Management of Intestinal Obstruction in the Patient With Ovarian Cancer

Intestinal obstruction in the patient with ovarian cancer is a difficult situation for both patient and physician. In women presenting with ovarian cancer, obstruction is almost never complete. These women should undergo aggressive bowel surgery only if it is part of an optimal surgical cytoreduction. Women known to have ovarian cancer who develop intestinal obstruction have a poor prognosis: Few will live more than a year from the time of obstruction. Some, however, have an excellent performance status, and would be relatively unimpaired were it not for their obstruction. These women, who usually have a discrete obstruction and still display some response to chemotherapy, may benefit from surgical correction of the obstruction. Women who are not candidates for surgery can be effectively palliated pharmacologically so that they are comfortable with the obstruction, often without intestinal drainage. Algorithms are available to assist in the management of ovarian cancer patients with obstruction, but ultimately the treatment decision rests with the patient. The oncologist must use his or her knowledge and clinical judgment to help the patient develop an appropriate, individualized plan. [ONCOLOGY 14(8):1159-1163, 2000]

Introduction

Ovarian cancer afflicts more than 26,600 women in the United States each year, and over 14,500 die of the disease.[1] It is thus the deadliest gynecologic malignancy, associated with more fatalities than all the other gynecologic cancers combined. Most patients with ovarian cancer present with advanced disease, with tumor spread throughout the abdominal cavity. It is less common to find extra-peritoneal disease at presentation, and frequently, the tumor remains confined to the peritoneal cavity throughout the natural history of the disease.

Regrettably, many women with ovarian cancer experience bowel obstruction.[2] This may occur on presentation or, more often, as a sign of progressive disease with ensuing death. It is critical for the physician participating in the care of women with ovarian cancer to have an understanding of the disease itself and the patient’s clinical course, expectations, and expected outcomes.

For many women with ovarian cancer, bowel obstruction is a sign of imminent demise. With this understanding, most surgeons have modified their approach over the past several decades-from one of reflexively operating on the patient with intestinal obstruction of any cause to one of greater individualization. Almost all women with intestinal obstruction will live less than a year, and the majority will live less than 6 months.[3] Conservative management of obstruction, as we will review, is not necessarily associated with more rapid death. Many published series have demonstrated that surgery is feasible, reasonably safe, and appears to improve quality of life in the majority of cases. These series have been reported from a variety of renowned gynecologic oncology centers, suggesting that surgery should not automatically be considered inappropriate.

There have been no prospective randomized trials to date comparing surgery to conservative management.[4] Given the dire straits that most women are in at the time of such interventions, a randomized trial seems unlikely to occur. It would be valuable, however, to rigorously measure quality of life in women managed surgically or conservatively in this situation. Until such information becomes available, the practicing physician must offer management options to patients based on the information that has been gathered to date. To this end, we will briefly review the natural history of ovarian cancer, the options for the initial and long-term management of intestinal obstruction in ovarian cancer patients, the predictors of the success and failure of such an intervention, and the techniques of surgery or medical management.

Natural History and Patterns of Spread

The surgeon managing a patient with ovarian cancer must understand as much as possible about the biology and behavior of the disease. This understanding is as vital to successful management as is a thorough knowledge of anatomy and proper surgical technique. It is essential to thoroughly evaluate and document where the patient is in the management of her disease. The implications of major surgery in a patient with a good performance status who will likely respond to therapy are very different from those of a similar surgery in a medically compromised patient who has exhausted all treatment options.

Epithelial ovarian carcinomas, which constitute approximately 90% of malignant ovarian neoplasms, spread to adjacent organs by direct extension, by lymphatic channels, and by dissemination of cells through the peritoneal cavity.[1] Hematogenous spread is rare. The dissemination of clonogenic cells through the peritoneal cavity is the most significant extraovarian spread of epithelial tumors. Malignant cells have been found in the peritoneal cavity even in cases where the ovarian capsule is intact.

