Vaginal Cancer

Overview
Malignant diseases of the vagina are either primary vaginal cancers or metastatic
cancers from adjacent or distant organs. Primary vaginal cancers are defined as
arising solely from the vagina, with no involvement of the external cervical os
proximally or the vulva distally. The importance of this definition lies in the different
clinical approaches to the treatment of upper and lower vaginal cancer.
According to the International Federation of Gynecology and Obstetrics (FIGO), a
vaginal lesion involving the external os of the cervix should be considered cervical
cancer and treated as such; a tumor involving both the vulva and the vagina should
be considered vulvar cancer.

Relevant Anatomy
The vagina is located in the true pelvis, which also contains the rest of the internal
genital tract, the rectosigmoid, the bladder, the proximal urethra, and the pelvic
portions of the ureters. The pelvic organs are partially covered by the peritoneum.
The endopelvic fascia covers these organs and forms their supporting ligaments in
conjunction with the pelvic vasculature and musculature.
The pelvic cavity is divided into anterior and posterior compartments by the
transversely positioned broad ligament. The uterus is centered within the broad
ligament and is attached to the round ligaments, which run anterolaterally within
the broad ligament from the uterus to the pelvic wall.
Anterior and posterior cul-de-sacs

About 80% of vaginal cancers are metastatic, primarily from the cervix or
endometrium. Metastatic cancer from the vulva, ovaries, choriocarcinoma,
rectosigmoid, and bladder are less common. These cancers usually invade the
vagina directly. Cancers from distant sites that metastasize to the vagina through
the blood or lymphatic system also occur, including colon cancer, renal cell
carcinoma,melanoma, and breast cancer.
Although primary vaginal carcinoma is a rare gynecologic malignancy, its impact on
women's health should not be underestimated, especially when considering the
demographic increase in elderly women. As more women survive past age 60 years,
physicians need to consider the likelihood that more women will present with
vaginal cancer.
Because the 5-year survival rate of treated early stage vaginal cancer is significantly
higher than that of vaginal cancer in the advanced stages, early detection is key to
improving treatment outcomes. To improve outcomes of primary vaginal
carcinoma, select referral oncology centers should see additional cases per month
in order to plan appropriate randomized, prospective studies. This would increase
the experience of any of these centers in treating primary vaginal carcinoma.
History of pelvic exenteration
In 1946, Alexander Brunschwig published the first cases of pelvic exenteration. In
his first series, 5 of 22 surgical patients died from the operation itself. The original
procedure consisted of connecting the ureters to the colostomy. In 1950, Bricker
modified the procedure by isolating a loop of ileum, closing one end,
anastomosing the ureters to it, and bringing the patent end out as a stoma.[1] Since
then, several other modifications have improved the outcome of this procedure.
Today, with vaginal reconstruction and continent vesicostomy, the procedure is
accepted as a surgical treatment in selected cases.
Occurrence of vaginal cancer
Primary vaginal carcinoma is rare, constituting only 1-2% of all malignant
gynecologic tumors. It ranks fifth in frequency behind cancer of the uterus, cervix,
ovary, and vulva. The age-adjusted incidence in the United States is 0.6 per 100,000
population. The strict criteria used in defining vaginal carcinoma contribute to this
low incidence.
HPV vaccine
In June 2006, the Advisory Committee on Immunization Practices (ACIP) voted to
recommend the first vaccine developed to prevent cervical cancer and other
diseases caused by HPV type 6, 11, 16, and 18. The vaccine is almost 100% effective
in preventing precancerous lesions of the cervix, vulva and vagina, and genital warts
caused by the HPV 6, 11, 16, and 18. The FDA has approved Gardasil for girls and
women ages 9-26. In 2014, Gardasil 9 was approved to prevent disease from HPV
type 6, 11, 16, 18, 31, 33, 45, 52 and 58.
Patient education
For patient education information, see the Cancer Center and the Women's Health
Center, as well as Vaginal Bleeding, Colposcopy, Cervical Cancer, and Bladder
Control Problems.

The anterior cul-de-sac, also known as the vesicouterine pouch, is located between
the uterus and the bladder. It has small, lateral recesses known as the paravesical
fossae. This pouch ends where the cervix and the bladder connect and does not
extend down to the vagina.
The posterior cul-de-sac, known as the rectouterine pouch of Douglas, is located
between the uterus (posteriorly) and the rectum (anteriorly). It is continuous with
the pararectal fossae and contrary to the anterior pouch. It extends about 1-2cm
down to the vagina, separating the cervix from the rectum.
Vaginal structure
The vagina itself is a muscular tube that extends from the cervix to the hymenal
ring, penetrating the levator ani and the urogenital diaphragm. These latter
structures provide vaginal support inferiorly. From the outermost to the innermost
layers, the vagina is composed of an endopelvic fasciawhich contains an abundant
plexus of vessels, lymphatics, and nervesas well as outer longitudinal and inner
circular smooth muscle layers, submucosa, and mucosa.
Rectal and bladder pillars
The vagina is attached to the rectum posteriorly by the rectal pillars, while the
bladder pillars provide anterior vaginal attachment to the bladder. During vaginal
inspection with a speculum, the anterior and posterior sulci provide the anatomic
landmark of the site of attachment of these pillars. These are most easily observed
in nulliparous women.
The rectal and bladder pillars are paired, parallel, longitudinal, fibrovascular bundles
containing extensive vascular and lymphatic networks between the vagina and the
rectum and bladder, respectively. They both run the entire length of the vagina. The
bladder pillars also contain the paravaginal tissues (paracolpium).
As it joins the lower end of the cervix, the upper end of the bladder pillar forms the
vesicouterine ligament. This ligament forms a tunnel through which the ureters run
inferomedially to reach the inferolateral portion of the bladder. The tunnel divides
the vesicouterine ligament into anterior and posterior leaves. This anatomic
structure is important during radical hysterectomy when careful dissection of the
ligament is needed to mobilize the ureters. The rectal pillars receive the middle
rectal arteries from the cardinal ligament.
Cardinal ligaments
The cardinal ligaments are wedge-shaped fibrovascular bundles containing the
uterine, vaginal, inferior vesical, and middle rectal arteries and veins, as well as the
lymphatic system. On each side, they run from the lateral aspect of the cervix to the
lateral pelvic sidewall, traversing the pelvic plane at a 30 angle from the transverse
pelvic diameter and dividing the paravesical and paravaginal spaces from the
pararectal spaces.
On the pelvic wall, they insert on the endopelvic fascia and the hypogastric
vasculature. The anterior part of the cardinal ligament is more vascular, while the
posterior part is more fibrous and contains the autonomic system of the bladder
and rectum.

An important landmark is the uterine artery that crosses the anterior-most portion
of the cardinal ligament. The ureter enters the upper portion of the ligament
beneath this artery (water under the bridge) and 1-2cm lateral to the isthmus of the
uterus. The uterine veins cross below the ureters.
Uterosacral ligaments
The uterosacral ligaments run from the posterolateral aspect of the cervix to the
anterolateral part of the rectum. They are in close contact to the rectal pillars and
straddle the posterior cul-de-sac.

Table 1. Most Common Forms of Primary Carcinoma of the Vagina (Open Table in a
new window)

Histologic Type

Cases of
Vaginal
Carcinoma

Peak
Age

Spread

Characteristics

Squamous cell
carcinoma

85-87%

60y

Local,
blood,
lymphatic

Most common in
upper third of vagina

Local

Variant of squamous
cell, cauliflowerlike,
aggressive,
radiotherapy
contraindicated

Local,
blood,
lymphatic

Associated with in
utero exposure to
diethylstilbestrol
(DES), tubulocystic
pattern most
favorable prognosis,
late recurrence
common

60y

Local,
blood,
lymphatic

White women, lower

anterior vaginal wall,
size more
prognostically
significant than
invasion, poor
prognosis
Most common vaginal
cancer among
children, grapelike
mass, strap cells

Paravesical, pararectal, rectovaginal, and vesicovaginal spaces

Several avascular tissue planes are developed during pelvic surgery. The paravesical
space is bordered by the symphysis pubis anteriorly, the cardinal ligaments
posteriorly, the obliterated umbilical artery along the bladder medially, and the
obturator internus laterally.
The pararectal space is bordered by the cardinal ligament anteriorly, the sacrum
posteriorly, the rectum medially, and the hypogastric artery laterally. The
rectovaginal space is bounded by the vagina anteriorly and the rectum posteriorly,
while the rectal pillars form its lateral walls.

Verrucous carcinoma

Clear cell
adenocarcinoma

Rare

9%

60y

19y

The vesicovaginal space is limited laterally by the bladder pillars, anteriorly by the
bladder, and posteriorly by the vagina. To develop this space, the peritoneal
reflection of the anterior cul-de-sac is entered.
Levator ani
The levator ani forms the major support of the pelvic structures and is the major
component of the pelvic diaphragm. It is penetrated anteriorly by the rectum,
vagina, and urethra. It forms the floor of all the planes discussed above.

