Chapter 39: Gynecology

Accurate diagnosis and treatment of gynecologic disease begins with obtaining a complete history and physical examination. A thorough history should include

• First day of the most recent menstrual cycle

• Current genital tract symptoms

• Age at first menses (menarche)

• Interval from starting one menses to the next (cycle length)

• Duration and amount of menstrual flow

• Presence or absence of irregular or unexplained bleeding

• Symptoms associated with each menstrual cycle such as cramping before or during menses

• Other genital tract symptoms such as urinary or fecal incontinence, prolapse, dyspareunia, discharge, or pruritus

• Sexual history including assessment of risk factors such as knowledge of safe sex practices, age of first intercourse (coitarche), number and gender of partners, and presence of any history of abuse

• Number of pregnancies and subsequent outcome including term delivery, mode of delivery, preterm delivery, miscarriage, or abortion

• Contraceptive use including type, duration

• History of sexually transmitted disease such as infection with human papillomavirus (HPV), gonorrhea, or Chlamydia

• Adequacy of cervical cancer screening with Pap tests including date of most recent screen and any prior history of abnormal screens

• History of any gynecologic surgery including type, date, and indication

• Age of menopause

• Presence of postmenopausal bleeding regardless of amount of flow

• Hormone therapy of any type including oral contraceptives, postmenopausal estrogen replacement therapy, hormone therapy of breast cancer, etc

• Family history of pertinent cancer sites including ovarian cancer, endometrial cancer, breast cancer, and colorectal cancer. Determine the age at time of cancer diagnosis and relationship of the affected individual to the patient

• Determine the ethnicity of the patient regarding potential for hereditary diseases

Perform a complete pelvic examination. Inspect external genitalia including vulva and urethra for development, symmetry, and visible lesions. Place a vaginal speculum to inspect the vagina and cervix for symmetry, or visible lesions and perform Pap test, cultures, or wet mount tests as indicated to evaluate symptoms or update screening. Bimanual examination is then performed with careful compression of pelvic viscera between the examiner’s hand on the abdominal wall and the finger(s) in the vagina. The process is repeated with the rectovaginal examination whereby one finger is placed in the vagina and one is inserted into the rectum. The rectovaginal exam allows the examiner to feel higher into the pelvis and may improve the ability to feel the cardinal and uterosacral ligaments, cul de sac peritoneum, ovaries, rectocele, and sphincter integrity. The rectovaginal exam is particularly important for assessing pelvic masses or malignancies, rectocele, and fecal incontinence.

Development of the reproductive tract in the female fetus results from fusion and differentiation of the Müllerian ducts and the urogenital sinus. Fusion defects may result in duplication, malformation, or absence of genital tract structures. The most common defects are imperforate hymen, presence of longitudinal or transverse septae within the vagina, congenital absence of the vagina, and duplication defects of the uterus (Figure 39–1). The etiology of most of these congenital defects is idiopathic, but some cases arise as a result of teratogens such as androgen exposure to the developing fetus during the first and second trimesters.

Careful examination of the newborn is necessary. Cursory examination of the genital structure of the newborn may result in errors of gender assignment. Ultrasound and/or MRI, examination under anesthesia, and possible laparoscopy or hysteroscopy provide information for accurate diagnosis. One-third or more of children diagnosed with genital tract anomalies will have associated with anomalies of the urinary tract such as absent kidney, horseshoe kidney, and duplication of ureters.

The pelvis is a space constrained by bony architecture and filled with gastrointestinal urologic and gynecologic viscera. The blood supply is rich, including the external and internal ileac arteries and veins, and numerous branches within the pelvis. Motor nerves including the sciatic, obturator, and femoral nerves transit the pelvis along the pelvic sidewall. Sensory nerves including the genitofemoral nerve are superficially located and easily injured. The ureter is closely placed to the uterine artery and is at risk for injury during hysterectomy procedures (Figures 39–2A and 39–2B). A pelvic surgeon must be intimately familiar with the close spacing of critical pelvic structures to minimize risk of injury.

SCREENING & TREATMENT OF PREMALIGNANT LOWER GENITAL TRACT NEOPLASIA

As recently as 1945, cervical cancer and related lower genital tract cancers were the most common cancers in women. With the advent of the Pap test in the 1940s, cervical cancer incidence began to fall with more than an 80% reduction of risk of mortality in the ensuing six decades. It is now understood that virtually all cervical cancers and some vaginal and vulvar cancers are caused by persistent infection with oncogenic strains of the human papillomavirus (HPV). There are more than 75 HPV types identified, with types 6 and 11 most commonly associated with condyloma and types 16 and 18 associated with preinvasive and invasive carcinoma. Prevalence of HPV infection is as high as 80% of the population, but most infections are transient in nature. With appropriate screening and treatment to detect individuals with persistent high-risk HPV infection, the risk of developing invasive cervical cancer is low. In parts of the world without screening, cervical cancer remains prevalent and is the second most common cancer diagnosis for unscreened women. FDA approval of vaccination effective for the prevention of oncogenic HPV strains occurred in 2006 and has the potential to greatly reduce HPV mediated lower genital tract cancers in women.

A number of professional groups, including the American Cancer Society, American College of Obstetricians and Gynecologists, American Society for Clinical Pathology, American Society for Colposcopy and Cervical Pathology (ASCCP), and the National Comprehensive Cancer Network have issued consensus guidelines for cervical cancer screening that were updated in 2012. The US Preventive Services Task Force issued nearly identical recommendations in 2012. The guidelines address initiation of screening, screening interval, and discontinuation of screening.

When to initiate screening

Begin at age 21

When to discontinue screening

1. Age > 65 with adequate negative prior screening

2. Hysterectomy

3. Discontinuation of screening should not occur if the patient has a history of CIN2, CIN3, or adenocarcinoma in situ. In this case screening should continue for 20 years

Screening interval

1. Women aged 21-29 years

   1. Cytology alone every 3 years

   2. Liquid-based or glass-smear cytology is acceptable

2. Women aged 30-65 years

   1. Cytology with high-risk HPV cotest every 5 years (preferred)

   2. Cytology alone every 3 years (acceptable)

3. Women vaccinated against HPV

Follow age-specific guidelines

If cytology or HPV testing results are abnormal, then further evaluation is warranted. The ASCCP issued guidelines in 2013 that addressed triage and treatment for women with screening test abnormalities. Key points are as follows:

1. Cytologic tests should be reported using standard nomenclature defined by the Bethesda System. Key preinvasive diagnoses with which the clinician should be familiar include

   1. Atypical squamous cells (ASC). The report will indicate either “uncertain significance” (ASC-US), or “cannot rule out high-grade dysplasia” (ASC-H). ASC-US should be further tested by ordering a reflex hybrid capture assay for high-risk HPV DNA unless the patient is an adolescent. ASC-H has a high risk of high-grade dysplasia and must be evaluated with colposcopy

   2. Low-grade squamous intraepithelial lesion (LSIL) is virtually always caused by HPV, and HPV testing has been shown not to be cost effective. In adolescent patients, a repeat cytology exam in 1 year is recommended. In adults, colposcopy is performed.

   3. High-grade squamous intraepithelial lesion (HSIL) has a high likelihood of high-grade dysplasia on biopsy and invasive cancer will sometimes be detected. Patients with HSIL, regardless of age, are evaluated with colposcopy

   4. Glandular abnormalities refer to disease in the endocervical canal. These lesions are difficult to see and may therefore be detected later. Skip lesions occur in 10%-15% of cases, indicating the importance of evaluating the entire canal with curettage or similar sampling methods. All three glandular lesions reported have a high likelihood of high-grade dysplasia and a moderate likelihood of associated invasive cancer. Colposcopy and endocervical gland sampling with curettage with possible endometrial sampling is required. Cells in this category will be reported as

   1. Atypical glands, not otherwise specified (AGC-NOS)

   2. Atypical glands, favor neoplasia

   3. Adenocarcinoma in situ (AIS)

2. Adolescents and young adult women, defined as being 24 years of age and younger, have a very high prevalence of HPV infection and a very low likelihood of cervical cancer. Because the disease will often regress in this age range, management guidelines have become progressively more conservative

3. The colposcope is a binocular microscope (Figure 39–3) that allows close inspection of the squamo-columnar junction (SCJ) on the cervix where the majority of squamous cervical cancers arise. High-grade lesions have a characteristic appearance including white light reflection after staining with acetic acid in areas of dysplasia (aceto-white change), abnormal vascular patterns (punctation, mosaic, and atypical vessels), and altered contours. Small biopsies are obtained with colposcopic guidance using cervical biopsy forceps designed for this task. Treatment decisions are based on biopsy results. (Figure 39–4).

4. Biopsy proven low-grade cervical intraepithelial neoplasia (CIN-1) has a high likelihood of spontaneous regression with a median time of 2 years and very little likelihood of progressing to cancer. Management is conservative in order to minimize treatment morbidity that has been shown to adversely affect fertility. Persistence of disease longer than 2 years may either be treated or surveillance may be continued

5. Biopsy-proven high-grade cervical intraepithelial neoplasia (CIN 2-3) has a much higher risk of progressing to invasive disease if left untreated. Treatment options are discussed in the section on Surgery for Benign Cervical Disease

6. HPV mediated disease may also affect the vagina and vulva. Colposcopic examination and directed biopsies allow triage of lesions into low-grade and high-grade lesions that are managed either by surveillance or removal, respectively

7. A new consensus system of nomenclature for squamous neoplasia of the anogenital tract was published in 2012. In this system, neoplasms of the cervix, vagina, and vulva are now classified as low-grade or high-grade squamous intraepithelial neoplasms (LSIL and HSIL, respectively). This two-tiered classification system was designed to reflect the understanding of the biology of these lesions, and recognizes that LSIL rarely progresses, while HSIL has a significant risk of progression to cancer

SURGERY FOR BENIGN VULVAR DISEASE

There are a large number of possible masses and benign neoplasms of the vulva. The clinical approach is to rule out potential malignancy and to treat symptomatic lesions. Biopsy or excision of small masses is usually performed in the office setting under a local anesthetic with either a punch biopsy instrument or scalpel. Punch biopsy sites are usually left open, while elliptical excisions are closed with fine, interrupted, absorbable sutures. The differential diagnosis for benign lesions is as follows:

1. Solid lesions

   1. Leiomyoma

      Natural History: Uncommon on vulva. Benign smooth muscle tumor that arises from deep connective tissues. Occurs at any age, predominating in fourth and fifth decades. May become very large. Rarely undergoes malignant degeneration

      Appearance: Slowly growing, firm, usually mobile subcutaneous nodule

      Diagnosis: Excisional biopsy

      Treatment: Local complete excision

   2. Lipoma

      Natural History: Uncommon on vulva. Benign tumor of histologically normal appearing adipose cells. Large lesions may ulcerate. Usually asymptomatic. Rarely associated with family Lipoma syndrome, an autosomal dominant disease. Rarely undergoes malignant degeneration

      Appearance: Soft, rounded, slowly growing sessile or pedunculated mass ranging widely in size

      Diagnosis: Excisional biopsy if symptomatic

      Treatment: Local excision if symptomatic

   3. Syringoma

      Natural History: Benign tumor of eccrine ductal origin within fibrous stroma. Occurs mostly after puberty

      Appearance: Multiple, 1-2 mm, flesh-colored or yellow papules on lateral labia major

      Diagnosis: Biopsy

      Treatment: Local excision

   4. Trichoepithelioma

      Natural History: Rare benign tumor on vulva, derived from hair follicle without hair development

      Appearance: Single or multiple small pink or flesh colored nodules that can mimic basal cell carcinoma

      Diagnosis: Biopsy

      Treatment: Local excision

   5. Granular cell tumor

      Natural History: Rare benign tumor of nerve sheath. Occurs in adults and children. Usually asymptomatic and solitary in 85%

      Appearance: Slow growing subcutaneous nodule, usually on labia majora, clitoris, or mons pubis

      Diagnosis: Biopsy

      Treatment: Wide local excision

   6. Neurofibroma

      Natural History: Rare on vulva. Benign tumor of nerve sheath. Half occur in patients with von Recklinghausen disease, an autosomal dominant heritable disease affecting skin, nervous system, bone, and endocrine glands. Rare before puberty. Rarely undergoes malignant degeneration

      Appearance: Solid, cutaneous nodules usually less than 3 cm, but reported as large as 25 cm.

      Diagnosis: Clinical appearance of von Recklinghausen disease or biopsy.

      Treatment: In asymptomatic patients with von Recklinghausen disease, no treatment for a vulvar lesion is needed. For symptomatic patients, local excision

   7. Schwannoma

      Natural History: Rare. Benign tumor of neuroectodermal nerve sheath

      Appearance: Usually solitary

      Diagnosis: Biopsy

      Treatment: Local excision

2. Glandular lesions

   1. Papillary hidradenoma

      Natural History: Benign tumor of apocrine sweat glands. Contains both glandular and myoepithelial elements. Occurs after puberty. Usually asymptomatic. Virtually always in Caucasian women

      Appearance: Hemispherical in shape, measuring less than 2 cm in diameter. Usually located in labia majora or lateral labia minora

      Diagnosis: Biopsy

      Treatment: Local Excision

   2. Nodular hidradenoma

      Natural History: Benign tumor of eccrine sweat glands. Probably arises from embryonic rests. Clear cells on biopsy. Rare on vulva

      Diagnosis: Biopsy

      Treatment: Local Excision

   3. Ectopic breast or nipple

      Natural History: Rare. May occur on the vulva with or without underlying glands and lactation has been reported. Rarely undergoes malignant degeneration

      Appearance: Amorphous swelling of the labia most often detected with pregnancy. Pigmented vestigial nipple may or may not be present

      Diagnosis: Biopsy

      Treatment: Local excision if symptomatic

   4. Endometriosis

      Natural History: Rare on vulva. Benign ectopic endometrial tissue. May cause cyclic pain and may ulcerate or bleed

      Appearance: Nodule with blue or red-brown appearance. Cyclic tenderness

      Diagnosis: Biopsy

      Treatment: Local excision

3. Cysts

   1. Bartholin cysts or masses

      Natural History: Cysts are common, arising in 1%-2% of women. Cysts often occur after gland abscesses, although the duct may become occluded any time. Small cysts usually asymptomatic. Large or infected cysts are painful

      Appearance: Spherical cyst or nodule in subcutaneous tissue of posterior labia majora

      Diagnosis

      1. Incise and drain abscesses

      2. Biopsy recurrent cysts or solid nodules

      Treatment

      1. Incise and drain abscesses using a small balloon-tip catheter (Word) catheter introduced through a stab incision in the medial aspect of the cyst cephalad to the hymen. The catheter should remain in place for 2 weeks to allow tract epithelialization. In the event of surrounding cellulitis, antibiotic therapy can be added

      2. Marsupialize or resect recurrent cysts

      3. Resect solid nodules since these may be malignant

   2. Epithelial inclusion cyst (sebaceous cyst)

      Natural History: Common. Usually on labia majora. Can occur at any age and may be solitary or multiple. Usually asymptomatic. Caused by trauma to skin or occlusion of pilosebaceous duct

      Appearance: Single or multiple, round cysts usually ranging from 2-3 mm up to 1-2 cm in diameter. Often have yellow color

      Diagnosis: Clinical appearance

      Treatment: No treatment if asymptomatic. If symptomatic, local excision

   3. Wolffian cyst (Mesonephric cyst)

      Natural History: Uncommon. Benign, thin-walled cysts on lateral vagina at the introitus

      Appearance: Round cysts with thin smooth walls on lateral vagina at the introitus (Diagnosis: Clinical appearance or biopsy

      Treatment: No treatment if asymptomatic. If symptomatic, local excision

   4. Cyst of canal of Nuck (Mesothelial cyst)

      Natural History: Uncommon. Benign cyst

      Appearance: Smooth cysts usually located in anterior labia majora or inguinal canal. Thought to be due to peritoneal inclusions. May become large. Differential diagnosis includes inguinal hernia