Once these cells have entered the peritoneal cavity, they appear to follow the normal circulation of the peritoneal fluid: up the right paracolic gutter, across the diaphragm from right to left, and down the left paracolic gutter. This pattern seems to be the result of both the respiratory motion of the diaphragm and the peristalsis of the bowel. Further peristaltic movement of the intestine can result in implantation on any of the peritoneal surfaces, including the mesentery and serosa of the large and small bowel.

Consistent with this predominantly intraperitoneal pattern of spread is the observation that implants of ovarian cancer on the intestines rarely invade the muscalaris propria. Even when complete obstruction is documented, the process is nearly always one of extrinsic compression rather than intraluminal obliteration. This is found even in the setting of advanced disease with bulky omental and/or pelvic encasement of tumor.

The lymphatic vessels of the ovary follow the course of the ovarian blood supply in the infundibulopelvic ligaments to terminate in the high para-aortic lymph nodes between the inferior mesenteric artery and the renal vessels. Collateral drainage occurs via the lymphatic channels in the broad ligament to the external iliac and hypogastric lymph nodes and via lymphatics in the round ligament to involve the inguinal lymph nodes.[5-7] In advanced ovarian cancer, the retroperitoneal lymph nodes are involved in 60% to 70% of patients.[8] Thus, evaluation and excision of the retroperitoneal lymph nodes may be an important component of an optimal surgical cytoreduction for ovarian cancer (see below).

Initial Therapy for Ovarian Cancer

Surgical Approaches

The initial management of ovarian cancer involves surgical exploration with systematic surgical staging for patients with apparent early-stage disease and aggressive surgical cytoreduction for patients with gross extraovarian disease. Clinical trials of surgical staging have demonstrated that, among women felt to have disease confined to the ovary at the time of laparotomy, 30% will be found to have occult metastases after thorough surgical staging.[8,9] An extensive body of retrospectively and prospectively acquired data has demonstrated that removal of all implants larger than 1 to 2 cm is associated with a dramatically increased survival.[10] This has been demonstrated even in patients with stage IV disease.

Bristow and colleagues, for example, reported that women with stage IV disease who underwent cytoreduction to < 1 cm disease had a median survival of 38 months, while those with stage IV disease and > 1 cm residual tumor had a median survival of 10 months.[11] This was found to be the case even when liver resection was required to attain optimal cytoreduction. It should be noted, however, that such aggressive surgical efforts are not associated with an improvement in survival unless all disease of 1 cm diameter or larger is removed.

Chemotherapy Regimens

Although it is commonly observed that the rate of cure of ovarian cancer has not changed significantly over the past 30 years, it is important to recognize that the duration of survival and quality of life of women with advanced ovarian cancer has improved dramatically over that interval. Much of this improvement is due to the stepwise evolution of chemotherapy regimens from single alkylating agents to combination chemotherapy regimens, and ultimately the emergence of platinum-based regimens.[1]

In reporting the addition of paclitaxel (Taxol) to platinum-based therapy for ovarian cancer, McGuire and colleagues observed a median survival of 38 months for women with surgically suboptimal disease.[12] This is in marked contrast to the median survival reported in trials of single alkylating agent therapy, which was generally found to be about 14 months. An important component of this improvement in survival is the fact that close to 70% of women with advanced ovarian cancer will achieve complete clinical remission after initial surgery and platinum-based chemotherapy. Thus, many women with significant gastrointestinal symptoms, or with intraoperative findings suggesting imminent bowel obstruction at the time of presentation will achieve complete resolution of their symptoms (at least transiently) even in the absence of an aggressive surgical effort.

Intestinal Obstruction in the Patient Presenting With Ovarian Cancer

Given the predilection of ovarian cancer for intraperitoneal spread, many patients are found to have symptoms of intestinal compromise when they present with ovarian cancer. This is most commonly caused by compression of the rectosigmoid by pelvic tumor or involvement of the transverse colon with a bulky omental tumor. In patients with such symptoms, a preoperative barium enema or colonoscopy is often helpful to exclude a primary colonic malignancy.

As suggested above, even patients with apparent extensive intestinal involvement at the time of presentation rarely benefit from aggressive bowel resection unless this effort is performed for a complete obstruction or as part of an optimal surgical cytoreduction. Surgeons experienced in the management of ovarian cancer are generally able to dissect bulky tumors from the bowel serosa, and thus achieve an optimal cytoreduction without resorting to intestinal diversion or resection.