Melanoma

0.5-2%

Vaginal blood supply

The upper part of the vagina receives its blood supply from the uterine and the
internal pudendal arteries, from which the vaginal artery arises. The inferior rectal
artery and other branches arising from the internal pudendal artery supply the
lower vagina. The vaginal venous plexus mainly drains into the pelvic wall through
the parametrial veins, and to a lesser degree to the vesical and rectal plexuses.
Vaginal lymphatic system
Crossover of the vaginal lymphatic system is extensive. The middle to upper vagina
communicates superiorly with the cervical lymphatics and drains into the pelvic
obturator node, the internal and external iliac chains, and then the para-aortic
nodes. The distal third of the vagina drains to the inguinal and then the pelvic
nodes. The posterior wall lymphatics communicate with the rectal lymphatics and
drain to the inferior gluteal, sacral, and rectal nodes.
Surgical considerations
The vagina stays in close proximity to the bladder and urethra anteriorly, which
increases the risk of accidental injury to these structures during surgery. The
sigmoid, on the other hand, reflects away from the posterior vaginal wall at its
midpoint, facilitating an approach to the vagina posteriorly through the posterior
cul-de-sac and a developed rectovaginal plane.
Risk Factors
The etiology of vaginal cancer has not been identified. Note that vaginal cancer is
not histologically homogeneous; several types of lesions exist, each with its own
characteristics, age predilection, aggressiveness, and prognosis (see Table 1, below).
This suggests that a single etiologic factor is unlikely. Although some histologic types
of vaginal cancer have been associated with exposure to certain agents, so far no
clear cause-and-effect relationship has been found between any of those agents
and vaginal carcinoma.

Sarcoma botryoides
(embryonal
rhabdomyosarcoma)

Rare

3y

Local,
blood,
lymphatic

Endodermal sinus
tumor (yolk sac
tumor)

Very rare

10mo

Local

Aggressive, alphafetoprotein (AFP) as

marker

Wide
range

Local,
blood,
lymphatic

Grade is most
important prognostic
factor, can be
secondary to pelvic
irradiation

Leiomyosarcoma

< 2%

HPV and other infectious agents

The identification of HPV deoxyribonucleic acid (DNA) in squamous cell cancer cells
by in situ hybridization (21%) and southern blot hybridization (56%) strongly
suggests a possible role for HPV in the pathogenesis of squamous cell vaginal
carcinoma.[2, 3]
HPV subtypes 16 and 18 have the highest oncogenic potential and are most
commonly linked to dysplastic changes in the female genital tract. Because HPV is
sexually transmitted, this association raises the question as to whether women who
engage in high-risk sexual behaviors, such as sex with multiple partners, are at risk
for developing vaginal cancer.
Another association that strengthens the link between HPV infection and vaginal
cancer is the presence of a premalignant lesion in the vagina, known as vaginal
intraepithelial neoplasia (VAIN). Aho and coworkers reported that 5-9% of patients
treated for VAIN progressed to invasive carcinoma.[4] This suggested that VAIN may
be a precursor to vaginal cancer even though the incidence of VAIN in the United
States is 0.2-0.3 per 100,000 women[5] , which is less than the incidence of
diagnosed vaginal cancer. This is because of the fact that women with VAIN are

usually asymptomatic and that screening for VAIN is not recommended for the
general population. Still, the true malignant potential of VAIN needs to be clarified.
Other infectious agents that appear to be associated with vaginal cancer are herpes
simplex virus (HSV) and Trichomonas vaginalis. In 2000, Lee and colleagues reported
a case of rapidly progressive vaginal squamous cell carcinoma in a young woman
with a 2-year history of human immunodeficiency virus (HIV) infection.[6]They
suggested that young women infected with both HIV and HPV are at increased risk
for a more aggressive and less responsive vaginal cancer.
History of carcinoma
A history of cervical intraepithelial neoplasia (CIN), invasive cervical carcinoma, or
invasive vulvar carcinoma has also been associated with vaginal carcinoma. Several
studies indicate that up to 30% of patients with primary vaginal carcinoma have a
history of in situ or invasive carcinoma that was treated at least 5 years before
diagnosis.
Diethylstilbestrol
Diethylstilbestrol (DES), a drug previously used in the first trimester to prevent
pregnancy loss, has a strong association with clear cell adenocarcinoma of the
vagina. Herbst and colleagues first observed this association in 1971,[7] which led to
the discontinuation of DES that same year.
By 1987, the Registry for Hormonal Transplacental Carcinogenesis, established by
Herbst and Scully, identified 524 women with clear cell adenocarcinoma, but only
60% had a history of DES exposure. Disease in the other 40% of patients with no
history of DES exposure could be explained by recall bias or exposure to other
unidentified factors. Women with in utero exposure to DES are at higher risk of
developing adenocarcinoma than the general population. The estimated risk in
these women is 1 in 1000.
Prior hysterectomy
Although 59% of women with vaginal cancer had a prior hysterectomy, in a 1986
report, Herman and colleagues demonstrated that when age and prior cervical
cancer are controlled for, risk of vaginal cancer is not increased following
hysterectomy for benign disease.[8] Note that hysterectomy by itself is not a risk
factor; rather, women who underwent hysterectomy were poorly monitored.
Age
In a 2004 publication, Hellman et al reviewed 341 cases of primary carcinoma of the
vagina from 1956-1996 and suggested that the etiology of vaginal cancer may be
age related.[9] In younger women, the disease occurred in the upper part of the
vagina and seemed to be related to cervical dysplasia and HPV infection, while in
older patients, the tumors were exophytic. There was significant correlation with
late menarche, suggesting hormonal factors and trauma to the vagina as probable
etiologies.
Additional factors
Long-term pessary use and chronic irritation of vaginal mucosa in women with
procidentia have been associated with vaginal cancer. Other predisposing factors
include cigarette smoking, immunosuppressive therapy, chemotherapy, and
radiation therapy. Approximately 10% of women diagnosed with primary vaginal
carcinoma have a previous history of irradiation to the pelvis.
Pukkala and colleagues reported an association between low socioeconomic class in
Finland and an increased incidence of cervical, endometrial, and vaginal cancer.[10]
Pathogenesis
The presence of different stages of histologic differentiation in vaginal cancer
VAIN, carcinoma in situ, possible microinvasive carcinoma, and invasive cancer
suggests a continuum of transformation from less malignant to more invasive; this is
similar to the continuum described for cervical cancer.

HPV and history of carcinoma

On the other hand, the significant association of vaginal cancer with a history of
cervical or vulvar cancer suggests that the entire genital tract is at risk for squamous
cell carcinoma once malignancy has occurred anywhere along the tract; this is a
phenomenon known as the "field effect."[11]
HPV infection, which evidence indicates is associated with the pathogenesis of
squamous cell vaginal carcinoma, could explain this phenomenon, because HPV is
associated with cervical, vaginal, and vulvar disease.
Koyamatsu et al suggested that in cervical cancer, HPV 16 and 18 plays a common
causal role, that in vulvar cancer, p53 gene mutations are the main carcinogenic
cause, and that vaginal cancer has transitional characteristics between cervical and
vulvar cancer. The investigators did a comparative analysis of the presence of HPV
types 16 and 18 by polymerase chain reaction (PCR) assay and expression of p53
gene and Ki-67 antigen using immunohistochemistry in cervical, vaginal, and vulvar
cancer.[12] There was no significant difference in overexpression of Ki-67 antigen
among the 3 cancers.
Another explanation for the association between vaginal cancer and cervical and
vulvar carcinoma is that an occult residual disease such as VAIN is trapped within
the vaginal cuff posthysterectomy and goes unnoticed until it develops into invasive
carcinoma. This possibility illustrates the theory of the field effect and HPV
infection, because HPV has also been linked to VAIN. It also partially explains why
vaginal cancer in women who have undergone a hysterectomy goes unnoticed until
the patients present with advanced-stage vaginal carcinoma.
A third possibility for the association between vaginal cancer and carcinoma of the
cervix or vulva is radiation carcinogenesis.
Diethylstilbestrol
The pathogenesis by which DES may play a role in inducing clear cell
adenocarcinoma is unclear. In 1972, Forsberg and colleagues[13] proposed the
possibility of estrogen-induced maturation arrest of the mllerian ducts, and in
1984, Robboy and colleagues[14] suggested that atypical vaginal adenosis and
atypical cervical ectropion of the tuboendometrial type might act as the precursors
of clear cell adenocarcinoma of the vagina and cervix.
Vaginal irritation
Most vaginal cancers occur in the upper third of the vagina. Reports are
contradictory as to whether the anterolateral wall or the posterior wall is the more
frequent site. Reports suggesting that the upper posterior wall is the most common
site favor the hypothesis that irritating substances, such as vaginal secretions and
semen, pool in the posterior fornix and cause chronic irritation, which could lead to
induction of a carcinogenic process.
Metastasis
The proximity of the bladder anteriorly and the rectum posteriorly to the vagina
predisposes these organs to direct invasion by the tumor. Lymphatic dissemination
follows the lymphatic drainage of the vagina. The middle-to-upper vagina
communicates superiorly with the lymphatics of the cervix and drains into the pelvic
obturator node, the internal and external iliac chains, and then to the para-aortic
nodes.
The distal third of vagina drains to the inguinal node and then the pelvic node.
Posterior wall lymphatics communicate with rectal lymphatics and drain to the
inferior gluteal, sacral, and rectal nodes. Hematogenous dissemination to distant
sites includes the lungs, liver, bone, and skin. A submucosal lesion suggests that the
malignancy is metastatic via the vaginal lymphatics.
Patient History
The duration of symptoms in vaginal cancer averages 6-12 months before diagnosis,
with a range of 0-11 years. Delay in the diagnosis of vaginal carcinoma is not
uncommon; this is partially due to the rarity of the disease, as well as with delays in

