Radical Hysterectomy Case File

Radical Hysterectomy Case File

Eugene C. Toy, MD, Konrad P. Harms, MD, Keith O. Reeves, MD, Cristo Papasakelariou, MD, FACOG

Case 18

A 32-year-old G3P3 Latin American woman presents to your clinic and reports several episodes of postcoital bleeding and a foul-smelling discharge for the last few months. She had her last Papanicolaou (Pap) smear 4 years ago after the birth of her last child but has not seen a physician since then. She has no history of medical problems. She has no history of abnormal Pap smears or sexually transmitted diseases. She had a tubal ligation at the time of her last delivery but no other surgeries. She smokes one pack of cigarettes daily. She first had intercourse at 15 years of age and has had five lifetime partners. She has been married to her current partner for 7 years.

On physical examination, she does not have a clinically visible lesion. Rectovaginal examination reveals that the cervix is approximately 4 cm in size and that the cervix is freely mobile. Supraclavicular and groin nodes are not palpable. You perform a Pap smear that is positive for a high-grade lesion. Colposcopy of the cervix shows areas of acetowhite epithelium and abnormal vessels. Pathological examination of the cervical biopsy reveals invasive squamous cell carcinoma approximately 2 mm below the basement membrane.

➤ What is your next step?

➤ What are your potential options for treatment?

➤ Would your management change if pathology revealed adenocarcinoma?

➤ What would you do if she were pregnant at 28 weeks’ gestation?

ANSWERS TO CASE 18:

Radical Hysterectomy

Summary: A 32-year-old G3P3 woman presents with postcoital bleeding. She does not have a clinically visible lesion. The Pap smear shows a high-grade lesion. She is diagnosed on colposcopically directed biopsy to have at least a microinvasive squamous cell carcinoma in that specimen.

➤ The next step: Cervical conization.

➤ Potential options for treatment:

➤ Stage IA1: Extrafascial (simple) abdominal or vaginal hysterectomy or cervical conization with clear margins. A patient with Stage IA1 cancer and lymphovascular space invasion (LVSI) diagnosed on conization specimen will need treatment with radical hysterectomy and pelvic lymphadenectomy. Radiation therapy with chemotherapy may also be considered for patients who are not surgical candidates.

➤ Stages IA2 to IIA: Radical hysterectomy with pelvic lymphadenectomy or primary radiation therapy and concurrent cisplatin-based chemotherapy.

➤ Stage IIB and beyond: Primary radiotherapy with concurrent cisplatinbased chemotherapy.

➤ If adenocarcinoma was found: Patients with cervical adenocarcinoma are usually treated in a similar manner as patients with the more common histology of squamous carcinoma. For patients with early-stage squamous cell carcinoma, there does not appear to be a survival advantage whether a patient is treated primarily with surgery or concurrent chemoradiation therapy. However, one study suggests that patients with primary adenocarcinoma may have an improved outcome if surgery is done, even if subsequent adjuvant radiotherapy is needed.

➤ If she were pregnant: As she has no clinically apparent cervical lesion, she needs to undergo cervical conization to determine the depth of invasion. This will determine her clinical stage. Therapy will depend on the stage of disease, the gestational age of the fetus, and the patient’s desires either for immediate treatment. Considerations include possible poor outcome for the pregnancy or for delayed therapy until the fetus reaches viability.

ANALYSIS

Objectives

1. Describe how to make the diagnosis of cervical cancer.
2. Describe how to stage cervical cancer.
3. Understand the options for treatment of cervical cancer, depending on the clinical stage.
4. List the pathologic indicators for adjuvant therapy after surgical treatment for cervical cancer.
5. Learn the options for management of a pregnant patient with cervical cancer.

