Obstetrics and Gynecology

Ovarian Cancer - Surgical Management

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Ovarian Cancer - Surgical Management

1. What every clinician should know Are you sure your patient has the disease? What should you expect to find?

It is estimated that there will be 21,990 new cases of ovarian cancer diagnosed in the United States in the year 2011. While the lifetime risk in the general population is relatively low (approximately 1.4%), in certain high-risk individuals, such as those with a BRCA1 or BRCA2 gene mutations, the lifetime risk can reach 40-50%.

In the United States, ovarian cancer remains the leading cause of death from a gynecologic malignancy. This is likely due to the fact that the majority of cases present in the advanced stage. Only approximately 35% of women will be diagnosed at an early stage with disease confined to the ovary or pelvis. Frequently, these women are diagnosed after an incidental adnexal mass is detected on routine gynecologic exam or imaging. It is not uncommon for these women to be completely asymptomatic, but they may also present with symptoms such as pelvic pain, abdominal discomfort, bloating, urinary symptoms, dyspareunia, or changes in bowel habits.

Unfortunately, the majority of women with ovarian cancer will be diagnosed after the disease has spread outside of the pelvis. Commonly, these women will experience symptoms such as abdominal distention/discomfort, increased abdominal girth, changes in bowel habits (nausea, vomiting, diarrhea, constipation, changes in stool caliber), early satiety, and/or shortness of breath. Any of these symptoms and/or the presence of a complex adnexal mass necessitate prompt evaluation and consideration of referral to a gynecologic oncologist, especially if the patient is postmenopausal, has a history of breast cancer, or has a family history of breast or ovarian cancer.

2. Diagnosis and differential diagnosis

A prompt evaluation is needed when a complex adnexal mass is present, or when advanced ovarian cancer is suspected based on patient symptoms or imaging. Studies have consistently shown that patients with ovarian cancer who receive their initial surgical care from a gynecologic oncologist have improved outcomes. Therefore a thorough and efficient workup followed by appropriate referral is imperative. Workup should include a careful history and physical exam including breast, gynecologic, and rectal exam. All screening – including colonoscopy, mammography, and cervical cytology – should be up to date.

If a pelvic mass is palpated on bimanual exam, the size, mobility, and extent of disease (i.e., sidewall and rectal involvement) should be noted. If a rectal mass is palpated, consider a flexible sigmoidoscopy to evaluate the lesion, even if the patient is up to date on screening colonoscopy. The abdomen should be assessed for the presence of ascites and the lungs examined for the presence of effusions.

Imaging studies may include transvaginal sonography, computed tomography (CT) scan of the abdomen and pelvis, pelvic magnetic resonance imaging (MRI), and positron emission tomography (PET) scan. The presence of a complex adnexal mass, pelvic tumor, lymphadenopathy, or peritoneal carcinomatosis all support the diagnosis of advanced ovarian cancer. If advanced disease is suspected or if the patient has shortness of breath, imaging should also include a chest CT, which can identify pleural disease, effusions, and enlarged mediastinal lymph nodes.

Tests for serum tumor markers, especially CA125, may be helpful in confirming the diagnosis of ovarian cancer or indicating the need for evaluation of other possible primary malignancies. Other relevant serum tumor markers include CEA, CA 19-9, LDH, AFP, inhibin, and HCG. Routine preoperative testing should also include a basic metabolic panel, complete blood count, coagulation studies, liver function tests, and serum albumin.

Ultimately, surgical pathology is required for the definitive diagnosis of ovarian cancer. If the preoperative suspicion for ovarian malignancy is high, the surgical procedure should be performed by (or in conjunction with) a gynecologic oncologist. Prior to surgical intervention, a thorough preoperative assessment should be performed in order to ensure that the patient is a suitable candidate for a potentially lengthy and extensive surgical procedure.

During the preoperative consent discussion, the patient should be informed of the potential need for extensive surgery (laparotomy, if laparoscopy is planned), for blood transfusion, or for the creation of a temporary or permanent ostomy. If there is a question of tumor resectability, it is reasonable to consider a diagnostic laparoscopy as the initial step. In women of childbearing age, it is crucial to discuss the patient's desire for future fertility prior to any surgical intervention and plan accordingly.

