Exenteration for gynecologic cancer

INTRODUCTION — Exenteration refers to an ultraradical surgical procedure consisting of an en bloc resection of the female reproductive organs, lower urinary tract, and a portion of the rectosigmoid [1]. Although rarely performed, it may be offered as a last hope of cure to patients with recurrent or advanced gynecologic cancer with extensive central pelvic disease that cannot be resected with a lesser procedure, and in whom radiation is not an option. If the disease is truly confined to the pelvis, then this extended surgical resection offers a chance of cure: five-year survival rates are approximately 50 percent [2,3].

This topic review will discuss the indications and operative technique for exenterative surgery of the female pelvis. The evolution of pelvic exenterative surgery can be found elsewhere [4-14].

TERMINOLOGY — Total exenteration refers to removal of the uterus, tubes, ovaries, parametrium, bladder, rectum or rectal segment, vagina, urethra, and a portion of the levator muscles. In an anterior exenteration, the rectum is spared, while in a posterior exenteration, the bladder and urethra are preserved. A perineal phase, resecting the anus, urethra, and portions of the vulva, may also be required (figure 1).

There is no "standard" exenteration. The choice of procedure is based upon the location of the cancer, difficulties that may arise during surgery, type and location of previous radiotherapy, anatomy, and the patient's postoperative goals and expectations.

INDICATIONS — The potential for cure by exenterative surgery requires that the patient's cancer be resected in its entirety with adequate margins. Thus, diseases that spread by lymphatic, blood, or peritoneal pathways early in their course will rarely lend themselves to ultraradical resection.

The extreme radical nature of exenterative surgery dictates that it be used only when less radical treatment options have failed or cannot be used. Essentially all patients will have received prior pelvic radiation. Occasionally, a patient will present with advanced vulvar or cervical cancer involving the bladder, urethra, anus, or rectum, which lends itself to primary exenterative surgery as definitive treatment. Before deciding, serious consideration must be given to brachytherapy (including interstitial placement of sources) and combined chemotherapy and radiotherapy, alternatives that may spare the urinary and gastrointestinal tracts.

Cervical cancer — Patients with cervical cancer who develop a central recurrence (vaginal apex or pelvis without side wall involvement) of cervical cancer after primary radiation therapy (RT) or after surgery followed by RT may be candidates for a potentially curative surgical procedure if a complete evaluation fails to reveal metastatic disease.

Biopsy confirmation of central recurrences should be pursued if possible. If the recurrence is small and centrally limited, the patient may be an appropriate candidate for radical hysterectomy and partial vaginectomy. If there is a larger central recurrence or if the patient had a radical hysterectomy previously and has received prior therapeutic doses of RT, the patient may be a candidate for pelvic exenteration. (See "Management of recurrent or metastatic cervical cancer", section on 'Candidates for surgical resection'.)

In a systematic review of 21 studies of pelvic exenteration for gynecologic malignancy, one-third to one-half of patients were found to have unresectable or extrapelvic disease found at exploration, and the exenteration was aborted [15]. Resection with a clear margin was achieved in 75 to 97 percent of cases. The operative mortality in patients who underwent exenteration was 3 to 5 percent [15].

Those who successfully undergo exenterative surgery (negative margins and no metastatic disease) have an approximately 50 percent chance of being cured; the remainder die of recurrent cancer (algorithm 1). Although the number of patients who are cured by exenterative surgery is small, this surgery is still an opportunity for survival when faced with certain death.

Vulvar cancer — Vulvar cancer, like cervical cancer, often stays confined to the pelvis until late in its natural history. Radiotherapy alone or with chemotherapy is able to effectively eliminate or markedly shrink large vulvar cancers, lessening the extent of surgery needed [16-18] (see "Vulvar cancer: Epidemiology, diagnosis, histopathology, and treatment"). Primary exenterative surgery is not appropriate for most patients presenting with advanced vulvar cancer, but there is a limited role for exenteration in patients whose cancer recurs or in whom the cancer has destroyed the urethra, bladder, or anus.

Ovarian and endometrial cancer — Patients with either ovarian or endometrial cancer, both of which have a propensity to spread beyond the pelvis, are poor candidates for exenterative surgery. Five-year survival for patients with these cancers undergoing exenteration is 20 to 40 percent [19,20]. An exception is "modified posterior exenteration," which has been proposed for primary and secondary cytoreduction of ovarian cancer [21]. This operation is an en bloc resection of the pelvic peritoneum, uterus, tubes, ovaries, and a segment of rectosigmoid. It is a supralevator ani resection, useful for dealing with a "frozen" pelvis obliterated by ovarian cancer, in which attempting to develop planes between the pelvis and intestinal tract is not feasible. Cytoreductive surgery is performed concurrently. (See "Epithelial carcinoma of the ovary, fallopian tube, and peritoneum: Surgical staging".)

It is often possible to restore the continuity of the GI tract using modern stapling devices at the time of modified posterior exenteration for cytoreduction of ovarian cancer. When this is done, some surgeons will do a diverting colostomy to allow the low pelvic anastomosis to heal, while others will not do so if they feel they have a healthy, tension-free anastomosis.

