Journal of Surgical Oncology
Surgical Management of Bowel Obstruction in Patients with Peritoneal Carcinomatosis BAHBAK SHARIAT-MADAR, BS, THEJUS T. JAYAKRISHNAN, MBBS, T. CLARK GAMBLIN, MD, MS, AND KIRAN K. TURAGA, MD, MPH* Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
Background: Due to low life expectancy, treatment strategies for malignant bowel obstruction (MBO) due to peritoneal carcinomatosis (PC) emphasize improved quality of life and symptom relief. Currently, the value of palliative surgery to treat obstructive PC is unclear. Methods: A prospectively registered search strategy (PROSPERO) was utilized to identify articles examining outcomes of patients undergoing surgical palliation for MBO from PC in PubMed (2003–2013). Primary outcomes of interest were median overall survival (OS) and treatment complications. Results: Of 730 articles screened, 64 were selected for full‐text review and 5 were quantitatively synthesized. This comprised 313 patients with MBO, of which 249 (79.5%) presented with PC. The mean age was 61.4 years (range 51–67). The OS for surgical patients was 6.4 months (2.8–19.7, n ¼ 190). Stratification by surgical technique suggested an OS of resection, ostomy, and enteral bypass as 7.2 months (n ¼ 174), 3.4 months (n ¼ 9), and 2.7 months (n ¼ 7), respectively. Major complications occurred in 37.0% of patients that underwent resection. Conclusions: This study supports surgical resection over surgical bypass to treat obstructive PC, as it offered better OS with fewer complications. Higher quality studies are needed to conclusively assess the role of surgery in patients with obstructive PC.
J. Surg. Oncol.
ß 2014 Wiley Periodicals, Inc.
KEY WORDS: neoplasms; intestinal bypasses; colostomy; palliative care; stents
INTRODUCTION
MATERIALS AND METHODS
Gastrointestinal and gynecological cancers are among the most prevalent cancer etiologies in the general population. Globally, four of the five cancers with the highest mortality (liver, stomach, colon, and breast) are cancers of gastrointestinal or gynecological origin [1]. Peritoneal carcinomatosis (PC) is a metastatic spread of cancer throughout the peritoneal surface, often leading to nausea, vomiting, significant patient discomfort, and imminent bowel obstruction [2]. Moreover, PC is relatively resistant to systemic chemotherapeutic strategies and malignant bowel obstruction (MBO) secondary to PC often dissuades further aggressive medical treatment and makes palliation a challenge. Prognosis is very poor for obstructive PC, and currently no established, evidence‐based medical guideline exists for its treatment [3]. Studies have suggested as many as 10–28% of patients with recurrent colorectal cancer and 20–50% of patients with recurrent ovarian cancer will present with MBO alone [4]. Consequently, patients with MBO have an average survival ranging from 3 to 8 months or 4 to 5 weeks in operable and inoperable cases, respectively [5]. MBO occurring due to dominant disease in the large intestine has been managed with endoluminal stents, while MBO from PC usually presents with multiple sites of disease making stent‐based strategies futile. The focus of treatment for MBO in the context of PC often times requires an individualized plan. Since aggressive surgical interventions are approached with trepidation, we attempt to outline the efficacy of different palliative surgical approaches, and under what circumstances would invasive surgical interventions improve patient outcomes and quality of life in the context of MBO due to PC. In this analysis, we place special focus on distinguishing the value of bypass, resection, and colostomy in patients with obstructive PC.
Search Strategy
ß 2014 Wiley Periodicals, Inc.
We conducted a literature review of MEDLINE to assess studies documenting reported outcomes of surgical interventions of obstructive PC that were reported between January 1, 2003 to February 13, 2013. The study was prospectively registered at PROSPERO (CRD42013003938). We included the following top‐level search terms and phrases in our strategy: “stent,” “stents,” “gastrostomy,” “resection,” “bypass,” “ileostomy,” “colostomy,” “obstruction,” “surgical stoma,” “stoma,” “surgery,” “surgical,” “pelvic neoplasms,” “peritoneal neoplasms,” “gastrointestinal neoplasms,” “pancreatic neoplasms,” “intestinal obstruction/surgery,” “intestinal obstruction/ therapy,” “palliative care,” and “gastrostomy.”