relating patient symptoms to a vaginal origin. As expected, the longer the delay, the
more advanced the cancer once the diagnosis is made, resulting in a poorer
outcome.
Painless vaginal bleeding is the most common symptom, accounting for 65-80% of
all presentations. Bleeding is postmenopausal in about 70% of patients, which is
consistent with the peak age of 60 years for squamous cell carcinoma, the most
common type. Menorrhagia, intermenstrual bleeding, and postcoital bleeding have
also been reported.
Vaginal discharge occurs in 30% of patients, while 20% of patients report urinary
symptoms, which are caused by an anterior lesion compressing or invading the
bladder, the urethra, or both. This causes bladder pain, dysuria, urgency, and
hematuria.
About 15-30% of patients present with pelvic pain. Posterior lesions compress or
invade the rectosigmoid, which causes tenesmus or constipation.
Only 10% of patients report a vaginal mass or vaginal prolapse. In 2000, Eltabbakh
and coworkers reported a single patient who presented with a cystic pelvic mass
arising from the posterior vaginal wall that mimicked an ovarian neoplasm.[15]
About 10-27% of patients are asymptomatic; diagnosis is made during routine pelvic
examination. These patients tend to be caught at a much earlier stage than those
presenting with symptoms, and their prognosis is much better.
Screening
Routine screening
Routine screening for vaginal carcinoma is not justified for all patients, because it is
not cost effective. Women at risk, however, particularly those with a history of
cervical neoplasia and risky sexual behavior, should receive a Papanicolaou test on a
regular basis.
Screening after hysterectomy
Screening women with previous hysterectomy is controversial. In 1990, Manetta
and colleagues suggested that women with previous hysterectomy should be
counseled to continue their gynecologic cancer surveillance program.[16] They
reported that 63% of patients who were diagnosed after the onset of their
symptoms and who tended to have an unfavorable prognosis had undergone a prior
hysterectomy.
In a 1996 report, however, Pearce et al reviewed 9,610 vaginal smears from 5,682
women who underwent hysterectomy for benign gynecologic diseases and found
that the probability of an abnormal Papanicolaou smear in these women was 1.1%,
with a 0% positive predictive value for detecting vaginal cancer.[17] Similarly, in 2000,
Videlefsky et al[18] and Fetters et al concluded that routine vaginal cuff testing for
most patients who underwent hysterectomy for benign conditions is not indicated.
The American College of Obstetricians and Gynecologists recommends
discontinuing screening in women who have undergone hysterectomy for benign
diseases who have no prior history of high-grade cervical dysplasia. Women with a
history of CIN 2 or CIN 3 are at increased risk of developing recurrent dysplasia or
carcinoma of the vaginal cuff; therefore, in these women and in those in whom a
negative history of high-grade dysplasia could not be verified, screening after
hysterectomy should continue.[19]

During routine vaginal examination, the speculum blades should be rotated laterally
in order to visualize the anterior and posterior vaginal walls. Inspect all vaginal
mucosa while withdrawing the speculum. Vaginal cancer is multifocal and, although
it is typically located in the vaginal apex, the disease may involve any part of the
vagina. Visual inspection alone is not enough, and careful circumferential palpation
of the entire vagina is required in order to feel any raised or hardened areas.
Vaginal lesions, particularly when small and located in the lower third of the vagina,
are often missed during the first vaginal inspection because the blades of the
speculum normally cover the anterior and posterior vaginal walls. This can lead to
diagnostic delays. Frick and colleagues reported that about 19% of cases of vaginal
cancer were missed on initial examination.
Other reasons for delay are the rarity of vaginal carcinoma (1-2%) and the
attribution of patient symptoms to more common diseases, such as
postmenopausal bleeding and endometrial cancer.
All visible lesions should be biopsied using either Eppendorf or Kevorkian punch
biopsy forceps or similar instruments. Although the procedure is uncomfortable,
local anesthesia is not recommended, because it is as uncomfortable as the biopsy
itself. In elderly patients, particularly those with some degree of vaginal stenosis,
the examination should be performed under general anesthesia to allow adequate
biopsy.
Colposcopy
Patients with carcinoma in situ or very early invasive carcinoma are usually
asymptomatic. Diagnosis is made when a routine Papanicolaou smear identifies
abnormal cells. If the cervix is present, then the physician must rule out cervical
neoplasia, because cervical cancer is much more common than vaginal cancer.
After a cervical origin has been ruled out through colposcopy, then the physician
should perform a vaginal colposcopy. Because this is a time-consuming and difficult
procedure, especially in elderly patients, it should be done under general
anesthesia. Lugol iodine solution can help to identify regions to obtain biopsies
from; malignant cells lack glycogen and so, unlike healthy vaginal mucosa, do not
stain dark brown.
Because healthy vaginal epithelium needs to be estrogenized in order to have
sufficient glycogen, use of local estrogen cream for 1-2 weeks before examination
may be helpful for postmenopausal patients. Estrogen cream should be
discontinued 2 days prior to colposcopy.
Patients with previous hysterectomy and abnormal cytologic findings should also
undergo vaginal colposcopy. If no lesion is observed and the abnormal cytology
persists, then resecting the vaginal cuff may be considered because the lesion may
be buried in the closed vaginal cuff at the time of hysterectomy.
Histologic Findings
As mentioned before, primary vaginal carcinoma is not homogeneous. It is classified
into several histologic types, each with its own characteristics (see Table 1). The
following are brief descriptions of the most common types.
Squamous cell carcinoma

Screening in women exposed to DES

Squamous cell carcinoma is by far the most common type, accounting for 85-87% of
all cases of primary vaginal carcinoma. It generally occurs in women older than 50
years and peak incidence is in people aged 60 years; however, several cases have
been reported in women as young as 18 years.

Young girls who were exposed to DES in utero should be routinely examined starting
at puberty or at the age of 14 years. Examination includes cytologic screening of the
cervix and vagina, followed by careful inspection and palpation of the genital tract.
Staining with half-strength Lugol iodine helps to mark areas of adenosis. As long as
cytologic findings are negative, colposcopy is unnecessary.

Grossly, it appears as an ulcerating lesion (50%), a fungating mass (30%), or an

annular, constricting mass (20%). Secondary infections in an ulcerating tumor are
common. Histologically, it resembles squamous cell carcinoma arising from the
cervix, confusing the physician as to whether the lesion is cervical or vaginal in
origin. This illustrates the need for a strict definition of primary vaginal carcinoma.

Visual Examination, Palpation, and Biopsy

The most common site of occurrence is the upper third of the vagina. Because of
the thin vaginal wall, squamous cell carcinoma tends to spread early by directly
invading the bladder and rectal walls. It also metastasizes through the blood or
lymphatics. In 1981, Al-Kurdi and coworkers reported that about 28.6% of patients
had pelvic lymph node involvement upon diagnosis.[20] Squamous cell carcinoma can
metastasize to virtually any organ; cutaneous metastasis was reported by Plataniotis
and colleagues.[21]
Verrucous carcinoma
Verrucous carcinoma is rare in the vagina and is more commonly observed in the
vulva. It is observed in women older than 50 years and is considered a variant of
squamous cell carcinoma. Its clinical and pathologic characteristics are similar to
their vulvar counterparts.
On visual examination, verrucous carcinoma has a large, warty, cauliflowerlike
appearance similar to that of condylomata acuminata, but the papillary fronds lack
a central core of connective tissue.
Verrucous carcinoma is slow growing, locally aggressive, and rarely metastatic.
Radiation is contraindicated because it has been implicated in potentiating this
tumor to a more malignant phenotype.
Clear cell adenocarcinoma
This is the second most common type of primary vaginal carcinoma, accounting for
about 9% of all cases. Unlike squamous cell carcinoma, clear cell adenocarcinoma
manifests in patients at a very early age, usually after age 14 years, with peak
incidence in people aged 19 years. As discussed previously, an association with
intrauterine exposure to DES has been established. The estimated risk in the
exposed population is about 1 in 1000.
Clear cell adenocarcinoma is thought to arise mainly from areas of vaginal adenosis
but may also arise in wolffian rest elements, periurethral glands, and foci of
endometriosis. In patients who have not been exposed to DES, ectopic cervical
glands are a possible origin.
Grossly, vaginal adenosis appears as multiple cysts 0.5-4cm in diameter or as a
diffuse, erythematous, granular mucosal lesion. The cancerous lesion appears
polypoid, papillary, flat, or ulcerated.
Microscopically, 3 histologic patterns are predominant: tubulocystic, solid, and
papillary. The tubulocystic pattern has the most favorable outcome.
The tumor can spread by local invasion or by hematogenous or lymphatic
dissemination. Upon presentation, 70% of cases are stage I disease, but recurrence
is frequent and can occur as late as 20 years after initial therapy. Secondary tumors
from the colon, endometrium, cervix, breast, or ovary should be considered.
Melanoma
Vaginal melanoma is rare, accounting for 0.5-2% of all primary vaginal cancers.
Fewer than 150 cases have been reported. Vaginal melanoma tends to occur in
white women; it usually manifests in women older than 50 years, with peak
incidence in women aged 60 years.
Melanoma is most commonly found in the lower anterior vaginal wall. Grossly, it
appears as blue or black, soft, mucosal or submucosal nodules, but it may also be
nonpigmented and is frequently ulcerated, mimicking squamous cell carcinoma.
Histologically, it is similar to cutaneous melanoma, except that it is more invasive.
Melanoma is thought to arise from melanocytes, which are present in 3% of healthy
vaginas. The source probably is an aberrant melanocyte migration or melanocyte
metaplasia.
The Breslow and Clark systems are used as part of staging; however, because deep
invasion is invariably present upon presentation, tumor size, rather than depth, is a