Other cancers — Exenteration has also been used for vaginal carcinomas, rhabdomyosarcomas, and other miscellaneous rare tumors. Whenever ultraradical central resection of cancer is feasible, and lesser therapy is not feasible, exenteration can be considered. Severe radiation necrosis, rarely seen with modern technology, has also been an indication for exenteration.

Palliation — The use of exenterative surgery for palliation is controversial. Traditionally, the associated morbidity, complications, risk of death, and long hospitalization were considered too high for a palliative procedure. Expert surgical judgment and discretion must be exercised in the selection of those patients who can tolerate the palliative operative procedures without excessive morbidity and who are likely to benefit from the additional survival potentially provided by the operation [22].

PATIENT SELECTION

Psychological issues — A candidate for pelvic exenteration must be able to accept major changes in body image that will occur despite the surgeon's best efforts at reconstruction. The patient needs a support system, intact mental faculties, and access to continued medical care. Extended conversations with other patients who have undergone this surgery are also invaluable. Nurses who deal with these patients should have a positive, frank, and understanding manner. The range of complications resulting from surgery must be explained.

Patients must understand there is a 3 to 5 percent operative mortality, they will spend several days in the intensive care unit, and they will likely have a prolonged hospitalization measured in weeks. It is also necessary to discuss the possibility of an aborted procedure if unresectable or metastatic disease is found. Sexual function will be altered, and the patient may need to become adept at caring for one or two stoma. Often, a patient will cry and verbalize considerable anguish when these discussions occur. This, however, is preferable to the patient who cheerfully demands that one proceed immediately and only begins to deal with these emotions postoperatively. The patient in tears is beginning to understand what is proposed. In one sense, this is a terrible operation to offer someone; it is justified by a chance for cure but must be approached thoughtfully and carefully. The surgeon discussing the procedure with the patient needs to have considerable maturity and experience and must be able to honestly answer the questions that are asked and relay the uncertainty of the operative result. Finally, the patient must accept that, even after all this, there is no guarantee of cure.

Medical evaluation — The patient's general medical condition should be adequate for a prolonged operative procedure (four to eight hours) with probable extensive fluid shifts, transfusion, and nutritional support; potentially fatal coexisting diseases are a contraindication to exenteration. Age over 65 may increase the operative mortality of exenteration, although this probably reflects concurrent medical problems. Biologic age is more important than simple chronological age.

Histologic confirmation that cancer is present is critical before initiating surgery. The authors rarely, if ever, accept slides from another institution, and they never accept only a pathology report. The goal of the medical evaluation (complete history and physical examination, laboratory and imaging studies) is to find evidence of unresectable or metastatic disease, which would make the patient an unsuitable candidate for exenteration. As an example, unilateral leg swelling and unilateral or bilateral sciatic pain are worrisome, as they suggest metastatic disease to the posterolateral pelvic sidewall. The triad of unilateral leg edema, ipsilateral sciatic pain, and hydronephrosis on intravenous pyelogram (IVP) contraindicates exenteration, as it indicates unresectable cancer metastatic to the posterolateral side wall. Patients with one or two of the triad have a high likelihood of metastatic disease, but they should not be precluded from exploration if metastasis cannot be documented.

Physical examination focuses on looking for evidence of cachexia, palpable supraclavicular or inguinal adenopathy, hepatomegaly, or intraabdominal masses. Rarely, skin metastasis is found. Routine biopsy of nonpalpable supraclavicular or inguinal lymph nodes is not recommended, as the yield is vanishingly low. Palpable nodes, by contrast, should be biopsied as they almost always represent metastatic disease and preclude exenteration. Aspiration is usually adequate to confirm cancer. Pelvic examination is extremely inaccurate in assessing resectability, since it is not possible to differentiate radiation fibrosis, endometriosis, or igneous cellulitis from cancer. Fixation to the side wall on examination is not a contraindication to exploration.

Laboratory and imaging tests — Appropriate laboratory studies include screening for chronic active hepatitis and human immunodeficiency virus, which probably contraindicate exenteration. Elevated liver enzymes require excluding the possibility of liver metastasis. Additional routine laboratory tests include a complete blood count, platelet count, glucose, electrolytes, urinalysis, urine culture, and renal function tests. Anemia and any bleeding diathesis must be corrected preoperatively and intercurrent infections cleared, if possible.

The role of imaging prior to exploration for exenterative surgery is not well defined. The appropriate imaging tests should be performed to evaluate for distant metastases. Abnormal imaging alone should usually not be relied upon to remove exenterative surgery from consideration; computed tomography (CT)-directed fine needle aspiration cytologic analysis may also be used for confirmation.