      Diagnosis: Clinical appearance or excisional biopsy

      Treatment: No treatment if asymptomatic. If symptomatic, local excision

4. Vascular lesions

   1. Angiokeratoma

      Natural History: Very common. A clinically insignificant variant of hemangioma that occurs almost exclusively on vulva (and scrotum in men). Occurs during reproductive years. Contains dilated vessels and may have hyperkeratotic overlying epithelium. May resemble Kaposi sarcoma or angiosarcoma. Some forms associated with inborn errors of glycosphingolipid metabolism

      Appearance: Red to purple to brown-black 2-5 mm papules usually in large numbers anywhere on the vulva

      Diagnosis: Clinical appearance. Occurrence of multifocal lesions in childhood may indicate inborn errors of glycosphingolipid metabolism

      Treatment: None, if asymptomatic. Symptomatic lesions treated with laser ablation, electrodessication, or local excision

   2. Capillary hemangioma

      Natural History: Capillary hemangioma (strawberry hemangioma) occurs in infants and young children. Usually regresses spontaneously over time. May ulcerate or bleed

      Appearance: Well demarcated, red, slightly raised lesion

      Diagnosis: Clinical appearance

      Treatment: None if asymptomatic

   3. Cavernous hemangioma

      Natural History: Rare on vulva. Dilated vessels that may be associated with underlying pelvic hemangioma. Usually regresses spontaneously over time. May ulcerate or bleed

      Appearance: Dilated vessels

      Diagnosis: Clinical appearance

      Treatment: None if asymptomatic

5. Nevi and pigmented skin lesions

   1. Vitiligo

      Natural History: Inherited disorder with loss of melanocytes. Asymptomatic

      Appearance: Depigmented skin in well-circumscribed macular pattern

      Diagnosis: Clinical appearance

      Treatment: None

   2. Fibroepithelial polyp (skin tag, acrochordon)

      Natural History: Very common. Single or multiple. Hormonal factors are implicated in development and lesions are more common in obese or diabetic patients (Fisher, Nucci). Also common in axilla

      Appearance: Multiple soft skin colored or pigmented lesions. Usually painless unless inflamed or torsed

      Diagnosis: Gross recognition. Biopsy or excision if symptomatic

      Treatment: Excise, electrodesiccate or freeze with liquid nitrogen if symptomatic

   3. Seborrheic keratosis

      Natural History: Common on body but uncommon on vulva. Usually occur after age 30. Probably autosomal dominant inheritance (Fitzpatrick). Multiple lesions occurring over a short period of time may indicate internal malignancy (Leser-Trelat syndrome)

      Appearance: Lesions appear “stuck on” and are brown to black in color. Most are asymptomatic but can be pruritic. Occur on hair bearing skin

      Diagnosis: Gross appearance, biopsy or excision

      Treatment: If asymptomatic, no treatment. If symptomatic, excise, electrodesiccate, curette, or freeze with liquid nitrogen

   4. Lentigo simplex

      Natural History: Most common hyperpigmentation lesion on vulva. Occurs on skin and mucous membranes

      Appearance: Usually small, less than 4 mm, flat, uniformly pigmented. Often resemble junctional nevi

      Diagnosis: Clinical appearance. Biopsy only if clinical morphology worrisome. Remember ABCDE criteria: Asymmetry, Border irregularity, Color variegations, Diameter larger than 6 mm, Enlargement or Elevation

      Treatment: None required

   5. Vulvar melanosis

      Natural History: Hyperpigmented macules or freckles are benign and asymptomatic. They are usually acquired, beginning between ages 30 and 40

      Appearance: Asymptomatic brown to black irregular macular patches on vulva

      Diagnosis: Clinical appearance. Biopsy only if clinical morphology worrisome. Remember ABCDE criteria: Asymmetry, Border irregularity, Color variegations, Diameter larger than 6 mm, Enlargement or Elevation

      Treatment: None required

   6. Acquired melanocytic nevocellular nevus

      Natural History: Common, especially in Caucasians. Tend to develop in childhood and early adulthood, followed by gradual involution by age 60. Lesions are usually asymptomatic

      Classification (Fisher)

      1. Junctional nevus: melanocytes at the dermal-epidermal junction above the basement membrane. First stage of nevus evolution. Least common type on vulva

      2. Compound nevus: melanocytes in both the dermis and above the basement membrane. Second stage of nevus evolution

      3. Intradermal nevus: melanocytes exclusively in the dermis below the basement membrane. Final stage of evolution after which many nevi involute

      4. Other types include halo nevus, blue nevus

      Appearance:

      1. Junctional nevus: Pigmented macule with smooth border and uniform tan, brown or dark brown pigmentation

      2. Compound nevus: Papule with dome shape or macule. Dark brown or black color. May have hairs

      3. Intradermal nevus: Papule with dome shape or macule. Skin colored, tan or light brown

      Diagnosis: Clinical appearance. Biopsy if clinical morphology worrisome. Remember ABCDE criteria: Asymmetry, Border irregularity, Color variegations, Diameter larger than 6 mm, Enlargement or Elevation

      Treatment: None required if asymptomatic and if ABCD criteria are benign. All others: local excision

   7. Dysplastic nevus

      Natural History:

      1. Rare on the vulva

      2. Lesions arise later in childhood than nevi in general and continue to develop throughout life

      3. Sun exposure contributes to development of these lesions on other areas of the body. Several genetic loci have been implicated for development of melanoma

      4. Risk of melanoma doubles with one dysplastic nevus and increases 12-fold if 10 or more dysplastic nevi are present

      5. v.  Dysplastic nevi are sometimes associated with a hereditary propensity for melanoma

      Appearance

      1. On biopsy, atypical cells are superficial and the deeper cells are without atypia. Pagetoid spread of cells is noted in lower third of epithelium

      2. Tend to be larger in size than nevi (> 10 mm vs < 5 mm, respectively)

      3. Dysplastic nevi are asymmetrical, with variegation of color

      Diagnosis: Wood lamp accentuates pigmentation and margins are more easily delineated. Remember ABCDE criteria: Asymmetry, Border irregularity, Color variegations, Diameter larger than 6 mm, Enlargement or Elevation. Excisional biopsy

      Treatment: Excisional biopsy. Careful longitudinal skin surveillance exams

SURGERY FOR MALIGNANT VULVAR DISEASE

Vulvar cancer accounts for about 5% of gynecologic malignancies. At least 90% of vulvar cancers are of squamous cell type. Etiology of vulvar carcinoma is grouped into the HPV-associated basaloid-warty histological group and the non-HPV-associated keratinizing squamous cancers. The age distribution is bimodal with younger women more likely to develop HPV-associated disease and older women more likely to develop keratinizing squamous cell carcinoma. The latter group is often associated with lichen sclerosis of the vulva. Vulvar intraepithelial neoplasia (VIN) is a preinvasive form of HPV-associated neoplasia and is often associated with persistent pruritus. Uncommon histological types of vulvar cancer include melanoma (6%), Bartholin gland adenocarcinoma (4%), basal cell carcinoma (< 2%), extramammary Paget disease of the vulva (< 1%), and rare sarcomas, found arising primarily in the soft tissues, or metastases from other tumor sites.

Lesions arise in the labia majora in about 50% of cases and about 25% of cases occur on the labia minora. Clitoral lesions and Bartholin gland adenocarcinomas are less common. The natural history of vulvar carcinoma includes spread to inguinal lymph nodes. Lesion depth and diameter are of prognostic value for assessing risk of metastasis, and to a lesser degree histological type, and presence of lymphatic involvement. Lesions of ≤ 1 mm depth have less than 1% risk of nodal metastasis, and define a category of microinvasive disease that may be treated more conservatively by omitting the inguinal node dissection. Lymph node status is the most significant predictor of survival.

In patients with HPV-mediated disease, multifocal involvement of the vagina and cervix predisposes to a significantly higher risk of cancer at these sites. Smoking is a cofactor for the development of HPV-mediated disease. Smoking cessation may reduce risk of persistent or progressive disease. Women with extramammary Paget disease, in in situ apocrine adenocarcinoma related to breast tissue developed along the milk-line in utero, there is a significant risk of a second, underlying adenocarcinoma elsewhere. Sites that require evaluation include colon, especially for perianal lesions, Bartholin gland, cervix, endometrium, ovary, and breast.

Cancer of the vulva is staged by International Federation of Gynecology and Obstetrics (FIGO) criteria, which is a surgical staging system. Melanoma is staged using AJCC staging rules.

Appearance

VIN occurs in women 15-20 years before the average age of invasive disease. Incidence has risen strongly and the average age at time of incidence has fallen from 52.7 years in 1961 to 35 years in 1992. One-third of lesions are solitary, and two-thirds are multifocal. Lesions are widely variable in size and may be slightly raised or papillary. Color variation ranges from white, red, or brownish patches on the skin or mucosa. Ulcerated lesions or underlying subcutaneous induration may indicate invasion. Larger lesions have a higher probability of lymph node involvement, but metastatic disease in the lymph nodes may not be palpable. Local spread may involve the urethra, vagina, anus, and rarely the symphysis pubis or other pelvic bones.

Diagnosis

Biopsies are necessary to establish the correct diagnosis. The differential diagnosis is large and includes benign lesions discussed earlier in addition infections that mimic neoplasms and also vulvar dystrophies. Granulomatous infections such as lymphogranuloma venereum and granuloma inguinale of the vulva may be clinically suspicious, and biopsy of the involved may need to be supplemented with cultures for documentation of infection. These infections are rare unless a patient has traveled internationally. VIN is best diagnosed by colposcopic examination techniques including use if magnification and staining the epithelium with 5% acetic acid. Lesions usually appear acetowhite.

Treatment

Focal VIN may be treated by wide excision or CO₂ laser photoablation. Excision is preferred for lesions in the hair bearing skin and laser is generally less prone to cause scarring in the mucosal surfaces. Laser ablation is contraindicated if there is any suspicion of invasion. A skinning vulvectomy with split-thickness skin grafting is effective for widely multifocal disease. Extramammary Paget disease requires wide but superficial excision as the tumor cells often spread far wider than is visible to the surgeon. Local recurrences are common, but invasion is rare.

Vulvar cancer is staged using the international system developed by the FIGO (Table 39–1). Microinvasive lesions of less than or equal to1 mm invasion are adequately treated by wide and deep local excision with 1 cm margins due to the low likelihood of nodal spread. Stage I lesions are generally treated with radical local excision with a 1-2 cm margin. For lesions greater than 1 mm in depth, sentinel node mapping of inguinal nodes is carried out to assess for spread of disease. Radiation therapy with concurrent chemosensitization is required for inoperable lesions and for patients with positive nodes or involved resection margins.

Prognosis

Following radical resection with negative nodes and margins, a 5-year rate of 90% is anticipated. If nodes are involved, survival is linked to number of nodes involved, unilaterality versus bilaterality, and bulk of disease.

SURGERY FOR BENIGN VAGINAL DISEASE

Imperforate Hymen

Diagnosis of imperforate hymen is often delayed until puberty, when either a workup for primary amenorrhea has ensued or the patient presents with menstrual symptoms such as cramping, without associated menses. If the patient has obstructed flow of her menses, defined as hematocolpos, examination will reveal a bulging imperforate hymen. Confirmatory rectal exam will detect a bulging, cystic mass. In younger girls, the finding is more subtle due to the absence of swelling. Delay of diagnosis may result backpressure causing a cystically enlarged uterus (hematometra) and possible retrograde menstruation leading to endometriosis. In the presence of a tightly distended hematocolpos, compression of the bladder and ureters may result in urinary obstruction.

Imperforate hymen is treated with a hymenotomy, where the obstructed hymen is incised or resected with either a scalpel or laser.

Longitudinal Vaginal Septum

Duplication of the vagina resulting in a septum may occur with or without similar defects in the uterus based on where the defect of Müllerian duct fusion occurred. The duplication may take the form of a partial longitudinal septum or complete duplication of the vagina. Patients will occasionally report bleeding despite placing a tampon during menses, indicating the possibility of a second passage for menstrual flow. Excision is performed transvaginally for symptomatic patients including those with dyspareunia, obstruction of labor or similar problems.

Transverse Vaginal Septum

Occasionally, the vagina fails to communicate with the urogenital sinus at the introitus. This may result in formation of a transverse septum, most of which are partial. If the septum is imperforate, hematocolpos will develop following menarche. Marsupialization or excision of the septum restores vaginal patency.

Vaginal Agenesis

Vaginal agenesis, or absence of the vagina, is associated with absence of the uterus in most cases. The lower vagina, derived from the urogenital sinus may be present, but Müllerian ductal structures comprising the upper two-thirds of the vagina and the uterus are absent or deficient. Diagnosis is usually made at time of evaluation for primary amenorrhea.

Vaginal agenesis is treated by reconstruction of a functional vagina. Treatment is usually deferred until the patient wishes to become sexually active. In a motivated patient, the vagina may be created by nonoperative dilation and elongation of the vulvar vestibule or vaginal introitus. This method, called the Frank nonoperative technique, requires up to 2 hours of dilating per day for 4-6 months. Success has been reported with vaginal dilators, vaginal molds, modified bicycle seat, and with intercourse alone. If there is failure to progress, or if the anatomy does not favor dilation alone, surgical construction using a skin graft (McIndoe procedure), interposed bowel, or myocutaneous flaps from the perineum are effective.

Gartner Duct Cyst

Gartner duct cysts are derived from mesonephric (Wolffian) duct remnants and contain a serous fluid. They are usually located in the lateral walls of the upper vagina and are generally asymptomatic. These cysts are detected most often during a routine physical examination. Small asymptomatic cysts require no treatment. Gartner duct cysts may occasionally reach 5-6 cm diameter. Larger or symptomatic cysts should be excised.

SURGERY FOR MALIGNANT & PREMALIGNANT VAGINAL DISEASE

Vaginal intraepithelial neoplasia (VAIN) is the term used to describe the preinvasive neoplastic changes that arise in the vagina. VAIN is frequently present whenever carcinoma in situ or invasive carcinoma of the cervix or vulva is present, and it may develop in the vagina years after completion of treatment for cancers of these two sites. Carcinoma in situ, or VAIN 3, of the vagina is most often detected with a Pap test. Subsequent evaluation with colposcopy, staining with 5% acetic acid and directed biopsies provide an accurate assessment of grade and location of disease.

Treatment

Low-grade dysplasia (VAIN 1) has a low probability of progression and may be managed with surveillance using the same principles as for management of low-grade cervical dysplasia. High-grade dysplasia (VAIN 2-3) should be treated by local excision of involved areas or with CO₂ laser photoablation. New terminology for these lesions was published in 2012. Low-grade lesions are now referred to as LSIL and high-grade lesions previously called VAIN 2, VAIN 3 and carcinoma in situ, are now referred to as HSIL. The irregular surface topography of the vagina caused by rugae makes successful visualization of lesions for treatment challenging. Recurrence rates for dysplasia are higher for vaginal dysplasia than for similarly treated cervical dysplasia, with a failure rate in the 25% range. Intravaginal placement of topical 5-fluorouracil is an off-label indication that has been reported in the literature, and failure rates are higher than for resection or ablation. Topical 5-fluorouracil has been reported to cause painful vaginal ulcers that heal poorly, limiting the utility of this treatment to carefully selected patients. Extensive involvement of the vagina may require subtotal or complete vaginectomy with skin grafting for maintenance of sexual function. For the elderly, sexually inactive patient, colpocleisis, where the vagina is resected and closed permanently is an option.

Invasive carcinoma of the vagina is rare, accounting for less than 2% of gynecologic malignancies. Most vaginal cancers involve extension from either cervical or vulvar cancers, both of which are more common than lesions arising in the vagina. By convention, if the cancer involves cervix or vulva in addition to the vagina, the tumor is categorized as either cervical or vulvar cancer, respectively. True vaginal cancer arises only in the vagina. About 85% of vaginal cancers are of squamous type. The next most common type is adenocarcinoma, usually with clear cell type. Rare primary tumors of the vagina include mixed mesodermal tumors, sarcoma botryoides (embryonal rhabdomyosarcoma), sarcoma, adenocarcinoma arising from Gartner duct or Müllerian duct remnants, embryonal carcinoma, and malignant melanoma.