Conflicts of interest and source of funding: 1. There was no source of funding for this study. 2. All authors have no disclosures to make. This study was presented at the 11th Annual AMA Research Symposium held November 15, 2013, in conjunction with the 2013 AMA Interim Meeting in National Harbor, MD. *Correspondence to: Kiran K. Turaga, MD, MPH, 9200W Wisconsin Ave, Milwaukee, WI 53226. Fax: þ1‐414‐805‐5771. E‐mail: [email protected] Received 20 February 2014; Accepted 3 June 2014 DOI 10.1002/jso.23707 Published online in Wiley Online Library (wileyonlinelibrary.com).
2
Shariat‐Madar et al. Eligibility Criteria—Inclusion and Exclusion
We included all English‐language clinical trials, meta‐analyses, systematic reviews, prospective cohort studies, and retrospective studies conducted on human subjects that dealt with the following included factors: 1. MBO due to peritoneal metastases of all etiologies. 2. Treatment of MBO with bowel bypass, bowel resection, or colostomy. 3. Overall survival (OS) and complications were reported. We extracted information regarding demographic data, health‐related quality of life, concomitant therapeutics, performance status, hospital stay lengths, and complications when available in addition to our primary outcomes of interest. The following articles retrieved through the search were excluded: 1. Case reports and case series studies. 2. Studies in which bowel obstruction was due to a primary malignancy. 3. Studies in which exclusively non‐invasive techniques, such as gastrostomy, stenting, or medically conservative management were used. 4. Studies in which all patient groups underwent a combination of multiple surgical procedures. We also conducted hand searching of bibliographies of full text articles that were assessed for eligibility in order to capture studies that were potentially missed by the initial search strategy. The combination of hand‐searching select reference bibliographies and the use of a rigorous and comprehensive search strategy were intended to insure capture of all relevant articles.
Quality Assessment One reviewer evaluated all included trials using a list of pre‐selected quality criteria. All included trials in this study were non‐randomized, and were assessed for baseline characteristics, patient demographics, primary outcomes reporting, confounding, unexplained heterogeneity, and whether or not adjustment for confounders was utilized, limitations were discussed, and funding disclosures were made. All articles were then assessed an evidence level based on CEBM Oxford guidelines. A second reviewer confirmed the quality assessment.
Fig. 1. Flow diagram of search strategy and inclusion/exclusion process [17].
Quantitative Findings The characteristics of the nine studies are included in Table I. All five articles that could be quantitatively synthesized were observational studies. These studies included 313 patients with MBO, of which 249 (79.5%) presented with PC. The mean age was 61.4 (range, 51–67) (Table II). OS for surgical patients was 6.4 months (2.8–19.7, n ¼ 190, 3 studies) (Table II). When stratified for surgical technique, the survival for patients that underwent resection, colostomy, and bypass were 7.2 months (n ¼ 174, 3 studies), 3.4 months (n ¼ 9, 1 study), and 2.7 months (n ¼ 7, 1 study), respectively. Major complications occurred in 37.0% of patients that underwent resection (Table II). Major complications occurred in 37.0% of patients that underwent resection (n ¼ 94, 2 studies).
DISCUSSION Management of MBOs in the setting of PC is challenging clinical situation which requires significant time and thought from the patient and physician conservative measures such as octreotide and
an extremely investment of alike. While percutaneous
RESULTS Identification and Characteristics of Studies The search strategy returned 726 articles from MEDLINE. An additional four unique articles were retrieved through manual review of the bibliographies of included articles. Of these 730 total articles, 64 articles were selected for full text review. Nine of the 64 articles were included in the review for qualitative analysis, while 5 of those 9 included articles could be analyzed quantitatively. The search methodology, including reasons for article exclusion is diagrammed in Figure 1.
Quality of Studies All nine included studies were found to be of a 2b evidence level in accordance with CEBM Oxford guidelines. There were eight retrospective studies, and one was prospective cohort with poor follow up. Only three of the included studies identified confounders and used adjustments for confounders in their study. Only three studies provided a disclosure for a funding source. The quality of all nine articles included is outlined in Figure 2. Journal of Surgical Oncology
Fig. 2. Graph demonstrating risk of bias across the articles used in the study (n ¼ 9).
