eMedicine - Surgical Treatment of Vaginal Cancer : Article by Tarek Bardawil

You are in: eMedicine Specialties > Obstetrics and Gynecology > Gynecologic Surgery

Surgical Treatment of Vaginal Cancer

Article Last Updated: Dec 10, 2007

Malignant diseases of the vagina are either primary vaginal cancers or metastatic from adjacent or distant organs. Primary vaginal cancers are defined as arising solely from the vagina with no involvement of the external cervical os superiorly or the vulva inferiorly. The importance of this definition lies in the different clinical approach in 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 vulva and vagina should be considered vulvar cancer. A patient with history of a preinvasive lesion or an invasive carcinoma arising from the cervix or the vulva requires that 5-10 years of disease-free interval have past before diagnosing a new vaginal lesion as primary vaginal carcinoma. This criterion is required to rule out recurrent cervical or vulvar disease.

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.

History of the Procedure

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 widely accepted as a treatment in selective cases.

Frequency

Primary vaginal carcinoma is rare, constituting only 1-2% of all malignant gynecological 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.

Etiology

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 the Table). 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 exists between any of those agents and vaginal carcinoma.

The strongest association is between squamous cell carcinoma and human papilloma virus (HPV) infection, which is similar to cervical carcinoma. 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. Other associated infectious agents 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.² They suggest that young women infected with both HIV and HPV are at increased risk for a more aggressive and less responsive 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). In 1991, Aho and coworkers reported that 5-9% of patients treated for VAIN progressed to invasive carcinoma.³ This suggests 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, 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 identified.

A previous 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 previous history of in situ or invasive carcinoma that was treated at least 5 years before diagnosis.

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. In a 2000 report, Carthew and colleagues demonstrated that tamoxifen, a chemotherapeutic drug, induced endometrial and vaginal cancer in rats in the absence of endometrial hyperplasia.⁴

In 1999, Pukkala and colleagues reported an association between low socioeconomic class in Finland and an increased incidence of cervical, endometrial, and vaginal cancer.⁵

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 1971⁶, 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.

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.⁷ Note that hysterectomy by itself is not a risk factor, rather women who underwent hysterectomy were poorly monitored.

In a 2004 publication, Hellman et al in Sweden reviewed 341 cases of primary carcinoma of the vagina from 1956-1996 and suggested that the etiology of vaginal cancer may be age related.⁸ 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.

Pathophysiology

The presence of different stages of histologic differentiation—VAIN, carcinoma in situ, possible microinvasive carcinoma, and invasive cancer—suggests a continuum of transformation from less malignant to more invasive, which is similar to the continuum described for cervical cancer. As reported by Ikenberg et al in 1990⁹ and Ostraw et al in 1988¹⁰, identification of HPV DNA in squamous cell cancer cells by in situ hybridization (21%) and southern blot hybridization (56%) strongly suggests an association with HPV infection and a possible role of HPV in the pathogenesis of squamous cell vaginal carcinoma.

On the other hand, the significant association with a previous 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 postulated by Marcus and is known as the field effect. HPV infection could explain this phenomenon because HPV is associated with cervical, vaginal, and vulvar disease. Koyamatsu et al did a comparative analysis of the presence of HPV types 16 and 18 by polymerase chain reaction (PCR) and expression of p53 gene and Ki-67 antigen using immunohistochemistry in cervical, vaginal, and vulvar cancer.¹¹ They suggested that in cervical cancer, HPV 16 and 18 played a common causal role, and in vulvar cancer, p53 gene mutations were the main carcinogenic cause, while vaginal cancer has transitional characteristics between cervical and vulvar cancer. There was no significant difference in overexpression of Ki-67 antigen among the 3 cancers.

Another explanation for this association 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 women with previous hysterectomy go unnoticed until they present with advanced-stage vaginal carcinoma.

The pathogenesis by which DES might play a role in inducing clear cell adenocarcinoma is unclear. In 1972, Forsberg and colleagues¹² proposed the possibility of estrogen-induced maturation arrest of the müllerian ducts, and in 1984 Robboy and colleagues¹³ 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.

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.

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 cervix and drains into the pelvic obturator node, the internal and external iliac chains, then to the para-aortic nodes. The distal third of vagina drains to the inguinal node 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.

Clinical

Duration of symptoms averages 6-12 months before diagnosis, with a range of 0-11 years. Delay in diagnosis of vaginal carcinoma is not uncommon, and this is partially because of disease rarity and delay in relating patient symptoms to a vaginal origin. As expected, the longer the delay, the more advanced the cancer once the diagnosis is made, which results 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.¹⁴

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.

Consensus as to the proper treatment of 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:

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.

