. For example, in patients with
active Crohn disease or radiation injury of the surrounding tissue,
the fistula cannot be repaired with local procedures; Crohn disease
must go into remission before a fistula can be repaired. Radiation
injuries require that normal healthy tissue be brought from outside
the irradiated field.
Low rectovaginal fistulas (rectal opening near the dentate line
and vaginal opening just above the fourchette) commonly result from
obstetric injuries, trauma from foreign bodies, cryptoglandular
disease, or Crohn disease. Obstetric injuries often heal within
the first 3 months. Waiting 3 months allows inflammation to resolve, which
facilitates repair and allows for closure of those fistulas that
will spontaneously heal. Similarly, traumatic fistulas may be repaired
most easily after inflammation resolves. Fistulas secondary to cryptoglandular
disease may close spontaneously once the primary process is drained.
Fistulas secondary to Crohn disease rarely heal spontaneously.
Aggressive medical therapy and surgical control of perianal sepsis
are necessary to conserve the sphincters. Once the disease is in
remission, local advancement flap procedures may be performed. The
principle is to bring fresh, uninvolved tissue down over the fistulous
tract and excise the old rectal opening. This often delays proctectomy
and preserves the anal sphincter and rectum. Patients with severe
disease that does not respond to local measures may require a temporary
diverting colostomy. After diversion, a single focus of disease
is often found and an advancement procedure may be performed while the
fecal stream is diverted. Extensive destruction of the rectum or
sphincters may mandate immediate proctectomy without attempts at
local preservation. Early surgical intervention and conservative
drainage or diversion may postpone this situation.
Midrectal fistulas from cryptoglandular disease, Crohn disease,
or obstetric injury should be treated as outlined previously. Those
that occur secondary to radiation are not amenable to local procedures,
as the surrounding tissue is similarly affected. Transabdominal
resection and coloanal anastomosis is preferred. These are particularly
challenging patients. Other surgical options are beyond the scope
of this chapter.
High rectal fistulas result from Crohn disease, diverticular
disease, operative injury, malignancy, and radiation. High rectovaginal
fistulas are best treated via a transabdominal approach. This allows for
resection of the diseased bowel that created the fistula.
The prognosis is determined by the cause of the fistula.
Hull TL et al: Surgical approaches to low anovaginal fistula
in Crohn’s disease. Am J Surg 1997;173:95.
Hyman N: Endoanal advancement flap repair for complex anorectal
fistula. Am J Surg 1999;178:337.
Khanduja KS et al: Reconstruction of rectovaginal fistula with
sphincter disruption by combining rectal mucosal advancement flap
and anal sphincteroplasty. Dis Colon Rectum 1999;42:1432.
Marchesa P et al: Advancement sleeve flaps for treatment of
severe perianal Crohn’s disease. Br J Surg 1998;85:1695.
Ozuner G et al: Long-term analysis of the use of transanal rectal
advancement flaps for complicated anorectal/vaginal fistulas.
Dis Colon Rectum 1996;39:10.
Simmang CL et al: Rectal sleeve advancement: repair of rectovaginal
fistula associated with anorectal stricture in Crohn’s
disease. Dis Colon Rectum 1998;41:787.
Tsang CB et al: Anal sphincter integrity and function influences
outcome in rectovaginal fistula repair. Dis Colon Rectum 1998;41:1141.
Tsang CB et al: Rectovaginal fistulas. Therapeutic options.
Surg Clin North Am 1997;77:95.
Venkatesh KS et al: Fibrin glue application in the treatment
of recurrent anorectal fistulas. Dis Colon Rectum 1999;42:1136.
Yee LF et al: Use of endoanal ultrasound in patients with rectovaginal
fistulas. Dis Colon Rectum 1999;42:1057.
- Acute chronic recurring abscess or chronic draining sinus
over the sacrococcygeal or perianal region.
Pain, tenderness, purulent drainage, inspissated
The incidence of pilonidal disease is highest in white males
(3:1 male-to-female ratio) between ages 15 and 40, with a peak incidence
between 16 and 20 years. It rarely occurs in patients more than
50 years old. It was once thought that pilonidal disease was a congenital condition
that developed along an epithelialized tract of the natal cleft.
It is now considered to be an acquired infection of natal cleft
hair follicles, which become distended and obstructed and rupture into
the subcutaneous tissues to form a pilonidal abscess. Hair from
the surrounding skin is pulled into the abscess cavity by the friction
generated by the gluteal muscles during walking.
Patients with pilonidal disease may present with small midline
pits or abscesses on or off the midline near the coccyx or sacrum.
The patients are generally heavy hirsute males who perspire profusely.
The workup is limited to a physical examination unless one suspects
Crohn disease, in which case a more extensive evaluation may be
necessary. Physical examination may reveal a spectrum of disease
from acute suppuration and an undrained abscess or chronic draining
sinuses with multiple mature tracts with hairs protruding from the
The differential diagnosis includes cryptoglandular abscess-fistulous
disease of the anus, hidradenitis suppurativa, furuncle, and actinomycosis.
Untreated pilonidal disease may result in multiple draining sinuses
with chronic recurrent abscess, drainage, soiling of clothing, and,
rarely, necrotizing wound infections or malignant degeneration.
Pilonidal abscesses may be drained under local anesthesia. A
probe may be inserted into the primary opening and the abscess unroofed.