Considerations

This is a 32-year-old G3P3 woman who presents to your clinic with worrisome symptoms of post-coital spotting and malodorous vaginal discharge, but has no obvious cervical lesion. Any patient who presents with unexplained postcoital bleeding requires an in-depth evaluation. Evaluation with a Pap smear is mandatory. If no visible cervical or vaginal lesions are seen, further evaluation is necessary which may include colposcopy with endocervical curettage. In this case, a cervical biopsy diagnosed invasive carcinoma of 2 mm below the basement membrane in the one area that was sampled. It is critical that the surgeon understand that the depth of this biopsy may not represent the worse invasion. The next step is cervical conization to determine the extent of the depth of invasion as this is difficult to determine the full extent on a small cervical biopsy specimen. If a cone biopsy reveals microinvasion less than 3 mm with clear margins (stage IA1) and no LVSI, the conization alone is adequate therapy if future fertility is desired. For patients with stage IA1 disease who are not interested in future fertility, simple hysterectomy is indicated. A lymph node dissection is unnecessary as the incidence of lymph node metastases in this clinical scenario is very low.

APPROACH TO

Radical Hysterectomy

DEFINITIONS

RADICAL HYSTERECTOMY: A type of hysterectomy in which the uterus, upper-third vagina, cervix, and parametrial tissues are removed. The ureters are also dissected to ureterovesical junction (Class III hysterectomy).

EXTRAFASCIAL HYSTERECTOMY: A hysterectomy performed that develops the pubocervical fascia to allow total removal of uterus and cervix (Class I hysterectomy).

LYMPH-VASCULAR SPACE INVASION (LVSI): Small lymphatic and capillaries within the cervical stroma which can be seen on histologic sections. The presence of tumor near these vessels increases the risk of metastasis and leads to a poorer prognosis.

PARAMETRIUM: The tissue within the broad ligament and lateral to uterus and cervix.

CLINICAL APPROACH

Etiology

Epidemiologic risk factors for cervical cancer include early age at first coitus, multiple sexual partners, tobacco usage, low socioeconomic status, and immunosuppressive states (ie, transplant patients or patients with HIV). Human papillomaviruses 16 and 18 are most commonly associated with cervical dysplastic lesions and cervical carcinomas. However, not all infections of type 16 or 18 will progress to cervical cancer.

Clinical Presentation

The most common presenting symptom of invasive carcinoma of the cervix is abnormal vaginal bleeding or watery vaginal discharge. Among sexually active women, postcoital bleeding is usually a presenting symptom, but intermenstrual or postmenopausal bleeding may also occur. In some cases, symptoms of cervical cancer may not be recognized until the disease becomes advanced. As tumors grow, they can become infected and present with a malodorous vaginal discharge instead of vaginal bleeding. With very advanced disease, patients may present with pelvic or sciatic nerve pain or even with symptoms of a vesicovaginal or rectovaginal fistula.

Diagnosis

Any visible cervical lesion should be biopsied. The false-negative rate for Pap smears in patients with invasive carcinoma may be as high as 50% due to the presence of necrosis limiting the cytologic diagnosis. If a definitive diagnosis cannot be made on the basis of office colposcopic–guided biopsies, a diagnostic cervical conization may be required.

Staging of cervical cancer is clinical and International Federation of Gynecology and Obstetrics (FIGO) standards limit radiographic evaluation to chest radiography, intravenous pyelography, and barium enema (see Table 18–1). An examination under anesthesia is occasionally helpful if a good examination is not possible with the patient awake. A rectovaginal examination with emphasis on the presence of tumor in the parametrial tissue or the uterosacral ligament is mandatory. Under anesthesia, cystoscopy or proctoscopy is indicated if the patient has symptoms that are worrisome for either bladder or rectal involvement (hematuria or passage of stool per vagina). The FIGO classification system is not altered by lymph nodal involvement that is diagnosed radiographically. Computed tomography (CT), magnetic resonance imaging (MRI), or positron emission tomography (PET) scans are not acceptable for formalized staging purposes although these tests are routinely ordered to assist in treatment planning.1