Ovarian cancer is surgically staged. Intraoperatively, the peritoneal surfaces in all 4 quadrants should be carefully examined. In cases where disease is grossly limited to the ovary, it is crucial that the specimen be removed intact to avoid spillage of tumor into the abdomen. Frozen section can be utilized intraoperatively to confirm malignancy and gynecologic origin and to assist in planning the remainder of the procedure.

Surgical staging of ovarian cancer includes peritoneal cytology, total hysterectomy, bilateral salpingo-oophorectomy, omentectomy, pelvic and paraaortic lymphadenectomy (up to the level of the renal vessels), peritoneal biopsies from anterior/posterior cul-de-sac, pelvic sidewalls, paracolic gutters, and bilateral diaphragms. A systematic and thorough approach should be taken during surgical staging, as incomplete staging can lead to underestimation of disease and, subsequently, undertreatment.

In women of childbearing age who desire future fertility, it is reasonable to consider conservation of the uterus and non-affected ovary. In a young and otherwise healthy woman, it is far more prudent to perform a two-step procedure after a definitive pathologic diagnosis than to proceed with a surgical resection that renders her infertile. In young women, preoperative consultation with a reproductive endocrinologist is recommended to discuss options for oocyte or embryo cryopreservation or other techniques to protect ovarian reserve. If extra-ovarian disease is identified, the goal of surgery should be complete staging in addition to complete resection of all visible disease.

3. Management

A. What therapies should you initiate immediately, i.e., emergently?

Initial treatment of advanced ovarian cancer consists of primary cytoreductive surgery (CRS) followed by a platinum-based chemotherapy regimen. Surgical cytoreduction has consistently been shown to improve response to adjuvant chemotherapy. The mechanism of this is likely related to the elimination of a large volume, poorly perfused tumor, allowing for more efficient delivery of chemotherapy to tumor cells, and the increased proportion of rapidly dividing, and therefore highly chemosensitive, tumor cells.

In this section, we will focus on primary CRS. While an “optimal” CRS is considered resection of tumor down to less than 1cm of visible disease, referring to the single largest residual tumor nodule, each incremental decrease in residual tumor burden results in improved patient outcomes. Therefore, the standard of care should remain an extensive effort to resect all visible disease prior to initiation of chemotherapy.

There are some instances where primary CRS is not appropriate, such as in the setting of extensive thoracic disease, as seen on preoperative CT or in video-assisted thoracic surgery; unresectable abdominal metastases, such as extensive involvement of the mesentery of the small bowel; parenchymal liver disease; unresectable portal disease; or medical contraindications to an extensive surgical procedure. Additionally, if resection of the tumor down to less than 1cm is not deemed possible at the time of exploration, then the surgical effort should be aborted and the patient treated with systemic chemotherapy, possibly followed by another attempt at CRS.

B. What should the initial definitive therapy for the cancer be?

After preoperative assessment and evaluation are complete, every effort should be made to perform surgical staging and cytoreduction in an efficient and timely fashion. The anesthesia and perioperative teams should be prepared for a potentially lengthy and extensive surgical effort, and appropriate consultants should be available for assistance if needed.

The patient should be placed in the dorsal lithotomy position, allowing for a thorough exam under anesthesia and optimal access for a rectosigmoid resection and anastomosis if needed. The anesthesia team should ensure adequate vascular access and have blood products available for transfusion should they be required. Sequential compression devices should be in place prior to the initiation of anesthesia, and a sterile Foley catheter should be placed in the bladder prior to the skin incision.

Assessment of tumor burden and location should always be the first step after entry into the abdomen, or during diagnostic laparoscopy, if planned. Once the decision is made to proceed with CRS, a generous vertical midline incision (from pubis to xiphoid) and placement of a fixed, self-retaining retractor, such as a Bookwalter or Omni, is recommended. As it is frequently the most challenging portion of the case, we recommend starting the resection in the upper abdomen. The following sections review procedures commonly required during extensive CRS.

Omentectomy

The omentum is a frequent site of ovarian cancer metastases or tumor “caking." An infracolic omentectomy is often sufficient. However, in cases where tumor is present in the gastrocolic omentum, a supracolic omentectomy may also be required. Mobilization of the hepatic and splenic flexures are often necessary when omental disease is extensive.