Granulation tissue and inspissated hair are pulled out, but definitive
therapy is not required at the first procedure. Cure rates of 60–80% have
been reported after primary unroofing and extraction of hair. For
those that fail to heal after 3 months or develop a chronic draining
sinus, definitive therapy may be considered.
Nonoperative therapy with meticulous skin care (shaving of the
natal cleft, perineal hygiene) and drainage of abscesses will substantially
reduce the need for surgery.
Conservative excision of midline pits with removal of hair from
lateral tracts and postoperative weekly shaving has a 90% success
rate. Excision with open packing, marsupialization, or primary closure
with or without flaps have all been advocated. Either open packing
or marsupialization leaves the patient with painful wounds slow
to heal, and marsupialization has a reported recurrence rate of
10%. Simple primary closure often results in dehiscence
because the midline skin has a poor blood supply, the wounds are closed
under tension, and there is often dead space at the base of the
defect that is susceptible to infection. Closure over suction drainage
or the use of lateral incisions with excision of the tracts decreases
the rate of wound dehiscence. A recent Cochrane review showed no
clear benefit supporting either primary closure or open healing
by secondary intention. However, when primary closure was chosen,
off-midline repairs were favored over midline repairs.
The prognosis after surgery is excellent. Recurrent or persistent
disease has been reported to be 0–15% and is likely due
to inadequate excision where external openings or occult tracts
are missed. Inadequate postoperative hygiene with ingrowth of hair
into the wound also leads to recurrence.
Abu Galala KH et al: Treatment of pilonidal sinus
by primary closure with a transposed rhomboid flap compared with
deep suturing: a prospective randomised clinical trial. Eur J Surg 1999;165:468.
Akinci OF et al: Simple and effective surgical treatment of
pilonidal sinus: asymmetric excision and primary closure using suction
drain and subcuticular skin closure. Dis Colon Rectum 2000;43:701.
Armstrong JH et al: Pilonidal sinus disease. The conservative
approach. Arch Surg 1994;129:914.
Bozkurt MK et al: Management of pilonidal sinus with the Limberg
flap. Dis Colon Rectum 1998;41:775.
McCallum I et al: Healing by primary versus secondary intention
after surgical treatment for pilonidal sinus. Cochrane Database
Syst Rev 2007;4:CD006213
Peterson S et al: Primary closure techniques in chronic pilonidal
sinus: a survey of the results of different surgical approaches.
Dis Colon Rectum 2002;45:1458.
Senapati A et al: Bascom’s operation in the day-surgical
management of symptomatic pilonidal sinus. Br J Surg 2000;87:1067.
Spivak H et al: Treatment of chronic pilonidal disease. Dis
Colon Rectum 1996;39:1136.
- Severe perianal itching, often at night.
- When chronic, skin becomes white, leathery, and thickened.
Pruritus ani is usually idiopathic. Most patients have tried
many over-the-counter preparations without relief. These agents
may exacerbate the problem by keeping the perineum moist, causing
further irritation, or by creating a contact dermatitis (especially
local anesthetics). Poor cleansing of the perineum may lead to irritation
of the exquisitely sensitive anoderm and subsequent pruritus. In
contrast, frequent washing with soaps and detergents dries the skin,
also leading to pruritus. Pinworms (Enterobius vermicularis)
are the most common cause of perianal itching in children.
The patient experiences severe perianal itching, often worse
at night. The skin is thickened, white, and leathery in the chronic
state but may be normal to weeping in the acute stage. In children
with pinworms, perianal itching is most severe at night, when the
pinworm deposits its eggs on the perianal skin.
and Imaging Studies
The diagnosis of pinworms is made by applying cellophane tape
to the perianal skin, which collects the eggs and allows them to
be viewed under a microscope. Scrapings of the perianal skin viewed microscopically
may reveal fungi or parasites. Biopsy and histologic evaluation may
be necessary in refractory cases to rule out underlying malignancy.
Pruritus may be associated with other perianal lesions that distort
normal anal anatomy, such as hemorrhoids, fistulas, fissures, tumors
of the anorectum, previous surgery, and radiation therapy. As noted
above, it may be secondary to excessive cleaning or application
of ointments to the perianal region. Primary dermatologic diseases
such as lichen planus, atopic eczema, psoriasis, and seborrheic
dermatitis may all affect the perineum. Fungal (dermatophytosis, candidiasis),
parasitic (Enterobius vermicularis, scabies, or
pediculosis), and bacterial superinfection should be considered. Other
causes include contact dermatitis from local anesthetic creams or
soaps, recent antibiotic usage, systemic diseases (diabetes, liver
disease), dietary factors, and perianal neoplasms (Bowen disease
and extramammary Paget disease). Pruritus may result from tight clothing,
obesity, and living in a hot climate. When a specific cause cannot
be found, it is considered idiopathic.
Complications include severe excoriation, ulceration, and secondary
infection of the perineum.
Identifiable causes of pruritus ani, such as hemorrhoids, yeast
infection, or parasites, should be treated. Patients should be educated
about proper perineal care, and the use of soaps and topical ointments
should be discouraged. The perineum should be kept dry. Use of a blow
dryer on the perineum after bathing may be helpful. Alteration in
dietary habits may be necessary. Coffee, tea, cola drinks, beer,
chocolate, and tomatoes cause perianal itching and should be excluded
from the diet for at least 2 weeks. Symptoms should resolve with alterations
in dietary and cleaning habits. After symptoms resolve, each food
group may be added sequentially to identify the causative agent.
