Reoperations for Ovarian Cancer

Ovarian cancer is the fifth leading cause of cancer deaths in women. Ovarian cancer kills an estimated 13,850 women per year and 21,880 new cases are projected to be diagnosed in 2010.¹ In the US, about 1 woman in 70 will develop ovarian cancer and 1 in 100 will die of the disease. While women diagnosed with stage I disease have up to a 90% 5-year survival, women with stage III–IV disease have only a 30–35% 5-year. Despite initial aggressive surgery and postoperative adjuvant chemotherapy, approximately 85% of women with advanced ovarian cancer will recur and require additional therapy.

In the past, reoperation was the most accurate means of assessing a patient’s response to therapy and second-look laparotomies were performed routinely. Today, repeat operations for ovarian cancer are valuable for resecting previously unresectable disease following a partial response to chemotherapy, establishing the presence and sites of residual disease, removing or reducing tumor mass to improve the patient’s chances of responding to a different treatment regimen, and for correcting complications that arise from either the treatment for ovarian cancer or the growth of cancer. This chapter reviews the current literature on reoperations for ovarian cancer and defines their place and value in the treatment of ovarian malignancies.

The second-look laparotomy was introduced 50 years ago by Wangensteen for periodic evaluation of patients who had undergone surgery for gastrointestinal carcinomas.² The group demonstrated that the prognosis of some patients with residual disease following primary treatment was improved following a second-look surgery. Second-look laparotomies were then extended to the management of ovarian cancer with the purpose to define the presence of disease, resect disease if possible, and help plan further therapy for the patient if needed. If there was no evidence of gross or microscopic disease, treatment was discontinued in order to avoid toxicities. Whether the second look should occur laparoscopically or via laparotomy was evaluated. It was determined that if there was no evidence of disease at laparoscopy, patients should have conversion to laparotomy owing to the higher false negative and relapse rates for second-look laparoscopy compared to laparotomy.^{3, 4, 5}

In order for second-look operations to be useful to patients with ovarian cancer, they need to be highly sensitive for predicting disease and must aid in treatment decisions. Approximately 5–12% of patients with early stage disease and 50% of patients with advanced stage disease will have a positive second-look laparotomy. There are no data to suggest an improved survival rate with second-look laparotomy.^{6, 7} In addition, 40–60% of patients with a negative second-look laparotomy will experience a relapse within 5 years.⁸ The Gynecologic Oncology Group (GOG) conducted a nonrandomized comparison of outcomes in women with optimally resected stage III ovarian cancer followed by six cycles of paclitaxel-platinum chemotherapy who underwent second-look laparotomy versus those had undergone surveillance only. Second-look laparotomy was not associated with any survival benefit and cancer was found in 75% of patients undergoing second-look laparotomy.⁹ In summary, as up to 50% of patients who have a negative second-look laparotomy will ultimately recur and as studies have shown no solid survival benefit, there is no clear role for the routine use of these procedures at this time.

Reoperations afford the surgeon the opportunity to resect recurrent or residual disease and, hopefully, favorably affect survival. Initial optimal cytoreduction has been shown to impact chemotherapeutic response and survival. Several reports have also documented the usefulness of secondary cytoreduction in patients with recurrent ovarian cancer. One must keep in mind that the benefits of such surgery are generally afforded to patients with less widespread chemosensitive disease. Recurrent cancer tends to invade tissues more aggressively and can cause tissue destruction obscuring operative planes thus making reoperations more difficult.

Patients with platinum-resistant disease, defined as those patients who progress during initial chemotherapy or have a response to platinum agents that lasts 6 months or less from the time of initial treatment completion, generally have response rates of less than 20% to second-line chemotherapeutic agents. Only a few studies have included this group of patients or patients who recur early in the course of their disease in an effort to determine whether secondary cytoreduction may be of benefit.

