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10.1245/s10434-006-9303-6
Annals of Surgical Oncology 14:1264-1271 (2007)
© 2007 Society of Surgical Oncology
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Original Article

Surgery as a Bridge to Palliative Chemotherapy in Patients with Malignant Bowel Obstruction from Colorectal Cancer

Lucy K. Helyer1, Calvin H. L. Law1, Mathew Butler1,2, Linda D. Last1, Andrew J. Smith1 and Frances C. Wright1

1 Department of Surgical Oncology, Sunnybrook and Women’s College Health Sciences Centre, University of Toronto, 2075 Bayview Ave., Room T2-063, Toronto, ON M4N 3M5, Canada
2 Department of Surgery, University of Alberta, Alberta, Canada

Correspondence: Address correspondence and reprint requests to: Frances C. Wright; E-mail: frances.wright{at}sunnybrook.ca


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Background: Malignant bowel obstruction (MBO) is a feature of the clinical course of 10–28% of colorectal cancer (CRC) patients and is associated with a poor prognosis. Recent advancements in palliative chemotherapy regimens have prolonged survival in patients with stage IV CRC. Few reports exist that describe outcomes in patients who have had surgery for MBO and subsequent chemotherapy as part of their treatment. The objective of this study was to review surgical outcomes in patients with MBO for CRC and to evaluate the extent to which surgery can serve as a bridge to palliative chemotherapy.

Methods: Patients who presented with MBO and had surgical treatment were identified from a prospectively kept database at a single tertiary care center between 09/99 and 08/04. Charts were retrospectively reviewed and clinical and outcomes data were abstracted.

Results: Forty-seven patients were identified who had surgery as part of the treatment for MBO from CRC. Operations included resections, bypasses and stoma creation. Overall, 80% of patients were able to tolerate solid food post-operatively and return home. The median survival for the entire cohort was 3.5 months. Seven patients died within 30 days of surgery. Of the remainder, 24 patients were palliated with surgery alone and 16 patients ultimately received palliative chemotherapy. Survival in the final cohort was significantly prolonged (P < 0.001).

Conclusion: Surgery can adequately palliate a substantial proportion of patients with MBO from CRC with acceptable morbidity and mortality. In addition, in a subset of patients it can facilitate palliative chemotherapy that is associated with improved overall survival.

Key Words: Malignant bowel obstruction • Colorectal adenocarcinoma • Palliative chemotherapy • Survival • Surgery


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
Malignant bowel obstruction (MBO) occurs in approximately 15% of patients admitted to palliative care wards1 and at some point in the clinical course 10–28% of patients diagnosed with a colorectal cancer (CRC).1,2 Obstructive symptoms can result from intra-luminal disease, extra-luminal compression or from motility disorders from tumor infiltration of the mesentery, enteric plexus or bowel wall.3 As a result, treatment is complex and optimal management may involve one or a combination of pharmaceutical, endoscopic or surgical therapies. Goals of treatment are individualized and predominantly focus on symptom control and restoration of enteric intake.4

Previous authors have described patient outcomes in the context of MBO for CRC (Table 1Go). Typically, these studies describe high perioperative rates of morbidity and mortality and median overall survivals ranging from 2 to 10 months.4–22 The literature to date has not focused on the impact of rapidly evolving and increasingly effective palliative chemotherapy regimens for the group of patients who are managed surgically for MBO.23–25


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  		TABLE 1. Outcomes data for patients surgically treated for a MBO from CRC
 
This study is a retrospective review of 47 consecutive patients who were treated surgically for a MBO due to CRC at a tertiary care cancer center. We describe patient outcomes including those of a select group of patients who were able to further undertake palliative chemotherapy.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
A prospectively collected surgical CRC database maintained at a tertiary care center that focuses on the management of CRC including locally advanced and recurrent neoplasms was used to identify eligible patients. All patients who underwent palliative surgery for MBO between June 2000 and June 2004 were identified. Demographic information, clinical parameters, treatment-related variables and outcomes were extracted. In addition to review of the database, three surgeons retrospectively reviewed charts. Care was taken to review the specific operative procedures chosen to palliate MBO as well as the pattern of disease. Discrepancies in coding were resolved through careful discussion among the three investigators. Co-morbidities were recorded and graded using the Charlson Co-morbidity Index.26

Patients were excluded from the cohort if colorectal adenocarcinoma was not the underlying etiology of the MBO or if patient factors such as patient frailty or co-morbidity rather than tumor factors (extent of disease) indicated a palliative operation rather than curative-intent operation. For example, an 85-year-old frail patient who would have required a pelvic exenteration for potential cure, but was not offered this operation as the risk of intra or postoperative death was considered too high, was excluded from this study.