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 1-2 cm down to the vagina, separating the cervix from the rectum.

The vagina 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 fascia, which contains an abundant plexus of vessels, lymphatics, and nerves as well as outer longitudinal and inner circular smooth muscle layers, submucosa, and mucosa. 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.

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 30º angle from 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 1-2 cm lateral to the isthmus of the uterus. The uterine veins cross below the ureters.

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.

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, sacrum posteriorly, rectum medially, and hypogastric artery laterally. The rectovaginal space is bounded by the vagina anteriorly and the rectum posteriorly, while the rectal pillars form its lateral walls. 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.

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.

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.

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 then the pelvic nodes. The posterior wall lymphatics communicate with the rectal lymphatics and drain to the inferior gluteal, sacral, and rectal nodes.

The vagina stays in close proximity to the bladder and urethra anteriorly, which increases 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 approaching the vagina posteriorly through the posterior cul-de-sac and a developed rectovaginal plane.

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.

Lab Studies

Diagnostic Procedures

Histologic Findings

As mentioned before, primary vaginal carcinoma is not homogeneous. It is classified into several histologic types, each with its own characteristics (see the Table). The following are brief descriptions of the most common types.

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

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.

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.¹⁷ Squamous cell carcinoma can metastasize to virtually any organ, and in 1999 cutaneous metastasis was reported by Plataniotis and colleagues.¹⁸

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 pathological characteristics are similar to their vulvar counterparts. On visual examination, it has a large, warty, cauliflowerlike appearance similar to condylomata acuminata, but the papillary fronds lack a central core of connective tissue. They are slow growing, locally aggressive, and rarely metastatic. Radiation is contraindicated because it has been implicated in potentiating this tumor to a more malignant phenotype.

This is the second most common type and accounts for about 9% of all primary vaginal carcinoma. Unlike squamous cell carcinoma, clear cell adenocarcinoma manifests in patients at a very early age, usually after age 14 years, and peak incidence is 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 non–DES-exposed patients, ectopic cervical glands are a possible origin.

Grossly, vaginal adenosis appears as multiple cysts 0.5-4 cm in diameter or as a diffuse erythematous granular mucosal lesion. The cancerous lesion appears polypoid, papillary, flat, or ulcerated. Microscopically, 3 histological 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.

Vaginal melanoma is rare and accounts for 0.5-2% of all primary vaginal cancers. Fewer than 150 cases have been reported. Vaginal melanoma usually manifests in women older than 50 years, peak incidence is in women aged 60 years, and it tends to occur in white women.

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. It 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.

Although this tumor is rare, it is the most common vaginal cancer in children. It manifests in girls younger than 8 years, and peak incidence is in girls aged 3 years. Sarcoma botryoides is highly malignant and very aggressive. Initially, it tends to invade locally, then it metastasizes to inguinal, pelvic, retroperitoneal, and mediastinal lymph nodes as well as the lungs, pericardium, liver, kidney, and bones.

Grossly, it 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. Patients occasionally present with a polypoid mass protruding from the introitus.

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.

This tumor of smooth muscle origin is rare and accounts for fewer than 2% of all primary vaginal cancers. It has a wide age range of 25-86 years.

Grossly, it manifests as a bulky submucosal lesion, mainly in the upper vagina. Histologically, it is similar to leiomyosarcoma of the uterus. In a 1979 report, 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.¹⁹ Leiomyosarcoma may follow radiation therapy to the genital tract.

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 (see FIGO staging classification of vaginal carcinoma ). 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.

CT scanning or 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 (FDG-PET) provides a more accurate assessment of the extent of disease in a patient with malignant melanoma as compared to conventional methods.²⁰

Baseline levels of carcinoembryonic antigen (CEA), cancer antigen–125 (CA-125), and squamous cell carcinoma antigen are recommended because they are elevated in patients with some carcinoma types. 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. Also, 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.

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 one 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. Also, 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.

Medical therapy

Until the discovery of radium, surgical excision was the only available treatment. In 1929, Taussig first reported radiation therapy at the Barnard Free Skin and Cancer Clinic in Boston, where he treated 18 patients with vaginal carcinoma. Only 2 of the patients survived longer than 5 years. During October of 1934, Taussig stated before the Clinical Congress of the American College of Surgeons that "primary cancer of the vagina is very rare and almost universally fatal. We acknowledge our total inability to do anything effective" to treat this disease.