Berek and colleagues retrospectively reviewed 33 patients with persistent or progressive ovarian cancer following primary surgery and adjuvant chemotherapy in order to examine the survival of these patients after secondary cytoreductive surgery.¹⁰ The median interval between the first and second surgeries was 12 months (6–48 months). Optimal cytoreduction was achieved in 12 (38%). The 20 patients who did not achieve optimal secondary cytoreduction had a 5-month median survival compared with a 20-month median survival in the 12 patients who underwent optimal cytoreduction. Eleven patients (34%) had postsurgical complications, with the most common being prolonged ileus, but there was no operative mortality. In addition to the ability of the surgeon to achieve optimal cytoreduction, tumor size was found to significantly affect survival; patients having tumors 5 cm or larger had a median survival of only 6 months. The interval between the first and second surgeries was also significantly associated with survival, as patients who underwent a second surgery less than 12 months after the first had a median survival of 9 months as compared with 16 months for those who underwent reoperation more than 12 months after the first. In conclusion, in patients who cannot be classified as “no evidence of disease” after primary surgery and adjuvant chemotherapy, secondary cytoreductive surgery can enhance survival if the second surgery renders the patient optimally debulked. In this group of patients, 38% were able to undergo a second resection and median survival was greater in those who could be optimally cytoreduced, in those with smaller tumors, and in those presenting more than 12 months after their first surgery. From this study, one can conclude that secondary cytoreduction followed by additional chemotherapy may benefit a select group of patients presenting less than 12 months after their primary surgery.

Bristow and colleagues in 2009 completed a meta-analysis examining the effect of several prognostic variables on the survival of patients with recurrent ovarian cancer undergoing secondary cytoreduction.¹¹ They found that the median disease-free survival had an effect on median survival, although it was not statistically significant. Patients who had a disease-free interval less than 12 months lived on average 6 months less than those patients with a disease-free interval greater than 24 months. Importantly, they also noted that for each 10% increase in the proportion of patients undergoing complete surgical resection there was an increase in the median cohort survival of 2.84 months. Thus, it seems that optimal secondary cytoreduction, similarly to optimal primary debulking, benefits some patients with recurrent or persistent ovarian cancer.

Secondary cytoreduction seems to specifically benefit platinum-sensitive patients. Park and colleagues in 2009 retrospectively reviewed the records of platinum-sensitive patients with recurrent ovarian cancer who underwent secondary cytoreductive surgery.¹² On univariate analysis, disease-free interval, initial FIGO stage, site and number of recurrences, and size of the recurrent tumor were significantly associated with disease-free survival. On multivariate analysis, optimal secondary cytoreduction and disease-free interval greater than 24 months were significantly associated with a higher disease-free survival, as noted in other studies. Tebes and colleagues in 2007 also noted optimal secondary cytoreduction to less than 1 cm disease was associated with a statistically significant 13-month increase in survival (17 vs. 30 months) as compared with those patients left with more than 1 cm disease.¹³ Similar to other studies, this study noted that ascites, the location of disease, and the multicentricity of disease all adversely affected survival. Finally, Chi and colleagues also retrospectively reviewed prognostic indicators in patients with recurrent, platinum-sensitive ovarian cancer.¹⁴ This study found that disease-free interval of more than 12 months, fewer sites of recurrence, and residual disease less than 0.5 cm were associated with statistically significant improvements in survival. Thus one can predict that a patient who is more than 12 months from primary surgery, has one or two recurrence sites, and can be optimally debulked to less than 1 cm will have a prolonged survival as compared with a patient without these prognostic factors.

The Desktop trials were conceived with the idea of selecting appropriate candidates for secondary cytoreduction. Desktop I was a retrospective review of patients with recurrent ovarian cancer who underwent surgery at 50 sites in Germany or Switzerland between 2000 and 2003.¹⁵ The majority of patients had a disease-free interval of more than 12 months. Patients with complete macroscopic resection of disease were more likely to have ascites less than 500 ml, performance status of 0, and prior complete debulking. This trial identified that the strongest predictive factor for survival was remaining residual disease following surgery. From this analysis, the authors tried to create a model of predictive scores in order to determine which patient would more likely benefit from secondary cytoreduction. Desktop II prospectively evaluated this score enrolling 120 patients with a positive score and found a complete resection rate in 76% of these patients. Desktop III will evaluate the use of chemotherapy alone versus surgery followed by chemotherapy in patients with a positive score.¹⁶

A review of ten publications by Munkarah and colleagues nicely summarized several important points regarding secondary cytoreduction, appropriate patient selection, and counseling patients about this procedure.¹⁷ First, complete macroscopic resection of disease was possible in 41% of patients and major perioperative complications were noted in 11%. Perioperative mortality averaged 1.4%. A longer disease-free interval, complete resection of macroscopic disease, localized recurrences, and surgery followed by chemotherapy all lengthened the duration of survival.