CT of the pelvic side walls is less clear cut and should not be relied on for determining resectability on the basis of apparent absence of tissue planes lateral to the tumor. Even at exploration, frozen section is often needed to confirm planes of resection. Magnetic resonance imaging (MRI) has been evaluated for accuracy in determining the extent of local and sidewall invasion. As an example, a study of preoperative MRI in 23 patients before pelvic exenteration reported that in four patients, the MRI was falsely positive for pelvic sidewall infiltration, and in one patient, it was falsely negative [23]. In another study of MRI, 50 patients were assessed prior to exenteration by two readers for bladder, rectal, and pelvic sidewall invasion [24]. Among patients with bladder invasion on final pathology, both readers correctly identified 20 of 23 (86 percent). There were two false-positives for bladder invasion (4 percent). Rectal invasion occurred in 16 patients and was correctly identified in 13 (81 percent) and 12 (75 percent) patients by the two readers. There was one false-positive for rectal invasion (2 percent). Rectal or bladder invasion would not preclude exenterative surgery, but knowing its likely presence may aid in patient counseling and procedure planning. More important is pelvic sidewall invasion. Eight patients had pelvic sidewall invasion, and six (75 percent) and seven (87.5 percent) were correctly identified by the two readers. Pelvic sidewall invasion was overcalled by one and two patients by the two readers (2 to 4 percent). Thus, it appears that MRI evidence of sidewall disease is still not conclusive evidence of unresectability.

The discovery of metastatic disease prior to exploration is more important than the investigation for bladder, bowel, or sidewall disease. As an example, a study of positron emission tomography (PET) scan for the restaging of cervical carcinoma at the time of first recurrence included 40 patients who underwent PET scan, together with CT or MRI [25]. Twenty-two patients (55 percent) had their treatment modified as a result of the PET findings. PET was significantly superior to CT/MRI (sensitivity = 92 versus 60 percent) in identifying metastatic lesions. When compared with an earlier cohort of patients who did not undergo restaging with PET, there was a significantly better two-year overall survival (72 versus 36 percent). This improvement is attributed to finding of metastatic disease, and thus not subjecting the patient to exenterative surgery. In many centers, PET/CT has replaced CT for metastasis outside the pelvis.

The role of PET/CT in detecting the extent of pelvic recurrence was recently addressed in a study of 31 patients who had PET/CT within 90 days of a pelvic exenteration [26]. Two readers blindly read the PET/CT to determine invasion of bladder, rectum, vagina, and pelvic sidewall. Bladder invasion was found in 13 patients and correctly identified in nine cases by one reader and 10 cases by the second reader. Rectal invasion was found in nine cases and correctly identified in six by both readers. Pelvic sidewall invasion is the most important local recurrence to identify for the surgeon. In this study, pelvic sidewall involvement was found in five patients at the time of surgery, and it was correctly identified in three cases by one reader and four cases by the other. Both readers had one false-positive case for pelvic sidewall involvement. Thus, PET/CT was not effective in detecting pelvic sidewall disease.

Cystoscopy and sigmoidoscopy — Cystoscopy and sigmoidoscopy are not necessary unless there are plans to preserve either the bladder or rectum, in which case, they must be examined to ensure the absence of occult metastasis. In patients undergoing exenteration following radiotherapy for cervical cancer, the bladder is usually removed, as its preservation leads to increased risk of recurrence and urinary tract fistula or stricture.

PREOPERATIVE PATIENT PREPARATION — Informed consent for surgery is obtained before admission. The patient's medical condition should be made optimal. A mechanical bowel preparation is given with intravenous fluids started at the same time to avoid dehydration (see "Overview of preoperative evaluation and preparation for gynecologic surgery"). If the patient is severely malnourished, total parenteral nutrition (TPN) may be started in advance of surgery. Patients are taught incentive spirometry preoperatively and given a broad-spectrum prophylactic antibiotic (eg, cefazolin 1 g IV 30 minutes prior to incision).

The sites for stoma are marked by the ostomy team the morning of surgery, and they are checked when the patient sits, stands, and lies down. Care is taken to avoid skin creases, scars, and the site where the patient may normally wear a belt and elastic waistband.

Patients may remain NPO (nothing by mouth) for extended periods postoperatively. A central line can be placed in the operating room during the procedure, and TPN started. Central lines with multiple ports facilitate postoperative fluid management.

Six units of packed red blood cells are ordered, and incentive spirometry is taught preoperatively. Preoperatively, if time permits, we correct anemia, begin iron replacement, including parenteral iron therapy if necessary, and will use erythropoietin to raise hemoglobin to 11 g/dL.

OPERATIVE TECHNIQUE — The technique presented here uses an open approach (movie 1). Minimally invasive pelvic exenteration, including a traditional laparoscopic or robotic-assisted approach, is performed much less frequently and outcomes with this approach require further evaluation [27-31].

The patient is placed in a low dorsal lithotomy position, using stirrups to support the hips, knees, and thighs (picture 1). The assistants can be positioned on each side of the table, as well as between the legs, to allow for a double-team approach. The lithotomy position aids in allowing simultaneous abdominal-pelvic examination when the abdomen is open and resectability is being assessed and is helpful with the perineal phase of the procedure, or if myocutaneous grafts are planned for reconstruction. The patient is prepared and draped from nipples to knees, and a catheter is placed. Appropriate lines are inserted. The instrument stand is placed over the leg opposite the primary surgeon.

Intermittent pneumatic compression devices are applied as prophylaxis for deep vein thrombosis (picture 2A-B). Combined epidural and general anesthesia is preferred, as maintaining the epidural for 72 hours after surgery gives good pain control while keeping the patient alert and able to comply with respiratory toilet.