No patients had chemotherapy during the perioperative period. Post-operative patient treatment was reviewed to assess if palliative chemotherapy was instituted following recovery from operation.

Successful palliation was defined as the ability to tolerate solid food post-operatively. Post-operative death was defined as any death within 30 days of the operation. Follow-up was continued until death or the end of study. Statistical analysis was performed by SAS 8.20E. Significance of difference was assumed at P values of 0.05 or less.


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Patient Selection
Review of the CRC database identified 66 patients from June 2000 to June 2004 who had undergone intra-abdominal palliative surgery. Nineteen of these 66 patients were excluded from the present study. Of these 19 patients, 14 were excluded as they had potentially curable low volume disease but due to medical conditions were treated with a less extensive palliative operation. This was usually a diverting end colostomy. These patients were left out of the analysis as they were thought to represent a different patient population with different tumor biology. Four patients were excluded, as they did not have colonic adenocarcinoma as the underlying cause of MBO [squamous carcinoma (n = 2), carcinoid (n = 1), lymphoma (n = 1)]. One patient was excluded as they were decompressed and treated with an endoscopically placed colonic stent. Patients were included if they had a MBO and unresectable metastatic disease or a locally advanced unresectable lesion that would not have allowed R0 excision even with neo-adjuvant therapy and/or aggressive multi-visceral resection. Our cohort was, thus, comprised of forty-seven patients who were clinically obstructed from a MBO from CRC and had palliative intra-abdominal surgery (Fig. 1Go).


Figure 1
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  		FIG. 1. Study patients.

 
Patient Demographics
Fifty-seven percent of the 47 patients were male and the entire cohort had a median age of 65 years, (range 19–89 years) (Table 2Go). Presentation with a MBO was the initial point of diagnosis of CRC for 14 patients (30%). The level of obstruction was determined to be small bowel in 47% of patients and large bowel in 53%. The median age adjusted Charlson Co-morbidity score of the entire population was 8 (Table 5Go). Follow-up until death or last clinic visit was complete for 46/47 patients.


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  		TABLE 2. Patient demographics
 

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  		TABLE 5. Three cohorts survival and predictive factors
 
Radiologic Assessment
All patients (n = 47) had a pre-operative CT scan of the abdomen and pelvis. Thirty percent of patients were unresectable as a result of locally advanced disease as defined as metastatic spread to adjacent organs, vascular structures or abdominal or pelvic wall (retroperitoneal mass/nodes n = 4, sacral involvement and hydroureter n = 5 and adjacent organ, pelvic side wall invasion n = 5). Seventy percent of patients had evidence of non-resectable discontiguous metastatic disease (liver, lung or peritoneal). In this series, two patients (4%) were operated on who had radiologic evidence of significant ascites (Table 2Go).

Treatment Approach
Operative approaches were individualized to each patient’s presentation of disease by the attending surgeon in an attempt to achieve palliation. Surgery typically involved one or a combination of resection, bypass, or ostomy creation. Sixty-three percent of patients had an ostomy created, of which 87% were loop stomas (ileostomy 47%, colostomy 53%). Six patients had disease resected to relieve the obstruction. Of these six patients, three patients had a small bowel resection, two had large bowel resection and one patient had multi site resections (both large and small bowel). Seventeen bypass procedures were completed including four gastrojejunostomies for gastric outlet obstruction, eight enteroenterostomies and five enterocolostomies. Seven gastrostomy tubes were placed for gastric decompression (Table 5Go). The palliative care team (palliative care physician and palliative care nurse) was involved in patient management in 31 patients (66%).

Patient Outcomes
Successful palliation, with the restoration of oral intake, was achieved in 80% of patients. The overall median length of stay on the acute care ward was 10 days. Two patients (4%) died within 48 h of operation, one due to sepsis and another due to tumor causing iliac artery rupture. Five additional patients died within 30 days of surgery as a result of progressive disease (Table 3Go). Eleven patients were recorded as having 13 post-operative complications causing two deaths. Post-operative morbidities included thromboembolic complications, septic complications, wound dehiscence or wound infection (Table 5Go). One patient re-obstructed and required readmission and re-operation (loop stoma). Sixteen patients went on to receive palliative chemotherapy. Median overall survival was 3.5 months (range 2 days to 32.8 months) (Fig. 2Go, Table 5Go).