While mobilizing the splenic flexure, care must be taken to avoid excess traction on the omentum, which can cause tears and bleeding from the splenic capsule. At the transverse colon, the mesocolon and middle colic artery should be preserved in order to maintain adequate blood supply to the colon. If no plane exists, it may be necessary to resect the omentum and transverse colon en bloc. Resection of a large omental cake may improve exposure to other areas of the abdomen, in addition to providing a tumor specimen for frozen section, and is therefore a common first step during CRS.

Right upper quadrant (RUQ)

The right upper quadrant is a frequent site of metastatic disease in advanced ovarian cancer, partially due to the clockwise flow of peritoneal fluid in the abdominal cavity. The liver (surface and/or parenchyma), the right diaphragm, the peritoneum overlying Gerota’s fascia and Morrison’s pouch, the gallbladder, and the porta hepatis are all potential sites of tumor infiltration. While it can present a challenge, tumor involvement of these sites is not an absolute contraindication to optimal or complete CRS.

Liver mobilization

This is an important first step in adequately evaluating and treating right diaphragm disease, without which the extent of tumor involvement can be significantly underestimated. The patient should be positioned in reverse Trendelenberg in the “RUQ up” position. The xiphoid can be resected in order to maximize exposure through the vertical midline incision and the retractors replaced to elevate the ribs, more effectively exposing the liver and right diaphragm.

The falciform ligament should be identified and the free edge containing the round ligament (remnant of the umbilical vein) divided and tagged to assist in gentle downward traction on the liver. The falciform’s attachment to the anterior abdominal wall should be separated in a cephalad fashion using electrocautery until the layers of the peritoneum split laterally to form the right and left coronary ligaments.

During this dissection, we recommend staying adjacent to the liver surface. Dissection should then continue along the right coronary ligament, taking extreme care to identify and avoid the right hepatic vein and inferior vena cava. At this point in the dissection, a combination of medial and lateral approaches is frequently necessary, depending on the disease volume and distribution. The lateral triangular ligament can be divided and the dissection continued medially until the bare posterior surface of the liver is exposed. The liver mobilization will be complete once the right posterior coronary ligament is completely free. Gentle medial traction on the liver will expose the right diaphragm as well as the peritoneum overlying Gerota’s fascia and Morrison’s pouch.

Right diaphragm peritonectomy and resection

Tumor implants can be superficially present on the peritoneum of the diaphragm or deeply invasive into the muscle. Once areas of disease are identified, the peritoneum at the level of the costal margin can be incised using electrocautery. The peritoneal edge can be grasped using a clamp and dissection continued posteriorly. Similar to liver mobilization, a combination of medial and lateral approach is often necessary to achieve optimal results.

A combination of blunt dissection (using a sponge stick) and electrocautery can be used as gentle downward traction is placed on the peritoneal edge to free it from the underlying muscle of the diaphragm. While this technique works very well for superficial implants, in areas where the tumor is deeply infiltrative (or at the central tendon of the diaphragm), dissection may become more difficult and may necessitate utilization of more electrocautery, sharp dissection, or ablative techniques, such as argon beam coagulation. A vessel-sealing device may also be useful in controlling small bleeding vessels.

Once the diaphragm peritoneum is resected, the muscle of the diaphragm should be carefully inspected for defects, which can be repaired primarily using delayed-absorbable figure-8 sutures. A tumor that has invaded through the peritoneum and into the underlying muscle may require full thickness resection of the diaphragm. In addition to the right hepatic artery, the right phrenic nerve can be injured if the resection extends medially. Anesthesia personnel should be notified of impending pneumothorax as the pleural cavity is entered. The involved diaphragm can be resected using electrocautery, a vessel-sealing device, or an endo-GIA stapler.

Once the disease is resected, often the diaphragm can be closed using permanent sutures (1-0 polypropylene) in either an interrupted, figure-8, or running fashion. A synthetic tissue can be utilized to repair larger defects and secured with a running permanent suture. After closing the diaphragm, air, blood, and fluid should be evacuated from the pleural space using either a red rubber catheter or chest tube placement. In addition to evacuating the acute pneumo/hemothorax, the chest tube can be used to drain post-operative pleural effusions, which are common after extensive diaphragm peritonectomies.