A midline incision adequate for exploring upper and lower abdomen is made and extended upward as needed. In a systematic manner, the diaphragm, liver, gallbladder, stomach, spleen, omentum, large and small bowel, and abdominal and pelvic peritoneum are examined for metastatic disease, a second primary lesion (ie, from a different cancer), or unexpected or known incidental pathology (eg, gallstones, hepatic cysts). The pelvis is inspected, looking for evidence of tumor breakthrough into the peritoneal cavity or metastasis to pelvic peritoneum or adnexa. The retroperitoneum and paraaortic areas are carefully palpated for masses. Any suspicious findings are biopsied and sent for frozen section to confirm unresectability. If no evidence of metastasis outside of the pelvis is found, the peritoneum over the paraaortic area is incised and a paraaortic biopsy is obtained and sent for frozen section. If pelvic nodes have not been previously removed, these are dissected and sent for frozen section. If negative, the pelvic exploration begins. Disseminated peritoneal disease is not compatible with cure, but patients with limited peritoneal involvement (sigmoid or ileum) have cure rates of 10 to 15 percent [15].

It is not uncommon to encounter small bowel adhesions, which must be lysed to allow adequate exploration of the abdomen. On occasion, a loop of small bowel will be found densely adherent to the uterus and rarely, there will be actual invasion directly into the loop of small bowel. Although most would resect or bypass the involved loop, reanastomose the bowel, and abort the procedure, there are case reports of patients who underwent exenteration with resection of the small bowel and survived more than five years (6 of 49 patients) [32]. Fecal spillage during surgery is handled by copious irrigation and by beginning antibiotics that cover anaerobic and gram-negative organisms.

If exenterative surgery is being considered for ovarian cancer, abdominal exploration is aimed at assessing whether disease outside of the pelvis can be cytoreduced to a maximum lesion size of 1 cm or less. If gross disease greater than 2 cm in diameter in the upper abdomen cannot be resected, then the patient will be suboptimally cytoreduced, and exenterative surgery would be futile. In this circumstance, should disease in the pelvis obstruct or invade the rectosigmoid, simple diverting colostomy would be preferred.

The round ligaments can be divided at the side wall and the prevesical and pararectal spaces developed. Alternatively, the prevesical space can be opened, dissected to the urethra, then extended laterally to both side walls, where the round ligaments can then be divided retroperitoneally, the lateral pelvic peritoneum reflected medially, and the spaces then developed.

Biopsy of the pelvic nodes is done if suspicious areas are seen. Routine lymphadenectomy is not done, as it would, at best, be of prognostic value, and of no therapeutic value. However, some gynecologic oncologists routinely perform pelvic lymph node sampling and abort the procedure if the nodes are positive, although some would consider intraoperative radiation therapy (IORT) if there was just limited lymph node involvement (ie, one lymph node positive). In the infrequent event of exenteration being done as primary therapy without prior radiation, lymphadenectomy may be appropriate.

The infundibulopelvic ligaments are divided well above the common iliac vessels. The ureters are dissected free for several centimeters past their point of crossing the common iliac vessels. If preoperative studies showed hydronephrosis, the point of obstruction is identified, and biopsies are taken to determine if unresectable cancer is causing the blockage. If the ureter is obstructed below the bifurcation of the iliac vessels, but medially, this is not a contraindication to resection and does not need to be dissected, as this area will be included in the major specimen. After resectability is determined, the ureters are divided on an angle to facilitate anastomosis to bowel. There is no point in trying to gain an extra centimeter or two in dividing the ureter; rather, it is important to ensure an adequate margin from cancer. In carefully selected cases, IORT contributes to radical salvage of patients with recurrent cervical cancer involving the pelvic wall [33].

The spaces lateral to the rectum are sharply developed and carried across the midline, where blunt dissection can be used to develop the potential space posterior to the rectum. At this point, the anterior tissue planes will have been developed down to the levator ani muscles, as will the bilateral perivesical and perirectal spaces, and the rectum will be freed posteriorly down to the sacral curve. This is usually a relatively bloodless dissection.

Beginning on the side most likely to contain cancer, the parametrium is sharply divided at the side wall. The internal iliac artery (hypogastric artery) is ligated just after it crosses the internal iliac vein. This results in loss of perfusion to the uterine artery, vesicle arteries, and the obliterated umbilical artery. The remainder of the internal iliac artery is left intact. It gives rise to the internal pudendal and inferior hemorrhoidal arteries, which are important to maintain vascularity to the anal canal and lower rectum, a potential site of anastomosis. It also carries the obturator artery, which provides significant blood supply to the gracilis muscle, and is necessarily preserved if planning a gracilis muscle neovagina. The cardinal ligament is divided and ligated at the side wall, and the broad attachments of the rectum to the sacrum are also divided. The vaginal attachments to the tendinous arch are divided, and the vaginal arteries and vein are located on the lateral margin of this pedicle. The specimen is now completely mobilized, so that penetration of the rectum and vagina through the pubococcygeus muscle can be identified. A combined abdominal-pelvic examination can be carried out at any point to identify areas suspicious for cancer, which are biopsied.