Pruritus refractory to the above measures may be treated by intradermal
injection of 1% methylene blue solution.
Relapse is common, and reeducation is often effective. In refractory
cases, dermatologic and psychiatric consultation may be necessary.
Proctitis and anusitis are nonspecific terms for varying degrees
of inflammation due to infectious or inflammatory diseases. The
causative agent or event determines the symptoms, signs, and appropriate
management. In considering these diseases, particular attention should
be paid to sexual practices and sexually transmitted diseases.
Lesions appear as vesicles, which rupture to form ulcers that
may become secondarily infected. Patients may present early with
anal pain and vesicles or later with ulcerations, discharge, rectal
bleeding, tenesmus, and even fear of defecation because of severe
pain. Fever and generalized malaise are often noted. No history
of anoreceptive intercourse is required, as the disease may spread
by extension from the vagina. Viral culture of the vesicle or biopsy
of the ulcer is diagnostic. Herpes simplex type 2 is most common.
Oral acyclovir is the treatment of choice but is not curative.
It decreases the duration of outbreaks and viral shedding and increases
the interval between attacks. The first episode is associated with
the most pain and longest duration of ulceration. Subsequent episodes
are generally shorter and not as painful.
The chancre is an indurated, nontender perianal ulcer at the
site of inoculation. Proctitis, pseudotumors, and condylomata lata
may also be present. Condylomata lata are contiguous hypertrophic papules
associated with secondary syphilis. Darkfield microscopy of exudate
for Treponema pallidum and serologic testing are
the preferred methods of diagnosis. Serologic tests may initially
be negative and should be repeated several months later.
Penicillin is the treatment of choice. The prognosis is good.
Contacts must be sought and treated.
Symptoms range from none to painful defecation. Rectal bleeding
and discharge, perianal excoriation, and fistulas may develop. The
mucosa may appear friable and edematous. Cultures of the anus, vagina,
urethra, and pharynx should be obtained and plated on Thayer-Martin
medium. The gram-negative diplococcus Neisseria gonorrhoeae is
the causative agent.
Intramuscular procaine penicillin G and oral probenecid is the
treatment of choice. Resistant strains should be treated with spectinomycin.
Follow-up examination and cultures should be performed to confirm
adequate therapy. The prognosis is excellent.
Proctitis & Lymphogranuloma Venereum
As in gonococcal proctitis, the symptoms of chlamydial proctitis
range from none to rectal pain, bleeding, and discharge. The small
shallow ulcer of lymphogranuloma venereum (LGV) may go unnoticed,
but the inguinal adenopathy may become quite marked. Late findings
include hemorrhagic proctitis and rectal stricture. The causative
agent is Chlamydia trachomatis, an intracellular
parasite spread by anal intercourse or direct extension through the
lymphatics of the rectovaginal septum. The diagnosis is made with
the LGV complement fixation test. Tissue cultures are also used.
Treatment with 21 days of tetracycline is recommended, but erythromycin
is an acceptable alternative. Early strictures may be dilated. Although
uncommon, strictures may cause bowel obstruction and require colostomy.
Human papilloma virus (HPV) is the cause of condylomata acuminata.
Multiple types have been identified. Types HPV-6 and HPV-11 are
associated with the common, benign genital wart, whereas HPV-16
and HPV-18 are associated with the development of high-grade anal
dysplasia and anal cancer. In the United States, condyloma acuminatum
is the most common sexually transmitted viral disease, with 1 million
new cases reported per year. It is the most common anorectal infection
of homosexual men and is particularly prevalent in HIV-positive
patients. However, the disease is not limited to men or women who
practice anoreceptive intercourse. In women, the virus may track
down from the vagina, and in men it may pool and track from the
base of the scrotum. Immunosuppression, either from drugs after
transplantation or from HIV, increases susceptibility to condylomatous
disease with prevalence rates of 5% and 85%, respectively.
The most frequent complaint is that of a perianal growth. Pruritus,
discharge, bleeding, odor, and anal pain are present to a lesser
degree. Physical examination reveals the classic cauliflower-like
lesion, which may be isolated, clustered, or coalescent. The warts
tend to run in radial rows out from the anus. The lesions may be
surprisingly large at the time of presentation.
and Imaging Studies
Anoscopy or proctosigmoidoscopy are essential because the disease
extends internally in more than three fourths of patients and because
intra-anal disease is present in 95% of cases in homosexual
men. Material for cultures and serologic tests for other venereal
diseases may be taken from the penis, anus, mouth, and vagina.
These lesions must be distinguished from condylomata lata, the
lesions of secondary syphilis, and anal squamous cell carcinoma.
Condylomata lata are flatter, paler, and smoother than condylomata
acuminata. Anal squamous cell carcinoma is generally painful and
may be tender and ulcerated, whereas condylomas are not tender or
Squamous cell carcinoma of the anal canal is the major complication.
The extent of the disease and the risk of malignancy determine
the treatment. Minimal disease is treated in the office with topical
agents such as bichloracetic acid or 25% podophyllum resin
in tincture of benzoin. The former is preferred, and there are fewer
complications (scarring) because the latter must be washed off within
4–6 hours to limit pain. The warts respond promptly to
therapy. Patients should be seen at regular intervals until resolution
is complete. More extensive disease may require an initial treatment session
under anesthesia so that random lesions can be excised for pathologic
evaluation to rule out dysplasia and so that the remainder can be
coagulated. Electrocautery coagulates the lesions. Care is taken
to spare surrounding skin. Follow-up evaluation may reveal residual disease,
but this is often easily treated with topical agents in the office.