Table 18–1 FIGO STAGING FOR CERVICAL CANCER

Stage I The carcinoma is strictly confined to the cervix (extension to the corpus would be disregarded) IA Invasive carcinoma which can be diagnosed only by microscopy, with deepest invasion < 5 mm and largest extension > 7 mm IA1 Measured stromal invasion of ≤3.0 mm in depth and extension of < 7.0 mm IA2 Measured stromal invasion of N3.0 mm and not N5.0 mm with an extension of not N7.0 mm IB Clinically visible lesions limited to the cervix uteri or pre-clinical cancers greater than stage IA * IB1 Clinically visible lesion < 4.0 cm in greatest dimension IB2 Clinically visible lesion N4.0 cm in greatest dimension   Stage II Cervical carcinoma invades beyond the uterus, but not to the pelvicwall or to the lower third of the vagina IIA Without parametrial invasion IIA1 Clinically visible lesion < 4.0 cm in greatest dimension IIA2 Clinically visible lesion N4 cm in greatest dimension IIB With obvious parametrial invasion   Stage III The tumor extends to the pelvic wall and/or involves lower third of the vagina and/or causes hydronephrosis or non-functioning kidney ** IIIA Tumor involves lower third of the vagina,with no extension to the pelvicwall IIIB Extension to the pelvic wall and/or hydronephrosis or non-functioning kidney   Stage IV The carcinoma has extended beyond the true pelvis or has involved (biopsy proven) the mucosa of the bladder or rectum. A bullous edema, as such, does not permit a case to be allotted to Stage IV IVA Spread of the growth to adjacent organs IVB Spread to distant organs

Abbreviations: CIN, cervical intraepithelial neoplasia; FIGO, International Federation of Gynecology

and Obstetrics.

Fifteen to thirty percent of patients with advanced cervical cancer may have metastatic disease to para-aortic lymph nodes. PET scans have recently been shown to have a high sensitivity (75%-86%) to diagnose para-aortic metastases among patients with advanced disease. However, PET scans have a much lower sensitivity (50% for para-aortic metastases and 10%-53% for pelvic metastases) in diagnosing metastatic disease in patients with earlystage disease. Combination PET-CT scans may have an improved diagnostic yield over each modality individually.1

Treatment

Depending on clinical staging, surgery or chemoradiation will be offered to patients. The outcome of patients with stage IA2 or IIA who receive radical hysterectomy or primary radiotherapy is similar, with overall survival ranging from 75% to 92%. Therapeutic decisions are made after a thorough discussion of morbidities associated with each treatment type.2,3

Surgical management offers distinct advantages and disadvantages. Advantages include surgical staging, removal of bulky lymph nodes, ovarian conservation with transposition in younger patients, and preservation of vaginal function. The most common complication among patients undergoing radical hysterectomy is bladder dysfunction in the postoperative period, resulting in prolonged bladder catheterization or the need for intermittent self-catheterization. This is most likely due to injury to the sensory and motor nerve supply of the bladder. Pulmonary embolism, lymphocyst formation, and febrile morbidity from atelectasis and wound complications are less common, but not rare complications from surgery. Vesicovaginal or ureterovaginal fistulas occur in about 1% of cases.4

Some studies have also reported increased sexual dysfunction, including reduced arousal, decreased vaginal lubrication, and dyspareunia, among patients treated by radical hysterectomy.5 Lymphedema may occur in patients who undergo pelvic lymphadenectomy, particularly if they need postoperative radiation therapy. Radiation therapy after radical pelvic surgery also increases the risk of developing bowel obstruction or fistulas.

Primary chemoradiation may be offered to patients at high risk for intraoperative complications to avoid surgical morbidity and mortality. However, radiation therapy may lead to vaginal shortening as well as a decrease in lubrication and worsened sexual functioning. Other morbidities associated with radiation therapy include bowel obstruction, fistula formation, chronic radiation cystitis and proctitis, and ovarian failure. Complications from radiation therapy tend to occur more distant from treatment and are usually chronic, whereas complications from surgery usually occur in the immediate postoperative period and do not usually persist.6-8

Patients with stage IB2 lesions (> 4 cm) are candidates for either surgery or primary chemoradiation. In a randomized trial of primary surgery versus radiation, 84% of patients with stage IB2 to IIA disease who underwent radical hysterectomy required postoperative adjuvant radiation therapy with more than 25% of patients experiencing severe morbidity. Based on these results, many centers counsel patients with stage IB2 or more advanced lesions to have primary chemoradiation.