Surgical Treatment of MBO
3
TABLE I. Characteristics of Study Populations Included in the Systematic Review Along With Details of Surgical Interventions Utilized in the Respective Studies
Source Higashi et al. [9] Costi et al. [10] Abbas and Merrie [11]
Amikura et al. [12] Lee et al. [13] Chakraborty et al. [3] Parveen et al. [14] Kim et al. [15] Wong and Tan [16]
Sample size
Mean age in years (range)
21 31 79 31 16 19 13 51 73 71 35 30 69 111 27
61.7 (20–88) 62 (19–91) 62 51 58 67 – 62 (29–88) 64.14 (26–87) 61 (19–85) – 55 (20–86) 59 (26–88) 69 (28–85)
Etiology
Patients with peritoneal carcinomatosis (%)
Colorectal Colorectal
100 100 100 100 100 100 100 100 20
Colorectal Melanoma Gynecological Other Gastrointestinal Colorectal Colorectal Multiple Ovarian Gastric
43 40 93.30
Multiple
92.50
Surgical intervention of interest (n) Bypass (9), resection (1), colostomy (7) Resection (15), non‐resective surgery (16) Resection (79) Resection (31) Resection (16) Resection (19) Resection (13) Bypass, resection, enterostomy (51) Resection, bypass ( 73) Stenting (71) Bypass (3), resection (3), colostomy (5), adhesiolysis (1) Bypass (7), resection (10), colostomy (3), adhesiolysis (14) Bypass (69) Stenting (111) Bypass (14), resection (6), colostomy (5), adhesiolysis (2)
Represents the 5 articles that could be quantitatively synthesized.
gastrostomy tubes can help patients improve their quality of life, palliation of an obstruction remains suboptimal [6,7]. Consideration for surgical palliation should be undertaken in situations where the patients are not actively dying and reversal of enteral failure could make therapeutic options viable. Treatment goals should be centered on relief of nausea, vomiting, pain, enabling oral intake, and allowing the patient to return to the care setting of their choice, if feasible. Surgery has had variable success in symptomatic relief, and likely offers an improvement in survival. Resection, bypass, and colostomy may prove to be the best surgical options available, while cytoreductive procedures are generally acceptable in situations where complete cytoreduction can be achieved, although MBO generally precludes complete cytoreduction [7]. Incorporation of parenteral nutrition has allowed patients with enteral failure to live longer, albeit their quality of life has not been studied extensively. TPN may alleviate hunger and achieve patient specific goals especially toward closure, and although chemotherapeutics can be administered concomitantly with TPN, this strategy is generally discouraged. Surgical palliation of enteral failure can yield significantly improved quality of life when bowel function is restored, but there remains a high morbidity likely from inanition and cachexia of patients. When cytoreduction is not possible, palliation by surgical resection might be the most effective strategy based on our data synthesis. Our practice at the Medical College of Wisconsin includes aggressive palliative care interventions for nausea, and pain control with the appropriate use of medical management of secretions, spasms, and nausea (Fig. 3). Goals of care including advanced directives are generally discussed early on during the hospital course and family meetings are encouraged. In patients with low burden of peritoneal disease, low‐grade histologies and good performance status, considerations for surgical palliation of bowel obstructions are frequently made. Functional contrast
studies often demonstrate numerous bowel obstructions and patients with 3 or less bowel obstructions are often good candidates for palliation (Fig. 3). Laparoscopy and laparoscopic assisted gastrostomy tubes are placed in patients not suitable for palliation by surgery. Nutritional support by TPN is initiated until goals of care as indicated by the patient and family are clarified further. Poor operative candidates can benefit from stenting when a single obstruction is seen or by venting gastrostomy tubes. Stenting can result in successful palliation, with major complications of concern being perforation, stent migration, or re‐occlusion [7]. Gastrostomy can be particularly effective for upper GI obstructions that may result in vomiting and nausea and may be effective in re‐enabling oral intake [7]. In patients that have poor performance status or actively dying, medical management with total parenteral nutrition or nasogastric tubes are able to effectively