Types of Surgery for Ovarian Cancer

The type of surgery performed for ovarian cancer appears to vary according to the training and specialization of the operating physician. In a review of ovarian cancer patients in the West Midlands Cancer Registry in Britain, for example, Kehoe and colleagues found that patients primarily operated on by general surgeons were significantly more likely to undergo an intestinal resection or colostomy than were those women who were primarily operated on by gynecologists.[13] In addition, ovarian cancer patients operated on by general surgeons were significantly less likely to be optimally cytoreduced via surgery and had a significantly lower survival.

Although it was observed that the patients taken to the operating room by general surgeons were older and more frequently had advanced-stage disease, adjustment for these factors by multivariate analysis correlated poor prognosis with advanced-stage disease, older age, the presence of bulky residual tumor, and the presence of a general surgeon as the principle operator. In a similar report, Eisenkopf and colleagues found that ovarian cancer patients who were operated on by general surgeons were significantly more likely to undergo intestinal surgery and significantly less likely to achieve an optimal surgical cytoreduction.[14] A report by Ngyen et al based on the American College of Surgeons national survey of ovarian cancer had similar findings.[15]

These data reinforce our understanding that intestinal resection per se does not improve the clinical course of patients presenting with ovarian cancer, and that an optimal surgery is usually feasible without intestinal resection or bypass even in patients with very advanced disease. The patient presenting with ovarian cancer should therefore ideally only have intestinal surgery in the presence of a true complete obstruction or if an otherwise optimal surgical cytoreduction cannot be achieved without bowel surgery.

This caveat notwithstanding, it should be recognized that intestinal involvement does not obviate surgical cytoreduction. It is occasionally necessary to resect the rectosigmoid colon as well as the uterus, cervix, and adnexae en bloc, as is done in a posterior exenteration, in order to optimally cytoreduce a patient with extensive rectosigmoid and other pelvic involvement of tumor. Even in the majority of these cases, the availability of gastrointestinal stapling devices facilitates the performance of a low end-to-end anastomosis rather than a colostomy.[16]

Intestinal Obstruction in the Patient With Recurrent Ovarian Cancer

Although most patients achieve a complete clinical remission with contemporary surgery and chemotherapy, the majority will regrettably recur within 5 years of their initial diagnosis. In most patients, ovarian cancer remains confined to the abdominal cavity; thus it is inevitable that many patients will develop increasing intestinal involvement and symptoms from their disease and ultimately succumb from malnutrition and dehydration. For the majority of women with ovarian cancer therefore, intestinal obstruction is a final common pathway in the failure of cancer therapy, and is a sign of their deteriorating clinical course.

Patients with known ovarian cancer can have intestinal obstructions with various causes-focal obstruction by a discrete tumor mass, functional obstruction from disseminated disease causing a “carcinomatous ileus,” an exacerbation of a partial obstruction of any cause, postoperative adhesions, or, less frequently, a primary gastrointestinal process such as diverticulitis or a second primary carcinoma.

A recent review of 92 women with bowel obstruction in the setting of gynecologic malignancy found that 31 (34%) had benign disease.[17] Determining the cause of the obstruction as well as determining the patient’s disease status and prognosis are the keys to satisfactory management of this dire clinical scenario.

Initial Management of Intestinal Obstruction

In some cases, patients are known to be failing or have failed all reasonable therapy for their disease and subsequently develop intestinal obstruction. In this situation, it may be suitable to expeditiously arrange for long-term intestinal decompression and/or other forms of conservative comfort care (see below).

Other patients may either be under treatment or without other evidence of disease when they present with obstruction. These patients may or may not have at least transiently reversible causes of their symptoms, and it is appropriate to consider a more extensive evaluation and more invasive care.

Most patients presenting with obstruction require intravenous hydration and intestinal decompression with a nasogastric tube. We have found the use of “long tubes,” such as the Cantor or Miller-Abbott, which are placed through the pylorus into the small bowel, to be cumbersome and not more therapeutic than simple gastric drainage. Abdominal radiographs may or may not display findings suggestive of obstruction and should not distract the clinician from the diagnosis when clinical findings such as poor tolerance of oral intake, vomiting, and dehydration indicate obstruction.