Lymph node metastases

Published rates of recurrence of ovarian cancer in lymph nodes vary from 12 to 37%.^{18, 19, 20, 21} The data available for outcomes in patients with isolated lymph node recurrences come from retrospective studies in platinum-sensitive patients. Uzan and colleagues in 2004 sought to evaluate the prognosis of 12 platinum-sensitive patients with an isolated lymph node recurrence undergoing surgical resection.²² Nine of the 12 patients who had isolated lymph node recurrence did not have a pelvic or para-aortic lymph node dissection at their initial surgery. The median disease-free interval between the initial treatment and nodal relapse was 21 months. All patients received surgery followed by either chemotherapy or radiation. Five-year overall survival in these patients was 71%. Santillan and colleagues in 2007 retrospectively reviewed the charts of 25 patients with an isolated nodal recurrence, 10 of whom had not undergone pelvic or para-aortic lymphadenectomy at the time of primary surgery.²³ The median disease-free interval was 16 months from the time of completion of primary chemotherapy. All patients were optimally debulked at the time of secondary cytoreduction and the median overall survival after secondary cytoreduction was 37 months. At the time of publication, 40% of these patients were recurrence free. Finally, Fotiou and colleagues reviewed the records of 21 patients with an isolated nodal recurrence undergoing secondary cytoreduction.²⁴ Cytoreduction to less than 1 cm disease was achieved in all patients. Median disease-free recurrence interval was 21 months. They did not note any relationship between postrecurrence survival and prerecurrence disease-free interval, although the number of patients in this study was small. These studies indicate that, in general, patients with isolated lymph node recurrences have a good prognosis and can undergo debulking with little morbidity/mortality. The favorable survival may be due in part to the fact that most of the patients in these studies had favorable prognostic factors to begin with, such as a disease-free interval of more than 12 months, and they were surgically rendered free of macroscopic disease. These studies also raise two important questions: (1) should all patients with ovarian cancer routinely undergo pelvic and para-aortic lymphadenectomies at the time of primary surgery; and (2) should patients with recurrent ovarian cancer undergo a complete lymph node dissection or simply removal of affected nodes at the time of secondary surgery for recurrence?       

Liver metastases

The liver is a common site of ovarian cancer recurrence. In an autopsy study of 428 patients with ovarian cancer, 47% were noted to have hepatic metastases at the time of death.²⁵ Debulking of upper abdominal disease, including parenchymal liver disease, has become more prevalent in recent years. Cheol Lim and colleagues retrospectively identified all patients with ovarian cancer and pathology proven hepatic parenchymal metastases at the time of primary debulking.²⁶ All patients who had resectable disease (14/16) underwent surgery with clear margins and there were no direct complications from the resections. One can extrapolate from this study and from the literature on hepatic resections in the setting of gastrointestinal malignancies that hepatic resection is a safe procedure in the proper hands.²⁷ In most series in the GI literature reporting on patients with colorectal carcinoma and hepatic metastases, the operative mortality of hepatic resection is 5% or less and morbidity ranges from 13% to 51%.

Merideth and colleagues from the Mayo Clinic retrospectively reviewed the charts of patients who underwent hepatic resection for metastatic recurrent ovarian carcinoma.²⁷ The median disease-free interval at which these patients presented was 29.4 months and the majority of patients (69.2%) had a single liver metastasis removed with segmentectomy. Optimal cytoreduction was achieved in 21/26 patients without any mortality. Median disease-related survival after resection was 26.3 months. In this study, patients with parenchymal liver metastases undergoing optimal secondary cytoreduction had similar survival to patients without liver metastases. If optimal cytoreduction of liver metastases was achieved, patients had improved survival.

Bosquet and colleagues retrospectively reviewed the charts of 35 patients who underwent hepatic resection for metastatic ovarian cancer.²⁸ They noted an overall median survival of 27.4 months which increased to 41.3 months after resection of all macroscopic disease and decreased to 11.7 months when gross tumor was left behind. Residual tumor 1 cm or less and disease-free interval 12 months or more were the two factors most significantly associated with improved disease-specific survival. Yoon and colleagues retrospectively reviewed the charts of 24 patients with recurrent ovarian cancer undergoing resection of hepatic metastases to determine complication rates and which patients were the best candidates.²⁹ The median disease-free interval in these patients was 36.5 months. Median blood loss was 750 ml, median hospital stay was 8 days, and complications occurred in 21% of patients with no operative mortalities. The authors concluded that ideal candidates for hepatic resection were those with a long disease-free interval, platinum-sensitive disease and good performance status, as well as those who could be optimally cytoreduced.