Patients who undergo surgery may need postoperative chemoradiation if certain high-risk features are present. If any of the following features are present, positive pelvic lymph nodes, positive parametria, or positive margins, patients should undergo concurrent radiation and cisplatin chemotherapy.

Approximately 25% of patients with stage IB1 disease will need adjuvant radiation therapy due to the presence of certain intermediate risk factors (deep stromal invasion, LVSI, or lesion size > 4 cm). In a trial randomizing patients with these risk factors between no further therapy and pelvic radiation, patients who received radiation therapy had a 46% decreased risk of recurrence (18% among patients receiving radiation therapy vs 31% in patients with no further treatment).9

Surgical Therapy

For patients with stage IA1 with LVSI, IA2, IB, and IIA cervical cancer, radical hysterectomy and pelvic lymph node dissection is the surgical treatment option. In a modified radical hysterectomy (type II), the uterine artery is ligated as it crosses the ureter. The medial half of the cardinal ligaments and proximal uterosacral ligaments are resected. A more extensive dissection is done during a radical hysterectomy (type III). In the type III radical hysterectomy, the uterine artery is ligated at its point of origin at the superior vesical artery and the entire cardinal ligament is removed. The uterosacral ligament is resected from the attachment to the posterior pelvis. In clinical practice, aspects of both types II and III radical hysterectomies are done during each surgical case. More extensive radical hysterectomy options have been described, involving resection of the superior vesical artery, portions of the ureter, or the bladder. These operations are rarely done today to treat cervical cancer as patients with larger cervical lesions are treated primarily with chemoradiation therapy.

Specific anatomic spaces are opened during the radical hysterectomy. The paravesical space is bordered by the pubic symphysis anteriorly, the cardinal ligament posteriorly, the obliterated umbilical artery medially, and the obturator internus muscles laterally. The pararectal space is bordered by the cardinal ligament anteriorly, the sacrum posteriorly, the rectum medially, and the hypogastric artery laterally. The rectovaginal space is developed by opening the peritoneum at the pouch of Douglas and gently opening the space between the vagina and rectum with blunt dissection.

A pelvic lymphadenectomy is performed to remove lymphatic tissue within the following landmarks: lateral to the ureter, medial to the psoas muscle, inferior to the middle of the common iliac artery, and superior to the deep circumflex vein. The obturator space is opened by retracting the external artery and vein and identifying the obturator nerve. All lymphatic and fatty tissue is then removed out of the obturator space.

For patients with larger stage IB lesions (> 4 cm) and patients with stage IIA disease who opted for radical hysterectomy, there is an 80% chance that adjuvant radiation therapy will be recommended based on operative findings. Adjuvant radiation therapy, often with concurrent chemotherapy, is offered when patients have positive margins on the radical hysterectomy specimen, or metastatic disease in the lymph nodes. Adjuvant therapy is also considered when there are poor prognostic factors, for example, lymphovascular space invasion, large primary tumor size, or deep cervical stromal invasion, noted on the radical hysterectomy specimen.

Complications of a Radical Hysterectomy Urinary tract complications are frequently encountered after radical hysterectomy. It has been reported that up to 50% of radical hysterectomy cases have bladder dysfunction. The extensive dissection required for the surgery often results in denervation of the bladder and upper urethra. The majority of patients have normal bladder function within a year of the surgery. However, some patients require prolonged catheterization until bladder function returns. The use of either a suprapubic or transurethral catheter as well as intermittent self-catheterization have been described. Ureteral injury and fistula formation are not as common as bladder dysfunction and can be minimized by careful surgical technique.

The risk of infection is no different than in the case of a traditional hysterectomy. Preoperative single-agent broad-spectrum antibiotic is all that is necessary for infection prophylaxis. Depending on the length of surgery and blood loss, an additional dose of antibiotics may be required.