have their symptoms managed. Both opioids and anti‐ emetics can effectively curtail pain and vomiting, while anticholinergics can aid in treating colicky pain [6]. Somatostatin analogs are also effective in treating nausea, vomiting, and abdominal pain [6]. Patients with PC are often treated with systemic chemotherapy only, although the response rates to chemotherapy alone for most malignancies are poor when there is peritoneal disease compared to other visceral sites of metastases [8]. In the setting of a bowel obstruction, treating patients with systemic chemotherapy while a patient continues on TPN is fairly difficult and adds a significant burden to the patient and his/her family. Hence, an MBO can often be a terminal event for a patient, which could occasionally be a surprise given the poor ability of current imaging modalities to detect such disease early. Our analysis did not separate different histologies since we did not have access to patient level data which would have afforded us the ability to the do the same. An MBO in a patient with gastric cancer and well‐
TABLE II. Baseline Demographics and Primary and Secondary Outcomes Associated with Surgical Interventions Studied Outcome
Bypass (n ¼ 7)
Resection (n ¼ 174)
Colostomy (n ¼ 9)
Stenting (n ¼ 182)
Overall (n ¼ 372)
Mean age (range) in years Male% Median survival, months ECOG baseline% Mean hospital length of stay, days Time to chemotherapy, days
63.1 (61–64.5) – 2.7 – – –
61.0 (51–67) 54.8% 7.2 (3.5–19.7) – – –
64.0 (61.7–64.5) 48% 3.4 – 12 –
61.0 (59–64.1) 50.5% 10.8 (8.5–13) 52% 14.4 (13.2–15.5) 16.2
61.4 (51–67) 51.7% 7.1 (2.7–19.7) 52% 13.6 (12–15.5) 16.2
Ranges are included where the results were reported by more than one study.
Journal of Surgical Oncology
4
Shariat‐Madar et al. study is limited in its generalizability due to difficulty to control for patient performance status.
REFERENCES
Fig. 3. Algorithm for management of malignant bowel obstruction utilized at Medical College of Wisconsin.
differentiated appendiceal carcinoma are vastly different in the alternatives, longevity, and expectations of care. Nevertheless, we believe that our review adds to the body of evidence about surgical management of the majority of patients with an MBO.
Limitations Our study was limited by a number of different factors. Although we used a focused search strategy that sought to be broad enough to retrieve a wide range of articles that met our criteria, no randomized control trials were uncovered in our literature review and only one of the studies we uncovered was a prospective cohort study. All of the studies included were of a 2b evidence level in accordance with the CEBM Oxford guidelines. Of the studies included, only five identified and discussed confounding factors and only three of those five incorporated statistical analysis to adjust for those confounders. Additionally, very limited data were reported on colostomy and bypass; namely, there were no studies that had reported complication rates for the use of these procedures in obstructive PC. All etiologies were included in this study, and it is also possible that the site of origin leads to a different disease course or to different responses to medical treatment. Lastly, selection bias was a significant potential for limitation in the analysis. Surgical candidacy criteria, such as resectable disease and performance status, impact the medical or surgical management of patients. Unfortunately there were no uniformly used performance status criteria modules used across the studies included in order to control for this factor. With these factors in mind, the level of quality in the articles and the number of articles included limits the generalizability of the results determined from this study.
CONCLUSIONS Of the surgical techniques investigated, resection appeared to provide the greatest improvement in survival. It is important to note that this
Journal of Surgical Oncology
