Introduction to Pelvic Exenteration
Pelvic exenteration is a salvage procedure performed for centrally recurrent gynecologic cancers. To a greater or lesser degree, the procedure involves en bloc resection of all pelvic structures, including the uterus, cervix, vagina, bladder, and rectum. Most candidates for this procedure have a diagnosis of recurrent cervical cancer that has previously been treated with surgery and radiation or radiation alone. In some cases, patients with recurrent uterine, vulvar, or vaginal cancers may benefit from pelvic exenteration. [1, 2] In general, patients with ovarian cancer are not candidates because of the distant pattern of spread associated with ovarian cancers.
Pelvic exenteration was first reported by Brunschwig in 1948 as an especially radical surgical treatment for advanced and recurrent cervical cancer. It was described as "the most radical surgical attack so far described for pelvic cancer" and at the time had an operative mortality rate of 23%.  Since Brunschwig's time, improvements in critical care, antibiotics, hyperalimentation, and thromboembolism prophylaxis, accompanied by similar advances in surgical technique, including the use of stapling devices, separate urinary conduits, and pelvic reconstruction, have improved the morbidity and mortality rates associated with the procedure. Currently, operative mortality rates are 3-5%, the major perioperative complication rate is 30-44%, and the overall 5-year survival rate in patients who successfully undergo the procedure is 20-50%. [4, 5, 6, 7]
Pelvic exenteration continues to be the only curative option in certain patients with centrally recurrent cervical, vaginal, or vulvar cancers. Although patients with other gynecologic malignancies generally are not candidates for exenterative procedures, some centers have reported exenterations in select cases of central pelvic recurrences, such as low-grade uterine sarcomas.
Procedures preceding recurrence
Patients with recurrent cervical cancer after primary treatment with surgery and radiation or radiation alone are faced with few options, because chemotherapy is at best palliative, and the 1- and 5-year survival rates are, respectively, 15% and less than 5%. [1, 2]
Cancers arising in the pelvis are often treated with multimodality therapies, including surgical resection and radiation. When these cancers recur, many may be locally advanced but still limited to the pelvis; however, previous treatment with high doses of radiation makes limited surgical resection a difficult undertaking fraught with complications. Furthermore, the response of tumors to chemotherapy within a previously radiated field is extremely poor. In some instances, the only opportunity for cure may lie in complete resection.
Clinical presentation and confirmation of recurrence
Patients with recurrent cervical cancer after radiation therapy usually present with bleeding, hematuria, or pelvic pain.  In some cases, the first sign of recurrence is the discovery of hydronephrosis or abnormal cytology on routine follow-up. Before proceeding with the surgical procedure, confirming a recurrence with a pathologic specimen obtained by biopsy is essential. In patients who have previously had high doses of pelvic radiation, physical examination is notoriously unreliable, and bleeding and pain may be related to radiation changes rather than recurrent disease.
Approach to treatment
The first steps in the approach to treating a patient with a biopsy-proven central recurrence are an exhaustive search for distant metastatic disease and evaluation for comorbid conditions. The initial surgical exploration involves a further search for disseminated disease and necessitates a complete assessment of intraperitoneal and retroperitoneal areas that would preclude proceeding with exenteration.  This task can be accomplished by laparoscopy in selected patients. 
Chemotherapy and other controversies
Chemotherapy in patients with recurrent cervical cancer is an option for patients with distant metastatic disease and for those who are not candidates for pelvic exenteration. Several regimens have been evaluated, and response rates of 5-40% are described. A Gynecologic Oncology Group (GOG) phase III study of cisplatin versus cisplatin and topotecan in patients with advanced (stage IVB), recurrent, or persistent cervical cancer reported a survival advantage in the combination arm (9.4 vs 6.5 mo).  However, most responses to chemotherapy are at best partial and of short duration; therefore, chemotherapy is generally a poor alternative to surgery in patients with recurrent disease who are candidates for a surgical approach.  Controversy continues regarding the appropriate selection of patients for exenteration and the use of intraoperative radiation therapy (IORT), pre-exenteration chemotherapy,  concomitant continent urinary diversion, and low rectal anastomosis.
Indications for Pelvic Exenteration
Pelvic exenteration is primarily indicated for centrally recurrent cervical cancers in patients who have received definitive radiation therapy. The procedure is appropriate in patients who meet criteria for any recurrent pelvic tumor if a chance of cure exists with the procedure. On occasion, pelvic exenteration can be performed as a palliative procedure for control of local disease causing severe fistulas or other unmanageable symptoms. 
Contraindications to Pelvic Exenteration
Absolute contraindications for pelvic exenteration include peritoneal metastasis, skip metastasis to the bowel, and metastases at other distant sites, such as pulmonary metastases. Relative contraindications include metastasis to retroperitoneal nodes, direct tumor invasion of adherent bowel loops, and hydroureter or hydronephrosis. Determination of the extent of resection is based on sidewall involvement, infralevator versus supralevator, and anterior versus posterior versus total exenteration.