Laser therapy is another method of condyloma destruction. Recurrence
rates are low, but the equipment is expensive.
Recurrent disease may respond to repeat excision or destruction.
Imiquimod is a topically applied immune modulator that induces interferon
and cytokine release by the host tissues. It activates the host
immune system to clear the HPV infection by both the innate and cell-mediated
pathways. In select patients, external wart clearance has been achieved
in 72–84%. Imiquimod may also be a useful adjunctive
therapy following excision.
The first description of autologous vaccines was reported in
1944, but it is only recently that vaccines have shown more promise.
The current vaccines target the late structural proteins of the
viral capsid (E6, E7) to engender a cytotoxic T lymphocyte cell–mediated
immune response. Recently, a quadrivalent vaccine that targets HPV-6,
HPV-11, HPV-16, and HPV-18 has been developed for the prevention
of cervical dysplasia and may have a role for the prevention of anal
condylomas and anal dysplasia. Its impact on specifically preventing
anal dysplasia is still being evaluated in a prospective trial.
HPV-16 and HPV-18 are causally associated with squamous cell
carcinomas of the anal canal. This association has led to new screening
techniques to evaluate high-risk patients for occult disease. These
techniques are discussed in the section on Anal & Perianal Neoplasms.
Representative biopsies of clinically apparent condylomas should
be sent for pathologic study because unsuspected low-grade or high-grade dysplasia
or squamous cell carcinoma of the anal canal may be found.
Buschke-Löwenstein tumors are giant condylomata acuminata
that are locally aggressive and exhibit malignant behavior but benign
histology. Radical excision is often the only therapeutic option
for either palliation or cure. Wide local excision and even surgery
with adjuvant chemotherapy and radiotherapy have been used with
Haemophilus ducreyi causes a soft perianal ulcer
that is painful, often multiple, and bleeds easily. Autoinoculation
is common. Inguinal lymph nodes become fluctuant, rupture, and drain.
Cultures are diagnostic.
Treatment options include azithromycin, 1 g orally in a single
dose; or ceftriaxone, 250 mg intramuscularly in a single dose; or
ciprofloxacin, 500 mg orally twice daily for 3 days; or erythromycin
base, 500 mg orally four times daily for 7 days. All are effective.
Inflammatory proctitis is a mild form of ulcerative colitis that is
limited to the rectum. Rectal bleeding, discharge, diarrhea, and
tenesmus are common. The rectal mucosa is inflamed and friable,
but the remainder of the colon appears normal on examination. The
disease course is often self-limited. Only about 10% of
patients ever develop colonic manifestations of ulcerative colitis.
Biopsies are taken at endoscopy to rule out infectious processes
and Crohn disease.
An infectious process must be ruled out before initiating steroid
therapy. Distinguishing between Crohn disease and inflammatory proctitis
may be difficult. Lack of response to appropriate therapy calls
for reassessment of the patient.
Steroid retention enemas are given for 2 weeks. If there is no
response, a short course of oral steroids may be given. In addition,
mesalamine (5-aminosalicylic acid) may be given orally or rectally
in an enema or suppository. Patients should avoid milk and milk
products, fruit, and dietary fiber. The disease usually responds
to these measures and resolves rapidly.
Radiation proctitis in a patient with a history of radiation
to the rectum is manifested early by diarrhea, rectal bleeding, discharge,
tenesmus, pain, and incontinence. Late disease may develop months
to years after the injury. Symptoms of late disease are secondary
to strictures, fistulas, and telangiectasias, which may present
as recurrent urinary tract infections, vaginal discharge, fecal incontinence,
rectal bleeding, changes in stool caliber, and constipation. The symptoms
include bleeding, change in bowel habits, urinary tract infections,
and vaginal discharge. Endoscopy may reveal friable edematous mucosa, telangiectasias,
or strictures and may show internal openings of fistulas.
Initial therapy includes bulk-forming agents, antidiarrheals,
and antispasmodics. Topical steroids, mesalamine preparations, misoprostol
suppositories, and short-chain fatty acids have all been used in
acute and chronic disease. Refractory hemorrhagic proctitis may
be treated with the application of formalin to the rectal mucosa.
Dilatation of strictures and laser coagulation of telangiectasias are
useful in late disease. The key to surgical success in treating
fistulas to the bladder or vagina is interposition or transposition
of healthy nonirradiated tissue into the field. Only infrequently
is the rectum so badly irradiated that it must be removed. The prognosis,
therefore, is good.
Babb RR: Radiation proctitis: a review. Am J Gastroenterol 1996;91:1309.
Berry JM, Palefsky JM: A review of human papillomavirus vaccines:
from basic science to clinical trials. Frontiers Biosci 2003;8:s333.
Bjork M et al: Giant condyloma acuminatum (Buschke-Löwenstein
tumor) of the anorectum with malignant transformation. Eur J Surg
Breese PL et al: Anal human papillomavirus infection among homosexual
and bisexual men: prevalence of type-specific infection and association
with human immunodeficiency virus. Sex Transm Dis 1995;22:7.