To summarize, the proper patients for consideration of resection of hepatic metastases are those with a favorable disease-free interval (more than 12 months), hepatic disease that can be optimally resected, four or fewer liver metastases, good medical condition, and resectable extrahepatic disease if present.³⁰ Hepatic resection is a safe procedure in the appropriate candidate and appears to prolong survival if optimal cytoreduction can be achieved.

Splenic metastases

In order to optimally cytoreduce a patient at the time of recurrence it may be necessary to perform a splenectomy. The role of secondary cytoreductive surgery in a patient with a parenchymal splenic metastasis, rather than diffuse carcinomatosis, has not been well defined as isolated metastases to the spleen are rare. Ramirez and colleagues have outlined the surgical technique for performing splenectomy as part of cytoreductive surgery for ovarian cancer.³¹ In general, a nasogastric tube should be placed to decompress the stomach, and if the procedure is performed for a recurrence where there is a question of other disease an adequate midline vertical incision should be made. The spleen should be mobilized from its connecting ligaments and dissected off the splenic flexure of the colon. Once the spleen is isolated, the vessels supplying the spleen must be isolated and transected with care taken to avoid the tail of the pancreas. Using this technique, the authors noted that the most frequent postoperative complications were atelectasis, pneumonia and pleural effusions. More serious, but infrequent, complications included injury to the pancreas and subphrenic hematomas. Patients may have an increased platelet count in the immediate postoperative period. Patients should receive vaccinations against Haemophilus influenzae, pneumococcus, and meningococcus preoperatively or in the immediate postoperative period.

A few studies have been published looking at patients with recurrent ovarian carcinoma and splenic metastases. In 2006 Magtibay and colleagues retrospectively reviewed data from 112 patients undergoing splenectomy as a part of either primary or secondary cytoreductive surgery.³² Of these patients, 46 were undergoing surgery for a recurrence. Perioperative morbidity was 15% and mortality was 5%. Of the total cohort, seven had wound infections, five had postoperative pneumonias, nine had thromboembolic events, and five had sepsis; no pancreatic injuries were identified. The patients undergoing surgery for recurrence had a median survival of 20.3 months. Patients with cancer involving the splenic parenchyma did not have a less favorable survival compared to patients with disease involving the splenic hilum or capsule.

Manci and colleagues also performed a retrospective review in order to identify prognostic factors for patients most likely to benefit from splenectomy during secondary cytoreduction.³³ They identified 25 patients who underwent splenectomy as a part of secondary cytoreduction. The majority of patients (67%) also underwent other procedures including bowel resection, pancreatectomy, peritoneal stripping, and lymphadenectomy. Intraparenchymal splenic involvement was usually a solitary lesion while superficial splenic lesions usually involved multiple sites of tumor on the spleen. Intraoperative complications included blood loss of more than 1000 ml in five patients and blood transfusions in five patients, while postoperative complications included one pulmonary embolus, one pancreatic fistula, and one partial small bowel obstruction. At a median follow-up of 27.5 months, all patients with an isolated splenic parenchymal metastasis were alive and optimal cytoreduction was significantly related to a higher overall survival. Based on this study, splenectomy at the time of secondary cytoreduction seems reasonable, especially in patients with a solitary parenchymal metastasis.

Finally, Gemignani and colleagues in 1999 also showed that patients with an isolated splenic parenchymal metastasis do well after splenectomy at the time of secondary cytoreduction.³⁴ They retrospectively reviewed the charts of six patients who underwent splenectomy for an isolated parenchymal metastasis. The median disease-free interval of these patients was 57 months. One patient had a perioperative complication of diaphragmatic tear which required chest tube placement. The median blood loss was 350 ml. At a median follow-up of 25.5 months, all patients were alive and free of disease. It appears from these studies that patients with isolated splenic parenchymal metastases are appropriate candidates for splenectomy at the time of optimal secondary cytoreduction, resulting in improved survival.