The most common presenting symptoms of vaginal cancer include postmenopausal bleeding in about 65% of patients and persistent vaginal discharge in about 30%. Most tumors arise in the upper third of the vagina along the anterior and posterior surfaces. These sites are usually covered by the vaginal speculum and can easily be missed unless the physician observes all vaginal surfaces upon insertions and withdrawal of the speculum. Diagnosis is confirmed by biopsy.

Staging of carcinoma of the vagina is defined by FIGO and is clinical rather than surgical (Table 39–2). Squamous cancers are most commonly found in postmenopausal patients, although they may occur even in adolescent patients. Clear cell adenocarcinoma of the vagina is more likely to occur in women below the age of 25, generally arising in vaginal adenosis. Diethylstilbestrol (DES) has been implicated in increasing the incidence of clear cell carcinoma from 1:50,000 in the unexposed population to 1:1000 in women exposed to DES in utero. Although DES is no longer produced or prescribed in this country, DES and similar substances have been detected in the environment and in some food supplies.

Treatment of vaginal cancer is most often a combination of radiation therapy and chemosensitization using treatment plans similar to cervical cancer. Radical surgery such as radical hysterectomy with vaginectomy is possible for selected, small, upper vaginal lesions, favoring lesions on the posterior wall due to the improved likelihood of attaining adequate margins. Surgery is preferred for young patients with clear cell carcinoma as long as negative margins can be attained. In over 50% of patients tumor has penetrated the vaginal wall at the time of the initial examination. Involvement of the bladder and rectum is common. Survival for stage I disease is about 70%, but falls to about 40% for stage II and stage III disease.

SURGERY FOR MALIGNANT CERVICAL DISEASE

Cervical cancer is the twelfth most common cancer of women in the United States, but remains the second most common cancer of women worldwide. Almost all cervical cancers arise because of persistent infection with high-risk human papillomavirus (HPV) types, most commonly types 16 and 18. Low-risk HPV types such as types 6 and 11 are usually associated with condyloma and rarely, if ever, are associated with cancer. Cervical cancer can be considered a sexually transmitted disease since most HPV infections are transmitted via sexual contact. Early sexual debut and multiple partners greatly increase the risk of exposure to high-risk HPV types. HPV infections are common and about 80% of the population will have detectable HPV antibodies indicating prior infection. In most infected individuals, the immune system will mount a successful response, with a median time to regression of infection of about 2 years. Persistent infection with a high-risk HPV type after age 30 increases the relative risk of cervical cancer more than 400-fold for HPV 16 over the population at large. Persistent infections and progression to cancer may be more likely in women who smoke or those with dietary deficiency of folate, and beta-carotene. Progression to cancer is usually gradual, allowing development of effective screening strategies with Pap tests and testing for high-risk HPV DNA in addition to effective triage with colposcopy. Low-grade lesions usually regress, making potentially destructive treatments that have an adverse effect on fertility unnecessary. In 2006, the FDA first approved a vaccine for primary prevention of HPV infection. The vaccine is targeted for adolescents prior to their sexual debut. Widespread vaccination may largely eradicate cervical cancer in the future, although the vaccines are selective only for the most common of high-risk HPV types raising the possibility of shifting prevalence of HPV types.

About 75% of cervical cancers are squamous type; the remainder consist of adenocarcinomas, mixed carcinomas (adenosquamous), and rare sarcomas (mixed mesodermal tumors, lymphosarcomas). The relative prevalence of cervical adenocarcinoma has risen in recent years and now accounts for about 25% of cases.

Most cervical cancers arise from a preinvasive dysplastic lesion through a process that generally lasts for years. Carcinoma in situ occurs most frequently in the fourth decade, whereas invasive carcinoma is encountered most often in perimenopausal women between ages 40 and 50. Once invasion occurs, spread is by direct extension to the vagina and the parametrium in addition to lymphatic channels to the iliac and obturator nodes, with occasional direct spread to para-aortic nodes. Staging is clinical, since not all stages will require surgery. The staging system defined by FIGO is used internationally, and is included in Table 39–3. Probability of lymph node metastasis increases according to the extent of the primary lesion, being approximately 12% in stage I, 30% in stage II, and 45% in stage III. About 80% of patients with stage IV cancer have lymph node involvement.

Dysplasia & Carcinoma In Situ

Successful screening has greatly reduced the incidence and mortality of cervical cancer and its precursors over the last 50 years. Current screening recommendations for lower genital tract cancers of the vulva, vagina, and cervix have been discussed previously in this chapter. When a neoplastic lesion is detected by screening, proper and timely triage is needed. High-grade squamous intraepithelial lesions are typically asymptomatic.

Colposcopic examination of the cervix is the gold standard for assessing dysplasia, carcinoma in situ and early invasive disease. Application of Lugol iodine can be a useful adjunct to the colposcopic exam. Normal mature squamous epithelium of the cervix and vagina contains glycogen and stains a dark brown color, whereas dysplastic cells lack glycogen and stain a light yellow color.

Colposcopically directed biopsy is performed for visible abnormalities including acetowhite change, abnormal vessels, ulceration, and papillary lesions. Biopsy confirmed CIN-1 is managed conservatively since most of these lesions regress spontaneously and there is very little risk of progression to cancer. Biopsy showing a high-grade dysplastic lesion including moderate dysplasia (CIN-2), severe dysplasia (CIN-3), and carcinoma in situ (CIN-3), are treated with either ablative therapy or resection using cryotherapy or electrosurgical loop excision, respectively. Treatment is directed to either ablation or removal of the entire transformation zone, defined as the area bounded by the original and current squamocolumnar junction. These two treatment modalities are usually performed in the office setting and are well tolerated. There are some exceptions when treating adolescent and young adult patients under age 25, so the clinician must be familiar with current guidelines. Some dysplastic lesions may extend into the endocervical canal including squamous lesions and most glandular lesions. The preferred treatment for lesions extending out of colposcopic view into the endocervical canal is usually excision with a cold-knife cone biopsy in the operating room. Both electrosurgical loop excision and cold-knife cone biopsy increase future risk of preterm delivery, mandating careful triage of only those individuals truly requiring an excisional therapy.

Invasive Carcinoma

Early stromal defined as microinvasion, is usually asymptomatic. Larger lesions frequently cause postmenopausal bleeding (46%), intermenstrual bleeding (20%), or postcoital bleeding (10%). A watery or malodorous vaginal discharge may be the only symptom. Pain is a manifestation of advanced stage disease typically extending to the pelvic sidewall with entrapment of the sciatic nerve or femoral nerve. Inspection of the cervix typically reveals an ulcerated or papillary lesion of the cervix that bleeds on contact. The cytologic examination almost always demonstrates exfoliated malignant cells, although the false-negative rate for Pap tests approach 50% for invasive lesions due to obscuration of malignant cells by inflammation and necrotic debris.

Differential Diagnosis

Chronic cervicitis may appear similar to cancer of the cervix. Polyps of the cervix are often benign, but malignancy can only be ruled out with biopsy. Nabothian cysts are benign, common, and can appear bizarre to the untrained eye, but are readily distinguished from cancer by biopsy.

Natural History

Spread of cervical cancer into the parametrium may cause obstruction of the ureter, resulting in hydroureter, hydronephrosis, and uremia. Bilateral obstruction of the ureters leads to failure of kidney function and death. Involvement of the iliac and obturator lymph nodes may lead to lymphatic obstruction resulting in lymphedema. Pelvic sidewall nerves, especially the sciatic nerve, may become compressed, causing sciatica or pain in the low back, hip, and leg. Tumor invasion into the bladder or rectum sometime causes vesicovaginal or rectovaginal fistula, especially following radiation therapy. Widespread metastases to lung, liver, brain, and bone may occur.

Treatment

Treatment of cervical cancer is stratified by stage. Microinvasive disease, defined as FIGO stage IA-1, has less than a 1% chance of lymphatic metastasis and may be managed conservatively with cone biopsy for preservation of fertility or with simple hysterectomy when preservation of fertility is not desired or relevant. Radical hysterectomy with bilateral pelvic lymph node dissection is the preferred treatment for FIGO stage IA-2, IB, and IIA lesions. Radical hysterectomy results is resection of much wider margins than is performed with a simple hysterectomy, including removal of cardinal and uterosacral ligaments and the upper third of the vagina, in addition to pelvic, obturator and para-aortic nodes. Radical hysterectomy procedures may be performed either via laparotomy or laparoscopy. The radical hysterectomy is a completely different type of hysterectomy than the simple or total hysterectomy. Procedural details for the most commonly used hysterectomy types are described in Table 39–4.

Complications of radical surgery include hemorrhage, infection, thromboembolism, and less than 1% risk of ureterovaginal, vesicovaginal, or rectovaginal fistula. Early stage lesions may also be treated with radiation therapy and concurrent chemosensitization with cisplatin with equal likelihood of cure but higher potential morbidity.

The recently developed radical trachelectomy with laparoscopic lymphadenectomy offers carefully selected individuals with stage IA-2 or stage IB-1 squamous lesions of ≤ 2 cm diameter a fertility sparing option. The cervix, upper vagina, and supporting ligaments are removed as with a radical hysterectomy, but the uterine corpus is preserved. In the posttrachelectomy pregnancies currently reported, there is a 10% likelihood of second trimester loss, but 72% of patients carry their gestation to 37 weeks or more.

Advanced-stage disease, including FIGO stage IIB and above, requires treatment with external radiation, brachytherapy implants and concurrent chemosensitization. At least five randomized trials have confirmed a survival advantage for cisplatin-based therapy given weekly during radiation therapy. Delayed complications of radiation therapy affect quality of life and include cystitis and proctitis, but are uncommon and usually. Severe radiation cystitis or proctitis may result in hemorrhage, fistula, or strictures, typically arising several years after treatment in about 1%-3% of patients. Radiation necrosis of the cervix and diffuse radiation pelvic fibrosis are rare complications. Radiating the reproductive tract destroys the function of the uterus, and unless the ovaries have been surgically transposed out of the pelvis, ovarian failure is unavoidable. Recurrent or persistent disease in the central pelvis following radiation therapy may potentially be cured with the ultraradical pelvic exenteration procedure.

Prognosis

Survival is strongly linked to stage at time of diagnosis. Properly treated stage I disease averages 90% survival at 5 years, and approaches 96% in radical hysterectomy cases with negative margins and negative nodes. For stage II, 5-year survival is about 65%; dropping to about 45% for stage III and to less than 10% for stage IV.

SURGERY FOR PELVIC FLOOR DEFECTS

Cystocele, Rectocele, & Incontinence

An understanding of pelvic support defects requires a thorough knowledge of the anatomic relationship of the pelvic viscera and their supporting tissues. These conditions were originally thought to result from stretching and tearing of the muscles, nerves, and connective tissues of the pelvis during vaginal childbirth. The current understanding is that many pelvic floor defects arise from site-specific tears or breaks of pelvic connective tissue. Causes can include stretching, compression, or tearing during parturition; in addition to behaviors that increase intra-abdominal pressure such as chronic constipation, heavy lifting, obesity, and chronic cough. Smoking, poor nutrition and lack of pelvic floor exercise my exacerbate pelvic floor defects. The symptoms of pelvic floor defects may include: pelvic pressure or a sensation of “falling out” of the pelvic organs, a mass protruding from the vagina (which may be a cystocele, rectocele, cervix, or all of these), stress incontinence, fecal incontinence, and other difficulties with defecation.

Complete examination generally requires evaluating the patient in the lithotomy and standing position, and by asking her to Valsalva or cough. Vaginal support is described with three different levels, illustrated in Figure 39–5. Level I includes the cervix and upper third of the vagina. Level I support is comprised superiorly by uterosacral ligaments, endopelvic fascia, and smooth muscle; laterally by support from the cardinal ligaments; and anteriorly from the pubocervical fascia. Level II defines mid-vaginal support and is comprised laterally by attachments to the arcus tendineus fascia pelvis, anteriorly by the pubocervical fascia, and posteriorly by Denonvillier fascia. Level III refers to support of the lower vagina and urethra. Level III support is provided anteriorly by attachment of the urogenital membrane to the symphysis pubis, laterally to the levator ani muscle and posteriorly to the perineal body. A pelvic organ prolapse quantification profile (POPQ) has been defined by the International Continence Society, the American Urogynecology Society, and the Society of Gynecologic Surgeons (Figure 39–6). Use of the POPQ quantitates the extent and location of defects such that subsequent therapy is directed more specifically. Descent and bulging of the anterior vagina is usually a cystocele, a paravaginal defect, or an anterior enterocele. An anatomic defect in the posterior vagina is usually a rectocele or enterocele.

Additional testing that may be necessary for elucidation of the site-specific defect include assessment of urethral mobility with the so-called Q-tip test, cystourethroscopy, cystometrogram, anoscopy, colonoscopy, anal manometry, and transanal ultrasound. Chronic urinary tract infections must be ruled out prior to deciding upon surgical repair. For fecal incontinence, gastrointestinal disorders such as irritable bowel syndrome, infections such as Clostridium difficile or other causes of diarrhea, or malabsorption must be ruled out before proposing surgery.

Repair of pelvic floor defects is based on the principle of identification of the specific site of injury leading to site-specific repair. Pelvic support defects are often treated nonsurgically. For example, postmenopausal woman with mild to moderate defects as determined by the POPQ score may experience improvement of symptoms after the administration of a topical estrogen, initiation of Kegel exercises, or by fitting a pessary to support pelvic structures. Pessaries are inert material manufactured in many different sizes and shapes that can be fitted to the patient. When inserted in the vagina, a pessary mechanically supports pelvic structures resulting in temporary correction of the underlying symptoms. A pessary is a good option for patients choose not to undergo surgery or for those who cannot have surgery.

Differential Diagnosis

Urethral diverticulae may mimic cystocele and produce a bulge of the anterior vaginal wall. A discrete mass is usually palpable. Pressure or massage of the mass may result in turbid or purulent urethral drainage. Vaginal cysts such as Gartner duct or Skene duct cysts are occasionally mistaken for bladder support defects.

Treatment

Categories of pelvic floor defects include anterior compartment, vault prolapse, uterine prolapse, enterocele, posterior compartment, urinary incontinence, and fecal incontinence.

Anterior Compartment

Anterior compartment defects, including cystocele, paravaginal defects often are associated with concurrent urinary incontinence. Stress incontinence is involuntary loss of urine. Stress incontinence is associated with leakage caused by increases in intra-abdominal pressure including coughing, heavy lifting, or Valsalva maneuver in the absence of detrusor contraction. Stress incontinence is usually demonstrated during examination by asking the patient to cough. Stress incontinence should be distinguished from other common types of urinary incontinence including urge and overflow incontinence. With urge incontinence, the detrusor muscle contracts or spasms resulting in leakage with associated urgency. Mixed incontinence is defined as a combination of stress and urges incontinence. Overflow incontinence is often a continual slow leak of urine but may present with symptoms of any of the other types of incontinence. It can be ruled out by detecting large residual urine volume following voiding. Surgical correction of stress incontinence occasionally produces urge incontinence that may persist in 10%-15% of patients.

Normally, the proximal urethra is supported above the urogenital diaphragm and is subjected to the same intra-abdominal pressure changes as those applied to the bladder. In patients with anterior vaginal compartment defects, increased intra-abdominal pressure causes the hypermobile proximal urethra and bladder base to descend into the vagina. Pressure in the bladder thereby exceeds the sphincter pressure resulting in leakage of urine. Intrinsic sphincter deficiency is a second mechanism of stress incontinence. Risk factors include previous incontinence surgery, prior radiation therapy, and age over 50.