1. Ferlay J, Soerjomataram I, Ervik M, et al.: GLOBOCAN 2012 v1.0. In Cancer Incidence and Mortality Worldwide: IARC Cancer Base No. 11 [Internet]. Lyon, France: International Agency for Research on Cancer; 2013.Available from: http://globocan.iarc.fr 2. Deraco M, Santoro N, Carraro O, et al.: Peritoneal carcinomatosis: Feature of dissemination. A review. Tumori 1999;85:1–5. 3. Chakraborty A, Selby D, Gardiner K, et al.: Malignant bowel obstruction: Natural history of a heterogeneous patient population followed prospectively over two years. J Pain Symptom Manage 2011;41:412–420. 4. Ripamonti CI, Easson AM, Gerdes H: Management of malignant bowel obstruction. Eur J Cancer (Oxford, England) 2008;44:1105– 1115. 5. Tuca A, Guell E, Martinez‐Losada E, et al.: Malignant bowel obstruction in advanced cancer patients: Epidemiology, management, and factors influencing spontaneous resolution. Cancer Manage Res 2012;4:159–169. 6. Gunten CV, Muir J: Medical management of bowel obstructions. 2nd edition. Fast Facts and Concepts; August 2005;p. 45. Available from: http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ff_045. htm 7. Krouse R: Invasive treatment options for malignant bowel obstruction. Fast Facts and Concepts. August 2004;p. 119. Available from: http://www.eperc.mcw.edu/EPERC/FastFactsIndex/ ff_119.htm 8. Franko J, Shi Q, Goldman CD, et al.: Treatment of colorectal peritoneal carcinomatosis with systemic chemotherapy: A pooled analysis of north central cancer treatment group phase III trials N9741 and N9841. J Clin Oncol 2012;30:263–267. 9. Higashi H, Shida H, Ban K, et al.: Factors affecting successful palliative surgery for malignant bowel obstruction due to peritoneal dissemination from colorectal cancer. Jpn J Clin Oncol 2003;33: 357–359. 10. Costi R, Mazzeo A, Di Mauro D, et al.: Palliative resection of colorectal cancer: Does it prolong survival? Ann Surg Oncol 2007;14:2567–2576. 11. Abbas SM, Merrie AE: Resection of peritoneal metastases causing malignant small bowel obstruction. World J Surg Oncol 2007;5: 122. 12. Amikura K, Sakamoto H, Yatsuoka T, et al.: Surgical management for a malignant bowel obstruction with recurrent gastrointestinal carcinoma. J Surg Oncol 2010;101:228–232. 13. Lee HJ, Hong SP, Cheon JH, et al.: Long‐term outcome of palliative therapy for malignant colorectal obstruction in patients with unresectable metastatic colorectal cancers: Endoscopic stenting versus surgery. Gastrointest Endosc 2011;73:535–542. 14. Parveen Z, Qureshi AN, Akbar M, et al.: Palliative surgery for intestinal obstruction due to recurrent ovarian cancer. J Ayub Med Coll Abbottabad 2009;21:135–136. 15. Kim BK, Hong SP, Heo HM, et al.: Endoscopic stenting is not as effective for palliation of colorectal obstruction in patients with advanced gastric cancer as emergency surgery. Gastrointest Endosc 2012;75:294–301. 16. Wong TH, Tan YM: Surgery for the palliation of intestinal obstruction in advanced abdominal malignancy. Singapore Med J 2009;50:1139–1144. 17. Moher D, Liberati A, Tetzlaff J, et al.: Preferred reporting items for systematic reviews and meta‐analyses: The PRISMA statement. PLoS Med 2009;6:e1000097.
Surgical Management of Bowel Obstruction in Patients with Peritoneal Carcinomatosis BAHBAK SHARIAT-MADAR, BS, THEJUS T. JAYAKRISHNAN, MBBS, T. CLARK GAMBLIN, MD, MS, AND KIRAN K. TURAGA, MD, MPH* Division of Surgical Oncology, Department of Surgery, Medical College of Wisconsin, Milwaukee, Wisconsin
Background: Due to low life expectancy, treatment strategies for malignant bowel obstruction (MBO) due to peritoneal carcinomatosis (PC) emphasize improved quality of life and symptom relief. Currently, the value of palliative surgery to treat obstructive PC is unclear. Methods: A prospectively registered search strategy (PROSPERO) was utilized to identify articles examining outcomes of patients undergoing surgical palliation for MBO from PC in PubMed (2003–2013). Primary outcomes of interest were median overall survival (OS) and treatment complications. Results: Of 730 articles screened, 64 were selected for full‐text review and 5 were quantitatively synthesized. This comprised 313 patients with MBO, of which 249 (79.5%) presented with PC. The mean age was 61.4 years (range 51–67). The OS for surgical patients was 6.4 months (2.8–19.7, n ¼ 190). Stratification by surgical technique suggested an OS of resection, ostomy, and enteral bypass as 7.2 months (n ¼ 174), 3.4 months (n ¼ 9), and 2.7 months (n ¼ 7), respectively. Major complications occurred in 37.0% of patients that underwent resection. Conclusions: This study supports surgical resection over surgical bypass to treat obstructive PC, as it offered better OS with fewer complications. Higher quality studies are needed to conclusively assess the role of surgery in patients with obstructive PC.
J. Surg. Oncol.
ß 2014 Wiley Periodicals, Inc.