Lung metastases

In an autopsy study performed by Rose and colleagues in 1989, 34% of patients with epithelial ovarian cancer were found to have lung metastases at the time of death.²⁵ The lung is one of the most common sites for distant metastases in patients with ovarian cancer. Few studies, other than case reports, exist which identify prognostic factors in these patients. Tangjitgamol and colleagues reviewed the literature on resection of lung metastases in ovarian cancer and found that the disease-free interval, size of the lung metastasis, number of metastases, and ability to achieve resection with clear margins were important prognostic factors.³⁰ Hilar lymph node involvement portended a worse prognosis. Surgical criteria for removal of lung lesions included resectable pulmonary and extrapulmonary lesions (ideally with negative margins) and sufficient pulmonary function. The morbidity associated with removal of pulmonary lesions ranged from 10 to 18% with a mortality rate ranging from 0 to 5%. Complications included pneumonia, pneumothorax, pleural effusions and edema, and hemothorax. Without surgical resection, patients had a 5-year survival of about 6%, while resection improved survival up to 17–36%. The paucity of data on these patients limits any definitive conclusions; however, it appears that in properly selected patients lung resection can prolong survival.  

 
Serosal bowel metastases are commonly encountered in patients with ovarian cancer and these metastases can affect the function of the digestive tract. Tumor spread can cause extramural, intramural, and intraluminal points of bowel obstruction or disordered motility of the bowel owing to mesenteric tumor deposits. In addition, patients with prior surgery or radiation are at risk for obstruction owing to adhesions or radiation-induced bowel dysfunction. In an autopsy study of 428 patients with ovarian cancer performed by Rose and colleagues in 1989, 93% were noted to have metastases to either the small or large bowel at the time of death.²⁵

In 1983 Krebs and colleagues proposed a prognostic index based upon six criteria to be used as a measure of the success of a procedure to relieve bowel obstruction in a patient with recurrent ovarian carcinoma.³⁵ The authors reviewed the charts of 118 patients with advanced ovarian cancer undergoing exploratory laparotomy for bowel obstruction. They noted that 65% of the patients who underwent a procedure to relieve bowel obstruction benefited from the procedure, while 12% of the patients experienced fatal complications such as anastomotic dehiscence, sepsis, pulmonary embolism, or gastrointestinal hemorrhage. Older patients, those with low serum albumin or other nutritional deficiencies, ascites, and prior radiation therapy did worse overall. Patients were retrospectively given a score based upon their age, nutritional and tumor status, presence of ascites, and prior chemotherapy or radiotherapy. The authors concluded that those patients with higher scores tended to benefit less from surgical intervention. Since this publication, there have not been any defining studies which definitely aid a physician in choosing the “best” patient for surgical intervention of bowel obstruction related to recurrent ovarian cancer; however, studies have identified prognostic indicators which can help us better counsel a patient regarding surgery.

A Cochrane review was undertaken in 2000 with the purpose of defining the benefits of surgery for bowel obstructions in patients with ovarian cancer.³⁶ The majority of papers defined surgical benefit as survival more than 60 days after surgery; however, it was noted that up to 43% of patients who survived beyond 60 days still experienced occasional symptoms of obstruction until their deaths. The range for postoperative mortality was 5–32%. The most frequent morbidities following surgery were pulmonary embolism, deep vein thrombosis, wound infection and dehiscence, enterocutaneous fistula, and myocardial infarction. The authors noted wide ranges in outcomes in all the papers and concluded that without well-defined outcome measures each physician must make an individual decision about operating for bowel obstruction based upon the individual patient.

Several retrospective studies published since the Cochrane review provide some insight into which patients with bowel obstructions associated with recurrent ovarian cancer would most benefit from the procedure. Tamussino and colleagues in 2001 assessed the outcomes and morbidity of gastrointestinal procedures performed in 180 primary surgeries for ovarian cancer, 44 second-look laparotomies, and 267 procedures for recurrent ovarian cancer.³⁷ The most frequently performed procedure in patients undergoing surgery for recurrence or palliation was small bowel resection (51%). Of the patients undergoing gastrointestinal procedures for recurrence or palliation, the purpose of the bowel surgery was for tumor debulking in 62%, small bowel obstruction in 26%, and large bowel obstruction in 8.2%. The most common postoperative complication was febrile morbidity in 29% of patients, and 21% of patients experienced postoperative ileus lasting longer than 7 days. With a median follow-up of 11 months, 15.3% of the patients had to undergo a repeat gastrointestinal procedure. The authors estimated that only 11% of patients undergoing gastrointestinal surgery for recurrence or palliation would be alive 5 years after the procedure.