Venous thrombosis and pulmonary embolus are a particular concern to the surgeon. Given the extensive surgery, trauma to vein wall with lymphadenectomy, and immobility, these patients are at particularly high risk for venous thrombosis formation. Patients should receive intermittent pneumatic calf compression in the operating room, which is continued postoperatively until the patient is full ambulatory. High-risk patients may benefit from medical prophylaxis with either heparin or low-molecular-weight heparin.

Despite careful surgical technique, intraoperative hemorrhage may occur, and the surgeon must be prepared to deal with this complication. Blood products should be readily available at the time of surgery in the event that excessive bleeding occurs. The most frequent site of hemorrhage is venous bleeding from the pararectal fossa, presacral, and para-aortic regions. Unfortunately, as compared to arterial bleeding, venous bleeding is difficult to identify and is seldom improved with hypogastric artery ligation. A good understanding of anatomy is essential to try and minimize risk of hemorrhage.

Thankfully, nerve injury is not a frequent complication of a radical hysterectomy and rarely permanent. The obturator nerve is most likely nerve to be injured and results in inability to adduct lower extremities. Obturator nerve injury can occur with removal of obturator nodes and retractor use. Most nerve injuries can be minimized with proper patient placement/positioning, careful use of self-retaining retractors, careful surgical technique in dissection with good understanding of pelvic anatomy, and maintaining hemostasis.10

Radical Trachelectomy Patients with stage IA2 and IB1 (< 4 cm tumor size) lesions who desire future fertility may elect to undergo a radical trachelectomy with pelvic lymphadenectomy. A complete lymphadenectomy is first performed to evaluate for the presence of metastatic disease. Subsequently, radical trachelectomy may be done to remove the cervix and the parametrial tissue. The procedure may be done abdominally, laparoscopically, or with a combined laparoscopic and vaginal portion. Often a cervical cerclage is placed in the newly formed exocervix, which is now located approximately 1 cm below the lower uterine segment.11

Primary Radiation Therapy with Concurrent Chemotherapy For patients with stage IIB disease or higher, the treatment is concurrent radiation and chemotherapy. This modality is also used for earlier-stage disease when the patient is not a surgical candidate. Typically, the patient receives external beam radiation to the pelvis followed by vaginal brachytherapy with tandem and ovoids placement. During radiation therapy, the patient will also receive concurrent platinum-based chemotherapy. Ideally, all radiation therapy is completed within a span of 56 days, as delays in treatment are associated with a decreased overall survival.

When counseling a patient with early-stage disease who is a candidate for either chemoradiation therapy or primary surgery, arguments in favor of primary surgery usually include better preservation of vaginal length and the avoidance of long-term risk of radiation (enteritis, bowel obstruction, etc), whereas the proponent of primary chemoradiation therapy cites the usual tolerability of treatment by most patients and the avoidance of surgery with its attendant risks. However, stage for stage, in those with early disease (<4 cm), neither modality has been shown to have a survival advantage over the other.

Patients with Adenocarcinoma In general, cervical adenocarcinoma is treated similarly, stage for stage, as squamous carcinoma. However, in one study of patients with stage IB to IIA cervical cancer randomized to primary radical surgery versus radiation therapy, those patients with adenocarcinoma who underwent primary surgery had improved progression-free and overall survival rates.

Pregnant Patients with Newly Diagnosed Cervical Cancer Delayed diagnosis of cervical cancer in pregnancy is common because symptoms of postcoital bleeding, vaginal discharge, vaginal bleeding, and pelvic pain are frequently associated with pregnancy. Most patients receive a Pap smear early on entry into prenatal care. If an abnormal Pap smear is found and the patient has no visible lesion, colposcopy without endocervical curettage is done. If the colposcopy is adequate and a biopsy reveals cervical intraepithelial neoplasia (CIN), the patient may undergo a vaginal delivery. Further evaluation and treatment are done at 6 weeks after delivery.