KEY WORDS: neoplasms; intestinal bypasses; colostomy; palliative care; stents
INTRODUCTION
MATERIALS AND METHODS
Gastrointestinal and gynecological cancers are among the most prevalent cancer etiologies in the general population. Globally, four of the five cancers with the highest mortality (liver, stomach, colon, and breast) are cancers of gastrointestinal or gynecological origin [1]. Peritoneal carcinomatosis (PC) is a metastatic spread of cancer throughout the peritoneal surface, often leading to nausea, vomiting, significant patient discomfort, and imminent bowel obstruction [2]. Moreover, PC is relatively resistant to systemic chemotherapeutic strategies and malignant bowel obstruction (MBO) secondary to PC often dissuades further aggressive medical treatment and makes palliation a challenge. Prognosis is very poor for obstructive PC, and currently no established, evidence‐based medical guideline exists for its treatment [3]. Studies have suggested as many as 10–28% of patients with recurrent colorectal cancer and 20–50% of patients with recurrent ovarian cancer will present with MBO alone [4]. Consequently, patients with MBO have an average survival ranging from 3 to 8 months or 4 to 5 weeks in operable and inoperable cases, respectively [5]. MBO occurring due to dominant disease in the large intestine has been managed with endoluminal stents, while MBO from PC usually presents with multiple sites of disease making stent‐based strategies futile. The focus of treatment for MBO in the context of PC often times requires an individualized plan. Since aggressive surgical interventions are approached with trepidation, we attempt to outline the efficacy of different palliative surgical approaches, and under what circumstances would invasive surgical interventions improve patient outcomes and quality of life in the context of MBO due to PC. In this analysis, we place special focus on distinguishing the value of bypass, resection, and colostomy in patients with obstructive PC.
Search Strategy
ß 2014 Wiley Periodicals, Inc.
We conducted a literature review of MEDLINE to assess studies documenting reported outcomes of surgical interventions of obstructive PC that were reported between January 1, 2003 to February 13, 2013. The study was prospectively registered at PROSPERO (CRD42013003938). We included the following top‐level search terms and phrases in our strategy: “stent,” “stents,” “gastrostomy,” “resection,” “bypass,” “ileostomy,” “colostomy,” “obstruction,” “surgical stoma,” “stoma,” “surgery,” “surgical,” “pelvic neoplasms,” “peritoneal neoplasms,” “gastrointestinal neoplasms,” “pancreatic neoplasms,” “intestinal obstruction/surgery,” “intestinal obstruction/ therapy,” “palliative care,” and “gastrostomy.”
Conflicts of interest and source of funding: 1. There was no source of funding for this study. 2. All authors have no disclosures to make. This study was presented at the 11th Annual AMA Research Symposium held November 15, 2013, in conjunction with the 2013 AMA Interim Meeting in National Harbor, MD. *Correspondence to: Kiran K. Turaga, MD, MPH, 9200W Wisconsin Ave, Milwaukee, WI 53226. Fax: þ1‐414‐805‐5771. E‐mail: [email protected] Received 20 February 2014; Accepted 3 June 2014 DOI 10.1002/jso.23707 Published online in Wiley Online Library (wileyonlinelibrary.com).
2
Shariat‐Madar et al. Eligibility Criteria—Inclusion and Exclusion
We included all English‐language clinical trials, meta‐analyses, systematic reviews, prospective cohort studies, and retrospective studies conducted on human subjects that dealt with the following included factors: 1. MBO due to peritoneal metastases of all etiologies. 2. Treatment of MBO with bowel bypass, bowel resection, or colostomy. 3. Overall survival (OS) and complications were reported. We extracted information regarding demographic data, health‐related quality of life, concomitant therapeutics, performance status, hospital stay lengths, and complications when available in addition to our primary outcomes of interest. The following articles retrieved through the search were excluded: 1. Case reports and case series studies. 2. Studies in which bowel obstruction was due to a primary malignancy. 3. Studies in which exclusively non‐invasive techniques, such as gastrostomy, stenting, or medically conservative management were used. 4. Studies in which all patient groups underwent a combination of multiple surgical procedures. We also conducted hand searching of bibliographies of full text articles that were assessed for eligibility in order to capture studies that were potentially missed by the initial search strategy. The combination of hand‐searching select reference bibliographies and the use of a rigorous and comprehensive search strategy were intended to insure capture of all relevant articles.