Chang GJ, Welton ML: Human papillomavirus, condylomata acuminata,
and anal neoplasia. Clin Colon Rectal Surg 2004;17:55.
Centers for Disease Control and Prevention: Sexually transmitted
diseases treatment guidelines 2002. MMWR 2002;51.
Counter SF et al: Prospective evaluation of formalin therapy
for radiation proctitis. Am J Surg 1999;177:396.
El-Attar SM et al: Anal warts, sexually transmitted diseases,
and anorectal conditions associated with human immunodeficiency
virus. Prim Care 1999;26:81.
Fantin AC et al: Argon beam coagulation for treatment of symptomatic
radiation-induced proctitis. Gastrointest Endosc 1999;49(4 Part
Farouk R, Lee PW: Intradermal methylene blue injection for the
treatment of intractable idiopathic pruritus ani. Br J Surg 1997;84:670.
Hakim AA et al: Indications and efficacy of the human papillomavirus
vaccine. Curr Treat Options Oncol 2007;6:393.
Hemminki K et al: Cancer in husbands of cervical cancer patients.
Khan AM et al: A prospective randomized placebo-controlled double-blinded
pilot study of misoprostol rectal suppositories in the prevention
of acute and chronic radiation proctitis symptoms in prostate cancer
patients. Am J Gastroenterol 2000;95:1961.
Kobal B: Herpes simplex genitalis type 2: our experiences. Clin
Exp Obstet Gynec 1999;26:123.
Palefsky JM: Anal squamous intraepithelial lesions in human immunodeficiency
virus-positive men and women. Semin Oncol 2000;27:471.
Palefsky JM: Anal squamous intraepithelial lesions: relation
to HIV and human papillomavirus infection. J Acquir Immune Defic
Syndr 1999;21(Suppl 1):S42.
Pinto A et al: Short-chain fatty acids are effective in short-term
treatment of chronic radiation proctitis: randomized, double-blind,
controlled trial. Dis Colon Rectum 1999;42:788.
Rompalo AM: Diagnosis and treatment of sexually acquired proctitis
and proctocolitis: an update. Clin Infect Dis 1999;28(Suppl 1):S84.
Saclarides TJ et al: Formalin instillation for refractory radiation-induced
hemorrhagic proctitis. Report of 16 patients. Dis Colon Rectum 1996;39:196.
Tabet SR et al: Incidence of HIV and sexually transmitted diseases
(STD) in a cohort of HIV-negative men who have sex with men (MSM).
Talley NA et al: Short-chain fatty acids in the treatment of
radiation proctitis: a randomized, double-blind, placebo-controlled,
cross-over pilot trial. Dis Colon Rectum 1997;40:1046.
Taylor JG et al: KTP laser therapy for bleeding from chronic
radiation proctopathy. Gastrointest Endosc 2000;52:353.
Fecal impaction may develop after excisional hemorrhoidectomy,
in chronically debilitated patients, or from the use of constipating
pain medications without stool softeners and fiber. In the hemorrhoidectomy
population, preserving adequate anoderm between hemorrhoidal complexes
minimizes the incidence of this complication. Postoperative pain
control is essential because otherwise fear of defecation may develop.
Limited use of constipating opioids, addition of nonsteroidal medications,
stool bulking agents (fiber), and stool softeners will minimize
the incidence of fecal impaction.
All hospitalized and postoperative patients are at risk for developing
fecal impaction because of limitations on physical activity, disruption
of dietary and bowel habits, and initiation of constipating medications
(opioids, calcium-channel blockers, etc). Thus, patients at risk who
do not suffer from diarrhea should be started on stool softeners
and fiber-bulking agents to avoid this complication. Enemas and
laxatives may be given as needed.
Patients with fecal impaction commonly present with diarrhea,
as only liquid stool is able to pass the obstructing inspissated
fecal bolus. Some may complain of pelvic pain with episodic severe
spasms from the pressure of the mass on the pelvic floor. Digital
rectal examination may reveal hard, dry stool that obstructs the rectum.
Abdominal examination may reveal a pelvic or abdominal mass much like
a gravid uterus.
Once detected, a fecal impaction may be digitally dislodged at
the bedside, but treatment in the operating room with local or regional
anesthesia may be necessary to provide pelvic floor relaxation and
pain control. At completion of disimpaction, sigmoidoscopy is necessary
to rule out an obstructing inflammatory or malignant mass or rectal
injury incurred during the procedure.
Prather CM et al: Evaluation and treatment of
constipation and fecal impaction in adults. Mayo Clin Proc 1998;73:881.
Tiongco FP et al: Use of oral GoLytely solution in relief of
refractory fecal impaction. Dig Dis Sci 1997;42:1454.
Anal & Perianal
Tumors of the anal canal account for 1.5% of malignancies
of the gastrointestinal tract, with about 4650 new cases annually in
the United States. The incidence has been increasing over the last
30 years. Chronic anal irritation has historically been related
to the development of anal cancer, but there is an etiologic relationship
between chronic infection with HPV and the development of anal cancer.
Women are at increased risk for anal canal cancer, presumably because
the virus may pool in the vagina and track down to the anus. Women
also may practice anoreceptive intercourse in heterosexual relationships.
Although in general women are at increased risk for anal cancer
(9:106 versus 7:106 women versus men, respectively),
in HIV-negative and HIV-positive men who have sex with men, the
incidence is 360:106 and 700:106, respectively.