Intraoperative biopsy — When performing a biopsy to establish resectability, the specimen should be reflected medially, and the biopsy taken from tissue that will be left behind if the exenteration proceeds. The biopsy is meant to tell one what cannot be removed, so it is necessary to have one's planes of dissection well-formed before performing a biopsy. Anterolateral and posterolateral areas where tumor may extend to the side wall along the fascia or muscle fibers of the levator muscles are particularly difficult to biopsy. Kevorkian biopsy forceps, which are excellent for colposcopy, are also superb for biopsy of hard-to-reach areas (eg, diaphragm and liver). Occasionally, troublesome bleeding will be encountered and is best handled with pressure or by placing figure-of-eight sutures.

If a biopsy is positive for unresectable metastatic cancer, the procedure is terminated. The planes developed are copiously irrigated, and hemostasis is confirmed. No attempt is made to close these planes or to approximate peritoneal edges. Drains are not placed. A bulk closure of the abdomen is used, and the central line is left in place for fluid replacement. The surgeon needs to be available to talk with the patient when the patient awakens. Patients can usually be returned to the gynecology floor if they are stable in the recovery room.

If all biopsies return negative, then the exenterative specimen can begin to be removed. The ureters are now divided and placed into the upper abdomen, and the anesthesiologist is notified that there will no longer be any measurable urine output, and that urine will be mixed with blood loss.

Anterior exenteration — Anterior exenteration is suitable for lesions confined to the cervix and the anterior upper vagina. The goal is to remove the bladder, urethra, and anterior vagina, but to save the posterior vagina and rectum. Bimanual palpation, with the pelvic hand inserting one finger into the vagina and another into the rectum, while the abdominal hand palpates the posterior cul-de-sac (pouch of Douglas) and retracts the rectum posteriorly, will confirm the initial impression that an anterior resection is advisable. If the space posterior to the cervix feels free, then an incision can be made in the cul-de-sac to allow the rectum to drop away with sharp dissection from the upper vagina, leaving at least a 4 cm margin on the vagina. The potential space between the rectum and posterior vagina is developed abdominally, and adequacy of margin is confirmed by direct vision vaginally. The posterior vaginal incision is made from below, with the cancer in view, to ensure adequate margin. Biopsies of the vagina, which will be left intact over the rectum, are sent for frozen section if any question remains about cancer involvement. The perineal incision is made, removing the urethra and surrounding soft tissue, but preserving the clitoris and labia. Cautery reduces blood loss while doing this.

A pointed clamp such as a long tonsil is passed from the abdomen beneath the pubis and directed out superior to the urethra. The clamp is spread to open the space, and then widened from below with the two index fingers. Clamps are then passed under the pubic arch to allow the pubococcygeal muscles attached to the vagina at the three and nine o'clock positions to be divided. Clamps may also need to be passed from below upward to be sure the whole pedicle is taken. Large suture ligatures are used for hemostasis. The posterior vaginal wall is then separated from the rectum, and this posterior space (which communicates with the cul-de-sac) is joined with the anterior space, thus totally mobilizing the specimen, which can be delivered through the perineal opening. Warm laparotomy pads are placed abdominally into the defect, and pressure is applied from above and below. Cautery and ligature are used to obtain hemostasis. The specimen is then carefully inspected to be sure all margins are acceptable. It is often useful to place long sutures into the specimen to aid in orienting the pathologist, who must fix and section this specimen (picture 3). Many surgeons prefer to be present when the pathologist begins the gross examination of the specimen.

If at any time during the exenterative procedure there is difficulty separating the rectum and posterior vagina from the cancer, it is prudent to resect the piece of rectum to ensure an adequate margin.

Reconstruction of the vagina is done, if desired. If no vaginal reconstruction is planned, the omentum can be mobilized from the hepatic flexure to the splenic flexure, leaving 3 to 4 cm intact, and then loosely sewn over the pelvic defect. The perineal opening will close rapidly by granulation. Irrigations are usually started after 72 hours to keep the perineum clean, if no reconstruction is done.

Urinary diversion is then performed.

Total exenteration with perineal phase — If a total exenteration is planned and resectability is determined, the sigmoid and descending colon are mobilized, and the sigmoid is transected at the pelvic brim after dividing the ureters. The proximal end of the bowel, which will become the stoma, is packed into the upper abdomen. The rectosigmoid is elevated by an assistant, and the posterior attachments of the colon are freed down to the levator muscles. The sigmoid mesenteric arteries and the superior rectal artery are divided.

The perineal phase begins by making an incision sufficient to remove the urethra and entire vagina, and to include the anus. Cautery is used. The subcutaneous tissues are divided around the rectum, and then the urethra and anterior vagina are freed as in an anterior exenteration. In addition, the pubococcygeal attachments to the perineal body are identified, as is the anococcygeal ligament, and they are clamped, divided, and suture ligated. The specimen is removed through the perineal defect, and hemostasis is attained with ligature and cautery (picture 4). This leaves a huge pelvic defect, best filled with myocutaneous flaps of either gracilis or rectus abdominis muscles, and/or an omental flap. The colostomy and urinary diversion can then be constructed.