Site-directed repair of anterior compartment defects may include anterior colporrhaphy, or repair of paravaginal defect. Repair or stress urinary incontinence often involves retropubic colposuspension using either the Burch or Marshall-Marchetti-Krantz procedures. Success of these two procedures is approximately 85% at 5 years. Recurrent or difficult cases of stress urinary incontinence are often surgically treated with use of slings or grafts to augment support. Grafts may be created from endogenous fascia, usually harvested from the rectus fascia, or exogenous sources including allografts, xenografts, or synthetic mesh. Procedures utilizing the grafts may include sling procedures or the tension-free vaginal tape procedure (TVT), which has significantly reduced the morbidity of graft procedures compared to historical controls. For patients with intrinsic sphincter deficiency or for patients who are not candidates for more involved surgical procedures, a minimally invasive treatment involves injection of collagen at the urethrovesical junction as a bulking agent to increase outlet resistance.

Prolapse

Prolapse, where the level I support involving upper vagina or uterus is deficient, results in symptomatic descent of the upper vaginal tissues and/or uterus. Prolapse may also be associated with anterior and posterior compartment defects.

Repair of vaginal prolapse is generally performed with a unilateral sacrospinous ligament suspension (SSLS) procedure performed transvaginally or with an abdominal sacrocolpopexy procedure performed via laparotomy or laparoscopy. In the SSLS procedure, the upper vagina is sutured to the uterosacral ligament. In the abdominal sacrocolpopexy procedure, a retroperitoneal mesh is sutured from the upper vagina to the anterior longitudinal sacral ligament. Treatment of uterine prolapse sometimes involves hysterectomy combined with SSLS or with abdominal sacrocolpopexy procedures. Uterine preservation is permissible, combined with plication of uterosacral ligaments or the other procedures described above. Results of surgical correction of prolapse are not optimal since up to one-third of patients require reoperation for recurrent disease. Sacrocolpopexy outcomes appear to be more durable.

Enterocele

Enterocele is a hernia that develops between the vagina and the rectum. Diagnosis is confirmed by palpation on pelvic exam and can also be documented on transvaginal ultrasound. Surgical repair requires reapproximation of the fascial defect at the apex of the rectovaginal septum via laparotomy, laparoscopy, or by vaginal approach depending on other planned combined procedures such as hysterectomy.

Posterior Compartment

Posterior compartment defects, including rectocele and anal sphincter defects often are associated with concurrent fecal incontinence or difficulty with defecation. Fecal incontinence is involuntary loss of stool or flatus.

Etiology of fecal incontinence is associated with diarrhea; increased bowel motility; neurological disorders such as diabetes, spinal cord injury, or multiple sclerosis; and pelvic support defects including injury to the anal sphincter. Testing includes careful exam of level II and level III structures, anal sphincter tone, and voluntary anal sphincter contraction. Additional test that may be needed to elucidate the etiology of the lesion include anal manometry, transanal ultrasound, MRI, colonoscopy, defecography, and electromyography. Diarrheal illness and gastrointestinal disorders such as irritable bowel syndrome are treated prior to consideration of surgery.

Nonsurgical treatment may include use of medication to slow transit time, bulking agents, biofeedback, and electrical stimulation therapy.

Site-directed repair of posterior compartment defects may include posterior colporrhaphy, where posterior fascial defects are repaired primarily or with grafts, sphincteroplasty, or repair of rectal prolapse.

In patients for whom sexual activity is not an issue, closure (colpocleisis) or removal (colpectomy) of the vagina is an option.

Urinary Tract Fistula

Urinary tract fistulas to the vagina include vesicovaginal, ureterovaginal, and urethrovaginal types. Vesicovaginal fistula is the most common type. In the United States, most urinary tract fistulae occur following pelvic surgery with unrecognized injury or because of ischemia. Potential causes of ischemic change include effects of radiation therapy upon vasculature of pelvic organs. Less common in this country, but much more frequently in other parts of the world is ischemic injury following prolonged or obstructed labor. Fistulas may also occur as a result of tumor invasion, retained foreign bodies, and chronic inflammation.

Most urologic fistulae arise following gynecologic surgery rather than urologic or colorectal surgery. Total abdominal hysterectomy is the procedure most often complicated by the development of vesicovaginal fistula. A skillful surgeon using a technique of careful identification of anatomic structures can greatly minimize the risk of causing fistula formation. Injuries recognized at the time of primary surgery should be repaired immediately. Development of postoperative fistulae may require a waiting period to allow inflammation to subside before undertaking repair.

Symptoms & Signs

Vaginal leakage of urine or constant urinary leakage are symptoms of a urologic fistula. If the fistula involves the distal urethra, the patient may experience vaginal leakage only at the time of voiding. Vesicovaginal and ureterovaginal fistulae almost always develop near the vaginal vault. A urethrovaginal fistula opens into the anterior vagina.

On speculum exam, urine will usually be seen pooling at the vaginal apex. Most fistulae in nonradiated patients are small and may not be readily seen with the naked eye. Confirmation of a suspected vesicovaginal fistula may be demonstrated by instilling dilute methylene blue dye or sterile milk into the bladder with a catheter while inspecting the vaginal vault. A small fistula may leak very little and is often better seen by placing a tampon in the vagina when methylene blue dye is instilled and then removing the tampon to inspect for blue staining after 15-20 minutes. If a vesicovaginal fistula is not detected, IV methylene blue or indigo carmine blue dye will be excreted through the ureters. This is best detected by placement of a tampon for about 30 minutes followed by inspection for staining.

Other useful diagnostic tests include cystoscopy, cystogram, and intravenous pyelogram to assess for the site of injury.

Treatment

In nonradiated, noninfected tissue, many small fistulae will close spontaneously if the bladder is drained with an indwelling catheter. Larger fistulae or small fistulae that fail conservative management must be repaired surgically. Time of the order of 8-12 weeks must be allowed for resolution of edema and inflammatory reactions prior to undertaking repair. Premature repair has a high likelihood of being unsuccessful. Urinary tract infections should be treated and skin integrity should be protected with an occlusive barrier cream before surgical correction is attempted.

Repair of vesicovaginal fistulae involves a number of techniques including layered closure with the Latzko procedure via the vaginal approach, or via laparotomy with omental interposition. Principles of repair include meticulous and atraumatic technique using fine suture material; approximation without tension; and bladder decompression postoperatively. Ureterovaginal fistulae are repaired with ureteroneocystostomy if the ureteral injury is in the lower pelvis and with ureteroureterostomy for injury sites higher in the pelvis. These are usually performed via laparotomy, but the laparoscopic approach is also used. Fistulae in radiated tissue cannot be repaired primarily due to chronic tissue ischemia. These fistulae require the introduction of a nonradiated blood supply provided by bulbocavernosus or gracilis myocutaneous flaps for successful repair or permanent diversion.

Rectovaginal Fistula

Rectovaginal fistulae may occur following obstetrical injury, pelvic surgery, cervical or rectal cancer, radiation therapy, inflammatory bowel disease, or diverticular disease. The patient will report vaginal passage of flatus or feces, or foul vaginal discharge, sometimes associated with bleeding. The fistula can often be demonstrated upon speculum examination, or by palpation on rectovaginal exam. Diagnostic studies such as barium enema or sigmoidoscopy may be useful for smaller lesions.

To reduce the risk of infection and breakdown of a planned fistula repair, the bowel should be prepared with a low-residue diet, antibiotics, and a cathartic bowel regimen preoperatively. A rectovaginal fistula in the lower third of the vagina should be repaired after the surrounding inflammation and edema have resolved, usually requiring a delay on the order of 12 weeks. Rectovaginal fistulae in the upper two thirds of the vagina are best treated with a preliminary diverting colostomy, followed by fistula repair and subsequent colostomy take down 2-3 months after the repair.

Fistulae caused by inflammatory bowel disease such as Crohn disease have a high likelihood of recurrence unless the disease is clearly in remission. Ileostomy and abdominoperineal resection are necessary in patients whose symptoms are unacceptable despite medical management. Fistulae associated with radiation therapy can rarely be repaired and those associated with cancer are not amenable to surgical repair. A diverting colostomy provides considerable relief of symptoms.

SURGERY FOR BENIGN UTERINE DISEASE

Congenital Uterine Anomalies

Congenital duplication defects of the uterus are rare, with a reported incidence of 0.4%-1% and are usually diagnosed following investigation for recurrent spontaneous abortions, premature labor, fetal malpresentation, retained placenta, and postpartum hemorrhage. (Figure 39–1) Anomalies include septate uterus, comprised of a simple midline septum; bicornuate uterus, which is a duplication of the uterine horns; and uterus didelphys consisting of complete duplication of the corpus and cervix. These anomalies are often detected with physical examination, especially during or after pregnancies complicated by malpresentation, or preterm labor. Testing with MRI or hysterosalpingogram will usually confirm the diagnosis, and are combined with ultrasonography or laparoscopy if the diagnosis remains uncertain. Combined laparoscopy and hysteroscopy is useful for planning surgical correction.

Surgical correction of uterine anomalies is indicated for prevention of documented or anticipated pregnancy-related complications. A septate uterus is twice as likely to cause spontaneous abortion than a bicornuate uterus, with an overall loss rate of 88% reported for patients with a complete septum. The septate uterus is treated with a septoplasty, completed in most cases by hysteroscopic division or resection of the septum with up to an 86% success rate for subsequent pregnancy. Alternatively, the abdominal metroplasty is indicated for a large or thick septum or for the bicornuate uterus. A wedge of myometrium is resected allowing the two horns of the uterus to be reconstructed. This procedure results in measurable loss of uterine volume. Pregnancies occurring after abdominal metroplasty should be delivered by cesarean section as the risk of uterine rupture is increased.

Abnormal Uterine Bleeding

Abnormal uterine bleeding may occur at any age. It is not unusual for a female infant to have a small amount of self-limited vaginal bleeding attributable to the decline of circulating estrogen from maternal sources after delivery.

Abnormal uterine bleeding during the reproductive years is described according to the chronicity and amount of bleeding because this is often useful in elucidating the etiology. Hypermenorrhea, also referred to as menorrhagia, is defined as excessive or prolonged bleeding at the normal time of menstruation. Polymenorrhea is defined as bleeding that occurs more frequently than every 3 weeks, and metrorrhagia, defines intermenstrual bleeding that occurs in the interval between menses.

Hypermenorrhea may be due to such physical disease of the uterus including uterine leiomyoma, adenomyosis, and endometrial polyp. Dysfunctional uterine bleeding is abnormal uterine bleeding related to functional response of a normal uterus to extrauterine causes such as abnormal cycling of estrogen and progesterone in patients with anovulation, oligo-ovulation, or persistence of the corpus luteum. This condition is seen most often in adolescents and in perimenopausal women. Polymenorrhea is sometimes related to a shortened proliferative phase secondary to hypothyroidism. Causes of metrorrhagia include endometrial polyps, submucous leiomyoma, coagulopathy, granulomatous infections such as tuberculosis, or cancer of the cervix or uterine corpus. Complications of pregnancy should not be overlooked as a cause of abnormal bleeding in women of reproductive age.

Postmenopausal bleeding is defined as any vaginal bleeding occurring a year or more after menopause and is of concern because it may be a symptom of endometrial cancer. When postmenopausal bleeding is fully evaluated including biopsy and hormone studies, the majority will be attributed to benign etiologies such as atrophic change, benign polyp, cervicitis, and physiologic withdrawal from exogenous hormones. Endometrial cancer is detected in about 15% of cases of postmenopausal bleeding, but is also linked to the age of the patient: a 50-year-old woman has about a 2% chance of cancer, while an 80-year-old woman with the same symptom has about a 60% chance of malignancy. Cervical cancer may also present with postmenopausal bleeding. The exogenous administration of estrogenic substances, including hormone replacement therapy, and use of estrogen analogs such as tamoxifen cause postmenopausal bleeding. Much less likely are estrogen-producing tumors of the ovary, coagulopathy, or environmental sources of estrogenic substances. Postmenopausal bleeding in any amount ranging from scant brown vaginal discharge to frank, profuse, bright red bleeding should prompt further workup. Cancer should be considered the likely cause until proven otherwise.

Clinical Findings

Obtain a complete history and perform a careful pelvic examination including a Pap test. The exam will often reveal vaginal, cervical, uterine, or adnexal disease. A complete blood count and measurement of red cell indices will ascertain the degree of chronic blood loss. Additional blood studies including thyroid function testing and testing for coagulopathy may be necessary in some cases.

Abnormal bleeding in women over the age of 35 or with Pap test results showing atypical glandular cells of any type, or in women of any age with a Pap test showing atypical glandular cells, or women with risk factors for gynecologic cancer, endometrial biopsy is required to confirm a diagnosis. The biopsy should be timed at an appropriate time in the menstrual cycle, such as after the sixteenth day of the cycle if anovulatory bleeding is suspected, but may be performed at any time to evaluate for hyperplasia or carcinoma. Endometrial sampling with a disposable suction device can be accomplished in an office setting in most patients. Obese patients or patients with cervical stenosis may require dilatation and curettage in the operating room. Pregnancy should always be ruled out before performing a biopsy in a woman of reproductive age.

Hysteroscopy, involving insertion of a narrow diameter videoscope through the cervix while distending the uterine cavity allows inspection of the endometrium and directed biopsy of suspicious features. Hysteroscopy if very useful for determination of the cause of bleeding and offers the opportunity for simultaneous treatment such as hysteroscopic resection of a polyp. Hysteroscopy can be accomplished in an office or outpatient surgical setting and is recommended when bleeding is recurrent or resistant to therapy or when structural abnormalities of the endometrium such as polyps or submucous leiomyomata are suspected.

Transvaginal ultrasound is useful to measure endometrial thickness and structural abnormalities of the uterus such as a polyp or leiomyoma. In the postmenopausal patient, an endometrial strip of less than or equal to 4 mm virtually excludes the likelihood of cancer. Biopsy is still preferable unless it is unable to be performed for technical reasons. The sonohysterogram, where saline is introduced into the endometrial cavity during ultrasound increases diagnostic accuracy for defects in the endometrial cavity.

Treatment

Dilation and curettage is both diagnostic and therapeutic for many causes of uterine bleeding. Definitive treatment, however, will be targeted toward the etiology of the abnormal uterine bleeding.

Medical management of most nonneoplastic causes of abnormal uterine bleeding is generally prescribed before considering surgery because many symptoms will resolve or managed without surgical intervention. Chronic blood loss due to hypermenorrhea produced by leiomyoma or hyperplasia, can be reduced by the administration of a progestin. A gonadotropin-releasing hormone (GnRH) agonist will result in amenorrhea and is sometimes prescribed prior to planned surgery for leiomyomata. The antiprogestin mifepristone may significantly shrink leiomyomata, but a side effect includes increased risk of endometrial hyperplasia. Dysfunctional bleeding due to chronic anovulation is treated with cyclic progestin therapy, or oral contraceptives. For women who wish to conceive, ovulation induction with drugs such as with clomiphene are prescribed. Control of acute heavy bleeding may be achieved through the use of higher doses of combination oral contraceptives prescribed as one pill four times a day for 3 or 4 days, tapered to one pill a day over one week. Alternatively, intravenous conjugated estrogen, 25 mg every 4 hours, has been used also to control acute bleeding. Such a regimen must be followed by a progestin to prevent additional irregular bleeding at a later time. Following control of acute bleeding, maintenance therapy with an oral contraceptive is recommended. Another strategy for maintenance includes placement of an intrauterine device (IUD) containing levonorgestrel resulting in amenorrhea in about 25% of women and light menses in the remainder. In the absence of identified intrauterine pathology, hypermenorrhea associated with ovulatory cycles can be ameliorated with nonsteroidal anti-inflammatory drugs.