more significant prognostic factor. Tumors tend to recur locally, and metastasis to
the lungs is common.
Sarcoma botryoides (embryonal rhabdomyosarcoma)
Although this tumor is rare, it is the most common vaginal cancer in children. It
manifests in girls younger than 8 years, with peak incidence in girls aged 3 years.
Sarcoma botryoides is highly malignant and very aggressive. Initially, it tends to
invade locally; it then metastasizes to the inguinal, pelvic, retroperitoneal, and
mediastinal lymph nodes, as well as to the lungs, pericardium, liver, kidney, and
bones.
Grossly, sarcoma botryoides occurs in 2 structural forms: solid and multicystic
grapelike. (The term botryoides comes from the Greek word botrys, which means
grapes.) It originates in the subepithelial layers and expands outward to fill the
vaginal cavity. Histologically, it is characterized by a loose, myxomatous stroma with
malignant pleomorphic cells and characteristic cross-striated rhabdomyoblasts
(strap cells), staining positively for muscle markers. Patients most commonly
present with abnormal vaginal bleeding; they occasionally present with a polypoid
mass protruding from the introitus.
Endodermal sinus tumor (yolk sac tumor)
This type of adenocarcinoma is very rare. It is classified as a germ cell tumor and
most commonly occurs in the ovary. It manifests in patients at a very young age,
usually girls younger than 2 years, and peak incidence is in babies aged 10 months.
To date, about 20 vaginal cases have been documented. Characteristically, it
secretes alpha-fetoprotein (AFP), which is frequently used as a marker of
recurrence.
Vaginal leiomyosarcoma
This tumor of smooth muscle origin is rare and accounts for fewer than 2% of all
primary vaginal cancers. It occurs over a wide patient age range, from 25 to 86
years, and may follow radiation therapy to the genital tract.
Grossly, vaginal leiomyosarcoma manifests as a bulky submucosal lesion, mainly in
the upper vagina. Histologically, it is similar to leiomyosarcoma of the uterus.
Tavassoli and Norris established the following microscopic criteria to diagnose
leiomyosarcoma of the vagina: moderate to marked atypia with 5 or more mitotic
figures per 10 high-power fields (HPF). Histologic grade is the most important
predictor of outcome.[22]
Treatment Determination and Staging
Once the diagnosis of cancer is established, staging should proceed to determine
the best treatment. As with the other gynecologic cancers, staging is done according
to FIGO classification. For vaginal cancer, staging is clinical and based on findings
during general examination, pelvic examination, cystoscopy (for anterior wall
tumors), proctoscopy (for posterior wall tumors), and chest radiography. If the
patient reports bone pain, then skeletal radiography should be performed to rule
out bone involvement.
Imaging
Computed tomography (CT) scanning or magnetic resonance imaging (MRI) of the
upper abdomen and pelvis are not FIGO recommendations, although they are
frequently performed because they help in establishing the presence of enlarged
lymph nodes, ureteral compression, hydronephrosis, and liver metastasis. Oudouxa
et al suggested that F-18 fluorodeoxyglucose positron emission tomography (FDGPET) scanning provides a more accurate assessment of the extent of disease in a
patient with malignant melanoma as compared with conventional methods.[23]
Antigen testing
Baseline levels of carcinoembryonic antigen (CEA), cancer antigen125 (CA-125),
and squamous cell carcinoma antigen are recommended because they are elevated
in patients with some carcinoma types.

for primary vaginal carcinoma, however, the investigators warned that the
treatment carries a high risk of severe complications.[27]

Evaluation for origin and metastasis of adenocarcinoma

Patients in whom adenocarcinoma is diagnosed should undergo thorough
exploration for possible metastasis, mainly in the uterus, cervix, ovary, and colon. In
these patients, a fractional dilatation and curettage is indicated to rule out
endometrial origin. A barium enema with either sigmoidoscopy or colonoscopy is
also indicated to rule out colonic origin. In addition, mammography, chest
radiography, and CT scanning of the abdomen or pelvis should follow. CA-125
should be taken as baseline for post-treatment follow-up.

Indications and Contraindications for Surgery

Indications
Consensus as to the proper treatment for vaginal carcinoma is lacking, mainly
because of the rarity of the disease. The most commonly used treatment modality is
radiotherapy. Surgery, with or without concomitant radiation therapy, is indicated
in the following conditions:

Surgical staging
Surgical staging is not usually required, but it is performed in selected
premenopausal patients prior to radiotherapy. In these patients, pretreatment
laparotomy allows the transposition of at least 1 ovary away from the field of
radiation. It also allows for better assessment of the extent of the disease through
dissection of the pelvic lymph nodes. In addition, for patients scheduled for
exenterative surgery, an exploratory laparotomy is required to rule out metastasis
or lateral spread to the pelvic sidewall before proceeding with exenteration.

FIGO classification
FIGO staging classification of vaginal carcinoma is as follows:

Stage 0 - Carcinoma is carcinoma in situ (VAIN)

Stage I - Carcinoma is limited to the vaginal wall
Stage II - Carcinoma involves subvaginal tissue but has not extended to the pelvic
wall
Stage III - Carcinoma extends to the pelvic wall
Stage IV - Carcinoma extends beyond the true pelvis or involves mucosa of
bladder or rectum; bullous edema as such precludes inclusion in the stage IV
classification
Stage Iva - Carcinoma invades bladder or rectal mucosa or directly extends
beyond the true pelvis
Stage IVb - Carcinoma spreads to distant organs
Radiation Treatment and Chemotherapy
Primary vaginal cancer is so rare that large, randomized, controlled treatment trials
are nearly impossible and, therefore, most treatment novelties are adopted from
those for more common cancers, such as cervical and anal cancers.[24]
In 1999, the National Cancer Institute issued a clinical alert as to the importance of
adding cisplatin-based chemotherapy concurrently with radiation in the treatment
of locally advanced cervical cancer. This chemoradiation regimen led to significant
improvement in progression-free and overall survival.[25] Since then, chemoradiation
therapy has largely replaced radiation alone in the treatment of primary vaginal
cancer.
By analyzing data from 17 population-based cancer registries participating in the
Surveillance, Epidemiology, and End Results (SEERS) program, Shirag et al noted a
survival advantage in women treated for primary vaginal cancer that was temporally
related to the advent of chemoradiation.[26]
A retrospective study by Greenwalt et al indicated that radiotherapy is a very
effective definitive treatment for primary vaginal carcinoma. In the study, 71
individuals with primary vaginal adenocarcinoma or squamous cell carcinoma
underwent either external-beam radiotherapy plus brachytherapy (93% of patients)
or brachytherapy alone (7% of patients); median follow-up was 6.24 years. For
patients with stage I disease, the cause-specific survival rate at both 5 and 10 years
was 96%, while for stage II patients, the 5- and 10-year survival rates were 75% and
68%, respectively, and for stage III patients, 69% and 64%, respectively. The survival
rate for stage IVA patients at both 5 and 10 years was 53%.[27]
As evaluated for all patients in the study, distant metastasis-free survival rates at 5
and 10 years were 87% and 85%, respectively. Despite the efficacy of radiotherapy

Squamous cell carcinoma - Stage I disease in the upper posterior vagina; stage IVa
disease, particularly in the presence of a rectovaginal or vesicovaginal fistula;
central recurrence after radiotherapy; ovary transposition in young patients prior
to radiotherapy
Clear cell adenocarcinoma - Although the etiology is different, the presentation
may be similar to that of squamous cell carcinoma.
Verrucous carcinoma - Radiation therapy is contraindicated because it has been
implicated in potentiating this tumor to a more malignant phenotype; therefore,
surgery is the only treatment
Other cases - Melanoma, sarcoma, embryonal rhabdomyosarcoma, endodermal
sinus tumor
Contraindications
Metastasis and extension to pelvic sidewalls are contraindications for exenteration.
Microscopic pelvic node involvement is more of a controversy than a
contraindication, and patients with positive pelvic nodes and no other poor
prognostic factors can be considered candidates for exenteration. Involvement of
both the pelvic and para-aortic nodes should warrant aborting the surgery.
Squamous Cell Carcinoma Surgery
Stage I disease
Stage I disease involving the upper posterior vagina is treated by radical
hysterectomy, partial vaginectomy, and bilateral pelvic lymphadenectomy.
Lymphadenectomy is required to ensure that metastatic disease is not present.
If the patient had a previous hysterectomy, then a radical upper vaginectomy with
pelvic lymphadenectomy is performed after the paravesicular and pararectal spaces
are developed to avoid injury to the bladder and rectum, respectively. Each ureter is
also dissected out to its point of entry into the bladder.
If the lesion is multifocal or if it extends to the lower third of the vagina, inguinal
lymphadenectomy should also be performed, and a total vaginectomy is required. If
the depth of the invasion is questioned during the operation, then a frozen section
from the margins should be taken to ensure that tumor resection was adequate.
In general, tumors of the upper posterior wall are more operable because the
sigmoid reflects away from the posterior vaginal wall while the entire length of the
anterior vaginal wall stays in close proximity to the bladder. A lower vaginal lesion
can be treated with radical hemivulvectomy and lower vaginectomy with bilateral
inguinal node dissection. Radiation therapy is commonly used as an alternative to
surgery.
Stage II, III, and IV disease
Stages II and III are treated with radiation therapy. In premenopausal patients, a
pretreatment laparotomy is performed in order to transpose the ovaries away from
the field of radiation and to resect any enlarged lymph nodes. If the patient has a
central recurrence with no signs of metastasis after radiotherapy, then pelvic
exenteration is the only option.
Patients with stage IVa disease have the option of radiation therapy or pelvic
exenteration. The latter is highly recommended if a rectovaginal or vesicovaginal
fistula is present. Stage IVb is a contraindication for surgery.