Quality Assessment One reviewer evaluated all included trials using a list of pre‐selected quality criteria. All included trials in this study were non‐randomized, and were assessed for baseline characteristics, patient demographics, primary outcomes reporting, confounding, unexplained heterogeneity, and whether or not adjustment for confounders was utilized, limitations were discussed, and funding disclosures were made. All articles were then assessed an evidence level based on CEBM Oxford guidelines. A second reviewer confirmed the quality assessment.
Fig. 1. Flow diagram of search strategy and inclusion/exclusion process [17].
Quantitative Findings The characteristics of the nine studies are included in Table I. All five articles that could be quantitatively synthesized were observational studies. These studies included 313 patients with MBO, of which 249 (79.5%) presented with PC. The mean age was 61.4 (range, 51–67) (Table II). OS for surgical patients was 6.4 months (2.8–19.7, n ¼ 190, 3 studies) (Table II). When stratified for surgical technique, the survival for patients that underwent resection, colostomy, and bypass were 7.2 months (n ¼ 174, 3 studies), 3.4 months (n ¼ 9, 1 study), and 2.7 months (n ¼ 7, 1 study), respectively. Major complications occurred in 37.0% of patients that underwent resection (Table II). Major complications occurred in 37.0% of patients that underwent resection (n ¼ 94, 2 studies).
DISCUSSION Management of MBOs in the setting of PC is challenging clinical situation which requires significant time and thought from the patient and physician conservative measures such as octreotide and
an extremely investment of alike. While percutaneous
RESULTS Identification and Characteristics of Studies The search strategy returned 726 articles from MEDLINE. An additional four unique articles were retrieved through manual review of the bibliographies of included articles. Of these 730 total articles, 64 articles were selected for full text review. Nine of the 64 articles were included in the review for qualitative analysis, while 5 of those 9 included articles could be analyzed quantitatively. The search methodology, including reasons for article exclusion is diagrammed in Figure 1.
Quality of Studies All nine included studies were found to be of a 2b evidence level in accordance with CEBM Oxford guidelines. There were eight retrospective studies, and one was prospective cohort with poor follow up. Only three of the included studies identified confounders and used adjustments for confounders in their study. Only three studies provided a disclosure for a funding source. The quality of all nine articles included is outlined in Figure 2. Journal of Surgical Oncology
Fig. 2. Graph demonstrating risk of bias across the articles used in the study (n ¼ 9).
Surgical Treatment of MBO
3
TABLE I. Characteristics of Study Populations Included in the Systematic Review Along With Details of Surgical Interventions Utilized in the Respective Studies
Source Higashi et al. [9] Costi et al. [10] Abbas and Merrie [11]
Amikura et al. [12] Lee et al. [13] Chakraborty et al. [3] Parveen et al. [14] Kim et al. [15] Wong and Tan [16]
Sample size
Mean age in years (range)
21 31 79 31 16 19 13 51 73 71 35 30 69 111 27
61.7 (20–88) 62 (19–91) 62 51 58 67 – 62 (29–88) 64.14 (26–87) 61 (19–85) – 55 (20–86) 59 (26–88) 69 (28–85)
Etiology
Patients with peritoneal carcinomatosis (%)
Colorectal Colorectal
100 100 100 100 100 100 100 100 20
Colorectal Melanoma Gynecological Other Gastrointestinal Colorectal Colorectal Multiple Ovarian Gastric
43 40 93.30
Multiple
92.50
Surgical intervention of interest (n) Bypass (9), resection (1), colostomy (7) Resection (15), non‐resective surgery (16) Resection (79) Resection (31) Resection (16) Resection (19) Resection (13) Bypass, resection, enterostomy (51) Resection, bypass ( 73) Stenting (71) Bypass (3), resection (3), colostomy (5), adhesiolysis (1) Bypass (7), resection (10), colostomy (3), adhesiolysis (14) Bypass (69) Stenting (111) Bypass (14), resection (6), colostomy (5), adhesiolysis (2)
Represents the 5 articles that could be quantitatively synthesized.