Liver wedge resection

This is commonly required in the setting of superficial parenchymal liver metastases and is often performed in conjunction with a hepatobiliary surgical consultant. Superficial liver disease frequently can be ablated using the argon beam coagulator (ABC) or other devices, such as the Cavitron ultrasonic surgical aspirator (CUSA).

Left upper quadrant (LUQ)

While metastatic ovarian cancer is less commonly found in the LUQ, a thorough assessment is needed to evaluate for the presence of resectable disease. In order to gain exposure and appropriately identify all disease, entry into the lesser sac (by incising the posterior leaf of the omentum) is recommended. By reflecting the stomach and omentum anteriorly and medially, the spleen, pancreas, celiac axis, and porta hepatis can be accessed.

Left diaphragm peritonectomy and resection

The approach to the left diaphragm is similar to the approach to the right side (as described above). It is best performed after mobilization of the liver. If tumor involvement is excessive, the left diaphragm can be removed en bloc with other structures in the LUQ, such as the spleen and distal pancreas.

Splenectomy

Splenectomy is required in approximately 10% of cases, due to either superficial or parenchymal tumor involvement. Splenectomy can be performed via an anterior or posterior approach. In the presence of a tumor, a combination of the two approaches is generally the most efficient and safe. The patient should be placed in the “LUQ up” position and retractors adjusted accordingly. After entry into the lesser sac and retraction of the stomach medially, the gastrosplenic ligaments and short gastric vessels can be divided, taking care not to injure the posterior wall of the stomach. The spleen can be gently lifted and the distal pancreas examined.

After incising the splenorenal ligaments, the splenic artery can be identified, isolated, and doubly ligated using permanent sutures. The splenic vein should be ligated separately to allow for venous drainage and to prevent arteriovenous fistula. After the vasculature is secured, all remaining attachments can be divided, including the inferior splenocolic ligaments, the posterior and lateral lienorenal ligaments, and the splenophrenic ligaments. If extensive omental infiltration is present, it may be best to start with the posterior approach and transection of the lateral attachments. All vascular pedicles should be inspected thoroughly after completion of the procedure, as any unsecured vessel in this region can result in significant postoperative hemorrhage.

Distal pancreatectomy

Pancreatic involvement by metastatic ovarian cancer usually occurs in the setting of extensive omental involvement, when the disease extends beyond the splenic hilum. In such cases, distal pancreatectomy is generally performed in conjunction with splenectomy. After the gastrosplenic and short gastric vessels are divided, the peritoneum overlying the inferior border of the pancreas in incised proximal to the area of tumor infiltration. After the splenic vessels are secured, the distal pancreas can be transected using a TA or GIA stapler and reinforced using a 2-0 permanent running suture.

Similarly, if the pancreatic tail is injured during splenectomy, the defect can be reinforced with a continuous layer of 2-0 or 3-0 sutures. Recognition of injury and proper reinforcement of the transected edge/injured area are crucial to reduce the incidence of postoperative complications, such as pancreatic leak, development of a pseudocyst, and pancreatitis. During this procedure, it is also important to avoid injury to the underlying inferior mesenteric vein. Placement of a drain in the splenic bed can facilitate monitoring of pancreatic leak and should be continued until minimal output is noted and the patient is tolerating a regular diet.

Pelvis

While some women require a simple total hysterectomy and bilateral salpingo-oophorectomy to achieve optimal cytoreduction, many have a large conglomerate mass obliterating the pelvis that will require a more complicated dissection. This can frequently be accomplished by performing a modified posterior exenteration (MPE), which entails an en bloc resection of the uterus, adnexa, rectosigmoid colon, and pelvic peritoneum. This en bloc resection is best accomplished using a retroperitoneal approach, which allows for easier access, exposure, and safer resection of tumor and pelvic viscera.

At the start of the procedure, the pelvic sidewalls should be opened using lateral peritoneal incisions, and the ureters and pelvic vasculature identified. The left lateral peritoneal incision can be extended cephalad along the white line of Toldt to mobilize the descending colon. The ureters should be isolated and tagged with vessel loops and the infundibulopelvic ligaments identified and divided.

The pararectal and paravesical spaces should be developed and the ureters skeletonized from the pelvic brim to the tunnel of Wertheim. The peritoneum can be incised anteriorly and the vesicouterine space developed. Occasionally, this dissection is limited by tumor infiltration into the bladder, which may necessitate full thickness bladder resection.