Supralevator total exenteration with low rectal anastomosis — Patients with disease extending posteriorly from the cervix onto the vaginal epithelium or into the rectal wall are candidates for this procedure, provided the cancer does not extend to the lower third of the vagina posteriorly [2,34]. After the bladder, urethra, and anterior vagina are mobilized, as previously described, the posterior vaginal wall incision is made 4 cm below the tumor [35]. The vaginal epithelium is mobilized for 1 to 2 cm away from the rectal muscularis. The hand then encircles the mobilized rectum and pulls it cephalad. The specimen side is clamped to reduce spillage of feces and divided, leaving an anal and rectal stump. The length of the anal rectal stump from the anal sphincter is ideally 6 cm or greater. If less than 6 cm in length, the risk of fistula and incontinence is greater.

After mobilization of this lower specimen, the sigmoid colon is divided along with the sigmoidal arteries and the superior rectal artery. Ample mobilization for reanastomosis is accomplished by incising the lateral attachments of the sigmoid and descending colon, mobilizing it, and if necessary, sacrificing some of the sigmoidal vessels. The major blood supply is from the inferior mesenteric artery, which has significant anastomoses between it and the middle colic artery. After the sigmoid and left colon are mobilized, the colon should be observed for adequacy of blood supply and viability while the urinary diversion is done and the flaps for neovaginal construction are harvested. If the appearance of both cut edges is satisfactory, then the anastomosis can be carried out. If there is lack of vascularity to either stump, they should be trimmed back until bleeding is encountered. The anastomosis is accomplished by using 28 or 31 mm-diameter circular staplers. Following anastomosis, the omentum is mobilized and brought into the pelvis as an omental graft. It is used to wrap the low rectal anastomosis and to fill the presacral space (figure 2 and figure 3).

Neovagina — A neovagina can then be made. The type of neovagina selected depends on the amount of space to be filled and the patient's anatomy. (See "Vaginectomy", section on 'Vaginal reconstruction'.)

Posterior exenteration — Posterior exenterations are rarely performed, except for primary stage IVA cancers of the cervix invading the rectum. Before planning a posterior exenteration, radiotherapy must be seriously considered. For patients who have had recurrence following radiotherapy, a total exenteration with low rectal anastomosis should be the first option.

When a cervical cancer recurs after radiotherapy, even if it is confined to the posterior vagina and rectum, one should remove the distal ureters, bladder, and urethra in order to avoid the very significant morbidity and mortality of a urinary tract fistula. The technique of posterior exenteration differs from those described above in that the bladder, anterior vagina, and ureters are preserved. After posterior exenteration, patients have significant bladder dysfunction resulting from the extensive removal of the hypogastric plexus that innervates the bladder. There is a high likelihood of requiring long-term catheter drainage or self-catheterization.

The posterior exenteration differs from the low anterior resection of the rectosigmoid performed by general surgeons because the uterus or cardinal ligaments are not removed, and thus the ureters and bladder are not disturbed. It is the radical en bloc excision of the uterus, cardinal ligaments, rectum, and rectal pillars that removes the hypogastric plexus and severely injures bladder function.

After dividing the round ligaments and developing the perivesical and perirectal spaces, the peritoneum between bladder and uterus is incised, and the bladder is reflected as inferiorly as possible with sharp dissection. The ureters are then mobilized and dissected free of their soft tissue attachments, similar to the technique for radical hysterectomy. The uterine arteries are divided at their origin and reflected medially, trying to preserve the other branches of the internal iliac arteries. The cardinal ligaments are then divided laterally, the ureteral dissection is completed to the bladder, and the anterior vagina is entered. The rectosigmoid is freed posteriorly, the parametrium is mobilized medially, and the dissection is carried down to the levator muscles, identical to the posterior dissection in a total exenteration. The perineal incision will involve only the posterior aspect of the vulva and anus. An omental flap and small pack can be used to complete management of the defect, and colostomy is performed (figure 4).

"Modified" posterior exenteration, which does not go below the levator muscles, may be used to complete optimal resection of an ovarian cancer. There is no perineal phase in this operation.

Urinary diversion — The standard urinary diversion for several decades was the urinary conduit using a segment of ileum to which the ureters would be anastomosed and a stoma created in the right lower abdomen (figure 5). Currently, the preferred method of urinary diversion is a continent pouch, created from the distal ileum, ascending colon, and a portion of the transverse colon (figure 6) [2,11,36]. The ileum is divided 10 to 12 cm proximal to the ileocecal valve, and the transverse colon is divided just distal to the middle colic artery (ie, Miami pouch). An ileotransverse colon enteroenterostomy is performed to restore continuity to the gastrointestinal tract. The isolated segment of bowel is opened with cautery along the tenia. The bowel is then folded on itself in a U shape, and the edges are closed with staples. This division and closure of the bowel prevents subsequent peristalsis and generation of intermittent high pressures, which would overcome the continence mechanism.

The ureters are brought through stab wounds into the bowel reservoir, and the spatulated ends are anastomosed mucosa to mucosa. The left ureter is brought through the sigmoid mesentery to reach the reservoir. A 14 French catheter is placed into the ileum and passed through into the reservoir. Excess ileum is excised from the antimesenteric edge with a stapling device, and three pursestring sutures are placed at the ileocecal valve to tighten the ileum. The tapered end of the ileum is brought out as a stoma. The ureters are stented and, with a Malecot catheter, are brought out through the anterior wall of the reservoir and through a separate opening in the abdominal wall. Stents and catheter are removed two weeks postoperatively. The low-pressure reservoir can be catheterized as needed. Alternatively, a bladder catheter may be brought through the ileal stoma and down the ileal catheterizing segment.