Clear Cell Adenocarcinoma Surgery

Therapeutic considerations are very similar to those for patients with squamous cell
carcinoma, although most patients are young, and every effort should be made to
preserve functional ovaries and a functional vagina. Surgery is the primary
treatment modality.
In stage I and early stage II disease, radical hysterectomy, pelvic lymphadenectomy,
and vaginectomy with split-thickness skin graft have been successful.
Alternatively, in 1987, Senekjian and colleagues reported a 5-year survival rate of
92% for patients with very early, small lesions treated by wide local excision,
laparotomy for retroperitoneal lymphadenectomy, and local irradiation to the
immediate adjacent tissues.[28] The best candidates are patients with tumors of less
than 2cm in diameter, a predominant tubulocystic pattern, and a depth of invasion
of less than 3cm.
If radiation is used as the sole treatment, then transposition of at least 1 ovary up
into the paracolic gutter beyond the radiation field should be done with pelvic
lymph node dissection.
Local excision without radiation is not recommended, since Herbst and colleagues
reported that 16% of patients with stage I disease have positive pelvic nodes. Pelvic
exenteration is done for central recurrences after primary irradiation.
Matthews et al presented a case report on a fertility-sparing procedure, a radical
abdominal trachelectomy and upper vaginectomy performed on a 22-year-old
woman with clinical stage I vaginal clear cell adenocarcinoma in the left fornix. The
authors found 28 months after the initial surgery that the woman had no evidence
of recurrence and was having regular menstrual cycles. The authors concluded that
this procedure can be considered to conserve fertility in young women.[29]

Note that whenever vaginal mucosa is left in situ after partial or subtotal
vaginectomy, frozen sections should be obtained to exclude lateral superficial
spread, because the most common site of initial recurrence is the vagina.
Conservative therapy
Conservative management includes wide local excision and simple hysterectomy
combined with radiotherapy and/or chemotherapy. Radiation therapy with highdose fractions (>400cGy/fx) has been effective in selected patients. This type of
response is consistent with the higher response rate seen with cutaneous
melanoma when large, individual fractions are compared with conventional
fractionation.
Irvin et al reported in their case series higher locoregional control using wide local
excision followed by high-dose fractionation teletherapy, compared with more
radical surgical resection.[36]
Tumor Excision and Vaginal Resection in Other Cancers
Verrucous carcinoma
As mentioned previously, radiation therapy is contraindicated in verrucous
carcinoma because it tends to induce aggressive cancer types. The only treatment
option is surgical resection. If the lesion is small, a wide surgical excision is
performed. With larger lesions, vaginectomy or exenteration is recommended.
Because this tumor rarely metastasizes, dissecting the lymph nodes is unnecessary
unless they appear enlarged.
Sarcoma botryoides

Melanoma Surgery

Because the typical patient is prepubertal, preserve ovarian function and

reproductive organs. Currently, a conservative approach is used instead of
exenterative surgery. Preoperative and/or postoperative chemotherapy and
radiotherapy improve the outcome.

The best treatment for vaginal melanoma remains controversial. Radical surgery has
been the main treatment modality, although a more conservative approach has
been advocated by some authors. For example, Reid et al, in 1989,[30] and Buchanan
et al, in 1998,[31] , showed no significant difference in 5-year survival rates or
disease-free intervals for radical versus conservative surgery.

For small, easily resectable tumors, the lesion is excised. Chemotherapy VAC
(vincristine, actinomycin D, and cyclophosphamide) and radiotherapy follow. If the
tumor is bulky, preoperative chemotherapy or radiotherapy is administered before
the lesion is excised.

On the other hand, in 1994, Van Nostrand and colleagues demonstrated that radical
surgery had a significant 2-year survival advantage over conservative surgery (48%
vs 20%, respectively); they recommended a radical approach to patients with
lesions smaller than 10cm2.[32]
Detection of lymph node involvement
Recently, detection of nodal involvement prior to radical procedures has been
suggested because positive lymph nodes indicate poor prognosis and radical surgery
might be unjustified. Siu et al used laparoscopic ultrasonography to successfully
detect enlarged pelvic lymph nodes.[33]
Rodier et al used technetium-99m (99m Tc)-sulfur colloid injected around the lesion
and detected the sentinel lymph node with hot spot by
lymphoscintigraphy.[34]Nakagawa et al succeeded in evaluating the sentinel lymph
node to decide the extent of surgery using a dye injection method[35] ; 1mL of
methylene blue was injected into the subcutaneous layer at the boundary between
the lesion and the vaginal mucosa, followed by incision in the ipsilateral groin to
detect the stained lymph node.
Radical surgery
Radical surgery varies depending on tumor size and location. Small lesions in the
upper vagina are treated by radical hysterectomy, subtotal vaginectomy, and pelvic
lymphadenectomy. Lesions in the lower vagina are managed by partial vaginectomy,
total or partial vulvectomy, and bilateral inguinal lymphadenectomy. Larger and
more invasive lesions (>3 mm) are treated with exenterative surgery.

Endodermal sinus tumor

This very rare tumor is treated with chemotherapy VAC to reduce the tumor size.
Chemotherapy is followed by partial colpectomy, radiotherapy, or both.
Vaginal leiomyosarcoma
These tumors vary in their malignancy depending on how well they are
differentiated. Well-differentiated tumors are less likely to metastasize and are
managed by surgical excision. Frozen sections are taken to ensure that the tumor is
well contained within the surgical margins. Poorly differentiated tumors should
receive adjuvant radiotherapy.
Preoperative Evaluation for Exenterative Surgery
The first and most important requirement for exenterative surgery is that the
patient have no underlying medical illnesses. The patient must be fit for a prolonged
operation with potential blood loss and major fluid shifts. A psychological evaluation
is also necessary; owing to postoperative physical and physiologic changes, the
patient must have a stable personality and a supportive social environment.
Signs of systemic spread should be absent. Evaluation starts with a physical
examination, which includes palpation of all peripheral lymph nodes, especially the
inguinal and supraclavicular nodes. The clinical triad of unilateral leg edema, sciatic
pain, and ureteral obstruction suggest involvement of the posterolateral pelvic
sidewall, which is a sign of lack of resectability. (Thus, extension of the tumor into
the pelvic sidewall is a contraindication to the procedure.) Each sign by itself is not a
contraindication for exploratory laparotomy, although each is associated with

decreased probability of resection and decreased probability of long-term survival,

even if the cancer is resected with clear margins.

The patient should also expect an alteration in her physical appearance and
physiologic function, such as the presence of stomas, and should understand the
possible psychological impact such alteration will have on her.

Realize that age by itself is not a contraindication; the patient's health is the first
prerequisite for considering pelvic exenteration.

The patient should be offered vaginal reconstruction and be given the option, if it
exists, to choose the donor sites for skin grafts and musculocutaneous flaps.[38]

Imaging
Most importantly, the patient should know that despite the radical nature of the
surgery, cure is not guaranteed.

Chest radiography or CT scanning of the chest, upper abdomen, and pelvis are
mandatory to rule out lung, liver, and para-aortic metastasis, respectively. Any
suspicious lymph node should undergo fine-needle aspiration cytology to rule out
metastasis. In a 1989 report, Manetta and colleagues dismissed the need to biopsy
nonsuspicious supraclavicular lymph nodes in a random fashion.

Preoperative Preparation for Pelvic Exenteration

Mechanical bowel preparation
Mechanical bowel preparation was the standard practice and typically began 2 days
prior to the operation to reduce the incidence of postoperative infectious
complications. In a 1977 report, Clarke and colleagues demonstrated that
preoperative oral antibiotics reduce septic complications of colon surgery from 43%
in unprepared patients to 9% in prepared patients.[39]

Unfortunately, neither CT scanning nor MRI is sensitive and specific enough to rule
out pelvic sidewall involvement. This is because radiation fibrosis and chronic
inflammation cannot be differentiated from cancer with these techniques.
Laparotomy and biopsy

However, a meta-analysis of several randomized clinical trials involving patients

who had colorectal surgery, comparing outcomes in those who underwent
mechanical bowel preparation with those in patients who did not have such
preparation, failed to show any benefit from bowel preparation. The report also
found a significant increase in anastomotic leakages in patients who underwent
bowel preparation (specifically, those who underwent preparation with
polyethylene glycol) compared with those who did not (5.6% vs 3.2%,
respectively).[40, 41]

If resectability is questionable, then an exploratory laparotomy with parametrial

biopsies should be performed to rule out pelvic wall involvement. Alternatively,
laparoscopy could be performed to obtain a biopsy from the pelvic wall and any
suspicious lymph nodes. Miller and colleagues reported that nearly 30% of patients
undergoing exploratory laparotomy had unresectable cancer because of peritoneal
disease (44%), lymph node metastasis (40%), parametrial fixation (13%), and
hepatic or bowel involvement (4.5%).[37]
Nutritional assessment and laboratory studies

No similar clinical trials have been conducted on major gynecologic surgery; the
practice of mechanical bowel preparation depends on the surgeon's preference and
should be individualized to the patient.