Persistence of symptoms will generally require surgical intervention. Surgical treatment of bleeding caused by uterine leiomyoma is discussed later in this chapter. Severe or intractable dysfunctional uterine bleeding may require hysterectomy. Endometrial ablation by hysteroscopically directed electrosurgery, or use of proprietary endometrial ablation devices may avoid hysterectomy in the premenopausal patient with bleeding that cannot be managed medically. Ablation generally requires normal size and shape of the uterine cavity. Only about 20% of women report amenorrhea following endometrial ablation, and about one-third will undergo eventual hysterectomy. Placement of a levonorgestrel-containing IUD is nearly as effective as hysteroscopic endometrial ablation.

Postmenopausal bleeding due to atrophic changes may resolve with estrogen therapy, administered with progestin in either a cyclic or continuous fashion. Postmenopausal bleeding attributed to physiologic withdrawal bleeding from prescribed estrogen-based therapy is treated by discontinuing therapy or converting to a continuous regimen. Curettage for removal of benign endometrial polyps is often curative, although polyps may recur. Endometrial carcinoma is a relative contraindication to estrogen therapy and is treated surgically with possible postoperative adjuvant radiation or chemotherapy based upon stage and grade of the tumor. Well-differentiated endometrial adenocarcinoma in young women who desire to maintain fertility has been successfully treated using high-dose progestins in about three-fourths of cases.

Adenomyosis

Extension of endometrial glands and stroma into the myometrium is defined as adenomyosis. Symptomatic adenomyosis is most prevalent in the between age 35 and menopause. Symptoms include dysmenorrheal, hypermenorrhea, polymenorrhea, metrorrhagia, and dyspareunia. Concurrent endometriosis is common. Symptoms typically improve after menopause supports.

Upon pelvic examination, the uterus is slightly to moderately enlarged and is frequently tender to palpation, particularly in the secretory phase of the menstrual cycle. Preoperative confirmation of adenomyosis is challenging. Neither ultrasound nor endometrial biopsy is useful for making the diagnosis. The T2 weighted sequences on MRI is more effective, with sensitivity of 70% and specificity of 86%. Definitive diagnosis is confirmed after hysterectomy.

Differential Diagnosis

Leiomyomata of the uterus are common and cause many symptoms similar to adenomyosis. Low-grade endometrial stromal sarcoma is rare, but can be mistaken as adenomyosis. This is an indolent malignancy with a significant likelihood of local recurrence. Distant metastases to the ovary, peritoneal surfaces, and lung are occasionally seen. Tumors of this type should not be morcellated. Subsequent treatment may include pelvic radiation therapy and hormone therapy based on stage at time of diagnosis and presence of estrogen and progesterone receptors.

Treatment

Total hysterectomy with or without bilateral salpingo-oophorectomy is the only clearly effective treatment. Hormonal approaches may be successful in treating symptoms, particularly if the patient is nearing menopause. Menopause causes symptoms to regress.

Leiomyomata

Uterine leiomyomata, or fibroids, are present in 20%-30% of women of reproductive age. The true prevalence is unknown because many fibroids are asymptomatic. Black women have a threefold higher incidence than white, Asian, and Hispanic women. Other risk factors include obesity, nulliparity, and early menarche or infertility. Myomas arise from monoclonal proliferation and are stimulated by estrogen, progesterone, and growth factors. Fibroids increase growth rate during pregnancy and regress after menopause. Fibroids are usually multifocal and vary hugely in size, ranging from a few millimeters to masses that fill the abdomen. Location of leiomyomata can be nearly anywhere within the uterus. Descriptive terms for location include intramural for fibroids arising within the myometrium, subserosal for lesions below the exterior surface of the uterus, and submucosal for fibroids below or adjacent to the endometrium. Other types of leiomyomata include pedunculated lesions connected with a narrow vascular stalk to the uterus, intraligamentous lesions within the broad ligament, and parasitic leiomyomata, detached from the uterus and deriving blood supply from adjacent organs.

Clinical Findings

Symptoms are determined by location, number, and size of the lesions. Common symptoms include hypermenorrhea, prolonged menses, pelvic pressure, increased abdominal girth, urinary frequency, dyspareunia, low back pain, and constipation. Infertility may occur secondary to fibroids, particularly if the uterine cavity is enlarged or distorted by a submucous lesion. Adverse pregnancy outcomes such as abnormal placentation, malpresentation, abruption, and dysfunctional labor are recognized complications associated with fibroids. Degenerative changes may spontaneously occur, potentially causing significant pain that requires treatment. Submucous leiomyomata are more likely to cause hypermenorrhea, polymenorrhea, and metrorrhagia.

Palpation of the uterus during bimanual examination detects a lobular and enlarged structure with a characteristic rubbery consistency. Soft and tender lesions are characteristic of degenerating fibroids. Larger lesions may be felt on abdominal examination.

Anemia may result from acute or chronic abnormal uterine bleeding. Endometrial biopsy should be performed in women with abnormal uterine bleeding to rule out endometrial cancer. Pelvic ultrasound is the most useful study for diagnosis. Sonohysterogram or hysteroscopy are useful for confirmation of submucous leiomyomata. MRI is expensive and should be utilized selectively for evaluation of an atypical lesions that could represent sarcoma or for of lesions prior to a myomectomy. Hydronephrosis may be apparent on imaging studies, arising as a result of external compression of the by the mass.

Differential Diagnosis

Uterine leiomyosarcoma is a rare but aggressive neoplasm. Among women undergoing surgery for fibroids, only 0.23% is found to harbor sarcoma. The rapidly growing leiomyoma, defined as 6 cm growth in 1 year, will be malignant in less than 0.1% of cases. In a postmenopausal woman with an enlarging uterine mass, sarcoma is more likely. Most sarcomas are not detected prior to surgery, although a high T1/high T2 pattern on MRI has been reported to be predictive of sarcoma. On cut section, leiomyomata are well-circumscribed, solid tumors with a pseudocapsule and an off-white, whorled appearance. If a lesion lacks an apparent capsule, appears necrotic, is soft or friable, then a frozen section should be submitted. These findings are likely to represent a sarcoma.

Other potential diagnoses to consider include solid ovarian tumors. Enlargement of the uterus may arise due to adenomyosis or could represent an undiagnosed pregnancy. A pregnancy test should be considered.

Treatment

Asymptomatic fibroids require no therapy. Women with hypermenorrhea or polymenorrhea often benefit from a trial of cyclic or continuous oral contraceptives or progestins. GnRH agonists decrease myoma size and stop menstruation prior to surgery. However, long-term use of GnRH agonists causes osteoporosis. Treatment with the antiprogestin mifepristone may result in significant shrinkage of fibroids, but may cause endometrial hyperplasia. In premenopausal women, leiomyomata grow soon after medication is discontinued.

For women with symptoms unresponsive to medical management, several treatment options are available. Myomectomy is a procedure for removal of leiomyomata with subsequent repair of resultant defects in the uterine wall in order to preserve the uterus. Myomectomy is usually offered to women who desire to retain their fertility. Some women who do not desire pregnancy also choose this option. Myomectomy is performed via laparotomy, laparoscopy, or hysteroscopy depending on the location, number, and size of the leiomyomata. Women who have completed childbearing and desire an alternative to hysterectomy may choose uterine artery embolization or guided focused ultrasound surgery, both of which are designed to decrease the size of lesions. Embolization involves diminishing blood flow to the uterus by occluding vessels to the lesion using angiography. Uterus and fibroids have been reported to decrease in size by one-third to one half. Bleeding and pelvic pressure improve in 80%-90% of women. Hysterectomy is definitive treatment for women with symptomatic myomas. Alternatives to total abdominal hysterectomy include vaginal hysterectomy, supracervical hysterectomy, and laparoscopic hysterectomy.

Prognosis

Myomectomy results in improvement of symptoms in 80% of women. Ten percent of women undergoing myomectomy require additional surgery for recurrent lesions and 50% will develop recurrent leiomyomata.

Endometrial Cancer

Endometrial carcinoma is the most common gynecologic malignancy in the United States. It is primarily a disease of postmenopausal women. Tumors are grouped into type I and II categories based on their underlying etiology. The more common type I tumors arise due to prolonged estrogen stimulation of the endometrium. The estrogen is most commonly endogenously produced estrone arising by aromatase conversion of androstenedione in peripheral adipocytes. Obese women produce much more estrogen and are at much higher risk for developing this cancer. Exogenous estrogens prescribed without accompanying progestin in postmenopausal women greatly increases the risk of endometrial cancer as does treatment with other estrogen receptor agonists such as tamoxifen when prescribed for treatment or prevention of breast cancer. Other risk factors for development of endometrial cancer include diabetes, early menarche, late menopause, and low parity. Oral contraceptives are protective against this cancer. Also at risk are premenopausal women with chronic anovulation such as with polycystic ovary syndrome.

Complex hyperplasia with atypia is a precursor lesion for type I endometrial cancer. These tumors usually express estrogen and progesterone receptors. Type II endometrial cancer consists of anaplastic or high-grade, papillary serous, clear cell, and squamous carcinomas. These tumors rarely express estrogen or progesterone receptors and are not thought to arise as a result of estrogen stimulation. Adverse prognostic factors include grade, histology, depth of myometrial invasion, cervical extension, tumor size, and extension beyond the uterus.

Endometrial cancer is staged surgically as shown in Table 39–5.

Clinical Findings

Postmenopausal bleeding is the presenting symptom in about 90% of cases and should be considered to be cancer until proven otherwise. Common etiologies of postmenopausal bleeding include physiologic bleeding from hormone replacement therapy (27%), benign polyps (7%-23%), cervicitis (6%-14%), endometrial carcinoma (13%-16%), atrophy (10%), cervical carcinoma (1%-4%). Despite workup, up to 20%-23% of cases will have no identified etiology. Cervical stenosis with pyometrium or hematometrium is highly suggestive of endometrial carcinoma. Pain is not a common symptom. Vaginal cytology is positive in 40%-80% of cases but is entirely unreliable as a diagnostic tool for endometrial cancer. Endometrial biopsy performed in the office using a disposable biopsy instrument is highly sensitive. If endometrial biopsy fails to provide a definitive diagnosis, dilatation and curettage of endocervix and endometrium, is definitive.

Type II endometrial carcinoma comprised of poorly differentiated, or adverse histological types, may disseminate relatively early in the course of the disease. Metastatic spread may occur to the vagina, regional pelvic and para-aortic lymph nodes, ovaries, lungs, brain, and bone. The most frequent site of recurrence following treatment for endometrial carcinoma is the vaginal vault.

Prevention

Oral contraceptives have been shown to reduce the risk of endometrial cancer by up to 50% depending on duration of treatment. Progestin therapy will reduce the possibility of endometrial carcinoma in the anovulatory patient as well as in postmenopausal women receiving estrogen replacement therapy. Progestins in both OCP and hormone replacement regimens cause downregulation of estrogen receptors and atrophy of endometrium.

Treatment

Endometrial cancer is staged surgically. The route of surgical approach for the staging procedure can be either via laparotomy or laparoscopy. Definitive therapy includes total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy and pelvic washings for type I cancers. For type II lesions, omentectomy is usually added. Lymphadenectomy is sometimes omitted for patients with type I lesions with low-risk such as small, grade-1 cancers without myometrial invasion.

If the cervix is grossly involved, patients may receive preoperative radiation followed by total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy and pelvic washings. Alternatively, a radical hysterectomy bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy may be performed without preoperative radiation. The radical hysterectomy includes removal of the upper third of the vagina, cardinal, and uterosacral ligaments.

Adjuvant pelvic radiation therapy is administered to patients with cervical extension (stage II); deep myometrial invasion with a grade 3, type I lesion; or vaginal extension (stage IIIB). A randomized clinical trial comparing radiation to chemotherapy with cisplatin and doxorubicin showed a survival benefit for patients with positive nodes (stage IIIC) treated with chemotherapy. Metastatic and type II lesions such as papillary serous carcinomas are very likely to recur after surgery regardless of stage. These tumors are usually treated with multimodal therapy using a combination of radiation and chemotherapy.

Metastatic or recurrent disease is usually treated with multimodal therapy using surgery, radiation and/or chemotherapy based on the location, size, and histology of lesions. Chemotherapy combinations usually include either a doublet of cisplatin with paclitaxel or doxorubicin or a triplet regimen combining all three drugs. Metastatic cancer of type I may be treated with progestin therapy.

Prognosis

Survival at 5 years is about 70%-90% for stage I disease, depending on grade and myometrial invasion. Survival declines to about 60% in stage II. Anaplastic tumors, deep myometrial penetration, and absence of estrogen and progesterone receptors all worsen the prognosis.

Uterine Sarcoma

Uterine sarcomas fall into three histological groups including leiomyosarcoma, endometrial stromal sarcoma, and carcinosarcoma. These tumors are rare, accounting for about 3% of uterine neoplasms. Sarcomas of the uterus spread via hematogenous and lymphatic pathways in addition to direct extension. Lung and liver are frequent sites of metastases and recurrence.

In patients in whom the tumor is confined to the pelvic organs, treatment consists of total hysterectomy, bilateral salpingo-oophorectomy, pelvic and para-aortic lymphadenectomy, omentectomy and pelvic washings. There are no randomized trials documenting survival benefit for adjuvant therapy with either chemotherapy or radiation. However, individualized postoperative radiation and/or chemotherapy may be offered based on the poor prognosis of these tumors. Radiation reduces pelvic recurrences, but does not appear to improve overall survival.

The outlook for patients with uterine sarcoma is dependent on grade and stage of the tumor. Leiomyosarcomas with more than ten mitoses per ten high-power fields carry a poor prognosis, with recurrence within 5 years in about two-thirds of patients. About 40% of patients with carcinosarcoma survive. Isolated, late recurrence of leiomyosarcoma in the lung is treated by resection of the affected lobe with generally good salvage rates of about 50% at 2 years.

Gemcitabine and Taxotere is the combination with the highest likelihood of response for metastatic or recurrent leiomyosarcoma. High-dose progestin therapy is very effective for treatment of metastatic low-grade endometrial sarcoma. Carcinosarcoma is most effectively treated with combination of either cisplatin and ifosfamide or ifosfamide and paclitaxel.

Gestational Trophoblastic Disease

Gestational trophoblastic disease refers to tumors arising from placental tissue. They are unique among all neoplasms in that their genetic complement is provided by the father, thereby resulting in a tumor with genetic material and markers foreign to the patient. Gestational trophoblastic diseases may be divided into preinvasive and invasive types. The preinvasive types include complete and partial hydatidiform moles.

The frequency of hydatidiform mole is about 1:700 to 1:2000 pregnancies in the United States, Canada, and Western Europe and about 1:85 to 1:520 pregnancies in Asia. Hydatidiform mole is more common in women over 40. A prior history of gestational trophoblastic disease significantly increases the risk of recurrence with a future gestation.

The gross appearance of a hydatidiform mole is related to the hydropic villi in the absence of a fetal circulation. The histological appearance reveals varying degrees of trophoblastic proliferation. Hydatidiform moles can be classified as either complete or partial, based on cytogenetics and histopathology. These features are compared in Table 39–6. The majority of complete moles carry a 46XX karyotype, with chromosomes exclusively of paternal origin. Partial moles are typically triploid with 69XXX or 69XXY, where two or three sets of chromosomes are paternal in origin. Complete moles are not associated with a developing fetus, and partial moles may include a fetus that is typically small and with multiple anomalies.

Invasive gestational trophoblastic disease is categorized as invasive mole, choriocarcinoma, or placental site trophoblastic tumor. Invasive mole is diagnosed after 15% of complete moles and 3.5% of partial moles. Metastases occur following 4% of complete moles and 0.6% of partial moles. Choriocarcinoma occurs following 3%-7% of hydatidiform moles and 1:40,000 term pregnancies. Out of all choriocarcinoma cases, 50% are preceded by a mole, 25% by spontaneous abortion, and 25% by term pregnancy. Placental site trophoblast tumor (PSTT) is a very rare variant with only 55 cases reported in the literature by 1991.