Other factors associated with an increased risk for anal cancer
are anogenital warts; a history of sexually transmitted disease;
more than 10 sexual partners (but if one has HPV, only one is necessary);
a history of cervical, vulvar, or vaginal cancer; immunosuppression
(HIV-positive or transplantation); long-term corticosteroids; and cigarette
High-grade squamous intraepithelial lesions (HSIL) are the putative
precursor lesion to invasive squamous cell cancer of the anus. It
is an increasingly prevalent condition associated with HPV infection.
Treatment consists of targeted excision of involved tissues with
the aid of the operating microscope and the use of acetic acid to
aid in the identification of high-grade dysplasia. Such an approach
is effective in controlling disease in both immunocompetent and
immunocompromised patients. Recurrent disease is treated in the office
with infrared coagulator ablation or trichloroacetic acid. In this
way premalignant lesions can be controlled without radical surgery
and with minimal morbidity.
Although women are at increased risk for anal canal cancer, this
is not true of anal margin carcinoma, where men are at greater risk
(4:1). This difference highlights the importance of classification based
on anatomic landmarks such as the dentate line, the anal verge,
and the anal sphincters. These landmarks distinguish tumors of the
anal margin from tumors of the anal canal. Unfortunately, the literature
is not clear with regard to these landmarks, and efforts have been made
by the World Health Organization and the American Joint Committee
on Cancer (AJCC) to establish anatomic landmarks to distinguish
tumors of the anal canal from tumors of the anal margin. The definitions
are as follows: The anal canal extends from the upper to the lower
border of the internal anal sphincter (from the pelvic floor to
the anal verge). Anal margin tumors occur outside the anal verge
in the perianal skin but presumably within a 5–6 cm radius
of the anus. Tumors of the anal canal tend to be aggressive, nonkeratinizing,
and associated with HPV infection. Tumors of the anal margin are
generally well-differentiated keratinizing tumors that behave similarly
to other squamous cell carcinomas of the skin and are treated accordingly.
The authors have proposed a new classification to aid clinicians
across various specialties in the accurate description of anal neoplasms
by dividing the region into three regions: intra-anal, perianal,
and skin. Intra-anal lesions cannot be seen or are slightly visible
upon gentle traction of the buttocks. Perianal lesions are completely
visible and fall within a 5 cm radius of the anal opening upon gentle
traction of the buttocks. Finally, skin lesions fall outside this
5 cm radius.
Staging of anal and perianal malignancies is clinical. Physical
examination with digital rectal examination, paying attention to
pararectal nodes, anoscopy, bilateral groin palpation, biopsy (examination under
anesthesia, if necessary), endorectal ultrasound, CT, and MRI are used
as needed to assess tumor size and establish nodal and distant disease. The
AJCC staging classification for anal canal and anal margin tumors
is presented in Table 31–1.
Table 31–1. Staging
of Anal Cancer. |Favorite Table|Download (.pdf)
Table 31–1. Staging
of Anal Cancer.
|TX||Primary tumor cannot be assessed|
|T0||No evidence of primary tumor|
|Tis||Carcinoma in situ|
|T1||≤ 2 cm|
|T2||> 2–5 cm|
|T3||> 5 cm|
|T4||Invasion into adjacent organ(s)|
|NX||Regional nodes cannot
|N0||No regional nodal
iliac/inguinal nodal involvement|
bilateral internal iliac/inguinal nodal involvement|
cannot be assessed|
|M1||No distant metastasis|
|Any T||N2, N3||M0|
|Stage IV||Any T||Any N||M1|
Tumors of the
Patients complain of a mass, bleeding, pain, discharge, itching,
and pain or tenesmus (complaints common to most lesions of this
region). Typically, the lesions are large and centrally ulcerated, with
rolled, everted edges, and have been present for over 2 years before detection.
All chronic or nonhealing ulcers of the perineum should be biopsied
to rule out squamous cell carcinoma. Squamous cell carcinoma is
more common in men.
Small, well-differentiated lesions (≤ 4 cm) are treated by wide
local excision. Deep lesions that involve the sphincters require
abdominoperineal resection. Chemoradiation is used for less favorable
lesions. Spread is to the inguinal lymph nodes, which are generally
included in the radiation fields. Excision of inguinal nodal disease
is reserved for palpable and symptomatic disease. Disease recurring
in the skin may be treated with reexcision or abdominoperineal resection. The
T stage determines survival, with reports of 100% 5-year and
10-year survivals for T1 lesions, compared with 60% and 40% survival
rates for T2 lesions at 5 and 10 years, respectively.
Bleeding, itching, and pain are the presenting symptoms of basal
cell carcinoma. The superficial, mobile lesions have raised, irregular
edges and central ulceration. They are more frequent in men.
As with squamous cell carcinoma of the margin, treatment is by
wide local excision when possible. Deeply invasive lesions may require
abdominoperineal resection. Metastasis is rare, but the local recurrence
rate is 30%. Local recurrence is treated with reexcision.