Nutritional assessment is an important preoperative consideration because

malnourished patients are at higher intraoperative and postoperative risk.
Anthropometrics, serum electrolytes, total serum protein, albumin, transferrin, and
immunologic function need to be evaluated. The latter is assessed by calculating the
absolute lymphocyte count (reference range is >2000/mm3) and by examining
delayed cutaneous hypersensitivity responses to skin test antigens.

Antibiotic prophylaxis
Prophylactic antibiotics are administered intravenously or intramuscularly within 1
hour before incision. Cefazolin 1g (2g if the patients body mass index [BMI]
>35kg/m2) is most commonly used, due to its longer half-life of 1.8 hours and low
cost. Bacterial vaginosis should be treated prior to the surgery.[42]

Renal evaluation
Kidney function must be evaluated because the patient is at risk for massive fluid
shifts and major blood loss and because urinary diversion is likely to be performed.
A complete urine analysis with serum creatinine provides a good evaluation.

Thromboembolic prophylaxis
Because of the high risk of thromboembolic diseases in this category of patients,
vascular thromboembolic prophylaxis is recommended using either low-dose
unfractionated heparin (LDUH, 5000 units 2 hours prior to surgery and every 8
hours postoperatively), low-molecular weight heparin (LMWH, 12 hours prior to
surgery and daily postoperatively), or intermittent pneumatic compressors (IPC,
starting immediately before surgery and used continuously until the patient
ambulates).

Hematologic evaluation
A complete blood count (CBC) is required, and hemostatic function is evaluated
through patient history of bleeding and family history of coagulopathy. Also,
prothrombin time (PT) and activated partial thromboplastin time (aPTT) are
required because cancer is associated with coagulation abnormalities.
Cardiac evaluation

Although no randomized clinical trials have been performed, using a combination of

LMWH or LDUH with IPC has also been recommended for these high-risk
patients.[43]

Consult an electrocardiography (ECG) specialist and cardiologist. Clear the patient

from cardiac risks before surgery because most patients are older than 50 years and
may have underlying coronary heart disease. Also, the surgery is radical in nature,
with unavoidable blood and fluid losses.

Arterial evaluation for reconstruction

If vaginal reconstruction is desired and a transpelvic rectus abdominis
myocutaneous pedicle (TRAM) flap is considered, then the left epigastric artery
should be evaluated in patients with prior pelvic surgery, prior transverse
abdominal incision, or abdominoplasty. Preoperative evaluation of epigastric
patency can be performed with preoperative arteriography or intraoperative
Doppler ultrasonography.

Patient Counseling in Exenterative Surgery

Once the patient is medically cleared for surgery, she should undergo extensive
preoperative counseling. During counseling, the patient should be informed that
preoperative evaluation of tumor resectability is not as accurate as intraoperative
assessment; therefore, the possibility of aborting the procedure still exists.
The patient should also be informed of the radical nature of the surgery and of all
possible intraoperative and postoperative complications, including intraoperative
mortality. She should be informed that intraoperative and postoperative blood
product administration is inevitable and that a postoperative stay in the intensive
care unit (ICU) and prolonged hospitalization are common.

Preoperative bowel preparation

The protocol for preoperative bowel preparation is as follows:

Preoperative day 2 - Clear-liquid diet; tap water or Fleet enema at night (optional)

Preoperative day 1 - Clear-liquid diet; 1 bottle of mineral oil or 2L polyethylene

glycol at 8 am; oral neomycin base, 1g every 4 hours for 3 doses; oral
erythromycin base, 1g every 4 hours for 3 doses; tap water or Fleet enema
repeated until no solid stool at night
Operative day 0 - Fleet enema repeated until clear
Intraoperative Details of Pelvic Exenteration
Pelvic exenteration is classified as follows:

Total exenteration for apical lesions involving the bladder and rectum
Anterior exenteration for anterior lesions involving the bladder
Posterior exenteration for posterior lesions involving the rectum
Procedure
The patient is placed in the low lithotomy position with stirrups supporting the hips,
thighs, and knees. This allows surgeons to work on the abdominal and perineal
areas at the same time. Intermittent pneumatic compression of the calves should be
continued and deep vein thrombosis (DVT) prophylaxis given preoperatively. An
epidural catheter for postoperative pain control is inserted before general
anesthesia. A number 16 Foley catheter is placed in the bladder and connected to
straight drainage. A nasogastric (NG) tube is inserted. The stoma sites are marked.
A midline abdominal incision is made from the symphysis pubis to a point
approximately 3cm above and to the left of the umbilicus. This allows adequate
exploration of the upper abdomen (eg, liver and omentum) and good exposure for
pelvic surgery. The liver, omentum, abdominal peritoneum, and para-aortic nodes
should be carefully palpated and the rest of the abdomen explored. Obtain biopsies
from suspicious areas and send them for frozen section.
If pelvic nodes are involved, then bilateral frozen sections of the para-aortic nodes
should be taken before continuing the operation. These should be sent for frozen
section. The operation should be aborted if the frozen sections are positive for
malignancy, if both pelvic and para-aortic nodes are positive, if peritoneal
breakthrough of the tumor has occurred, or if tumor implants are present in the
abdomen or pelvis.
The round ligaments are then cut at the pelvic sidewall, and the anterior and
posterior leaves of the broad ligament are opened. The prevesical, paravesical,
pararectal, and presacral spaces are all developed. Any enlarged lymph node is
removed and sent for frozen section. If the lateral pelvic walls and ligaments are not
invaded by the tumor, the operation is continued.
The anterior division of the internal iliac arteries is ligated bilaterally just after they
cross the internal iliac veins. This cuts the blood supply of the uterine, vesical, and
obliterated umbilical arteries. The hypogastric artery is left untouched, as it carries
the blood supply to the internal pudendal and inferior hemorrhoidal arteries, which
constitute the main circulation to the anal canal and lower rectum. The latter are
needed to perform a low rectal anastomosis. Another artery of importance is the
obturator artery, which supplies the gracilis muscle used for vaginal reconstruction
(neovagina).

In the perineal phase, the urethra and anterior vagina are removed. A long, curved
clamp is placed beneath the pubis and directed caudad and anterior to the urethra.
Another clamp is placed lateral to the pubourethral ligaments and directed out
under the symphysis pubis at the 2-o'clock position and then at the 10-o'clock
position. This isolates the right and left pubourethral ligaments for division. The
anterior vaginal wall is incised with at least 4cm of margin under direct vision from
the vaginal side. The levator ani is divided anterior to rectum, allowing removal of
the specimen that includes the urethra and anterior vagina.
Abdominal phase
In the abdominal phase, the ureters are transected below the level of the common
iliac arteries. The bladder is separated from the retropubic space, and the lateral
vesicle attachments are sharply incised. The uterosacral ligaments are cut, and the
uterus is removed with the bladder, fallopian tubes, and ovaries.
An omental J-flap is made by incising the omental attachment to the colon from the
hepatic flexure medially to the midportion of the stomach. The left gastroepiploic
artery provides the blood supply to this pedicle.
The flap is mobilized and brought down to the left pelvic gutter and into the pelvis,
where it is sewn to the posterior vaginal mucosal over the rectum and to the pelvic
sidewalls. It will be used to cover the denuded area of the rectum and provide a
receptacle for neovaginal construction by a split-thickness skin graft. In 1984, Hatch
described the use of the bulbocavernosus flap if there is not enough omentum. A
continent vesicostomy is constructed, and Hemovac drains are placed in the pelvis.
Supralevator total exenteration
This procedure is similar to anterior exenteration, except that the rectum involved
by the tumor is removed en bloc with the whole vagina, cervix, uterus, and bladder.
It differs from the classic total exenteration by the performance of a low rectal
anastomosis, as opposed to a permanent colostomy. This procedure became
possible with the advent of circular stapling. In order to perform this anastomosis,
the anal canal and the levator ani should be free of any tumor involvement and
preserved during surgery.
The sigmoid is usually divided to allow for better exposure and development of the
presacral space. The superior rectal and middle rectal arteries are ligated and
severed, which allows the rectum to be cut from its blood supply.
The vaginal mucosa is incised about 1-2cm inside the hymenal ring. The bladder,
vagina, and urethra are detached from the pelvic walls above the levator ani, so
they are loose and attached only by the rectum.
Using a thoracoabdominal stapling device, the rectum is resected at its lower end,
which leaves a 4cm margin, and the whole specimen is removed en bloc. Before
applying the stapling device, continuous cephalad traction is applied to the rectum
while its base is held above the levator ani. This provides adequate exposure of the
rectum and easy access for the stapling device.
Preservation of the lower rectum

The cardinal ligaments are divided at the sidewall; the rectal attachment to the
sacrum and the vaginal attachment to the tendinous arch are divided. At this point,
the rectum and the vagina are completely mobilized, allowing free access to the
pubococcygeus muscle. The site of excision of the pubococcygeus muscle depends
on whether an anterior or total exenteration will be performed.
Anterior exenteration
The aim is to remove the uterus, cervix, bladder, urethra, and anterior vagina while
preserving the rectum and posterior vagina. This procedure is divided into a
perineal phase and an abdominal phase. Intraoperative, bimanual palpation ensures
that the mass is completely resected.
Perineal phase