Since then, radiation therapy has largely replaced surgical excision; today, radiotherapy is the treatment of choice for most cases of primary vaginal carcinoma. Still, no consensus exists regarding the proper treatment of this particular cancer, partly because of the rarity of the disease. Treatment is individualized and depends on the histologic type, stage, and location of the lesion; the presence or absence of the uterus; and whether the patient has received previous irradiation. It also depends on the medical condition of the patient and a risk-benefit analysis of all possible treatment modalities. Treatment consists of radiation therapy, surgery, or a combination of both with occasional chemotherapy.

Psychological and anatomic considerations are important in planning the treatment regimen. For example, the physician must ask the patient if she can withstand the physical and physiological alterations of an exenteration. Other issues that must be addressed are radical versus conservative approach, the patient's wishes regarding maintenance of a functional vagina, and the close proximity of the bladder and rectum to the vagina, which may limit the dose of radiation and restrict surgical margins.

Surgical therapy

The following are treatment options and surgical procedures in several types of primary vaginal cancer.

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.

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 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.

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 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 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.²¹ The best candidates are patients with tumors less than 2 cm in diameter, a predominant tubulocystic pattern, and depth of invasion less than 3 cm. If radiation is used as the sole treatment, then transposition of at least one 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 of 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.²² The woman had no evidence of recurrence with regular menstrual cycles 28 months after initial surgery. The authors concluded that this procedure could be considered to conserve fertility in young women.

Melanoma

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. In 1989 Reid et al²³ and Buchanan et al in 1998²⁴, for example, showed no significant difference in 5-year survival rates or disease-free intervals for radical versus conservative surgery. 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%); they recommend a radical approach to patients with lesions smaller than 10 cm².²⁵

Recently, detection of nodal involvement prior to radical procedures has been suggested because positive lymph nodes indicate poor prognosis; radical surgery might be unjustified. Siu et al used laparoscopic ultrasonography to successfully detect enlarged pelvic lymph nodes.²⁶ Rodier et al used 99mTc-sulfur colloid injected around the lesion and detected the sentinel lymph node with hot spot by lymphoscintigraphy.²⁷ Nakagawa et al succeeded in evaluating the sentinel lymph node to decide the extent of surgery using a dye injection method²⁸; 1 mL 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 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. 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 management includes wide local excision (WLE) and simple hysterectomy combined with radiotherapy and/or chemotherapy. Radiation therapy with high-dose fractions (>400 cGy/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 to conventional fractionation. Irvin et al reported in their case series a higher locoregional control using WLE followed by high-dose fractionation teletherapy compared to more radical surgical resection.²⁹

As mentioned previously, radiation therapy is contraindicated 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.

Because the typical patient is prepubertal, preserve ovarian function and reproductive organs. Currently, a conservative approach is used instead of an exenterative surgery. Preoperative and/or postoperative chemotherapy and radiotherapy improve the outcome. 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.

This very rare tumor is treated with chemotherapy VAC to reduce the tumor size. Chemotherapy is followed by partial colpectomy, radiotherapy, or both.

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 details

The first and most important requirement for exenterative surgery is that the patient should have no underlying medical illnesses. The patient must be fit for a prolonged operation with potential blood loss and major fluid shifts. Psychological evaluation is necessary because a stable personality and supportive social environment are required because of postoperative physical and physiologic changes. In addition to tumor resectability, patient evaluation centers on whether the patient can physiologically and psychologically withstand the surgery.

Signs of systemic spread should be absent. Evaluation starts with 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. 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 resected with clear margins. 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.

Extension of the tumor into the pelvic sidewall is a contraindication to the procedure. 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.

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. In 1993, 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%).³⁰

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.

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

Consult an 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 and risky with unavoidable blood and fluid losses.

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

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 the 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 postoperative ICU care and prolonged hospitalization are common.

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

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. According to a 1983 report by Andersen and colleagues, all women who underwent reconstruction thought that preoperative counseling was inadequate.³¹

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

Bowel preparation, mechanical and antibiotic, begins 2 days prior to the operation to reduce the incidence of postoperative infectious complications (see Protocol for preoperative bowel preparation). 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.³² Patients should be well hydrated (IV fluids) starting simultaneously with bowel preparation. Total parenteral nutrition (TPN) should be considered if patients are malnourished.

Prophylactic antibiotics (usually first- or second-generation cephalosporins) are administered IV or IM immediately before the operation and continued every 6 hours for 2 additional doses. In 1992, Classen et al found that antibiotics are most effective if administered within 2 hours of surgery.³³

Because of the high risk of thromboembolic diseases in this category of patients (eg, because of old age, prolonged bed rest, prolonged surgery, and cancer), prophylaxis should consist of low-dose heparin (5000 U bid), intraoperative external pneumatic compression, or both. More aggressive prophylaxis in very high-risk patients includes low molecular weight heparin (Lovenox 40 mg SC qd), warfarin, or placement of an inferior vena cava filter. When administering these medications, the surgeon must weigh the risk of postoperative bleeding against the risk of thromboembolism.