Pothuri and colleagues published two studies which add to the information available in relation to the ability of surgeons to successfully palliate patients with ovarian cancer causing small bowel obstruction. In the first study published in 2003, the group retrospectively analyzed all patients undergoing surgery for small bowel obstruction and separated them into two groups: those unable to undergo surgery and those whose disease was surgically correctable.³⁸ The majority of the 68 patients were able to undergo surgery to correct the bowel obstruction (84%) and the remaining patients who underwent exploration only had G-tubes placed. Colostomy or permanent G-tube placement occurred in 56% of the patients in this study. The authors also noted that 12% of patients had both small and large bowel obstructions, stressing the need for evaluation of the large bowel as well as small bowel prior to an attempt at surgery for correction of intestinal obstruction. Successful palliation was defined as the ability to tolerate a regular or low-residue diet for 60 days after the surgery. Of the group undergoing successful surgery, this was noted in 71% of patients. None of the patients undergoing G-tube placement were able to tolerate a normal diet postoperatively. Of the patients who underwent surgical correction of obstruction, 63.2% suffered a repeat small bowel obstruction with a mean time to reobstruction of 4.5 months. Grade 3 or 4 complications occurred in 22% of patients and the perioperative mortality rate was 6%. The median survival for all patients undergoing G-tube placement was 3.9 months, while patients who underwent successful surgical correction of intestinal obstruction had a median survival of 11.6 months. The authors noted that younger age, no prior radiation, longer interval from cancer diagnosis, site of obstruction (colonic versus small bowel), and presence of an intestinal mass correlated with the ability to successfully perform a palliative procedure. This study clearly demonstrated that there are patients whose bowel obstruction can be successfully palliated with surgery; however, this surgical correction also places the patient at high risk for morbidity and mortality related to the procedure.

The second study by this same group was a retrospective review of patients undergoing a repeat attempt at correction of intestinal obstruction.³⁹ Out of 10 patients, five were able to undergo a successful second surgical correction of bowel obstruction, of whom successful palliation was obtained in three. If patients had large bowel obstruction alone, they were more likely to be successfully palliated than those patients who had either small bowel obstruction or small and large bowel obstruction. No postoperative mortality was noted; however, the postoperative complication rate was 40% with three patients developing enterocutaneous fistulas. Of the three patients who were successfully palliated, two had repeat episodes of obstruction. The overall survival of the entire group was 4.5 months and the three patients who were successfully palliated had overall survivals of 4, 5, and 6 months, respectively. These two studies clearly indicate that some patients with ovarian cancer and symptoms of bowel obstruction can be successfully palliated; however, their risk of reobstruction is high. Complications of the procedures and the life expectancy postoperatively must be discussed with the patient. It appears that successful palliation of a bowel obstruction the first time can prolong survival in the appropriate patient, but this concept may not hold true if the patient presents again with an obstruction. A quality of life discussion will benefit the patient in addition to counseling regarding the surgical procedure itself.

The complication rates, types of complications, and success rates are important pieces of information to know before proceeding with a palliative procedure for malignant bowel obstruction. Chi and colleagues in 2009 prospectively evaluated all patients with ovarian cancer at their center undergoing surgery for malignant bowel obstruction between 2002 and 2003.⁴⁰ During this period, 26 patients underwent either an endoscopic or operative procedure for malignant bowel obstruction. The majority of patients had a performance status of 1 and a fatigue scale of 1; the median hemoglobin was 10.6 and the median serum albumin of 3.4. The small intestine was involved in 54% of patients, while the large intestine was involved in 46% of patients. An endoscopic procedure (colonic stent or percutaneous endoscopic gastrostomy (PEG) tube) was performed in 46%, intestinal bypass/resection in 23%, ileostomy in 8%, and colostomy in 23% of patients. The median hospital stay was 11 days and there were three grade 3 complications and one death. Of the complications, all occurred in the patients undergoing either an endoscopic procedure or an ileostomy. Successful palliation, defined as the ability to tolerate regular or low-residue diet for more than 30 days after the procedure, was noted in 88% of patients. Recurrence of symptoms or death occurred in 46% of patients within 90 days of the procedure. Median survival from the time of the procedure was 78 days for patients undergoing an endoscopic procedure and 191 days for patients undergoing an operative procedure.  This study again demonstrated that most ovarian cancer patients with malignant bowel obstruction do not have a prolonged life expectancy following surgery. This study also reiterated that the majority of these patients have small intestinal involvement, which perhaps portends a worse prognosis.