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  		TABLE 3. Patient outcomes (n = 47)
 

Figure 2
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  		FIG. 2. Overall survival—entire cohort.

 
Three distinct patient groups were identified from the overall patient cohort (n = 47). The first group (n = 7) was comprised of patients who died in hospital. The second group (n = 24) included patients who left hospital and received best supportive care only (no palliative chemotherapy). The third group (n = 16) included those patients who received postoperative palliative chemotherapy (Tables 4Go, 5Go).


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  		TABLE 4. Treatment of CRC prior to presentation with MBO
 
In group one, four of the seven patients presented with recurrent disease. None of these patients were able to resume oral intake post-operatively. Two patients died of post-operative complications, and the remaining five of progressive malignant disease. Median post-operative survival was 9 days (range 2 days to 1.3 months) (Fig. 3Go). No preoperative radiologic factors, such as presence of ascites or metastatic disease, were found on statistical analysis to be predictive of failure of surgical palliation. Only three of the seven patients had the palliative care service involved in their treatment plan perioperatively. Age-adjusted Charlson Co-morbidity index scores were slightly higher when compared to the overall study group with a median score of 9.


Figure 3
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  		FIG. 3. Overall survival—in hospital death, best supportive care and chemotherapy.

 
Group two was composed of 24 patients who were palliated with surgery and best supportive care. Interval from initial CRC presentation to MBO was 17.7 months, (range 3–59 months). Twenty-nine percent of these patients had prior treatment with chemotherapy and/or radiation therapy (Table 4Go). Ninety-six percent of these patients were able to resume oral intake post-operatively. One patient was able to leave the hospital but unable to tolerate solid foods consistently and died of disease at 39 days. Median survival for the group was 2.69 months (range 17 days to 12. 9 months) (Fig. 3Go). Palliative care was involved perioperatively in 71% of cases. The median age-adjusted Charlson co-morbidity score was 8.5.

Finally, sixteen patients who underwent surgery for MBO subsequently were treated with chemotherapy. Eighty-one percent of these patients had recurrent disease and the interval from primary presentation to MBO was 36.5 months (range 12–132 months). Ten patients had previously received chemotherapy and five received radiation prior to their diagnosis of MBO (Table 4Go). All were able to resume oral intake post-operatively. Median survival was 10.3 months (range 21 days to 32.8 months) (Fig. 3Go). Patients in this group had a median age-adjusted Charlson Co-morbidity score of 8.

Additional Palliative Therapy
Four patients underwent post-operative palliative radiotherapy to the pelvis (one patient also had palliative chemotherapy). These patients were all female, had a median age of 65 and presented with recurrent CRC and a large bowel obstruction. All received decompressing colostomies, and two patients required additional small bowel resections.

Patients were offered and treated with chemotherapy by our center’s medical oncologists. All patients who were offered chemotherapy had to have an ECOG performance status of 1 or 2, and have no symptoms of a bowel obstruction. Sixteen patients received post-operative palliative chemotherapy. Fourteen patients received FOLFOX (oxaliplatin/flurouracil/leucovorin) as 80% had been previously exposed to flurouracil/leucovorin (FU/LV). One patient was treated solely with FU/LV and one with irinotecan. One patient progressed after FOLFOX and went on to receive mitomycin and irinotecan as third line palliative therapy (survival 428 days). No patients were admitted as a result of adverse chemotherapy effects.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
Patients with MBO represent a complex management challenge that often requires the expertise of surgeons, medical oncologists, radiation oncologists, palliative care specialists, radiologists, nurses and social workers. In this study, we confirm that surgery for MBO from CRC is associated with a range of outcomes. Importantly, we have demonstrated that a select cohort of patients who will receive post-operative palliative chemotherapy and can have a significantly prolonged survival following surgery for MBO.

Previous studies of surgical management of MBO are largely retrospective and centered on gynecologic malignancies, although a few have included small numbers of patients with various GI malignancies (Table 1Go).4,7 A retrospective review and meta-analysis by Ripamonti and Feuer documented that 30-day post-operative mortality after surgery for MBO varied between 5 and 40% and morbidity rates were as high as 90%.3,7 Median survival was reported to be between 2 and 6 months.6,7 More recent studies of surgery for MBO due to CRC, report lower morbidity (13–21%) and mortality rates (27–67%).6,8,9 In our patient population the 30-day mortality was 14% (7/47) and morbidity rate of 30% (14/47). Our median overall survival is similar to that reported in the literature at 3.5 months.