If vaginal reconstruction is desired and a transpelvic rectus abdominis myocutaneous pedicle flap (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.

Intraoperative details

Pelvic exenteration is classified as total exenteration for apical lesions involving the bladder and rectum, anterior exenteration for anterior lesions involving the bladder, and posterior exenteration for posterior lesions involving the rectum.

The patient is placed in the low lithotomy position with stirrups supporting the hips, thighs, and knees. This allows the 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 3 cm 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).

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.

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.

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 the 10-o'clock position. This isolates the right and left pubourethral ligaments for division. The anterior vaginal wall is incised with at least 4 cm 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.

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 becomes the blood supply of 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 use of the bulbocavernosus flap if there is not enough omentum. A continent vesicostomy is constructed, and Hemovac drains are placed in the pelvis.

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 1-2 cm 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 4-cm margin, and the whole specimen is removed en bloc. Before applying this device, continuous cephalad traction is applied to the rectum while holding its base above the levator ani. This provides adequate exposure of the rectum and easy access for the stapling device. 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 J-pouch 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.

A continent vesicostomy and a neovagina are performed. Contrary to the neovagina constructed in the anterior exenteration in which the posterior vaginal wall is preserved, the omentum in this case might 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.

As mentioned above, 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. Both 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.

The procedure is similar to the total exenteration, but the bladder and urethra are preserved.

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.

A split-thickness graft is usually used when an anterior or a supralevator exenteration was performed because these procedures leave a smaller defect. The mobilized omentum is used to create a pocket to receive the neovagina. A split-thickness 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 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.

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 sutured to the intact vaginal introitus.

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 10 cm 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. The TRAM has the disadvantage of a limited amount of tissue that can be mobilized from the anterior abdomen without causing much tension during closure of the abdominal incision and creating an abdominal wall distortion.

A third myocutaneous flap, the vulvobulbocavernosus pedicle, was described in 1984 by Hatch in the construction of a neovagina after exenteration.³⁴ 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.

Other procedures discussed in the treatment section are briefly described below.

The objective of a radical hysterectomy is to resect the tissue adjacent to the cervix and vaginal fornices along with removal of the uterus, cervix, and 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 done 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 mid way 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 might increase febrile morbidity, pelvic cellulites, and postoperative ileus.³⁵ A suprapubic catheter is placed in the bladder.

Vaginectomy for invasive vaginal carcinoma is radical as opposed to simple vaginectomy for VAIN. 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 2 cm 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.

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- to 5-mm 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.

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 similar manner as 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.

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 1000 mL over 24 hours.

An arterial line should be available for blood products, 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 RBCs or whole blood when needed. PT and aPTT are kept within the reference range with administration of fresh frozen plasma (FFP).

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

Antibiotic prophylaxis is discontinued after 48 hours if no postoperative fever was 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 both anaerobic and gram-negative organisms.

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, and 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.

Follow-up

After the surgery, monitor the patient for complications and monitor for 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 Pap 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 of split-thickness skin grafts and musculocutaneous flaps. Psychologic evaluation includes questions about quality of life, body image, and sexual satisfaction. Patients should be counseled about these issues.

The overall mortality rate is less than 5%, but 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 (1.5-4 L).

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 (see Postoperative details).

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.

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.

Anastomosis leak depends on the distance of the anastomosis from the anus as well as 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 was performed, and it most frequently occurs when previous irradiation was 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.

TPN complications include pneumothorax (1-2%), which is diagnosed on the basis of chest radiographic findings. It usually resolves spontaneously, but a chest tube might be required.

Subclavian venous thrombosis occurs in 5-10% of patients. Flush with heparin solution (300 U/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).

Complications from vaginal reconstruction include necrosis of graft and stenosis of neovagina.

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%³⁶; in 1989, Morley et al reported an operative mortality rate of 2% and a 5-year survival rate of 61%³⁷. In general, the operative mortality rate is less than 5%, and the 5-year survival rate is about 40%. Improv

Surgical Treatment of Vaginal Cancer

AUTHOR AND EDITOR INFORMATION

INTRODUCTION

History of the Procedure

Frequency

Etiology

Pathophysiology

Clinical

INDICATIONS

RELEVANT ANATOMY

CONTRAINDICATIONS

WORKUP

Lab Studies

Diagnostic Procedures

Histologic Findings

Staging

TREATMENT

Medical therapy

Surgical therapy

Preoperative details

Intraoperative details

Postoperative details

Follow-up

COMPLICATIONS

OUTCOME AND PROGNOSIS