If the colposcopy is inadequate or the biopsy reveals microinvasion or possible carcinoma, cervical conization is needed in a similar manner as if the patient were not pregnant. Ideally, conizations are performed during the second trimester because the risk of fetal loss is less than 10%. If performed in the first trimester, the rate of fetal loss may be as high as 24%. In the third trimester, the risk of loss is less, but the risk of hemorrhage is significant.

A cervical conization in pregnancy should be performed only if necessary to diagnose or stage a cervical cancer due to the high risk of potential complications, including premature labor, spontaneous abortion, infection, and hemorrhage. Pregnant patients may safely undergo MRI to determine tumor volume, nodal enlargement, and potential metastasis.12 Consultation with gynecologic oncologists and maternal-fetal medicine specialists is highly recommended to help manage these difficult patients.

Careful counseling with the patient and her family must be undertaken for the management of any patient diagnosed with cervical cancer during pregnancy as the treatment is dependent on the stage of disease and the wishes of the mother. Patients with stage IA1 cervical cancer diagnosed by conization may be safely followed throughout pregnancy.13 Patients at less than 20 weeks’ gestation who have more advanced lesions and do not desire continuation of the pregnancy may undergo radical surgery or radiation therapy with cisplatin as definitive treatment. Patients who have pregnancies exceeding 20 weeks’ gestation can generally be expectantly managed to await fetal maturity. While the number of patients reported in the literature is small, the current data suggest that delaying treatment for stage I disease during pregnancy does not decrease survival as compared to undergoing immediate therapy.

Because patients with cervical cancer are at higher risk for hemorrhage or failure to dilate, some advocate for cesarean section delivery. Among patients with advanced-stage disease, radiation therapy is the preferred treatment modality. Definitive data are not available regarding delays in treatment and potential effects on advanced disease.

Comprehension Questions

18.1 A 39-year-old woman is noted to have an exophytic cervical lesion, which on biopsy reveals invasive squamous cell carcinoma. Which of the following diagnostic aids is used in staging cervical cancer?

A. MRI

B. PET scan

C. Chest x-ray

D. CT scan of the abdomen and pelvis

18.2 A patient has a biopsy of a 5-cm cervical lesion showing squamous carcinoma. A rectovaginal examination shows obvious evidence of parametrial involvement on the left, but no sidewall involvement. The lesion invades the mucosa of the left vaginal fornix. A CT scan shows pathologically enlarged pelvic and para-aortic lymph nodes. Which of the following is her cancer stage?

A. Stage IIA

B. Stage IIAB

C. Stage IIIA

D. Stage IVB

18.3 Which of the following is the most common complication of radical hysterectomy?

A. Bladder atony

B. Pulmonary embolism

C. Massive blood loss

D. Lymphedema

E. Small bowel obstruction

18.4 For which of the following cervical cancer patients is a radical hysterectomy and lymphadenectomy the most appropriate treatment?

A. A 46-year-old woman with a conization specimen showing 2-mm stromal invasion

B. A 25-year-old nulligravida woman with a 5-cm cervical lesion with vaginal or parametrial involvement

C. A 23-year-old nulligravida woman with a cervical conization showing 5-mm stromal invasion

D. A 25-year-old G1P1 woman with a cervical conization showing 3-mm stromal invasion and no lymphovascular space invasion

ANSWERS

18.1 C. FIGO staging of cervical cancer is clinical and relies on a good pelvic examination. Radiographic evaluation is limited to chest radiography, barium enema, and intravenous pyelogram. In current practice, a CT scan, a PET scan, or combination PET-CT scan are often done. Information obtained on these tests is included in the treatment planning for the patient; however, it does not influence the stage of the patient.

18.2 B. The patient has a cervical cancer that involves the upper vagina (IIA), but also parametria but not to the side wall (IIB). Thus, she has stage IIB disease. The information obtained on the CT scan may influence treatment planning. In this case, she is a candidate for extended-field radiation therapy for the enlarged para-aortic lymph node.

18.3 A. The most common complication of radical hysterectomy is bladder atony. This is most likely due to bladder denervation from the extensive dissection.