Preserving enough of the lower rectum to allow the patient good continence and
stool storage after the low rectal anastomosis is advisable. This step is performed by
first severing the sigmoidal arteries in order to mobilize the left colon. The inferior
mesenteric arteries are preserved because they will supply the sigmoid. A colonic Jpouch is formed from the sigmoid, and the low anastomosis to the stump of the
lower rectum is performed using the stapling device. As with the anterior
exenteration, the omentum is mobilized and used to cover the denuded pelvic area
and reinforce the stapled anastomosis.
Continent vesicostomy and neovaginal construction
Continent vesicostomy and neovaginal construction are performed. Unlike the
neovagina constructed in anterior exenteration, in which the posterior vaginal wall
is preserved, the omentum in this case may be insufficient for a split-thickness skin

graft. For this reason, the rectus abdominis muscle or the gracilis muscles in the
medial thigh are good alternatives as a source of a myocutaneous graft.
Classic total exenteration
This procedure is indicated when the levator ani are involved and need to be
resected with the rest of the anus. The procedure is similar to the supralevator total
exenteration; however, after mobilizing the whole specimen, a perineal incision is
made around the anus, leaving a generous margin from the center of the tumor.
The anococcygeal and pubococcygeal muscles are divided along the margin.
This procedure results in a large defect in the perineum, and reconstruction is done
using the bilateral gracilis or the rectus abdominis muscles as a myocutaneous flap
to fill in the defect. The omentum flap is used as a protective barrier against
potential intestinal adhesions, and it provides additional blood supply to the
reconstructed pelvis and perineum. A permanent colostomy and continent
vesicostomy are performed.
Posterior exenteration
The procedure is similar to total exenteration, but the bladder and urethra are
preserved.
Vaginal Reconstruction
A neovagina can be constructed in several ways. The procedure depends on how
much vaginal tissue is preserved after the exenteration as well as the size of the
pelvic or perineal defect.
Split-thickness graft
A split-thickness graft is usually used when an anterior or a supralevator
exenteration has been performed, because these procedures leave a smaller defect.
The mobilized omentum is used to create a pocket to receive the neovagina. A splitthickness skin graft is obtained from either the buttock (cosmetic advantage) or the
anterior or medial thigh (more accessible and more comfortable postoperatively).
The skin graft is sewn over a vaginal stent, preferably a Heyer-Schulte stent because
it is inflatable and has its own drainage. The stent is inserted through the introitus
into the omental pocket, which provides a blood supply to the graft.
Myocutaneous flaps
Myocutaneous flaps are preferred whenever the defect is larger, such as after a
total exenteration. The 2 most common flaps are the TRAM flap and the gracilis
myocutaneous flap.
TRAM flap
For a TRAM flap, the rectus abdominis on the side of the abdominal incision is used.
The full thickness of the muscle, fascia, and skin are sutured from side to side, with
one end left open and the skin facing the inside, which forms a tubular
musculocutaneous mass. The tubular neovagina is mobilized into the pelvis, and the
open end is sutured to the intact vaginal introitus.
Gracilis myocutaneous flap
For a gracilis myocutaneous flap, 2 flaps are needed. They are obtained from both
medial thighs after incising the overlying skin and transecting the gracilis muscles
distally. On each side, the flap is mobilized beneath a skin bridge of the vulva, which
separates the vaginal introitus from the proximal pedicle. The flap should be about
5 X 10cm to be adequate.
The 2 flaps are sutured end to end into a cylindrical shape, with the skin facing the
inside. The neovagina is inserted into the pelvis, and the open end is sutured to the
introitus. The apex is sutured to the symphysis pubis and to the anterior sacrum.
Finally, the omentum is mobilized to cover the neovagina and the rest of the pelvic
floor.

The disadvantage of the gracilis myocutaneous flap is the presence of incisions on

both inner thighs; the TRAM flap requires no additional incisions. A disadvantage of
the TRAM flap, however, is that a limited amount of tissue can be mobilized from
the anterior abdomen without causing much tension during closure of the
abdominal incision and creating an abdominal wall distortion.
Vulvobulbocavernosus pedicle
A third myocutaneous flap, the vulvobulbocavernosus pedicle, was described in
1984 by Hatch in the construction of a neovagina after exenteration.[44] Originally,
this pedicle was used in repairing radiation-induced rectovaginal fistulae (Martius
procedure). An incision is made over each labia majora, and the bulbocavernosus
muscles are mobilized on their posterior pedicles by transecting them anteriorly.
Each flap is tunneled under the skin just lateral to the posterior introitus, and once
inside the perineal defect, they are sutured together, forming a neovagina.
Radical Hysterectomy
The objective of a radical hysterectomy is resection of the tissue adjacent to the
cervix and vaginal fornices, along with removal of the uterus and cervix and the part
of the vagina involved by the lesion, while preserving a functional urinary apparatus
and rectum.
The procedure starts with a midline incision as previously described for
exenteration. Alternatively, a low transverse Maylard or Cherney incision provides
adequate exposure to the pelvis but not enough to explore the entire abdomen. For
this reason, a midline incision is preferable. Abdominal exploration is performed as
previously described.
Steady upward traction is applied to the uterus, and the retroperitoneum is entered
through the round ligaments on both sides. Once the ureter is identified as it
crosses the pelvic rim, the pelvic spaces are developed as before. The vesicouterine
fold of the peritoneum is opened, and the bladder is dissected away from the cervix
and upper vagina. If the bladder is involved, then an anterior exenteration is
performed. The uterine artery is ligated at its origin from the superior vesicle or
internal iliac artery and then mobilized over the ureter. The uterine veins are
clipped to avoid excessive bleeding.
The anterior vesicouterine ligament, which forms the roof of the uteric tunnel, is
carefully dissected. This allows mobilization of the ureters off their peritoneal
attachments and away from the uterus. Care must be taken to avoid severing the
blood supply to the ureters. Once this is done, the posterior vesicouterine ligament
could be divided. This frees the uterus from its anterior attachments in the pelvis.
Posteriorly, the peritoneum over the Douglas pouch is incised and the rectovaginal
space developed by applying smooth traction on the rectum. This allows dissection
and division of the uterosacral ligaments midway from the sacrum, which frees the
uterus from its posterior attachment in the pelvis. To release the uterus from its
lateral pelvic attachment, the cardinal ligaments are clamped and divided at the
level of the pelvic sidewall, all the way across the paravaginal tissues down to the
vagina.
If the ovaries are to be preserved, then the ovarian ligaments and fallopian tubes
are transected. Otherwise, the infundibulopelvic ligaments are divided and the
ovaries are freed from the pelvic attachments and removed with the uterus.
A vaginectomy is performed by continuing the dissection of the vesicovaginal and
rectovaginal spaces and dividing the bladder and rectal pillars down to the pelvic
floor. The vagina is entered anteriorly and transected at the desired level using a
knife or scissors. The vault is closed, and the vaginal angles are sutured to the
paravaginal tissues. The pelvic peritoneum is not closed, and drains are used only if
doubt exists regarding the adequacy of hemostasis. In 1993, Jensen and colleagues
reported that drains may increase febrile morbidity, pelvic cellulitis, and
postoperative ileus.[45] A suprapubic catheter is placed in the bladder.
Vaginectomy

Radical vaginectomy is employed for invasive vaginal carcinoma, while simple

vaginectomy is performed in cases of VAIN.

Ganz catheter is J-wired and a central line is placed for total parenteral nutrition
(TPN), usually on postoperative day 2 or 3.

Vaginectomy may be partial, subtotal, or total, depending on the extent of the

disease, how well-circumscribed the lesion is, and whether it is multifocal. The
excision should include 2cm of normal vagina distal to the lesion and the entire
vagina proximal to the lesion. If more than a third of the upper vagina is removed,
then vaginal reconstruction using a split-thickness skin graft is required in order to
have normal sexual function.

Antibiotic prophylaxis is discontinued after 48 hours if no postoperative fever has

been reported. Otherwise, the antibiotic is changed according to the fever workup
and cultures are obtained. If the cultures are negative for infection, then the
antibiotics should be changed to cover anaerobic and gram-negative organisms.

Simple vaginectomy
Simple vaginectomy is indicated when invasion is suspected in a patient with VAIN.
The approach usually is vaginal. In postmenopausal women with poorly
estrogenized vaginal mucosa, estrogen cream can be used 2-4 weeks prior to the
operation. Lugol solution is used to delineate the abnormal mucosa. Injecting saline
solution into the submucosa elevates the lesion from the underlying tissue layer and
helps in the excision. Usually, a 3-5mm margin of healthy mucosa is adequate. For
lesions located in the upper vagina, sutures are placed in the apex to place traction
and the upper vagina is excised. The bladder and rectal pillars (lymph vascular
pillars) are transected from their vaginal attachments. Blunt dissection is used to
further remove the specimen. The surgeon must keep in mind the proximity of the
ureters to the corners of the apex. The vagina is closed with interrupted
biodegradable sutures.
Radical vaginectomy
When the uterus is in situ, radical vaginectomy can be approached vaginally or
abdominally. If two thirds of the vagina needs to be removed, however, a combined
approach is required to mobilize the distant vagina. In patients with previous
hysterectomy, the abdominal approach or a combined approach is required because
of a higher risk of injury to the ureters during resection of the cardinal ligaments
and the proximal bladder pillars.
The vesicovaginal (anterior), rectovaginal (posterior), and 2 lateral paravaginal
spaces are developed, and the bladder and rectal pillars are transected at their
attachments to the bladder and rectum, respectively (as opposed to their vaginal
attachments in simple vaginectomy). The ureters should be dissected away before
resection of the vagina with the cardinal and vesicouterine ligaments. The specimen
is resected in a manner similar to that used in simple vaginectomy.
Postoperative Details
The NG tube is removed in the recovery room or at the end of the surgery. Upon
admission to the recovery room, chest radiography is performed to rule out
pneumothorax and to check the tip of the central line. When stabilized, the patient
is transferred to the ICU.