In this study, we have identified three subsets of patients who had surgery for a MBO from CRC. The first cohort (n = 7) did poorly with all patients dying within a thirty day post-operative time period. We could not identify any predictive factors that would have indicated pre-operatively that these patients were likely to have a poor outcome except that they were older and had non-significantly higher Charlson Co-morbidities scores.

Identifying patients who would have a poor outcome with surgery for MBO is challenging. One potential marker of diffuse peritoneal involvement is small bowel obstruction, or multi-level obstruction.4 However, despite the existence of intra-operative staging systems for grading peritoneal carcinomatosis, burden of disease can be difficult to evaluate pre-operatively10,11 and extent of disease is routinely underestimated by helical CT.12,13

Prognostic variables for success and overall survival with respect to surgery for MBO have been described and include patient age, performance status, albumin level, presence of ascites, previous treatment with chemotherapy or radiation, volume of secondary disease, grade of primary tumor, interval since initial surgery, and presentation of MBO as the primary presentation of disease.4,7,14,15 In our patient population we observed that increasing age, and short time between initial resection and presentation with MBO were negative predictive factors. This is consistent with the literature. However, we did not find that primary presentation of CRC with MBO or treatment with chemotherapy or radiation prior to MBO diagnosis were negative prognosticators.

Palliative care consultations were made in a nonstandardized fashion for patients with MBO in this study. Indeed, it was in the first cohort (n = 7) that the incidence of a palliative care consult was lowest (33%) and it is probable that this group would have most benefited from a non-surgical multidisciplinary approach to their MBO.1,16 Treatment decisions and ultimately overall survival in oncology patients with complex and multi-factorial problems have been shown to benefit from a multidisciplinary team approach.17 Indeed palliative care specialists have been suggested as the "treatment brokers" as they are able to clarify both patients’ and physicians’ assumptions and expectations for patient care.18 Consistent with that observed by others, our center’s non-standardized approach to palliative care consultations is reflective of a worldwide tendency as the proportion of patients referred to palliative care varies widely in different countries, specialties, hospitals and amongst practioners.18

In this study, sixteen patients (group 3) were able to receive palliative chemotherapy and had a significantly longer median survival of 10.3 months (range 21 days to 32.8 months). A recent Japanese study also has described improved patient (n = 21) survival after surgery for a MBO from CRC and palliative chemotherapy.6 Further improvements in CRC chemotherapy may offer further survival benefits.23–25

In our patient population we have not extensively used gastrointestinal stenting as a means to relieve gastric-outlet or distal colonic obstructions. Colorectal stenting has been described in patients with a large bowel obstruction, typically when the lesion lies between the rectum and splenic flexure both as a "bridge to surgery" for potentially curable patients and in patients who are incurable.27,28 The overall clinical success in relieving a colorectal obstruction is 90%; however, 4% of patients will perforate, 10% will experience stent migration and 1% will have a significant bleed.27,28 In addition, within the MBO population, 16% will re-obstruct after stent placement.27,28 Stenting was in its initial stages at our center within the study time period; however, we are now considering its use in appropriate patients with a MBO from CRC as we have gained expertise and experience with this technique.

This study has a number of limitations. It is retrospective and thus it is not always clear what factors were involved in making the decision to take a patient to the operating room. The patient population was small (n = 47) and it is a non-uniform population although we limited the cohort to patients with only CRC as the underlying etiology of the MBO. Surgery was non-standardized, although again, these patients have unique patterns of disease and it would be very difficult to standardize any type of surgery in this situation. Moreover, as many other studies have done, successful palliation was defined as the ability to resume oral intake and no quality of life measures were assessed.4 Our group is now undertaking a prospective assessment of patients with MBO to identify how many patients are eligible for surgical intervention, to determine prognostic factors for the success of surgical intervention and to assess quality of life after a diagnosis of MBO for patients who do and do not undergo surgical intervention.

This study has demonstrated that surgery can adequately palliate a substantial proportion of patients with MBO from CRC with acceptable morbidity and mortality. In addition, in a subset of patients it can facilitate palliative chemotherapy that is associated with improved overall survival. To ensure optimal patient selection, we advocate for a multidisciplinary discussion including the palliative care specialists with emphasis on short-term goals of symptom remission and long-term goals of extending life.


   FOOTNOTES
 
Dr. Calvin Law is a Career Scientist of the Ontario Ministry of Health and Long Term Care and is supported through a Health Research Personnel Development—Career Scientist Award.

Received for publication January 31, 2006. Accepted for publication July 20, 2006.


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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