Bladder defects can be repaired primarily, but care must be taken to avoid the trigone and bilateral ureteral insertions. The uterine vessels should be secured and divided laterally at their origin from the hypogastric arteries. After unroofing the ureter from the bladder pillars, the ureters can be reflected laterally away from the specimen using the vessel loops for gentle traction. The bladder is then dissected off of the vagina approximately 2-3 cm distal to the cervicovaginal junction.

At this point, a vaginal probe or sponge stick can be inserted into the vagina to assist in the anterior colpotomy, which ideally should be 1-2 cm distal to the cervicovaginal junction. The colpotomy is then extended laterally with Heaney clamps (or a vessel sealing device) and the vaginal angles are secured using figure-8 sutures. The rectovaginal septum can then be safely entered by incising the posterior vaginal wall.

Depending on the degree of tumor involvement, the decision can be made to proceed with either a Type 1 procedure - resection of the pelvic peritoneum, including the peritoneum of the posterior cul-de-sac - or a Type 2 procedure - resection of the rectosigmoid colon en bloc with the uterus and adnexa. If the decision is made to proceed with a Type 2 resection, the rectosigmoid colon can be transected using a GIA stapler 2-3cm proximal to the affected colon.

The sigmoid mesentery can then be incised and transected perpendicular to the long axis of the sigmoid and the superior rectal vessels identified, ligated, and divided. During mobilization of the left colon, care should be taken to preserve the left colic artery in order to maintain adequate blood supply to the descending colon. The rectum can then be dissected off of the presacral fascia after development of the pararectal space using a combination of blunt dissection and electrocautery.

Once the dissection is carried distal to the area of tumor infiltration, the specimen can be lifted ventrally and the mesorectal fat cleared from the site of transection. After reconfirming the location of the ureters and pelvic vessels, a TA stapler can be used to transect the rectum 2-3 cm distal to the area involved by tumor. The rectum can then be anastomosed using an end-to-end stapling technique, with care to ensure that the anastomotic site is tension free, hemostatic, and secure, and has an adequate lumen and blood supply. If there are any concerns regarding the integrity or perfusion of the anastomosis, a diverting loop ileostomy should be considered.

Bowel resection

Approximately 35% of patients will require colon resection, and 5% will require small bowel resection to achieve optimal cytoreduction. In addition to the rectosigmoid resection, patients may require a transverse colectomy, an ileocecal resection, an extended right or left hemicolectomy, or a small bowel resection. Proper mobilization of the colon is a crucial first step of a safe resection. The peritoneum overlying the paracolic gutters should be incised along the white line of Toldt and the colon reflected medially.

The splenic flexure, hepatic flexure, and transverse colon can be further mobilized by transecting the gastrocolic ligaments and opening the lesser sac. The inferior mesenteric vein can be ligated and transected inferior to the pancreas to allow for greater descent of the mesentery. In general, the bowel can be transected using a GIA stapler, with care to maintain adequate blood supply, and a tension-free, stapled, side-to-side or end-to-end anastomosis can be performed.

Lymphadenectomy

In patients with grossly advanced disease (stage IIIC or IV), we recommend routine removal of any enlarged or grossly abnormal lymph nodes in the pelvis, abdomen, or chest. Mediastinal lymphadenectomy has been shown to be feasible and safe and can frequently be accomplished through the abdominal incision, with the assistance of a cardiothoracic surgeon, if needed. In patients without evidence of advanced disease, a full staging lymphadenectomy should be performed up to the level of the renal vessels. The utility of removing normal appearing lymph nodes in the setting of grossly advanced disease is unknown and left to the discretion of the operating surgeon.

Placement of an intraperitoneal catheter

If optimal cytoreduction is achieved, placement of an intraperitoneal catheter should be routinely performed for infusion of adjuvant chemotherapy. If there are doubts intraoperatively about the patient’s candidacy for intraperitoneal chemotherapy, we recommend proceeding with placement, as removal can be safely performed under local anesthesia in the clinic.