Results have been very encouraging, with most patients maintaining continence and catheterizing their stoma every several hours. The rate of postoperative complications (stricture, stones, fistulae, leakage, urinary infection, difficulty with self-catheterization) can be relatively high (>50 percent), especially in irradiated patients, but most complications have been treated successfully and without reoperation [36-39]. The best method of bladder reconstruction has not been determined in controlled trials [40].

Urinary diversion is discussed in more detail separately. (See "Urinary diversion and reconstruction following cystectomy".)

POSTOPERATIVE CARE — Many patients, particularly those with intercurrent renal or cardiac disease, will need to be followed in a surgical intensive care unit, with Swan-Ganz catheter monitoring to facilitate administration of blood products, colloid, and crystalloid. This is particularly important in patients with a large pelvic defect that will weep serum in large amounts comparable to a burn patient. Concealed hemorrhage and inadequate fluid replacement are constant considerations. It is advisable to keep the hematocrit stable (a level of 30 percent allows a reserve should bleeding occur) and to keep the prothrombin and partial thromboplastin time values normal with fresh frozen plasma and vitamin K, as needed (see "Use of blood products in the critically ill"). Measurement of serum protein levels may help appreciate the magnitude of loss. Frequent blood counts and electrolyte measurements are needed until the patient is believed to be stable, euvolemic, and has normal clotting parameters.

General care — Patients can be ambulated or at least out of bed within 48 hours. Adequate pain control must be maintained. Physical therapists are most useful in ensuring good range of motion and gradual increases in physical activity levels.

Respiratory care — Prompt extubation is preferred, with serial measurements of oxygen saturation used to ensure adequate pulmonary function. A postoperative chest film is needed to ensure that both lungs are expanded and to exclude pneumothorax from central line insertion. Since delayed pneumothorax can occur, a repeat film at 24 hours is useful. Vigorous respiratory toilet, including use of incentive spirometry and patient positioning, is an integral part of postoperative care. If acute respiratory distress occurs, pulmonary embolus, myocardial infarction, or congestive heart failure should be considered. The intermittent pneumatic compression devices, begun in the operating suite, are continued until discharge and are removed only when the patient is ambulating.

Fever — There are few hard data on which to base decisions concerning antibiotic usage after exenterative surgery. The source of postoperative fever should be identified, if possible, and appropriate antibiotics should be initiated; otherwise, antibiotics are begun empirically. Most postoperative febrile episodes remain unexplained and respond to broad spectrum antibiotic therapy. Before assuming that there is no identifiable source, the presence of ureteral obstruction, leaking anastomosis, or pelvic defect abscess should be excluded.

Nutrition — Chronically malnourished patients can be started on nutritional support in advance of their exenterative surgery. Postoperatively, it is not unusual for patients to go 14 days or longer without adequate oral intake, as ileus is common. There are no data on rapid resumption of oral feeding: we initiate early oral feeding in stable, alert patients. Total parenteral nutrition (TPN) may be started immediately after surgery and continued until the clinician feels the integrity of the bowel is confirmed and oral intake is adequate.

Drains — The role of drains is unclear. Personal bias and past experience will determine whether closed system, suction drains are placed and when they should be removed. We do not favor use of drains. (See "Principles of abdominal wall closure", section on 'Drains'.)

Packs — Patients who have a pelvic pack are usually kept on bedrest until it is removed, but the upper body can be elevated to improve respiratory toilet. If a pelvic pack was placed, the pursestring suture is cut after 48 to 72 hours, and one-half of the laparotomy pads are removed. The remainder of the pack is removed 24 hours later, and twice daily irrigations are begun of the pelvic defect. Warmed saline and peroxide, Lactated Ringer, or similar solutions may be used. Care is taken to ensure that fluid does not collect in the curve of the sacrum. It is usually sufficient to have the patient stand after each irrigation. The entire pelvic defect will slowly granulate in and close over time.

Bowel and ostomy issues — The continent reservoir is irrigated several times a day to remove mucus and clots. The mucus gradually disappears, but irrigations are necessary for up to six weeks. Self-catheterization is taught before discharge, with additional instruction provided by home health care nurses.

For patients with a low rectal anastomosis, initial stooling will be frequent, since rectal storage capacity is limited. Lomotil and Imodium can be used to decrease peristalsis. The goal is to have the patient pass stools three to six times a day. Gradually, the patient's lower rectum accommodates, and after four to six months, a more normal stooling pattern is usually achieved, and antiperistaltic drugs may be discontinued. When anastomoses are less than 6 cm, accommodation is more difficult, and incontinence and frequent stooling are more of a problem.

Frequent opportunities to speak with other patients who have successfully undergone exenteration help keep the patient's spirits high and attitude positive. Stomal therapists and home health care nurses are also important in aiding the patient in the immediate postoperative period and after discharge.