Bowen disease (intraepithelial squamous cell carcinoma) is often
associated with condylomas and can involve both the anal margin
and the anal canal. Patients often complain of perianal burning,
itching, or pain. Lesions are often found on routine histologic
evaluation of specimens acquired during investigation of unrelated
disorders. When grossly visible, the lesions appear scaly, discrete, erythematous,
and sometimes pigmented. In immunocompromised patients (HIV-positive,
transplantation), a Pap smear is a useful screening technique to
detect dysplasia. If the Pap smear is positive, high-resolution
anoscopy with acetic acid painting may reveal otherwise occult condyloma
Wide local excision with four-quadrant biopsies to establish that
no residual disease persists has been the treatment of choice. Skin
grafts may be necessary for larger lesions. However, there is no
histologic difference between Bowen disease and HSIL, and radical
skin excision ignores the intra-anal dysplastic lesions that may
be even more aggressive than perianal disease. These intra-anal
dysplastic lesions have been successfully managed with local excision
or destruction, even in the immunocompromised host. Furthermore,
fewer than 10% of patients with Bowen disease will develop
invasive squamous cell carcinoma of the anus. Therefore, the need
to perform radical excision and flap procedures has been questioned.
Paget disease (intraepithelial adenocarcinoma) occurs predominantly
in women. Patients are usually in the seventh or eighth decade of
life. Severe, intractable anal pruritus is characteristic. On physical
examination, an erythematous, eczematoid rash is apparent. Biopsy
of any nonhealing lesion should be taken to rule out this diagnosis.
If Paget disease is diagnosed, a thorough workup for an occult malignancy
is indicated because up to 50% of patients have a coexistent gastrointestinal
Wide local excision is the treatment of choice. Abdominoperineal
resection may be indicated for advanced disease. Lymph node dissection
should be done only for palpable adenopathy. The role of chemoradiation
is less clear. The prognosis is good unless there is metastatic disease
or an underlying neoplasm.
Beck DE: Paget’s disease and Bowen’s
disease of the anus. Semin Colon Rectal Surg 1995;6:143.
Chang GJ et al: Surgical treatment of high-grade anal squamous
intraepithelial lesions: a prospective study. Dis Colon Rectum 2002;45:453.
Frisch M et al: Sexually transmitted infection as a cause of
anal cancer. N Engl J Med 1997;337:1350.
Fuchshuber PR et al: Anal canal and perianal epidermoid cancers.
J Am Coll Surg 1997;185:494.
Marchesa P et al: Perianal Bowen’s disease: a clinicopathologic
study of 47 patients. Dis Colon Rectum 1997;40:1286.
Marchesa P et al: Long-term outcome of patients with perianal
Paget’s disease. Ann Surg Oncol 1997;4:475.
Peiffert D et al: Conservative treatment by irradiation of epidermoid
carcinomas of the anal margin. Int J Radiat Oncol Biol Phys 1997;39:57.
Pineda CE et al: High-resolution anoscopy targeted surgical
destruction of anal high-grade squamous intraepithelial lesions:
a ten-year experience. Dis Colon Rectum 2008;51:829.
Sarmiento JM et al: Paget’s disease of the perianal
region: an aggressive disease? Dis Colon Rectum 1997;40:1187.
Touboul E et al: Epidermoid carcinoma of the anal margin: 17
cases treated with curative-intent radiation therapy. Radiother
Welton ML et al: The etiology and epidemiology of anal cancer. Surg
Oncol Clin North Am 2004;13:263.
(Squamous, Basaloid, Mucoepidermoid) Carcinoma
In most cases, there is a long history of minor perianal complaints
such as bleeding, itching, or discomfort. An indurated anal mass
may be present. Disease may be extensive at presentation, with approximately
half of the lesions extending beyond the bowel wall or perianal skin
at presentation. Inguinal nodal metastases are found in 20% at
diagnosis and another 15% over time. The workup is discussed
in the section on Anal & Perianal Neoplasms.
Abdominal CT and chest radiographs may reveal liver or lung metastases. Endorectal
ultrasound can determine the depth of invasion of the primary lesion and
may identify pararectal nodes.
Early lesions that are small, mobile, confined to the submucosa,
and well differentiated may be treated with local excision. Overall
reported recurrence rates with local excision alone are high, with
an average survival rate of 70% at 5 years. Local excision
of the most favorable lesions results in less than 10% recurrence
and 5-year survival of 100%. Larger lesions of the anal
canal call for radiation therapy or multimodality treatment with
chemotherapy and radiation.
Chemoradiation has now replaced surgery as first-line therapy
for all but the earliest lesions, and surgery is advised only as
a salvage procedure for persistent or recurrent disease. The Nigro
regimen consisted of 30 Gy to the primary tumor and to the pelvic
and inguinal nodes. Mitomycin (15 mg/m2 as an
intravenous bolus) was delivered on day 1 of radiation therapy.
Two 4-day infusions of fluorouracil (5-FU) (1000 mg/m2 per
day) were given starting on days 1 and 28 of chemoradiation therapy.
Excellent tumor responses with 80% disease-free survivals
have been reported. Because of the morbidity associated with this
regimen, the amount and type of chemotherapy and radiation have
been modified. Radiation only, without chemotherapy, has resulted
in higher local recurrence rates in multicenter randomized trials.
Much of the chemotherapy toxicity is related to the mitomycin, which has
increasingly been replaced by cisplatin, which is effective and
is associated with fewer side effects. However, colostomy-free survival
rates are higher with mitomycin C. External beam radiotherapy doses
range from 35 Gy to 59 Gy; some centers use brachytherapy catheters
Treatment failures occur most commonly in the pelvis at the primary
site or in the locoregional lymph nodes, with disease occurring
outside the pelvis in just 15% of patients. The most common
site of extrapelvic failure is the liver. Salvage abdominoperineal
resection for local failure with recurrent or persistent disease
is associated with a 50% 5-year survival rate. Survival
is related to the extent of disease at the time of failure and to
nodal status before initiation of chemoradiation therapy.