Computed tomography (CT) scan with oral and intravenous contrast is usually the most useful subsequent step in the evaluation. The CT scan gives an indication of the site of obstruction as well as the disease status of the patient. It is usually easier to clear the water-soluble contrast used for CT if an upper gastrointestinal contrast series is subsequently needed to evaluate the site or nature of the obstruction.

It is not unusual for patients to have no frank obstruction on radiology studies, and the symptoms of a proportion of these women will resolve simply with bowel rest with decompression and rehydration. Women who do not experience such a resolution must decide whether they will undergo surgery or a more conservative approach to treatment.

Surgery for Intestinal Obstruction in Patients With Recurrent Disease

Because of the propensity of ovarian cancer to spread through the peritoneal cavity, many women develop bowel obstruction without impairment of other vital organs. Thus, even if these women have exhausted all reasonable therapeutic options, it is often possible to surgically relieve their obstruction and allow them to return home on an oral diet.

A number of series have been published describing the results of palliative surgery in this setting. Krebs and Gopelrud reviewed 98 patients who experienced a total of 118 episodes of bowel obstruction over a 20-year interval.[18] They observed an operative mortality of 12%, and found that a total of 35% of patients who underwent surgery expired within 8 weeks of the procedure. In the interest of proactively identifying the patients who would benefit from surgery (ie, live at least 8 weeks after the procedure), they developed a prognostic index for successful operation. In their cohort, age less than 45 years, normal nutritional status, the absence of palpable tumor, absence of ascites, fewer courses of preceding chemotherapy, and the absence of preceding radiation therapy were associated with “success.”

In a follow-up study, Clarke-Pearson et al found that the presence of ascites, a clinical assessment of tumor volume, and a score of the patient’s nutritional status were predictive of survival in their patients.[19] Similarly, Larson and colleagues evaluated the surgical outcomes of 33 women with intestinal obstruction from ovarian cancer and confirmed that the criteria of Krebs and Gopelrud were predictive of a successful operation.[20]

Rubin and colleagues described the outcomes for 52 patients with recurrent ovarian cancer who underwent surgery for intestinal obstruction at Memorial Sloan-Kettering Cancer Center in New York City.[21] Of 54 procedures performed, intestinal surgery was feasible in 43 cases. Of these 43 cases, 4 expired without leaving the hospital, 3 developed enterocutaneous fistulas, and 34 (79%) were able to leave the hospital and eat a regular or low-residue diet. While this degree of morbidity and mortality would be unacceptably high in another clinical setting, in this severely compromised cohort of patients with less than 12 months to live and no other means of returning to a relatively normal lifestyle, it may be acceptable.

In this series, the mean survival of the 43 patients who underwent intestinal surgery was 6.8 months, whereas that of women who underwent exploration was only 1.8 months. No clinical factors were indicative of a poor operative result. Given the high rate of success that was seen in this series, it may be that clinical judgment eliminated unfavorable patients prior to surgery. Other investigators have reported similar findings, although not all have observed an improvement in survival with surgery.[22,23]

Fernandes and colleagues, for example, reported a series of 62 patients with ovarian cancer and intestinal obstruction and found no difference in survival between those treated medically and those treated surgically for obstruction, with both groups having a 1-year survival of about 35%.[24] In their patient population, survival was related to age less than 60 years, a longer interval between the diagnosis of cancer and the development of intestinal obstruction, earlier-stage disease, the absence of ascites, normal serum albumin, blood urea nitrogen and alkaline phosphatase levels, and the presence of a discrete obstruction on imaging studies.

Lund et al also found no difference in survival between 16 patients with conservatively managed obstruction and 25 surgically treated patients. The short survival (30 and 68 days, respectively), however, and very high (64%) surgical complication rates are inconsistent with other series and call these findings into question somewhat.[25]

In a recent report, Zoetmulder and colleagues evaluated a series of 58 patients with intestinal obstruction in the setting of ovarian cancer and compared the survival of women who had undergone conservative or surgical management.[26] For all patients, they found that the absence of ascites and an interval of at least 6 months since the last chemotherapy treatment were each predictive of survival.