Ideal placement is in the midclavicular line in the RUQ or LUQ over the distal ribs. A 4 cm transverse incision is made and carried down to the fascia, at which point blunt dissection can be used to make a pocket to accommodate the reservoir of the port. A long, fine-tipped clamp can be used to create a tunnel from the incision into the mid abdomen, under direct visualization while elevating the abdominal wall. This clamp can be used to grasp the catheter tubing and pull it back through the incision. The tubing should be trimmed, and the reservoir attached as directed by the manufacturer. The port should then be flushed with heparinized saline and each component examined for patency and leaks. Delayed absorbable sutures can be used to secure the reservoir to the fascia. Finally, the incision can be closed in layers.

Closure

Women with advanced ovarian cancer have been shown to be at high risk for the development of incisional hernias, especially if they go on to receive intraperitoneal chemotherapy. Abdominal closure should be performed with a continuous running delayed, absorbable, monofilament suture (we recommend #1 looped polydioxanone/PDS) with a suture length to wound length ratio of at least 4:1. Randomized data suggest that sutures should be placed 5-8 mm from the fascial edge to decrease the amount of tissue necrosis. Subcutaneous tissue should be copiously irrigated and closed after hemostasis is assured.

B. What complications could arise as a consequence of the management – chemo, radiation and surgical?

Complications after extensive CRS are extremely common, and prompt identification of these complications is an important aspect of postoperative care. Due to the length and extent of surgical effort, many patients will require intensive care unit (ICU) admission for postoperative fluid management and supportive care. Malnutrition, ascites, and comorbidities should all be considered high-risk features for needing postoperative ICU care. The following list highlights some of the most commonly experienced complications following CRS, in addition to some clinical pearls regarding their diagnosis and management.

Infectious complications

During physical exam in the first several weeks after surgery, patients should be monitored closely for fever, elevated white blood cell count, and abnormalities. Each of these abnormalities can indicate an underlying infectious process. Some of the most common infectious processes are described below.

Wound infection

Cellulitis frequently resolves with antibiotic treatment, but we recommend opening surgical wounds to facilitate drainage of underlying collections in the setting of cellulitis that persists despite appropriate antibiotic therapy, purulent drainage, or fluctuance on exam. Twice daily wet-to-dry dressing changes can be utilized until the infection resolves, at which point a wound vacuum system can be placed to expedite healing.

Hospital acquired pneumonia

All hospitalized patients, especially those with prolonged stays, are at risk for developing pneumonia. This should be considered in patients with fever, leukocytosis, hypoxia, or respiratory symptoms such as cough. A chest x-ray should be ordered and if an infiltrate is identified, appropriate antibiotic.

Intraabdominal or peritoneal abscess

This should be considered in the setting of unexplained leukocytosis, fever, prolonged ileus, or failure to spontaneously diurese by postoperative day seven. Most abscesses can be managed with intravenous antibiotics and interventional radiology drainage.

Peritonitis/sepsis

If peritoneal signs or sepsis are suspected, workup should include CT scan with contrast to identify any possible areas of bowel injury or anastomotic compromise.

Hematologic complications

Bleeding/coagulopathy

Bleeding/coagulopathy usually occurs within 24-48 hours of surgery. Monitoring of vital signs, blood counts, and coagulation profiles should allow for prompt identification. If aggressive transfusion of blood products fails to stabilize the patient and resolve coagulopathy in a timely fashion, prompt reoperation may be necessary. If any concerns exist postoperatively about hemodynamic stability, patients should be observed and managed in an ICU setting.

Venous thromboembolism (VTE)

Patients undergoing surgery for advanced ovarian cancer are at extremely high risk for VTE. Acute shortness of breath, hypoxia, unexplained tachycardia, or lower extremity tenderness/edema (especially if unilateral) should prompt a workup. We recommend that all patients receive postoperative prophylactic anticoagulation therapy after CRS unless significant concerns exist regarding active bleeding or coagulopathy. Consideration should be given to provide the patient with an extended course (four to six weeks) of anticoagulants at discharge.

Cardiovascular complications

Intravascular depletion and third spacing

This is extremely common in women with advanced ovarian cancer, especially in the setting of large volume ascites. To assess renal perfusion, urine output should be monitored closely with a Foley catheter and serum creatinine tests. Most patients will begin to spontaneously diurese within three to four days after surgery. In our experience, failure to diurese within seven days postoperatively may indicate an infectious or other significant intra-abdominal process.