Invasive mole is comprised of hyperplastic trophoblasts with villi invading myometrium. Choriocarcinoma involves sheets of syncytiotrophoblasts with no villi and demonstrates invasion into myometrium or other tissues. Necrosis and hemorrhage are common. PSTT is comprised of intermediate cytotrophoblasts.

Human chorionic gonadotropin (β-hCG) is a clinically useful tumor marker for all types of preinvasive and invasive gestational trophoblastic disease except PSTT, where human placental lactogen (hPL) may be elevated.

Clinical Findings

The most common presenting symptom with hydatidiform mole is vaginal bleeding, occurring in 97% of complete moles and 73% of partial moles. On pelvic exam, about 50% of complete moles and 8% of partial moles will reveal uterine size greater than expected for a given estimated gestational age. Theca lutein cysts are physiologic ovarian cysts as a result of hyperstimulation by very high levels of β-hCG produced by 50% of complete moles. These cysts typically resolve once the β-hCG level regresses following appropriate treatment. Preeclampsia may develop in 27% of women with complete moles and virtually never with partial moles. Clinical hyperthyroidism can develop in about 7% of women with complete moles with very high β-hCG levels due to cross reactivity of this hormone with thyroid stimulating hormone. A rare but potentially fatal complication is trophoblastic embolization to the lung during or after evacuation of large complete moles.

Diagnosis is usually confirmed with either ultrasound or β-hCG values. Serum β-hCG levels are above 100,000 mIU/mL in 46% of women with complete moles and these values persist beyond the twelfth week gestation, neither of which should be observed in a normal pregnancy. Ultrasound will usually demonstrate multiple small sonolucencies due to the hydropic villi. In a partial mole, the fetus, if present, will usually be small and afflicted with multiple anomalies.

Differential Diagnosis

Threatened abortion or missed abortion will often present with similar symptoms of bleeding and both are more likely than gestational trophoblastic disease. A multiple gestation must be considered because it may produce unusually high levels of β-hCG in addition to uterine size greater than the gestational date.

Complications

Metastasis is most common with choriocarcinoma, but may occur with any of the invasive types of gestational trophoblastic disease. The most common sites of spread include lung (80%), vagina (30%), pelvis (20%), brain or liver (10%), bowel or kidney or spleen (<5%). Unlike virtually any other tumor, metastatic disease is still potentially curable in many patients.

Treatment

Once the diagnosis of a molar pregnancy has been established, the uterus should be evacuated by suction curettage. All specimens are submitted for histology and cytogenetics. Theca lutein cysts of the ovaries regress following treatment of the mole and should not be surgically excised.

Following evacuation of the uterus, weekly serum β-hCG levels should be monitored until normalized for 3 weeks; followed by monthly testing for 6-12 months depending on assessment of pretreatment risk factors. If the β-hCG value plateaus for 3 weeks or rises for 2 weeks, invasive gestational trophoblastic disease including either invasive mole or choriocarcinoma should be suspected. Effective contraception during the surveillance phase is important in order not to complicate interpretation of the β-hCG.

Patients with invasive or persistent gestational trophoblastic disease should be evaluated with a metastatic workup including pelvic examination, CT scan of the head, chest, abdomen, and pelvis, a complete blood count, and renal and liver function tests. Lumber puncture to detect occult central nervous system metastases is sometimes necessary.

Staging of gestational trophoblastic tumors is outlined in Table 39–7. Unlike most neoplasms, gestational trophoblastic disease is staged using a nonanatomic staging system based on prognostic factors. Current FIGO staging combines anatomic staging with the modified WHO prognostic scoring system. For anatomic stage I disease, risk is usually low and for anatomic stage IV disease, risk is usually high. Stage II and III disease is best stratified with the modified WHO prognostic scoring system. Stage is recorded as anatomic stage and FIGO modified WHO score, separated by colon.

Single-agent chemotherapy is the preferred treatment for patients with stage I or low-risk disease who wish to maintain reproductive options. If future childbearing is not an issue, patients with invasive mole may be treated with a hysterectomy and possible adjuvant chemotherapy. Preferred regimens for single-agent therapy include methotrexate or dactinomycin. Both of these regimens can be toxic and should be administered under the guidance of a gynecologic oncologist or medical oncologist. Intermediate and high-risk gestational trophoblastic disease should receive aggressive combination chemotherapy. The most effective regimen reported includes etoposide, methotrexate, dactinomycin, cyclophosphamide, and vincristine (EMACO). There is occasionally a role for surgery or radiation for selected metastatic disease sites and intrathecal methotrexate is sometimes needed for treatment of central nervous system disease.

Prognosis

The prognosis for cure of gestational trophoblastic tumors is excellent, including cases with pulmonary metastases, which are still considered low risk. Five-year survival of up to 85% is reported in cases with high-risk metastatic disease. The risk of recurrence of gestational trophoblastic disease in a future pregnancy has a relative risk of 20-40, but in absolute terms, this translates to a recurrence risk of less than 5%. During any subsequent pregnancy, ultrasound is recommended. The placenta should be examined after delivery, and β-hCG should be monitored until normalization.

SURGERY FOR BENIGN FALLOPIAN TUBE DISEASE

Infertility Attributed to Fallopian Tube Disease

Infertility is defined as failure to conceive after 1 year of normal coital activity without use of contraceptives. About 15% of couples are infertile within this definition. When the etiology of infertility is evaluated, approximately 40% will be attributable to male factor infertility including low sperm count, impaired motility, or abnormal morphology of sperm. Anatomic abnormality of the pelvic organs is the single most common cause of infertility in women, and tubal factor infertility is the most common cause of infertility.

Common causes for tubal factor infertility include acute and chronic salpingitis, endometriosis, and adhesions from previous appendicitis with rupture or surgery. Chlamydia and gonorrhea infections are the most common causes of tubal damage causing infertility. Desire to reverse previous tubal sterilization may also be a reason for tubal surgery. One-third of infertile couples have more than one problem.

History

It is important to elicit any history of sexually transmitted disease, pelvic inflammatory disease, pelvic surgery, cyclic pain, or dyspareunia.

Clinical Findings

The size and mobility of the uterus should be assessed. Adnexae should be palpated for masses consistent with endometrioma or hydrosalpinx, in particular. Cul de sac or uterosacral ligament nodularity and tenderness suggest endometriosis. Ultrasound may reveal the presence of isoechoic masses suggesting endometriosis or a tubular mass consistent with hydrosalpinx. Hysterosalpingogram, a test that involves fluoroscopic assessment of tubal patency by transcervical injection of the uterus with radiocontrast, may reveal an obstruction including its location. Use of a water-based dye is indicated for the first attempt, and if occlusion is noted, an oil contrast medium may be used subsequently. The oil based hysterosalpingogram is reported to have therapeutic benefit.

Laparoscopy is warranted if the evaluation for anatomic abnormalities is inconclusive. Therapeutic interventions including lysis of adhesions or ablation of endometrial implants may be efficacious. If laparoscopy is performed following a normal hysterosalpingogram 24% will have mild endometriosis and 6% of patients will have adhesions.

Treatment

Tuboplasty procedures may be performed to restore tubal patency. However, in vitro fertilization has become a much more popular intervention in recent years for treatment of infertility attributed to tubal occlusion or when multiple infertility factors affect the couple. Hydrosalpinx is usually treated by salpingectomy in order to optimize subsequent in vitro fertilization. Other factors of prognostic significance include age of the couple, and presence of other causes of infertility including ovulatory dysfunction or male factor infertility.

Heterotopic pregnancies and multiple gestation pregnancies are much more likely than the general population for patients undergoing in vitro fertilization.

Prognosis

Age and severity of tubal disease are predictors of success. Women with mild adhesive disease and age less than 35 have the highest success rates, approaching 70%. For severe tubal disease, success is less than 15%. Ectopic pregnancy is twenty times more likely with a history of Fallopian tube surgery or preexisting scar resulting in a 10% incidence. IVF success rates vary by program and have generally been improving steadily in recent years. Decisions regarding planned tubal surgery versus IVF should take into account the relative costs and success rates.

Ectopic Pregnancy

Ectopic pregnancy is implantation of a viable pregnancy in a location other than within the endometrium lining the uterus. Risk factors for ectopic pregnancy include prior tubal surgery, previous ectopic pregnancy, history of pelvic inflammatory disease or Chlamydia infection, and pregnancy arising from assisted reproduction techniques. Smoking and history of infertility are also associated with increased risk of ectopic pregnancy. Over 95% of ectopic pregnancies occur in the Fallopian tube, generally within the ampullary portion. A less common location includes interstitial pregnancy within the tubal lumen where it passes through the myometrium. Rare sites include cervix, ovary, omentum, pelvis, and abdomen. Heterotopic pregnancy refers to the rare occurrence of an intrauterine pregnancy with a synchronous ectopic pregnancy. The incidence of heterotopic pregnancy has increased from a spontaneous rate of 1:30,000 pregnancies to 0.1%-1% for pregnancies arising from assisted reproductive technology.

The incidence of ectopic pregnancy has been reported to occur in approximately 2% of pregnancies, although the true incidence is difficult to ascertain due to the potential for spontaneous resolution of some ectopic pregnancies resulting in unrecognized disease in addition to under reporting of early ectopic pregnancies treated medically rather than surgically. Pregnant women with pain or bleeding have a fourfold higher incidence of ectopic pregnancy. The primary potential morbidity of ectopic pregnancy is the potential rupture of the Fallopian tube or other implantation site resulting in hemorrhage. Failure to make a timely diagnosis can result in hemorrhagic shock and death.

Symptoms & Signs

Patients will usually present with amenorrhea and a diagnosis of pregnancy. Subsequent irregular bleeding occurs in many but not all cases. In the early evolution of the ectopic pregnancy, patients may be asymptomatic. Presence of pain is also variable. Classic symptoms of a ruptured ectopic include severe abdominal pain, referred pain to the shoulder and hemodynamic instability. Upon pelvic examination an adnexal mass may or may not be present. The uterus is usually slightly enlarged and softened secondary to hormonal influence of the ectopic pregnancy.

Diagnostic Studies

Trophoblastic cells of the blastocyst produce β-hCG that may be detected shortly after implantation. The rise of β-hCG is logarithmic, with a doubling time of about 48 hours. The β-hCG should rise at least 66% every 48 hours in 85% of normal pregnancies and will plateau in normal pregnancy late in the first trimester. Ectopic pregnancies show a slower rise of β-hCG in all but 15% of cases. An absolute β-hCG does not permit distinction between an ectopic and a nonviable intrauterine pregnancy.

Transvaginal ultrasound has almost 100% sensitivity for detection of intrauterine pregnancy as long as care is taken to discriminate between an actual pregnancy and the pseudo sac, defined as intrauterine fluid that can be mistaken for an intrauterine pregnancy. A true gestational sac is located eccentrically in the uterus and should demonstrate a fetal pole. The absence of an intrauterine pregnancy in the setting of a positive β-hCG is strongly suggestive of an ectopic pregnancy if the β-hCG value is above the discriminatory threshold of transvaginal ultrasound to detect a gestational sac. The discriminatory threshold has been reported to occur with β-hCG values above 1500-3000 mIU/mL, although variables such as body mass index, quality of ultrasound equipment, and experience of the sonographer all impact on the threshold value. Diagnosis of the ectopic pregnancy by direct ultrasound localization of the pregnancy is much less accurate than detection of intrauterine implantation.

Other tests that are of value include obtaining a blood count to assess for anemia in addition to serum progesterone levels. Variability of progesterone values in normal pregnancy limits the utility of this test for diagnosis of ectopic pregnancy.

Treatment

If the β-hCG shows an abnormal rate of rise, including plateau, slow rise, or declining values, then ultrasound is warranted. However, if the β-hCG value is below the discriminatory threshold, suction curettage is useful to distinguish between a nonviable intrauterine pregnancy and an ectopic gestation. The absence of chorionic villi in the curettage specimen in the presence of an elevated hCG is predictive of an ectopic pregnancy, though in early gestation the curettage may be falsely negative for villi.

Treatment of ectopic pregnancy is either surgical or medical depending on several variables. The surgical approach is definitive, but invasive and more costly than medical management. Medical management results in successful treatment for 90% of appropriately selected patients. Methotrexate is utilized for medical management. Appropriate indications for medical management require a hemodynamically stable patient who is compliant and has no medical contraindication to methotrexate. Relative contraindications include a gestational sac > 3.5 cm, presence of fetal cardiac motion, or a β-hCG value of > 15,000 mIU/mL. Administration of a single dose of methotrexate has reported efficacy of 84%. Use of multidose regimens increases the rate of success. Failure of the β-hCG value to fall by at least 15% within 4-7 days after treatment indicates that additional methotrexate or surgery is indicated. Patients who are Rh negative are given RH_o(D) immune globulin whether treated medically or surgically. Other developments in medical management include the use of other agents such as potassium chloride, prostaglandins, and mifepristone, but these have not been studied as well as methotrexate.

Surgical options for treatment of ectopic pregnancy are intended to remove the ectopic gestation and preserve functional Fallopian tube, if possible. If the patient is hemodynamically stable, the laparoscopic approach is usually preferred. If she is in shock or if the abdomen is distended with blood, emergent laparotomy is necessary. If the Fallopian tube is generally healthy, a salpingostomy is possible whereby the involved section of the Fallopian tube is removed through an incision in the antimesenteric portion of the tube, while leaving the remainder of the tube intact. If the tube is more extensively damaged, complete or partial salpingectomy is recommended. If conservative approaches to preserve the Fallopian tube are utilized, the β-hCG value should be monitored postoperatively until normalization occurs.

Expectant management of a documented ectopic pregnancy may be an option in stable patients if the β-hCG value is less than 200 mIU/mL and declining. Patients must be counseled regarding the risks of rupture and hemorrhage, and emergency management must be readily available.

Contraception

Contraception to prevent unwanted pregnancy may be attained using either reversible or permanent methods. Reversible methods include hormonal contraceptives via oral, transcutaneous or subcutaneous routes; injectable long acting progestins; IUD; and condoms, to name a few. Modern IUD contraceptives contain progestational hormones or copper, delivered in low doses to the uterine cavity where they inhibit sperm motility and block fertilization. They are inserted as an office procedure without requiring local anesthetic or cervical dilation in most cases. Both copper and progestin devices are highly effective and long lasting. Contemporary IUD contraceptives do not increase the risk of pelvic infection. Progestin-releasing IUD devices menstrual flow by about 50% and have been shown to be as effective for control of abnormal uterine bleeding, prevention of hyperplasia during estrogen replacement therapy, and treatment of hyperplasia.

Subdermal implant contraception uses low serum concentrations of contraceptive progestins found in birth control pills to thicken cervical mucus and inhibit ovulation. These actions result in failure rates comparable to those reported following sterilization and intrauterine contraception. Their duration of action is FDA approved for 3 years. As with intrauterine contraceptives, the principal side effect is change in menstrual bleeding; the majority of users experience a diminution in blood loss but an increase in number of days of bleeding, sometimes at unpredictable intervals.

Contraceptive implants require subdermal insertion with a disposable trocar with local anesthetic and are removed under local anesthetic through a small incision. These procedures take only a few minutes, and pain and infections are rare. Contemporary systems utilize a single-rod and are easier to use, have a shorter life, and are associated with somewhat more acceptable bleeding patterns than the now-discontinued multirod implants.

Unintended pregnancies result in about one million abortions per year in the United States. Uterine aspiration using either manual or electric vacuum pumps allows safe elective abortion in the first trimester, with a mortality rate of less than 1:200,000 procedures. Morbidity and mortality of abortion rises substantially as the length of gestation increases.