Among patients identified as having a poor prognosis by these criteria, survival was 1 month regardless of the intervention taken. For patients in the “favorable” prognosis group, however, survival was 8 months with a strong trend toward improved survival for those who were managed with surgery (P = .052).

Determination of Prognosis for Successful Therapy

It is clear that physicians must use careful judgment in selecting patients whose prognosis is sufficiently favorable so that they may enjoy some benefit in quality of life from surgical correction of intestinal obstruction. One significant indicator of disease status, which is not thoroughly addressed in the literature, is whether the patient is considered to have a platinum-sensitive tumor.

In our practice, we generally restrict major palliative surgery to this group of patients. Whether there is an improvement in survival from surgery in this setting is unclear given the retrospective nature of the data. Considering the universally poor prognosis conferred by the finding of intestinal obstruction in patients with ovarian cancer, however, this consideration may not be paramount.

It is fairly consistently stated or implied by experienced oncologists who reported the above series, that surgical relief of obstruction, when successful, is associated with a considerable improvement in quality of life. Although it is probably unrealistic to await a randomized trial of medical and surgical therapy in this setting, it would be worthwhile to prospectively acquire objective quality-of-life information from these women.

Conservative Management of Intestinal Obstruction

A significant number of patients with intestinal obstruction will either be assessed to be poor candidates for surgery or will decline to have surgery. Recent advances in end-of-life care have identified significant interventions that can improve the patient’s comfort. Although it may no longer be appropriate to continue aggressive anticancer therapy, these interventions offer a number of positive steps that may be taken to improve the patient’s situation. They should be presented as such, so that the patient is offered an alteration in treatment (positive intervention) rather than a withdrawal of care (a negative intervention that might be construed as abandonment).

Even in the setting of a complete large-bowel obstruction, acceptable symptom control can be achieved in the majority of patients. Agents to relieve abdominal pain, colic, and nausea and vomiting can be administered either rectally or by a subcutaneous pump. Stimulant laxatives and prokinetic agents should be discontinued to decrease colic. Antispasmodic agents are helpful in further controlling colic, and morphine or other opiates are generally needed.

Haloperidol (Haldol) or another phenothiazine is usually helpful in controlling nausea. Octreotide (Sandostatin) may further reduce colic and nausea by decreasing intestinal secretions. Patients managed medically for obstruction in this setting are generally comfortable and may be able to eat and drink as they desire (although this is usually not much.) Oncologists should discourage generalists from invoking treatment algorithms that are not suitable to the terminally ill.

Patients who are found to have a more proximal obstruction often require intestinal drainage in addition to medical management. As mentioned above, patients who are known to have progressive disease not amenable to surgery are unlikely to benefit from a prolonged hospitalization with nasogastric drainage. Intravenous hydration has not been shown to improve the quality of life of women with terminal ovarian cancer, unless they experience thirst that is not relieved by oral intake. In fact, this measure is probably detrimental in that intravenous hydration is likely to increase ascites production and intestinal secretions.[27]

Conclusions

Intestinal obstruction in the patient with ovarian cancer is a serious condition that can only be optimally managed after careful consideration of the nature of the obstruction, disease status, and overall medical condition. Patients who present with ovarian cancer should only undergo intestinal resection or diversion in the setting of complete obstruction, or if the procedure is necessary to achieve an optimal surgical cytoreduction. Patients who develop obstruction in the setting of recurrent cancer nearly always have a survival of less than 1 year.

Surgical correction may be appropriate in the patient who is likely to live long enough to benefit from the improvement in bowel function, and who is fit to withstand the surgery without undue morbidity. Published algorithms exist to assist the clinician in systematically making these decisions.

A significant proportion of women will not be suitable for surgery or will not desire surgery. These women should continue to be proactively managed in a humane and conscientious fashion that relieves their discomfort and illustrates our perpetual commitment to the care of women with ovarian cancer.

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