Respiratory complications

Pneumothorax

All patients undergoing diaphragm resection/peritonectomy should have a chest X-ray in the recovery room to assess for pneumothorax. If sudden symptoms of dyspnea or hypoxia occur at any time postoperatively, workup should include a repeat chest X-ray.

Pleural effusions

The development of pleural effusions postoperatively is extremely common after liver mobilization and diaphragm peritonectomy/resection, especially in patients with ascites. Routine chest X-ray can be used to diagnose and follow postoperative pleural effusions. If a symptomatic effusion develops, patients may benefit from thoracentesis or placement of a chest tube or drainage catheter. If a chest tube was placed intraoperatively, the output should be followed closely. We recommend continuing chest tube drainage until output is <200 cc per day on straight drainage alone.

Gastrointestinal complications

Ileus/obstruction

Postoperative ileus is extremely common, especially in patients who require bowel resection or extensive mobilization of the bowel. While we generally encourage early postoperative re-feeding, the initial step in the management of postoperative nausea and vomiting should be bowel rest. In the majority of cases, postoperative ileus will resolve with bowel rest and nasogastric decompression. In our experience, limiting narcotics and fluid overload can also decrease the incidence, severity, and duration of ileus.

Similarly, small bowel obstruction in the acute postoperative setting will frequently resolve with conservative management, including bowel rest and nasogastric decompression. However, surgical management may be required if these conservative measures fail. Parenteral nutrition should be considered in patients who require more than five to seven days of bowel rest postoperatively.

Anastomotic leak

In the setting of peritonitis, sepsis, drainage of enteric contents from surgical drains or incision, unexplained fever, or persistent leukocytosis, a CT scan should be obtained to evaluate all sites of anastomosis. In unstable or septic patients, prompt reoperation is generally required. In stable patients without evidence of sepsis or peritonitis, anastomotic leaks may be amenable to nonsurgical management with drainage, IV antibiotics, and, in some cases, endoscopic stent placement or repair.

Pancreatic leak/pancreatitis

In patients who underwent splenectomy or distal pancreatectomy, fever, nausea/vomiting, or unexplained leukocytosis may indicate a pancreatic leak. If a surgical drain was left in the LUQ, monitoring of daily output and drain amylase may assist in early identification of a leak (if drain amylase >3x serum amylase). In addition to bowel rest and drainage, somatastatin can be used to manage a postoperative pancreatic leak.

C. What other therapies are helpful for reducing complications?

All patients undergoing CRS for advanced ovarian cancer should receive VTE prophylaxis, including sequential compression devices and a prophylactic dose of anticoagulants, gastrointestinal prophylaxis (such as a proton pump inhibitor), pulmonary toileting, and assistance with early ambulation. Specialized postoperative ancillary services are an indispensible part of a surgical cytoreduction program and should be considered integral members of the cytoreductive team. These services may include (but are not limited to) physical therapy, respiratory therapy, pain management, nutrition, wound care, enterostomal care, social work, and case management.

5. Prognosis and outcome

A. What would you tell a patient and their family about the prognosis?

Advances in chemotherapy and surgery over the past several decades have resulted in improved outcomes for women with advanced ovarian cancer. In addition to the proper choice of adjuvant chemotherapy, residual tumor volume following CRS remains one of the only modifiable prognostic factors for these patients. While an optimal result is defined as <1 cm of visible tumor, each incremental decrease in residual tumor volume below 1 cm confers a survival benefit.

Complete gross resection of the tumor followed by intraperitoneal chemotherapy offers the best possible chance of complete response to treatment and long-term survival. Ideally, chemotherapy should be initiated within six weeks of CRS.

B. "What if" scenarios

At the start of any CRS, it is crucial to thoroughly assess the extent and resectability of disease. If it is determined at any point in the procedure that an optimal result cannot be achieved, the goal of the procedure should shift from cytoreduction to recovery of tissue for a pathologic diagnosis and alleviation of symptoms (i.e., drainage of ascites). If an optimal result is not possible, cytoreduction should be aborted in order to minimize postoperative complications and allow for an expeditious initiation of neoadjuvant chemotherapy. If frozen section does not support a gynecologic origin, the most appropriate course of action is to consult the appropriate surgical specialist intraoperatively.