Recently, Sartori et al. utilized the prognostic index proposed by Krebs in 1983 to retrospectively review patients with ovarian cancer who developed a small bowel obstruction at their institution.⁴¹ Out of their total cohort of 270 patients treated for ovarian cancer over 21 years, 75 (28%) developed malignant bowel obstruction. These patients presented at a median of 16.5 months after initial diagnosis; 50% had large and small bowel involvement, 25% had only small bowel involvement, and 25% had only large bowel involvement. Corrective surgical procedures were performed in 20 patients and these patients showed improved survival compared to the 55 patients who did not undergo surgery. The 53 patients with a Krebs score of 6 or less had a mean survival of 21.5 weeks compared to the 22 patients with a score greater than 6 whose mean survival was 14.2 weeks following diagnosis. Additional parameters were added to the Krebs model for a total of 15 prognostic factors and this was found to more accurately reflect differences in survival between the patients with high and low scores. Utilizing this more comprehensive prognostic index may allow physicians to better predict whether surgical correction of malignant bowel obstruction will afford a survival advantage.

With the increasing use of intraperitoneal (IP) chemotherapy in the treatment of advanced ovarian carcinoma, there have been questions regarding the rate of adhesion formation in these patients due to the changes on the surface of the bowel. Kehoe and colleagues in 2009 reviewed the charts of 307 patients who underwent at least one cycle of IP chemotherapy and experienced a subsequent bowel obstruction.⁴² During the follow-up period after IP chemotherapy, 104 patients (34%) were diagnosed with a bowel obstruction. Only 12% of these bowel obstructions were determined to be due to adhesions, while 85% were due to progressive or recurrent disease, and 3% of cases did not have a definable cause. Surgical intervention was successfully performed in 50% of the cases due to adhesions. A significant correlation was noted between mitoxantrone chemotherapy and development of a bowel obstruction due to adhesions. From this paper, we can conclude that the majority of bowel obstructions seen in patients who have received IP chemotherapy for ovarian cancer will be due to recurrent disease.

Another important consideration in the management of patients with malignant bowel obstruction is whether palliation should be performed via an endoscopic or operative procedure. Typically, patients who are not operative candidates are considered for PEG or colonic stent placement. Pothuri and colleagues in 2005 retrospectively analyzed 94 patients undergoing PEG placement for palliation of symptoms due to bowel obstruction.⁴³ All patients had successful PEG placement by either gastroenterology or interventional radiology, including 23% of the patients who had CT scans showing tumor encasing the stomach. Symptomatic success, defined as relief of nausea and/or vomiting within 1 week of the procedure, was seen in 91% of patients. In terms of the ability to eat after PEG placement, 42.5% could tolerate a soft diet, 42.5% could tolerate a regular diet, and the remainder of the patients either tolerated liquids only or nothing by mouth. Eighteen patients (19%) experienced complications and required PEG revision due to complications. In all, 75 patients were able to die either at home or under hospice care and the median overall survival after PEG placement was 8 weeks. Thus it appears that PEG placement may be a good option for symptomatic relief in patients who are not candidates for a bowel resection or other operative procedures.

In summary, explicit parameters do not exist for determining which patients with recurrent ovarian cancer and symptomatic bowel obstruction are candidates for an operative procedure. Increasing age, low serum albumin, the presence of significant ascites, marked weight loss, prior radiotherapy to the abdomen, and tumor progression are all poor prognostic indicators which need to be considered in the decision about whether to take a patient to the operating room.

Several types of reoperations hold benefit for patients with ovarian cancer. Second-look operations are no longer performed with the frequency that they used to be since they have not been shown to confer a survival advantage and up to 50% of patients who have a negative second look will ultimately recur. The benefit of secondary cytoreductive surgery seems to be confined to patients who have an excellent performance status, are likely to respond to additional chemotherapy, and have an isolated site of recurrence that can likely be removed with surgery resulting in only microscopic residual disease. Even resection of isolated liver, lung, splenic, and nodal lesions can confer a survival benefit in appropriately selected patients. The debate continues as to which patients are best served by a palliative procedure for bowel obstruction related to recurrent ovarian cancer, given the relatively high morbidity and mortality rates as well as the short postoperative survival associated with these procedures.