Check stomas daily for evidence of vascular perfusion. If a stoma becomes dusky,
then a scope is introduced to check the condition of the underlying bowel. Once
bowel sounds are auscultated and the patient passes flatus, then oral feeding is
initiated; the TPN is withdrawn when oral intake is adequate.
Intermittent, pneumatic calf compression is continued until the patient is fully
ambulatory. Ambulation should begin as soon as the patient's strength is regained
and pain is well controlled.
Postoperative Follow-Up
Regarding outcome and prognosis, the main concern of the patient and physician is
the possibility of recurrence of the primary disease.
After surgery, monitor the patient for complications and any sign of recurrence. No
data exist regarding the frequency and effectiveness of follow-up care for
recurrence. In general, patients receive a pelvic examination and Papanicolaou
smear every 3-6 months for the first 5 years. Patients treated for clear cell
adenocarcinoma need to be monitored for a long time because late recurrences and
second primaries in DES-exposed women have been reported to occur 17-20 years
after the initial treatment, particularly in the lungs and supraclavicular areas. As
many as 36% of recurrences appear in extrapelvic sites.
Follow-up for postoperative complications includes evaluation of the stomas,
observation of the incisions for healing, and evaluation for signs of necrosis in splitthickness skin grafts and musculocutaneous flaps. Psychological evaluation includes
questions about quality of life, body image, and sexual satisfaction. Patients should
be counseled about these issues.
Complications
Exenteration
The overall mortality rate for patients undergoing exenteration is less than 5%;
however, complications occur in about 50% of patients, because of the nature and
length of surgery, the advanced age of the patients, the large amount of blood loss,
and the inability to accurately monitor fluid intake and output secondary to urinary
diversion. Hemorrhage is the most significant intraoperative complication (1.5-4L).
Postoperative complications

Fluid status is accurately measured by Swan-Ganz catheter because urine output

may not be reliable (because of the diversion) and large loss of fluid is expected
because of third spacing and oozing of serum from the large abdominal and pelvic
defects. The urostomy is placed on continuous gravity drainage. Hemovac drainage
should be measured and used as an indication for proper replacement of protein
and electrolyte losses because drainage content is an approximation of serum
content. The volume of the pelvic drainage can reach up to 1000mL over 24 hours.

Hemorrhage should be dealt with promptly with percutaneous embolization

because reexploration carries high mortality and morbidity rates. Intravascular fluid
loss from wound oozing and third spacing is expected.

An arterial line should be available for blood product, colloid, and crystalloid
administration; fluid replacement should be adequate to avoid intravascular
compromise with renal hypoperfusion and failure. The hematocrit should be
carefully monitored and stabilized above 30% by infusing packed red blood cells
(RBCs) or whole blood when needed. PT and aPTT are kept within the reference
range with administration of fresh frozen plasma (FFP).

Pulmonary embolus occurs in 1.5% of patients despite prophylaxis. This is also due
to the length of the operation and prolonged bed rest after surgery.

Routinely check the lower extremities for evidence of adequate vascular perfusion,
with daily checks for evidence of DVT. Continuously monitor the patient's
respiratory and cardiac function for evidence of pulmonary embolus, atelectasis,
pleural effusion, and cardiac ischemia. When the patient is stabilized, the Swan-

Pelvic sepsis (10%) and wound sepsis and dehiscence (12%) are minimized by bowel
preparation, but the risk is still present because of the radical nature of the surgery,
the length of the operation, and the age of the patient.

Lower rectal anastomosis complications

Anastomotic leakage depends on the distance of the anastomosis from the anus, as
well as on the vascularity and tension on the anastomotic site. Along with fistulae, it
carries a very high mortality rate of approximately 50%.
Rectovaginal fistulae and strictures are more common in patients with previous
irradiation. Using the omentum as an additional blood supply could prevent this.

The inability to empty the J-pouch is the most significant drawback to this
procedure.
Small bowel obstruction occurs in 4-9% of patients. The most common site is the
distal ileum if an ileal anastomosis has been performed, with obstruction most
frequently occurring if irradiation was previously administered. Avoiding an ileal
anastomosis and generously reconstructing the pelvic floor decreases this
complication. In case of an obstruction, reoperation should not be considered,
because of its high mortality rate (8-10%). Instead, NG decompression should be
attempted and TPN feeding continued.
Fistulae (12-32%) are more common with ileoileal anastomosis and previous
irradiation. With the use of a transverse colon conduit for urinary diversion, this
complication now is uncommon.
With the use of a transverse colon, urinary leaks and intestinal fistulae now are rare.
In case they occur, management is conservative because of the high mortality rate
associated with reoperation. Percutaneous drainage is required. Ureteral strictures
are uncommon with the use of stents. The long-term complication is pyelonephritis,
[46]
with 2.7% risk of renal failure due to ureteral obstruction.
Vaginal reconstruction
Complications from vaginal reconstruction include necrosis of the graft and stenosis
of the neovagina.
Other complications
TPN complications include pneumothorax (1-2%), which is diagnosed on the basis of
chest radiographic findings. It usually resolves spontaneously, but a chest tube may
be required.
Subclavian venous thrombosis occurs in 5-10% of patients. Flush with heparin
solution (300U/mL) for prevention. Once it occurs, remove the catheter, administer
a full course of heparin, and continue nutrition through a peripheral vein.
Infection occurs in 2-5% of patients. If the patient is febrile and the source of
infection is not identified after 96 hours, remove the catheter and send the catheter
tip for culture. If a peripheral source was identified, then removing the catheter is
unnecessary; treat the infection accordingly.
Metabolic complications include overfeeding (most common; leads to excess carbon
dioxide production), hyperglycemia (treat with insulin), and metabolic acidosis (rare
with addition of acetate buffer).
Postoperative Prognosis Following Exenteration
The outcome of exenteration has improved significantly over time in terms of
operative mortality and 5-year survival rates. In 1965, Brunschwig reported an
operative mortality rate of 16% and a 5-year survival rate of 20%[47] ; in 1989, Morley
et al reported an operative mortality rate of 2% and a 5-year survival rate of 61%[48] .
In general, the operative mortality rate in exenteration is less than 5%, and the 5year survival rate is about 40%. Improved hemodynamic monitoring, nutritional
support, and advances in surgical techniques and instruments have contributed to
the decrease in intraoperative mortality and morbidity. Anterior exenteration has a
better survival rate than does total exenteration (30-60% versus 20-46%,
respectively).
In a study of outcomes from pelvic exenteration, Maggioni et al found that the 5year survival rate was highest for patients with cervical cancer (52%) but was only
19% for vaginal cancer. The authors published their 10-year experience with pelvic
exenteration between June 1996 and April 2007 for cancers of the cervix (62
patients), vagina (21 patients), vulva (9 patients), endometrium (9 patients), and
ovary (4 patients) and for uterine sarcoma (1 patient).
In the study, the survival of patients with cervical and vaginal cancer was
significantly affected by the presence of positive lymph node involvement (30% vs

60% at 5 years) and positive margins (25% vs 60% at 5 years). There was no
operative or early postoperative mortality (< 30 days after surgery), but the
postoperative complication rate was 66.6%, with 87% of early complications being
completely resolved.[49]
Clinical factors that affect survival
These include the following:

Length of time from initial radiation therapy to exenteration - Less than 1 year is a
poor prognostic sign.
Size of the central mass (>3 cm)
Preoperative sidewall fixation as determined by clinical examination
Pathologic factors that affect survival
Pathologic factors that impact survival include the following:

Tumor extension - In 1989, Anthopoulos and colleagues reported that the most
important risk factor for reduced survival was the extension of the tumor laterally
[50]
into the surgical margins
Positive nodes - In 1989, Morley et al reported a 5-year survival rate of 70% for
negative nodes versus 0% for positive nodes [48]
Spread of tumor to adjacent organs
Additional factors in prognosis
Age can affect the operative mortality rate but not the 5-year survival rate. In 1992,
Matthews et al reported that patients older than 65 years had the same 5-year
survival rate of 45% as patients younger than 65 years.[51] The operative mortality
rate of the older group was 11% versus 8.5% in the younger group.
Anthopoulos et al found that 84% of the patients were rehospitalized for
complications that occurred more than 30 days after surgery; complications usually
involved the gastrointestinal or urinary tract.[50] Surgical intervention was required
for 58% of patients with complications occurring 1 year after surgery, while 74%
required surgery within the first year.
Organ reconstruction, including low rectal anastomosis, continent vesicostomy, and
vaginal reconstruction, has significantly improved patients quality of life after pelvic
exenteration. In 1997, Hawighorst-Knapstein and colleagues reported that patients
with no ostomies have a much better quality of life and body image than patients
with 2 ostomies.[52] They also reported that women with vaginal reconstruction
reported fewer problems related to quality of life and significantly fewer sexual
problems