Prophylactic groin dissection is not recommended, but some experts
recommend that the groins be included in the radiation fields because
the failure rate in the groins is 20% if they are not treated.
Tumor size is the single-most important prognostic factor. Mobile
lesions up to 2 cm in diameter have cure rates of 80%, but
tumors 5 cm or more in diameter are associated with a 50% mortality.
There are reports of excellent 10-year survival for T1–3
node-negative disease (88%) and T1–3 node-positive
disease (50%). Metastatic disease is more likely to be present
with increasing depth of invasion and size and worsening histologic
grade. Distant disease is uncommon at the time of diagnosis but
most commonly involves the liver when present. Subsequent metastasis
out of the pelvis is not uncommon, and 40% of patients
die with disease that has spread to distant sites. Lymph node involvement
at the time of presentation is a bad prognostic sign.
of the Anal Canal
Melanoma of the anal canal accounts for less than 1% of
all anal canal tumors, yet it is a common site of primary melanoma. As
with other anal canal tumors, there is often a delay in diagnosis
that results in advanced-stage disease at the time of presentation.
Metastatic disease has been reported to be present in over one third
of patients at the time of diagnosis. The lesions can be located
in the anal canal, rectum, or both. The overall prognosis has been
poor, with 5-year survival rates of less than 25% in several
series. Most patients will die of disseminated disease.
Traditionally, treatment of primary melanoma of the anal canal
has been radical surgery to include an abdominoperineal resection
(APR) with or without bilateral inguinal lymph node dissection,
especially for localized small tumors. However, the uniformly poor
prognosis of all patients has led many surgeons to question the
appropriateness of this very morbid approach. The current approach favors
wide local excision, reserving APR for those patients with bulky
disease in whom a wide local excision is not possible. Very few
patients present with isolated local recurrences; rather, most have
disseminated disease at the time of recurrence.
Unfortunately, the prognosis for anorectal melanoma remains poor.
It remains a biologically aggressive disease that is often systemic
at the time of diagnosis. It is poorly responsive to chemotherapy
or radiation; however, some encouragement has been noted in a recent
series of adjuvant chemoradiation after sphincter-sparing local
excision, borrowing on the lessons learned from other disease sites,
with an actuarial 5-year survival of 31% and actuarial
local control rate of 74%. In addition to chemoradiation, some
series have also used interferon-α with some improvement
in survival. The development of novel therapies to treat malignant
melanoma will hopefully improve the outlook for these patients.
Allal AS et al: Effectiveness of surgical salvage therapy for
patients with locally uncontrolled anal carcinoma after sphincter-conserving
treatment. Cancer 1999;86:405.
Ballo MT et al: Sphincter-sparing local excision and adjuvant
radiation for anal-rectal melanoma. J Clin Oncol 2002;20:4555.
Brady MS et al: Anorectal melanoma. A 64-year experience at
Memorial Sloan-Kettering Cancer Center. Dis Col Rectum 1995;38:146.
Doci R et al: Primary chemoradiation therapy with fluorouracil
and cisplatin for cancer of the anus: results in 35 consecutive
patients. J Clin Oncol 1996;14:3121.
Eng C et al: Chemotherapy and radiation of anal canal cancer:
the first approach. Surg Onc Clinics N Am 2004;13:309.
Ellenhorn JD et al: Salvage abdominoperineal resection following
combined chemotherapy and radiotherapy for epidermoid carcinoma
of the anus. Ann Surg Oncol 1994;1:105.
Epidermoid anal cancer: results from the UKCCCR randomised trial
of radiotherapy alone versus radiotherapy, 5-fluorouracil, and mitomycin.
UKCCCR Anal Cancer Trial Working Party. UK Co-ordinating Committee
on Cancer Research. Lancet 1996;348:1049.
Flam M et al: Role of mitomycin in combination with fluorouracil
and radiotherapy, and of salvage chemoradiation in the definitive
nonsurgical treatment of epidermoid carcinoma of the anal canal: results
of a phase III randomized intergroup study. J Clin Oncol 1996;14:2527.
Homsi J et al: Melanoma of the anal canal: a case series. Dis
Colon Rectum 2007;50:1004.
Klas JV et al: Malignant tumors of the anal canal: the spectrum
of disease, treatment, and outcomes. Cancer 1999;85:1686.
Myerson RJ et al: Carcinoma of the anal canal. Am J Clin Oncol
Peiffert D et al: Preliminary results of a phase II study of
high-dose radiation therapy and neoadjuvant plus concomitant 5-fluorouracil
with CDDP chemotherapy for patients with anal canal cancer: a French
cooperative study. Ann Oncol 1997;8:575.
Nilsson PJ et al: Salvage abdominoperineal resection in anal
epidermoid cancer. Br J Surg 2002;89:1425.
Pocard M et al: Results of salvage abdominoperineal resection
for anal cancer after radiotherapy. Dis Colon Rectum 1998;41:1488.
Smith DE et al: Cancer of the anal canal: treatment with chemotherapy
and low-dose radiation therapy. Radiology 1994;191:569.
Thibault C et al: Anorectal melanoma: an incurable disease?
Dis Col Rectum 1997;40:661.