The clinical triad of leg edema, ureteral obstruction, and leg pain is almost pathognomonic for disease extending to the pelvic sidewall and, historically, has generally been considered a contraindication to surgery. However, some surgeons have reported on an even more radical resection, the laterally extended endopelvic resection (LEER), which extends the lateral extent of the resection to include structures of the pelvic sidewall, including striated muscle and vessels.  Further study is required to evaluate the indications and outcomes of these procedures.
Preoperative Laboratory Studies
Preoperative laboratory evaluations should include the following:
Complete blood cell (CBC) count
Comprehensive metabolic panel
Type and crossmatch for blood products
Because most patients have received previous treatment, including pelvic radiation therapy, an increased likelihood exists of preoperative anemia and, occasionally, neutropenia. A large number of patients also have poor nutritional status and electrolyte abnormalities. Other testing depends on the existence of other comorbid conditions in individual patients.
Preoperative Imaging Studies
The use of imaging studies in evaluating a patient for pelvic exenteration depends on the initial assessment of tumor size and location.
Most patients need a computed tomography (CT) scan of the abdomen and pelvis and a chest radiograph. For evaluation of potential areas that are suspicious for metastatic involvement, other imaging studies may be used as needed, including the following:
Chest radiograph or CT scan
CT scans of the abdomen and pelvis
Magnetic resonance imaging (MRI) to evaluate musculoskeletal involvement, particularly in the assessment of pelvic side wall disease, as well as major pelvic vessel involvement in large lesions
Liver ultrasonography to evaluate for metastatic disease
Bone scan to evaluate for metastatic disease
Positron emission tomography (PET) scanning remains investigational in the evaluation of cervical cancer but may be very useful in excluding small areas of distant metastatic disease. A recent prospective study of fluorodeoxyglucose-18 (18 FDG)-PET scanning reported a sensitivity of 100% and a specificity of 73% in detecting extrapelvic metastasis before exenterative procedures in patients with recurrent cervical and vaginal carcinomas. 
Before proceeding with the surgical procedure, confirming a recurrence with a pathologic specimen obtained by biopsy is essential. Most cervical cancers are squamous cell carcinomas, although the incidence of adenocarcinomas of the cervix is rising. Rare histologic types are occasionally encountered and include adenosarcomas, uterine sarcomas, and cervical or vulvar melanomas. In patients who have previously had high doses of pelvic radiation, physical examination is notoriously unreliable, and bleeding and pain may be related to radiation changes rather than recurrent disease.
Psychosocial assessments of a patient's ability to adequately manage postoperative physical and psychologic issues may be needed. Assessment of comorbid conditions is especially important.
Prophylaxis and Bowel Preparation
An antibiotic and a mechanical bowel preparation are administered on the day before surgery. The stoma sites are marked on the skin before surgery. Prophylactic antibiotics are administered in the operating room, and pneumatic calf compression units are placed on the legs before the anesthetic induction. The potential operative field, including the entire abdomen, perineum, vagina, rectum, and thighs, is prepared and draped. Adequate vascular access must be available to ensure that rapid fluid and blood product resuscitation can be instituted if needed. Vascular access also allows invasive cardiovascular monitoring as indicated.
The pelvic exenteration procedure is typically performed with the patient in the lithotomy position. The patient's legs are carefully placed in Allen or other supported stirrups. The correct positioning places the weight on the feet and includes padding to ensure protection from neurologic injury and to prevent compartment syndrome.
Exploration, Evaluation, and Identification
The patient undergoing pelvic exenteration is placed in the low lithotomy position, and through a midline incision, the abdomen and pelvis are thoroughly explored. The liver, peritoneal and bowel surfaces, aortic and pelvic nodal groups, and pelvic sidewall are carefully evaluated. Biopsies of any suspicious sites are obtained and examined by frozen section. Distant and peritoneal metastases are absolute contraindications to exenteration. [9, 17]
Controversy exists regarding whether to proceed in the presence of nodal metastasis, which reduces the survival rate to 5%, or direct tumor invasion of any adherent loop of sigmoid colon or small bowel. The issue of sidewall involvement is important in determining resectability, because the goal is to achieve negative surgical margins. In some centers, the availability of intraoperative radiation therapy (IORT) allows resection with close margins,  but grossly positive margins confer an extremely poor prognosis. The process of dissecting open avascular spaces allows for further determination of resectability with adequate margins.
The pararectal, paravesical, and Retzius spaces are developed under direct visualization, and the cardinal ligaments are isolated by this method. The pelvic retroperitoneal spaces are opened, and the ureters and internal and external iliac vessels are identified and tagged as necessary. This allows identification of pelvic nodal metastasis, dissection of the ureter, and visualization of vessels, which may require ligation to control or prevent excessive bleeding.