COMPLICATIONS — As many as 50 percent of patients suffer a major complication [2,3,15,41-45]. In one review, the most common complications related to the procedure were wound disruption/infection (39 percent), gastrointestinal fistula (10 percent), genitourinary fistula (8 percent), and ileus/small bowel obstruction (11 percent) [44]. In a large series, complications included infectious morbidity (86 percent), intestinal obstruction (33 percent), and fistulas (23 percent) [2]. Death in the perioperative period occurs in 3 to 5 percent of patients, with those over the age of 65 at highest risk. Sepsis, adult respiratory distress syndrome, heart failure, pulmonary embolus, and multiorgan system failure are typical terminal events.

Complications relating to prior medical problems and those seen with more commonly performed gynecologic procedures are discussed elsewhere. (See "Complications of gynecologic surgery".)

Intraoperative — Intraoperative complications are predominantly related to hemorrhage and problems associated with pelvic reconstruction. Blood loss of 6 units or more is not unusual [42,43,46], and delayed hemorrhage may occur in patients with an infected pelvic defect. Delayed hemorrhage is best managed with percutaneous embolization via interventional radiology, as reexploration is extremely morbid. (See "Management of hemorrhage in gynecologic surgery".)

During bowel anastomoses, segments of bowel may turn out to be too short, or ureteral anastomoses may tear. Patience and diligent attention to technique will minimize these occurrences.

Gastrointestinal — Gastrointestinal complications requiring surgical reexploration are usually attributable to problems with healing of the anastomosis in previously irradiated bowel. Bowel obstruction is managed conservatively, with decompression and fluid replacement. Similarly, fistulas that may be enterocutaneous or through the perineal defect are given a chance to heal, maintaining the patient NPO (nothing by mouth) and continuing total parenteral nutrition (TPN). Low output fistulas, in the absence of distal obstruction, occasionally heal. Usually, reexploration and surgical correction, with high patient morbidity and mortality, is required. In anterior exenterations, difficult extended dissections to preserve the rectum frequently lead to fistula. In these situations, a total exenteration or low rectal anastomosis may be preferable.

Use of colon conduits or reservoirs, thereby avoiding anastomosis in radiated bowel, lessens problems with anastomotic leaks. When leaks are encountered, management with percutaneous stenting and drainage is preferable to reoperation with attempts at reconstruction (image 1A-B) [47]. Percutaneous catheters can also be used to dilate areas of ureteral stenosis.

Body image and sexual function — A study of 16 patients found that sexual function and body image declined during the first three postoperative months and then returned to baseline by 12 months [48]. Following pelvic exenteration, patient interest in sexual function and body image is variable. Some patients have no interest in sexual activity, and others wish to undergo neo-vagina reconstruction with postoperative repeat dilation. The issue is made more complex by the impact of stoma(s) on body image and the occurrence of postoperative complications, which can be slow to resolve. Counseling of the patient regarding postoperative changes in anatomy and body function and involvement of the patient's sexual partner are important parts of exenterative surgery care. Referral to a gynecologist or other clinician or a psychotherapist with expertise in sexual health is often appropriate.

Delayed — Delayed complications include bowel obstruction, bowel or urinary fistula, ureteral obstruction with renal compromise, and stomal stenosis. Recurrent cancer must always be considered. Attempts at conservative management, without surgical exploration, are always wise.

OUTCOME — Survival and presumptive cure is possible in approximately one-half of patients undergoing exenteration as salvage therapy for pelvic cancers [2,49-52].

SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Treatment of cervical cancer".)

SUMMARY AND RECOMMENDATIONS

●Terminology – Total exenteration refers to an ultraradical surgical procedure in which the uterus, tubes, ovaries, parametrium, bladder, rectum or rectal segment, vagina, urethra, and a portion of the levator muscles are removed (figure 1 and picture 4). In an anterior exenteration, the rectum is spared, while in a posterior exenteration, the bladder and urethra are preserved. (See 'Introduction' above and 'Terminology' above.)

●Indications – Exenteration may be offered to patients with recurrent or advanced gynecologic cancer with extensive central pelvic disease that cannot be resected with a lesser procedure, and in whom radiation is not an option. Thus, patients with diseases that spread by lymphatic, blood, or peritoneal pathways early in their course will rarely be candidates for ultraradical resection. (See 'Indications' above.)

●Patient selection – The patient must be counseled thoroughly about the risks and long-term issues related to the procedure. Extended conversations with other patients who have undergone this surgery are invaluable. The patient should undergo a comprehensive evaluation with laboratories and imaging to make sure there is no evidence of unresectable or metastatic disease, which would make the patient an unsuitable candidate for exenteration. (See 'Patient selection' above.)

●Operative technique – An open approach is typically performed and the operative technique is presented in the movie (movie 1). (See 'Operative technique' above.)

●Complications – As many as 50 percent of patients suffer a major complication. The most common complications include wound disruption, infection, fistula, and ileus/small bowel obstruction. Death in the perioperative period occurs in 3 to 5 percent of patients. (See 'Complications' above.)

●Outcomes – Survival is possible in approximately one-half of patients undergoing exenteration as salvage therapy for pelvic cancers. (See 'Outcome' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Ken D Hatch, MD, now deceased, who contributed to an earlier version of this topic review.