18.4 C. Radical hysterectomy and lymph node dissection are appropriate therapies for patients with stages IA2 to IIA cervical cancer. Patients with stage IA1 disease who have lymphovascular space invasion also need radical hysterectomy with lymph node dissection as there is a risk of lymph node metastasis. A patient with 3-mm or less cervical stromal invasion without lymphovascular space invasion is adequately treated with cervical conization with negative margins or simple hysterectomy.

Clinical Pearls

See Table 1-2 for definition of level of evidence and strength of recommendation

➤ After radical hysterectomy, adjuvant radiation therapy is given if the patient has certain risk factors, including tumor size larger than 4 cm, the presence of lymphovascular space invasion, or deep stromal invasion (Level A).

➤ The survival data for patients undergoing radical hysterectomy versus patients undergoing radiation therapy are similar in patients with stages IB to IIA disease. Patients with stage IIB or higher disease are treated with primary chemoradiation therapy (Level A).

➤ Fifteen percent of patients with early disease will have lymphatic spread diagnosed after radical hysterectomy and pelvic lymphadenectomy (Level B).

➤ Patients who present with symptoms of postcoital bleeding should undergo complete evaluation, including Pap smear,endocervical curettage, and colposcopy (Level C).

➤ All visible cervical lesion needs to be biopsied. A Pap smear is inadequate to rule out invasive carcinoma of the cervix (Level C).

REFERENCES

1. Gold M. PET in cervical cancer—implications for “staging,” treatment planning, assessment of prognosis and prediction of response. J Natl Compr Canc Netw. 2008;6:37-45. 

2. Holtz D, Dunton C. Traditional management of invasive cervical cancer. Obstet Gynecol Clin North Am. 2002;29:645-657. 

3. Landoni F, Maneo A, Colombo A, et al. Randomized study of radical surgery versus radiotherapy for stage IB-IIA cervical cancer. Lancet. 1997;350:535-540. 

4. Covens A, Rosen B, Gibbons A, et al. Differences in the morbidity of radical hysterectomy between gynecologic oncologists. Gynecol Oncol. 1993;51:39-45. 

5. Bergmark K, Avall-Lundquist E, Dickman P, Hennignsohn L, Steineck G. Vaginal function and sexuality in women with a history of cervical cancer. N Engl J Med. 1999;340:1383-1389. 

6. Gray H. Primary management of early stage cervical cancer (IA1-IB) and appropriate selection of adjuvant therapy. J Natl Compr Canc Netw. 2008;6:47-51. 

7. Delgado G, Bundy B, Zaino R, Sevin B, Creasman W, Major F. Prospective surgical- pathological study of disease-free interval in patients with stage IB cervical cancer after radical hysterectomy and bilateral pelvic lymphadenectomy. Gynecol Oncol. 1990;38:352-357. 

8. Sedlis A, Bundy B, Rotman M, Lentz S, Muderspach L, Zaino R. A randomized trial of pelvic radiation therapy versus no further therapy in selected patients with stage IB carcinoma of the cervix after radical hysterectomy and pelvic lymphadenectomy: a Gynecologic Oncology Group Study. Gynecol Oncol. 1999;73:177-183. 

9. Rose P, Bundy B, Watkins E, et al. Concurrent cisplatin-based radiotherapy and chemotherapy for locally advanced cervical cancer. N Engl J Med. 1999;340:1144-1153. 

10. Rock J, Jones H. Cancer of the cervix. In: Te Linde’s Operative Gynecology. 10th ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008:1277-1281. 

11. Plante, M. Radical vaginal trachelectomy: a fertility preserving option for young women in early stage cervical cancer. Gynecol Oncol. 2005;99:S143-S146. 

12. Zanetta G, Pellegrino A, Vanzulli A, DiLelio A, Milani R, Mangioni C. Magnetic resonance imaging of cervical cancer in pregnancy. Int J Gynecol Cancer. 1998;8:265-269. 

13. Hannigan E, Whitehouse H, Atkinson W, Becker S. Cone biopsy during pregnancy. Obstet and Gynecol. 1982;60:450-455.

HomeGynecologic Surgery Case FileRadical Hysterectomy Case File