Permanent sterilization options are available for both men and women. Prior to performing any permanent sterilization procedure, the physician must carefully counsel and determine whether a permanent method of contraception is appropriate for the patient. Reversal of permanent sterilization is costly and often ineffective. Permanent male sterilization via vasectomy is safe, effective with reported failure rates of 1.5 per 1000, and minimally invasive. For women, there are several permanent sterilization options. Most of the procedures for women are designed to occlude or remove the Fallopian tube via laparotomy or laparoscopy. These include Pomeroy, Irving, Uchida, and Madelener laparotomy operations in addition to laparoscopic procedures using unipolar or bipolar electrosurgical coagulation of the Fallopian tubes, application of Silastic bands or proprietary clips (Filshie clips, Hulka clips). Mini laparotomy for Pomeroy-type tubal occlusion is often utilized for postpartum sterilization. There are now a limited number of proprietary methods of transcervical tubal occlusion based on intrauterine access to the tubal ostia using a hysteroscope.

The observed failure rate for tubal ligation procedures ranges from 0.7% to 3.6%, which is comparable to the failure rate of IUD and subdermal implants.

SURGERY FOR MALIGNANT FALLOPIAN TUBE DISEASE

Benign and malignant tumors of the Fallopian tubes are very rare. Adenocarcinoma of the Fallopian tube accounts for less than 1% of female reproductive tract cancers. Women with BRCA1 and 2 mutations are at increased risk for Fallopian tube cancer concordant with their increased risk for ovarian cancer.

The most common presenting symptoms for cancer of the Fallopian tubes are postmenopausal vaginal bleeding or history of intermittent and profuse, watery vaginal discharge. The latter symptom is referred to as hydrops tubae perfluens. An adnexal mass is sometimes, but not always palpable. Tumor markers such as CA-125 are usually elevated, although early stage disease may result in elevation of the CA-125 in less than half of patients with Fallopian tube or ovarian cancers. The diagnosis of the Fallopian tube carcinoma is usually not made preoperatively.

The differential diagnosis for Fallopian tube cancer includes disorders that may result in enlargement or obstruction of the distal Fallopian tube. The most common example would be hydrosalpinx whereby obstruction of the Fallopian tube results in accumulation of fluid within the lumen and causes distension of the tube. Common causes of hydrosalpinx include prior infection or endometriosis. Another potential confounding diagnosis is the presence of paratubal cysts, which are simple cysts arising in the mesosalpinx or loosely attached to the exterior of the tube. Paratubal cysts are nearly always benign and arise from Müllerian and Wolffian duct remnants.

Fallopian tube cancer is staged using the FIGO staging rules for ovarian cancer.

Treatment for Fallopian tube cancer is identical to treatment for ovarian cancer. Multimodal therapy including a primary surgery for staging and debulking of disease is followed by adjuvant chemotherapy based on the stage and grade of the disease. A more detailed discussion of the surgery and postoperative adjuvant therapy considerations is described in the ovarian cancer section of this chapter. If the disease is confined to the tube, the prognosis is good. Like ovarian cancer, most Fallopian tube cancers are of advanced stage at the time of diagnosis, and the subsequent survival is much lower.

SURGERY FOR BENIGN OVARIAN DISEASE

Adnexal Masses

Adnexal masses are abnormal structures arising in the ovary, Fallopian tube, or broad ligament. Preoperative assessment can narrow the differential diagnosis, but definitive diagnosis usually requires surgical resection or biopsy.

The differential diagnosis of adnexal masses is complex (Table 39–8). Every structure native to the pelvis can potentially present as a detectable adnexal mass. The majority is benign, but the probability of malignancy increases with age. About 10% of persistent adnexal masses attributable to the ovary are malignant in premenopausal women rising to nearly 50% in postmenopausal women.

Functional Cysts

Functional cysts are relatively common in reproductive age women, but are also reported in postmenopausal women. These cysts are usually larger than 3 cm in order to be diagnosed and may attain diameters of up to 10 cm. Histological examination reveals no pathologic features such as atypia, necrosis, or invasion. Follicular cysts produce estrogen until resolution of the cyst and the corpus luteum cyst produces progesterone until resolution. Because of the hormone production by these types of cysts, menses may be delayed or irregular, often leading to an incorrect clinical diagnosis of ectopic pregnancy. The least common type of functional cyst is the theca lutein cyst, which arises as a physiologic response to hyperstimulation by elevated β-hCG values produced by complete hydatidiform moles. Functional cysts usually regress spontaneously within 1-3 months, or in the case of theca lutein cysts, when the β-hCG value normalizes following treatment.

Correct identification of functional cysts prevents many unnecessary surgical procedures. The functional cyst is typically a smooth, unilateral cyst on pelvic examination. Transvaginal ultrasound will show a simple, sonolucent morphology and β-hCG is not elevated. Follow-up examination with ultrasound after 4-6 weeks will generally demonstrate resolution without treatment. About 85% of functional cysts smaller than 6 cm regress, but larger masses may be more likely to persist. Feedback inhibition on pituitary gonadotropin production by hormonal suppression with oral contraceptives may prevent development of additional functional cysts and are advocated by some clinicians to assist in the regression of existing cysts. Hormonal suppression is by no means required, however, since the majority of functional cysts will regress without intervention.

The majority of functional cysts remain asymptomatic, but they will occasionally rupture or undergo torsion resulting in acute colicky abdominal or flank pain. Torsion requires prompt surgical intervention, usually with laparoscopy, in order to restore the vascular supply to the ovary by untwisting the pedicle before significant ischemia or necrosis of the ovary can occur. If the functional cyst ruptures pain of varying levels may occur. In rare cases, bleeding from the ovary leads to hemodynamic instability requiring surgery. Hospitalization for observation for 24 hours, allowing serial examinations and blood counts is appropriate for patients with symptomatic cyst rupture.

Persistent Adnexal Masses

Adnexal masses that persist are likely to be neoplasms. Benign masses can generally be removed effectively by the general gynecologic surgeon, while malignancies are more effectively treated by gynecologic oncologists with expertise for surgical staging, debulking, and administration of adjuvant therapies to optimize outcome. Triage of adnexal masses provides the best opportunity to serve the patient’s interest by having the correct surgical team involved in care of the patient.

The most useful test for assessment of the newly diagnosed adnexal mass is transvaginal ultrasound. Ultrasound is particularly well suited for delineation of the morphologic features of adnexal masses. Medical literature abounds with description of morphology that correlates with benign and malignant neoplasms of the ovary. Figure 39–7 illustrates the morphologic features used to distinguish possible cancers from likely benign lesions. The reported sensitivity for identifying a malignant ovarian neoplasm is 90%-94%, but specificity is only about 60%. Specificity can be improved to about 85% without reducing sensitivity by evaluating Doppler waveforms in the tumor vessels. Vessels arising in malignant lesions have lower resistance to flow than in normal tissues: the ratio of diastolic to systolic flow is therefore higher than in normal tissue (Figure 39–8) and this can be quantitated by reporting the pulsatility index. This test is more specialized, costly and time consuming, limiting its effective use to selected lesions. MRI appears to have a promising role in the characterization of adnexal masses, but is much more costly than ultrasonography.

In addition to ultrasound, tumor markers can be very useful for triage of the palpable adnexal mass. The ideal tumor marker is elevated only in the presence of cancer and should correlate with the burden of disease. In reality, no marker is perfect. There are identified markers for ovarian malignancies arising from germ cell, epithelial and stromal origin. Optimal use of tumor markers involves ordering markers most likely to be clinically useful based on clinical presentation rather than to order all of them. Commonly used tumor markers are listed in Table 39–9. Many new markers will likely be validated in the next few years, including panels of multiple markers using gene chip technology. For example, malignant germ cell neoplasms usually arise in women younger than 35, are almost always unilateral, and typically demonstrate solid morphology on ultrasound evaluation. In this setting, it would be appropriate to order tumor markers including alpha fetoprotein (AFP), β-hCG, and lactate dehydrogenase (LDH). Epithelial tumors are more often complex cystic and solid, bilateral lesions. In this circumstance CA-125, CA-19-9 and CEA are better markers. Interpretation of CA-125 is difficult in premenopausal women because benign diseases such as endometriosis, which is much more common than ovarian cancer, will cause false positive test results. In addition, many tumor markers are normally elevated in pregnancy, thereby complicating evaluation of masses diagnosed during pregnancy.

The American College of Obstetricians and Gynecologists has issued a committee opinion regarding triage of adnexal masses that recommends referral of individuals with high-risk characteristics to gynecologic oncology subspecialists. For postmenopausal women, referral is warranted for patients with a pelvic mass and at least one of the following: CA-125 above 35 U/mL, ascites, nodular or fixed mass, evidence of abdominal or distant metastasis, or family history of one or more first-degree relatives with ovarian or breast cancer. In premenopausal women, the recommendations are identical except the threshold for CA-125 is raised to > 200 U/mL, to account for diseases such as endometriosis in this age group. Motivation for referral is based upon data showing higher staging accuracy and improved outcome when subspecialists treat ovarian cancer patients.

Low-risk masses thought to be functional cysts are managed expectantly. A mass that persists, or demonstrates worrisome features on exam, imaging studies or tumor marker measurement should be resected. A basic principle of surgical resection for ovarian neoplasms is not to allow spill or rupture of cyst contents into the abdomen. It is never appropriate to needle aspirate an ovarian mass that may harbor malignancy because of the potential to spread disease intra-abdominally. The surgical procedure to be performed is either oophorectomy or ovarian cystectomy for high-risk and low-risk lesions, respectively. The route of surgical approach may be either with laparoscopy or laparotomy. The laparoscopic approach is better suited for cystic masses that are small enough to be placed in a specimen retrieval bag without spill or rupture. Large or solid masses or evidence of metastatic disease such as ascites or omental caking require laparotomy for removal. Ovarian conservation is chosen after a balanced assessment of relative risk for cardiac disease versus ovarian cancer. In women with benign appearing masses under 60, they can expect some cardioprotective benefit even after menopause.

A simple cystic mass of less than 5 cm with normal CA-125 is considered low risk, even in the postmenopausal woman. Conservative management is reasonable.

SURGERY FOR MALIGNANT OVARIAN DISEASE

Ovarian cancer is stratified into three histological groups based on the cellular origin of the tumor. Epithelial tumors, germ cell tumors, and sex cord-stromal tumors comprise the primary lesions, and the fourth category is from disease arising elsewhere that metastasizes to ovary. Epithelial carcinoma accounts for about 85% of ovarian cancers, and about 5% arise from each of the remaining categories of germ cell, sex-cord stromal and metastatic disease from other sites. The peak incidence of epithelial ovarian cancer is in the fifth and sixth decades of life, while malignant germ cell tumors are more likely to occur under the age of 30. Stromal tumors have a bimodal distribution with peaks around ages 25 and 55 years of age. Malignant ovarian disease spreads by primary extension in the peritoneal cavity, in addition to lymphatic and hematogenous spread.

Epithelial ovarian cancer etiology can be either sporadic or hereditary. The sporadic cases appear to be strongly related to number of lifetime ovulations or chronicity of gonadotropin stimulation. There are also data to suggest environmental impact with the observation that tubal ligation results in reduction of risk, and diets with high lipids relative to omega-3 fatty acids increase risk. About 10% of ovarian cancers are hereditary. Three pedigrees account for most hereditary cases, including ovary-site specific, breast-ovary, and hereditary nonpolyposis colorectal cancer (HNPCC). Genetic inheritance of a mutation in the BRCA1 or BRCA2 gene imparts up to a 40% or a 25% lifetime risk of developing ovarian cancer, respectively. Ethnic groups including Ashkenazi Jews and Icelandic peoples have increased incidence of founder mutations that increase risk. Other reproductive factors associated with an increased risk include infertility, including use of ovulation induction agents. A recent discovery is that many if not the majority of epithelial cancers may arise in the fallopian tubes and subsequently spread to the ovaries.

Epithelial tumors are divided into invasive and low malignant potential (borderline) types. The invasive type accounts for 80% of epithelial cancer and is usually detected in advanced stages. The low malignant tumors occur in women with an average age 10-15 years younger than for invasive disease and up to 80% are stage I at diagnosis. Destructive stromal invasion is absent in low malignant potential tumors, but they are considered to be malignant and have the potential to metastasize. Epithelial tumors are subcategorized by histology as serous, mucinous, endometrioid, clear cell, transitional cell, or undifferentiated types. Serous tumors are the most common, comprising about 50% of epithelial carcinomas. Endometrioid carcinomas are the second most frequent variety, accounting for 24% of ovarian cancers, and are sometimes associated with endometriosis. Clear cell tumors, accounting for less than 5% of epithelial tumors, are also associated with endometriosis and have a more virulent natural history. Mucinous tumors account for 15% of epithelial cancers, and may become very large. Epithelial ovarian cancer is commonly involves both ovaries.

Germ cell cancer types include dysgerminomas, immature teratoma, endodermal sinus tumor, mixed types, and rare nongestational choriocarcinoma. Germ cell cancers are almost always unilateral and are commonly detected while stage I. Germ cell cancers are three time more common in women of Asian or African descent. A separate entity is adult-type cancer arising in an otherwise benign mature cystic teratoma. This can occur in up to 1% of mature cystic teratomas and is most commonly a squamous carcinoma.

The most common sex-cord stromal tumors include Sertoli-Leydig, adult granulosa, and juvenile granulosa cell tumors. These are frequently hormonally active tumors. Sertoli-Leydig cell tumors occur most often in the third decade, and arise from Wolffian duct remnants. They are rare and usually produce testosterone, resulting in manifest defeminization (amenorrhea, atrophy of the breast) and virilization (deepening of the voice, hirsutism, clitoral hypertrophy). Adult granulosa cell tumors arise in the sixth decade and are estrogen-producing tumors in most instances. Because of the estrogen production, postmenopausal bleeding is common, and endometrial cancer may arise in up to 15%. Juvenile granulosa cell tumors are similar, but arise in younger patients. Like germ cell tumors, the sex-cord stromal tumors are unilateral in most cases and detection is typically at early stages.

Metastatic carcinoma from other primary sites occurs not infrequently. Common sites include the gastrointestinal tract (Krukenberg tumor), breast, pancreas, lymphoma, and kidney. These tumors are classically solid, and bilateral. Prognosis for these tumors is especially poor.

Clinical Findings

Almost 90% of stage I patients have symptoms and only 5% are asymptomatic. The symptoms usually include gastrointestinal complaints that persist for an average of 12 days per month for 3 months. Less often, pelvic pain or metrorrhagia may be present. On examination, any mass should prompt further evaluation. An ovarian mass should be regarded as potentially malignant until proven otherwise. Smooth, mobile masses on exam indicate low risk and solid, irregular, or fixed pelvic masses are suggestive malignancy. Triage of the pelvic mass should include transvaginal pelvic ultrasound and selective tumor markers as described previously in the adnexal mass section of this chapter. It should be noted that CA-125 may be negative in half of early-stage ovarian cancers. If an ovarian malignancy is suspected preoperatively, referral to a gynecologic oncologist is recommended.

Occasionally, ovarian cancer is discovered during an operation for different indication or when triage has not been properly performed. If ascites, carcinomatosis, or papillary excrescences are noted, the tumor should be removed intact and submitted for frozen section. If cancer is diagnosed, a gynecologic or surgical oncologist should be consulted for surgical staging and debulking.

Treatment

Ovarian cancer is staged surgically (Table 39–10). When a complex adnexal mass is to be removed the procedure should begin with obtaining washings for cytology, and the mass should subsequently be removed intact. Upon removal of the mass, a frozen section should be obtained for definitive diagnosis. If an ovarian malignancy is confirmed, complete staging requires assessment and biopsy of the pelvic and para-aortic nodes, omentum, and peritoneum. All peritoneal surfaces are inspected and any suspicious lesions are biopsied. If no suspicious lesions are noted, a predetermined pattern of biopsies is taken from the pelvic sidewalls, cul de sac, bladder peritoneum, pericolic gutters and both hemidiaphragms. A decision must be made about possible resection of the uterus and contralateral ovary. If the patient is young and desires to retain her fertility, criteria to identify candidates for conservation of fertility should be applied. Factors that favor preservation of fertility include germ cell and sex-cord stromal tumors because they are usually unilateral, and subsequent chemotherapy, if needed, has curative potential. Low malignant potential tumors affecting one ovary or in select cases where extra-ovarian disease can be completely resected are also candidates. Patients with invasive epithelial tumors are poor candidates for conservative surgery because of the high likelihood of bilateral involvement and the primarily palliative role of chemotherapy for all but early stages of disease. If preservation of fertility is not appropriate, then hysterectomy and removal of the contralateral tube and ovary is completed.