Total Pelvic Exenteration
After the hypogastric artery is identified and its anterior division or the uterine artery is divided, the cardinal ligaments are divided at the pelvic sidewall. This can be accomplished using endoscopic stapling devices. The ureters are dissected free of the lateral peritoneum and are clipped and divided, leaving as much length as feasible. The retrorectal space between the sigmoid and the sacrum and coccyx is developed. The sigmoid arcade and the superior rectal vessels are ligated. The sigmoid is then divided using a gastrointestinal assistant (GIA) stapler.
The rectum is lifted off the sacral hollow posteriorly using blunt and sharp dissection. The lateral attachments are freed using the endoscopic GIA. Anteriorly, the bladder is completely freed from the public symphysis, and the vesicourethral junction is identified. (The resection is thus carried en bloc to the level of the levator ani.) If a supralevator exenteration is adequate, the urethra is divided anteriorly; the rectum, posteriorly at the level of the pelvic floor; and the vagina, below the level of the tumor with adequate margins.
For the perineal phase, a second team of surgeons is usually involved. A total vaginectomy and urethrectomy is accomplished by making a circumferential incision inside the vulva; if necessary, resection of the anus is also incorporated. The vagina is dissected off the levator muscles unless they have tumor involvement. If this is the case, the muscle is excised to obtain an adequate margin. The rectovaginal space is developed from above and below, and lateral rectal pillars are divided. The rectum is divided using the GIA stapler at the level of the mid vagina (if a complete perineal resection is not being performed), and the specimen is thus freed completely and removed.
Reconstruction procedures that may be necessary as a result of pelvic exenteration include rectal anastomosis, such as end-sigmoid colostomy or low rectal anastomosis; continent or noncontinent urinary diversion; and vaginal and pelvic reconstruction.
The decision to perform an end-sigmoid colostomy or a low rectal anastomosis is based on the level of the resection, the length of the rectal stump, and the extent of other concomitant procedures. A low rectal anastomosis can sometimes be accomplished using the circular end-to-end anastomotic stapling device. [19, 20] Reports have evaluated the complications associated with a rectal anastomosis at the time of pelvic exenteration, and the overall incidence of anastomotic leaks or fistula formation is 30-50%. A protective colostomy or omental wrap has not been found to have a significant impact on the incidence of successful healing. In recent years, data have suggested that a higher leak rate occurs in patients undergoing concomitant procedures such as IORT and continent urinary diversions.
Several options exist for urinary diversion, and the choice of continent versus noncontinent urinary diversion is based on assessment of the patient's ability to care for a continent pouch and availability of the right colon and ileum with the ileocecal valve.  The best option for noncontinent diversion is an ileal urinary conduit in which the ureters are implanted in an isoperistaltic manner into a segment of small bowel, one end of which is brought out as a cutaneous stoma.
The continent pouch uses the right colon as a low-pressure reservoir, with the ileum, ileocecal valve, or appendix specially configured to create the continence mechanism. A variety of continent pouches with small variations have been described.  Complications associated with both continent and noncontinent urinary diversions in women who are gynecologic oncology patients have been reported by several authors. A continent urinary diversion allows the patient to have only a single ostomy bag, or none at all, and it can be successfully accomplished in patients with gynecologic cancer. Early complication rates range from 12% to 53%, and long-term complication rates range from 33% to 37%. The reoperation rate is 6-8%.
Several methods for vaginal and pelvic reconstruction have been described. An omental flap can be accomplished, generally with minimal morbidity, and serves to carpet the raw exposed surfaces of the exenterated pelvis. Myocutaneous grafts, including rectus and gracilis muscle flaps, can be brought into the pelvis and perineum to create pelvic support and a neovagina. Split-thickness skin grafts have also been used to create neovaginas.
Outcome and Prognosis
Reported 5-year survival rates after pelvic exenteration range from 23% to 61%. The most common site of recurrence is the pelvis. Poor prognostic factors associated with recurrence after exenteration include tumor size greater than 3 cm, pelvic sidewall or resection margin involvement, nodal metastasis, and time interval of less than 1 year from previous radiation treatment.
Complications of Pelvic Exenteration
The potential complications after pelvic exenteration are numerous. Almost every patient develops at least 1 complication, and approximately 40-50% experience a major complication that requires further diagnostic and therapeutic procedures. [4, 6] The operative mortality rate is 2-5% in modern series.
The rate of late complications is lower, but approximately one third of patients experience fistula, bowel obstruction, ureteral strictures, renal failure, pyelonephritis, and chronic bowel obstructions. 
Other complications include deep venous thrombosis and pulmonary emboli, flap necrosis, and stomal necrosis.