6. Follow up surveillance and therapy management of recurrences

In the event of recurrence, secondary CRS should be strongly considered for patients who are platinum sensitive and have disease amenable to recurrence. In patients undergoing secondary CRS, residual disease of less than 5 mm has been shown to confer a significant survival benefit. Disease-free interval, number of sites of recurrent disease, and residual disease after CRS are all prognostic factors in patients undergoing secondary cytoreduction. The same surgical principles apply to both primary and secondary CRS.

7. What is the evidence for specific management and treatment recommendations?

Griffiths, CT. "Surgical resection of tumor bulk in the primary treatment of ovarian carcinoma". Natl Cancer Inst Monogr. vol. 42. 1975. pp. 101-104.

(This study of 102 patients with stage II and III ovarian cancer demonstrates that survival time is inversely proportional to residual tumor mass after cytoreduction.)

Hoskins, WJ. "The effect of diameter of largest residual disease on survival after primary cytoreductive surgery in patients with suboptimal residual epithelial ovarian carcinoma". Am J Obstet Gynecol. vol. 170. 1994. pp. 974-9.

(This landmark GOG study demonstrates the significant survival benefit associated with optimal surgical cytoreduction for advanced ovarian cancer.)

Bristow, RE. "Cytoreductive surgery during the platinum era: A meta-analysis". J Clin Oncol. vol. 20. 2002. pp. 1248-1259.

(This meta-analysis demonstrates that maximal surgical cytoreduction is one of the most powerful determinants of survival among patients with ovarian cancer during the platinum era.)

Chi, DS. "What is the optimal goal of primary cytoreductive surgery for bulky stage IIIC epithelial ovarian cancer (EOC)". Gynecol Oncol. vol. 103. 2006. pp. 559-64.

(This study of 465 patients with advanced ovarian cancer demonstrates that removal of all gross disease during cytoreductive surgery results in prolonged survival and should be the goal when possible

Chi, DS. "Improved progression-free and overall survival in advanced ovarian cancer as a result of a change in surgical paradigm". Gynecol Oncol. vol. 114. 2009. pp. 26-31.

(This study shows that the incorporation of extensive upper abdominal cytoreductive procedures resulted in improved optimal cytoreduction rates and overall improved outcomes in patients with advanced ovarian cancer.)

Aletti, GD, Dowdy, SC, Podratz, KC, Cliby, WA. "Surgical treatment of diaphragm disease correlates with improved survival in optimally debulked advanced stage ovarian cancer". Gynecol Oncol. vol. 100. 2006 Feb. pp. 283-7.

(This study demonstrates that the surgical resection of diaphragm disease in patients with stage IIIC and IV ovarian cancer resulted in improved complete and optimal cytoreduction rates as well as improved survival.)

Zivanovic, O. "The effect of primary cytoreduction on outcomes of patients with FIGO stage IIIC ovarian cancer stratified by the initial tumor burden in the upper abdomen cephalad to the greater omentum". Gynecol Oncol. vol. 116. 2010. pp. 351-7.

(This study demonstrated that even in patients with bulky upper abdominal disease, optimal cytoreductive surgery is feasible and yielded a significant survival benefit.)

Bristow, RE. "Radical oophorectomy with primary stapled anastomosis for resection of locally advanced epithelial ovarian cancer". J Am Coll Surg. vol. 197. 2003. pp. 565-74.

(This paper identified 31 patients undergoing radical oophorectomy with primary stapled anastomosis as part of their cytoreductive surgery. This technique was effective and contributed to a maximal cytoreductive effort with an acceptable morbidity.)

Brooks, SE. "Resources and the use of intensive care units in patients who undergo surgery for ovarian carcinoma". Cancer. vol. 95. 2002. pp. 1457-62.

(This study identified risk factors for length of stay among women undergoing cytoreductive surgery for ovarian cancer. These risk factors included advancing age, intensive care unit stay, African American race, and comorbid illness.)

Chi, DS. "Guidelines and selection criteria for secondary cytoreductive surgery in patients with recurrent, platinum sensitive epithelial ovarian cancer". Cancer. vol. 106. 2006. pp. 1933-9.

(This study of 157 patients undergoing secondary cytoreductive surgery for recurrent ovarian cancer showed a survival benefit for those with residual disease of 0.5 mm or less. In selecting patients for secondary cytoreductive surgery, disease-free interval and number of sites of recurrence should be used as selection criteria.)
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