When the disease spread into the pelvis or abdomen is documented, debulking of all resectable macroscopic disease is critically important. Numerous randomized clinical trials have demonstrated the concept of debulking and consistently show survival advantage for patients with maximal cytoreduction. Intraoperative decision making for debulking focuses effort on the biggest tumor, wherever it may be. If the largest lesion can be resected, attention is directed to the next largest lesion. This process continues until either all measurable disease is removed or a lesion that is unresectable is encountered. In order to resect the disease at each decision point of this algorithm, the surgeon may need to perform intestinal resection, splenectomy, modified posterior exenteration, culdotomy, diaphragm resection, and other upper abdominal procedures. In two prospective Gynecologic Oncology Group clinical trials survival for microscopically debulked ovarian cancer was 65% at 4 years, and fell to about 35% if less than 1 cm of macroscopic residual disease remained after surgery. If greater than 2 cm of residual disease remained, the 4-year survival was only 20%. Optimal debulking can be attained in up to 70% of patients who are operated on by subspecialists trained in ovarian cancer surgery.

Patients with stage IA grade 1 or grade 2 epithelial tumors have a very good prognosis and usually are not treated with additional chemotherapy. For more advanced stages of epithelial cancer, chemotherapy is very effective for inducing clinical remission but relapses are very common with an average progression interval between 2 and 3 years. The best chemotherapy combination for treating advanced stage epithelial cancer includes both taxane and platinum agents, administered either intravenously or intraperitoneally for at least six cycles. Intraperitoneal chemotherapy has been demonstrated to induce longer progression free intervals, but acute toxicity is much higher and only 40% of patients are able to complete planned therapy on this regimen. The CA-125 tumor marker is useful as a marker for assessing the effectiveness of therapy.

The best current regimen for malignant germ cell tumors is cisplatin, etoposide, and bleomycin, administered as a 3- or a 5-day treatment that is continued until at least one cycle after normalization of elevated tumor markers. Sex-cord stromal tumors are treated similarly.

Prognosis

The prognosis for epithelial ovarian carcinoma is related primarily to stage and histological grade. Because most ovarian cancers are of advanced stage at the time of initial diagnosis, the long-term survival rate for ovarian cancer is only 50%. Five-year survival rates for patients with stage III or stage IV disease are around 20%-35%. Prolonged disease-free intervals can be achieved by combining comprehensive surgical staging aggressive debulking and adjuvant chemotherapy.

Prevention

Oral contraceptives reduce the risk of ovarian epithelial carcinoma. The magnitude of risk reduction is based on dose and duration of therapy. The protective effects are durable, lasting for a decade or more after discontinuation of the medication.

Any woman with a strong family history should be considered for genetic counseling and testing. For patients with a confirmed hereditary risk of ovarian cancer based on careful pedigree analysis or genetic testing will benefit from prophylactic removal of ovaries and Fallopian tubes. The current recommendation is for removal after completion of childbearing at age 35 or 10 years younger than the earliest incidence of disease in the family. Prophylactic removal of ovaries and tubes reduces the risk of ovarian cancer at least 95%, but a small number of individuals may still develop primary peritoneal carcinoma.

To date, no screening test for ovarian cancer has proven to be sufficiently sensitive or specific enough to have earned the recommendation of the US Preventive Services Task Force, ACOG, or the American Cancer Society. Prospective ultrasound screening studies and combined CA-125/ultrasound studies show a trend toward earlier stage at time of diagnosis on screened patients, resulting in prolongation of progression-free intervals, but not survival.

SURGERY FOR MULTIORGAN DISEASE

Chronic Pelvic Pain

Chronic pelvic pain is generally defined as 6-12 months of pain below the umbilicus producing a significant impact on quality of life. Evaluation and treatment of chronic pelvic pain accounts for up to 40% of all referrals to gynecologists, leading to up to 40% of all laparoscopies, and 12% of all hysterectomies.

Diagnosis

The differential diagnosis chronic pelvic pain is complex. While many patients attribute their pain to a gynecologic cause, the physician must consider nongynecologic diagnoses of the gastrointestinal, urinary, and musculoskeletal systems in addition to psychological and psychosomatic problems. The most common nongynecologic diagnoses include irritable bowel syndrome, inflammatory bowel disease, nephrolithiasis, interstitial cystitis, ventral or inguinal hernia, muscle strain, nerve injury, depression, and somatization. Of note, patients are more likely to have suffered sexual assault as an adult or child.

The gynecologic causes of chronic pelvic pain are classified as cyclic or continuous in nature. Sources of cyclic pain include primary dysmenorrhea, defined as painful menses without identifiable pelvic pathology; and secondary dysmenorrhea attributable to pathologic conditions such as endometriosis or adenomyosis. Mid-cycle ovulatory pain may occur that produces unilateral pain at mid-cycle that resolves after a day or two. Continuous pain sources include endometriosis and adenomyosis, and pelvic organ prolapse, both discussed earlier in this chapter, in addition to chronic salpingitis, and pelvic adhesions. Another cause of continuous pain is ovarian remnant syndrome, which occurs when residual ovarian tissue after oophorectomy becomes retroperitoneal location. Pain may occasionally be caused by degenerating fibroids or by mass effect from large fibroids.

Clinical Findings

The pelvic examination requires careful communication with the patient to understand where and when her pain occurs. Identification of palpable abnormalities and localization of focal tenderness is important. If a pelvic mass is detected, it should be triaged as discussed previously in the adnexal mass section of this chapter. An abnormal pelvic examination has about an 80% predictive value for pelvic abnormalities noted at laparoscopy.

Treatment

Nongynecologic causes of pain are treated according to the diagnosis. Gynecologic pain etiology is also treated according to the diagnosis. Reproductive-age women with cyclic pain are offered treatment consisting of nonsteroidal anti-inflammatory drugs and ovulation suppression, usually with oral contraceptives if appropriate for the age and medical risk factors of the patient. Continuous pain attributable to endometriosis or adenomyosis is treated similarly. Other causes of continuous pain include spasm or tension in pelvic floor musculature. Physical therapy and “reverse Kegel” exercises to relax the muscles often result in improvement. An antibiotic may be prescribed if a chronic infection is suspected, but care should be taken to treat documented infection and not to over prescribe antibiotics. Concurrent depression is common, usually arising as a secondary effect of the pain rather than as the primary etiology. Treatment with antidepressant medication is often beneficial. The tricyclic antidepressant class is often more effective that serotonin reuptake inhibitors for this indication. Severe and refractory pain may require prescribing of narcotics to attain control. The physician must use careful judgment regarding initiation of narcotics in a chronic setting due to the potential for dependence and addiction. It is often useful to manage these patients with a narcotic contract between the patient and her physician to regulate drug use. Referral to a multidisciplinary pain service is often useful for difficult or refractory cases.

If the pain is refractory to medical management or if the physical examination is abnormal, then diagnostic laparoscopy is indicated. During the laparoscopic procedure, upper abdominal structures, pelvic organs and peritoneum, appendix, rectum, and sigmoid colon are carefully inspected. The most commonly identified pathology is endometriosis occurring in one-third of patients and adhesions in one third of cases. Most of the remaining cases will have no identified pathology. The presence of abnormalities may not explain the pain, and treatment of disease such as endometriosis may not resolve the pain.

The evidence for therapeutic benefit of laparoscopy for treatment of pelvic pain is tenuous, at best. Procedures that remove or ablate adhesions, endometriosis may or may not relieve pain. If pain is attributed to the uterus or cervix and cannot be controlled with lesser procedures or medical management, options include hysterectomy, or if fertility preservation is desired, interruption of the autonomic nerve tracts with a presacral neurectomy. Pain attributed to degenerating or large fibroids may be relieved either with uterine artery embolization procedures or surgical removal of the leiomyomata with either hysterectomy or myomectomy. Severe dysmenorrhea that is refractory to medical management may be significantly improved with endometrial ablation.

Published data indicate that laparoscopic treatment will produce a short-term reduction of pain in about 60%-80% of patients, but long-term benefits are not well documented. In patients who have completed their childbearing or who wish definitive treatment, hysterectomy has reported success rates of up to 95% if uterine pathology such as degenerating fibroids is present. If no pelvic pathology is noted, 50%-91% experience improvement. The success rate is poor if the patient has symptoms of depression. Patients with endometriosis should also be offered bilateral salpingo-oophorectomy to minimize pain from residual implants.

Endometriosis

Endometriosis is defined as extrauterine, functional endometrial tissue. The most common sites include ovaries, uterosacral ligaments, and the cul-de-sac. Less commonly, Fallopian tubes, uterine serosa, sigmoid colon and rectum, peritoneum, and small intestine or mesentery are involved. Ectopic endometrium is occasionally detected at distant sites including lung, lymph nodes, surgical incision sites, umbilicus, perineum, and breasts.

The etiology of endometriosis is thought to occur any of three potential mechanisms: (1) retrograde menstruation with implantation; (2) metaplasia of Müllerian duct remnants or coelomic epithelium; and (3) lymphatic or venous dissemination. Retrograde menstruation through the uterine tubes is common and yet rarely causes endometriosis. It is not known what factors contribute to implantation and growth of endometriosis. Uterine outflow obstruction from cervical stenosis or congenital anomalies such as imperforate hymen increases the likelihood of developing endometriosis.

Endometriosis may develop at any time after onset of menarche and will virtually regress after menopause. Prevalence of endometriosis is difficult to determine because many women with the disease are asymptomatic. The estimated prevalence of endometriosis is about 15%-20%. Endometriosis may cause scarring that impairs fertility. As a consequence, diagnosis of endometriosis during a workup for infertility is higher, with up to 20%-47% of patients affected. Conversely, in women with proven fertility who elect tubal sterilization are found to have endometriosis on only 1%-5% of cases. The incidence of endometriosis is higher in women who choose to delay childbearing, or in women with a family history of the disease. There may be environmental toxins that predispose to endometriosis, such as dioxin. Pregnancy and hormonal contraceptive hormones are protective.

Carcinoma may arise in endometriosis at any site and is most commonly of endometrioid histology. Clear cell carcinoma is rare and more aggressive.

Classification

An anatomic staging system for endometriosis has been developed by the American Society of Reproductive Medicine (Figure 39–9.) The Revised AFS classification system is accepted worldwide. The staging system is broadly predictive of outcome with treatment. The stage of endometriosis does not correlate well with pain symptoms. Alternate systems that recognize the varied presentation of endometriosis in addition to development of serum markers have been proposed.

Symptoms & Signs

Endometriosis frequently causes pain. The pain often begins shortly before menses and continues during menstruation. The presence of pain and its severity is highly variable. Some patients with extensive disease are asymptomatic, while others with small peritoneal implants may be incapacitated. Unexplained infertility may be present in asymptomatic endometriosis. Symptoms may occur at any time during reproductive years, but are most common in the third and fourth decades of life. Symptoms usually resolve with menopause unless the patient is prescribed a hormone replacement regimen. Patients may also complain of dyspareunia, tenesmus, back pain, or sciatica. Rare manifestations may include ureteral obstruction or bowel obstruction.

Pelvic Examination

Bimanual pelvic examination including the rectovaginal examination should be performed. Common findings include pelvic tenderness, adnexal masses, and soft nodularity in the cul de sac or along the uterosacral ligaments. Adnexal masses attributable to endometriosis are often bilateral and are frequently immobile due to adhesions along the posterior broad ligament.

Testing

Ultrasound description of isoechoic masses within the ovaries is highly suggestive of endometrioma. Serum concentrations of CA-125 are elevated above 35 U/mL in about one-third of patients with advanced disease, which complicates triage of adnexal masses that may be either benign (endometriosis) or malignant. Following surgical and medical treatment, measurement of the CA-125 trend is a useful marker of treatment efficacy and disease recurrence similar to how the marker is used for monitoring treatment of ovarian cancer.

Definitive diagnosis requires biopsy, usually obtained with a laparoscopic procedure. The biopsy diagnosis requires the presence of both glands and stroma. Location and extent of disease is noted at the time of surgery to complete disease staging. Characteristic peritoneal implants include the so called “powder-burn” marks of darkly colored endometrium, in addition to red, blue, and white lesions. Peritoneal disease may be flat or raised, including nodular or vesicular appearance. Laparotomy is occasionally necessary for large ovarian masses, or bowel and ureteral obstructions that may be present.

Treatment

Treatment should be tailored to severity of symptoms, age of the patient, desire for fertility, and the stage of disease. The range of therapeutic options includes observation, medical management with hormones and analgesics, up to hysterectomy with bilateral salpingo-oophorectomy. A conservative approach is preferred for patients with minimal symptoms or minimal measurable disease on pelvic exam. Surveillance examinations should be regularly performed, with the interval determined by severity of symptoms, age of the patient, desire for fertility, and the stage of disease. If symptoms or physical finding worsen, the management plan may be changed accordingly.

Medical Treatment

The goal of medical therapy is to control disease by inducing a remission. There are no known medical therapies that result in a cure. Hormonal therapy is not administered for patients actively attempting to conceive. Upon treatment discontinuation, symptoms commonly recur. Long-term suppression with hormonal contraceptive regimens should be considered.

Progestins

Norethynodrel, norethindrone acetate, and medroxyprogesterone acetate are commonly used. Continuous progestins induce amenorrhea resulting in decreased symptoms in more than three quarters of patients. Progestin therapy causes downregulation of estrogen receptors in endometrial tissue, resulting in atrophic change in both endometriosis and endometrium. Breakthrough bleeding is not unusual. Side effects include weight gain secondary to appetite stimulation, fluid retention, headaches, and mood swings.

Oral contraceptives

Oral contraceptives with a low estrogen dose and a high potency progestin are preferred and may be administered either as cyclic or as continuous regimens without withdrawal intervals each month. Symptoms are relieved in up to 80% of patients. Oral contraceptive may be continued long term as a maintenance therapy in healthy women. Women over 35 who smoke or individuals with hypertension are at increased risk of thromboembolic complications. Side effects include headaches, fluid retention, breast tenderness, breakthrough bleeding, and occasional nausea.

GnRH analogs

GnRH analogs act by negative feedback inhibition on the pituitary resulting in prevention of FSH and LH secretion. The consequence of low gonadotropin levels is absence of follicle development and low estrogen production. This treatment strategy induces the medical equivalent of the postmenopausal state. Endometrial implants atrophy in the hypoestrogenic environment and about 80% of patients report clinical improvement. Side effects mimic menopause with vasomotor symptoms, vaginal dryness, and mood swings. Long-term treatment causes osteopenia and osteoporosis. To prevent bone loss, “add-back” therapy with either norethindrone acetate or combined hormone replacement therapy concurrent with GnRH analog may be prescribed and does not interfere with treatment of the endometriosis.

Surgical Treatment

Indications for surgery include treatment of current infertility, treatment to preserve future fertility, or control of symptoms. Medical therapy is unlikely to result in reduction of symptoms for bulky disease, and surgery is recommended for any endometrioma larger than 4 cm. Options for preservation of fertility in symptomatic women who have failed medical therapy include laparoscopic procedures for resection or ablation of implants, lysis of adhesions, or presacral neurectomy. When definitive therapy is necessary and preservation of fertility is not an issue, total hysterectomy and bilateral salpingo-oophorectomy is indicated. Endometriosis is dependent upon estrogen. Preservation of an ovary in this setting causes symptoms sufficient to prompts additional surgery in 20% of cases. Bowel implants can be locally resected by appropriately trained surgeons.

Postoperative estrogen replacement therapy usually does not lead to exacerbation of endometriosis. The use of estrogen-progestin combinations is generally not required.