gastrostomy tubes can help patients improve their quality of life, palliation of an obstruction remains suboptimal [6,7]. Consideration for surgical palliation should be undertaken in situations where the patients are not actively dying and reversal of enteral failure could make therapeutic options viable. Treatment goals should be centered on relief of nausea, vomiting, pain, enabling oral intake, and allowing the patient to return to the care setting of their choice, if feasible. Surgery has had variable success in symptomatic relief, and likely offers an improvement in survival. Resection, bypass, and colostomy may prove to be the best surgical options available, while cytoreductive procedures are generally acceptable in situations where complete cytoreduction can be achieved, although MBO generally precludes complete cytoreduction [7]. Incorporation of parenteral nutrition has allowed patients with enteral failure to live longer, albeit their quality of life has not been studied extensively. TPN may alleviate hunger and achieve patient specific goals especially toward closure, and although chemotherapeutics can be administered concomitantly with TPN, this strategy is generally discouraged. Surgical palliation of enteral failure can yield significantly improved quality of life when bowel function is restored, but there remains a high morbidity likely from inanition and cachexia of patients. When cytoreduction is not possible, palliation by surgical resection might be the most effective strategy based on our data synthesis. Our practice at the Medical College of Wisconsin includes aggressive palliative care interventions for nausea, and pain control with the appropriate use of medical management of secretions, spasms, and nausea (Fig. 3). Goals of care including advanced directives are generally discussed early on during the hospital course and family meetings are encouraged. In patients with low burden of peritoneal disease, low‐grade histologies and good performance status, considerations for surgical palliation of bowel obstructions are frequently made. Functional contrast
studies often demonstrate numerous bowel obstructions and patients with 3 or less bowel obstructions are often good candidates for palliation (Fig. 3). Laparoscopy and laparoscopic assisted gastrostomy tubes are placed in patients not suitable for palliation by surgery. Nutritional support by TPN is initiated until goals of care as indicated by the patient and family are clarified further. Poor operative candidates can benefit from stenting when a single obstruction is seen or by venting gastrostomy tubes. Stenting can result in successful palliation, with major complications of concern being perforation, stent migration, or re‐occlusion [7]. Gastrostomy can be particularly effective for upper GI obstructions that may result in vomiting and nausea and may be effective in re‐enabling oral intake [7]. In patients that have poor performance status or actively dying, medical management with total parenteral nutrition or nasogastric tubes are able to effectively have their symptoms managed. Both opioids and anti‐ emetics can effectively curtail pain and vomiting, while anticholinergics can aid in treating colicky pain [6]. Somatostatin analogs are also effective in treating nausea, vomiting, and abdominal pain [6]. Patients with PC are often treated with systemic chemotherapy only, although the response rates to chemotherapy alone for most malignancies are poor when there is peritoneal disease compared to other visceral sites of metastases [8]. In the setting of a bowel obstruction, treating patients with systemic chemotherapy while a patient continues on TPN is fairly difficult and adds a significant burden to the patient and his/her family. Hence, an MBO can often be a terminal event for a patient, which could occasionally be a surprise given the poor ability of current imaging modalities to detect such disease early. Our analysis did not separate different histologies since we did not have access to patient level data which would have afforded us the ability to the do the same. An MBO in a patient with gastric cancer and well‐
TABLE II. Baseline Demographics and Primary and Secondary Outcomes Associated with Surgical Interventions Studied Outcome
Bypass (n ¼ 7)
Resection (n ¼ 174)
Colostomy (n ¼ 9)
Stenting (n ¼ 182)
Overall (n ¼ 372)
Mean age (range) in years Male% Median survival, months ECOG baseline% Mean hospital length of stay, days Time to chemotherapy, days
63.1 (61–64.5) – 2.7 – – –
61.0 (51–67) 54.8% 7.2 (3.5–19.7) – – –
64.0 (61.7–64.5) 48% 3.4 – 12 –
61.0 (59–64.1) 50.5% 10.8 (8.5–13) 52% 14.4 (13.2–15.5) 16.2
61.4 (51–67) 51.7% 7.1 (2.7–19.7) 52% 13.6 (12–15.5) 16.2
Ranges are included where the results were reported by more than one study.
Journal of Surgical Oncology
4
Shariat‐Madar et al. study is limited in its generalizability due to difficulty to control for patient performance status.
REFERENCES
Fig. 3. Algorithm for management of malignant bowel obstruction utilized at Medical College of Wisconsin.
differentiated appendiceal carcinoma are vastly different in the alternatives, longevity, and expectations of care. Nevertheless, we believe that our review adds to the body of evidence about surgical management of the majority of patients with an MBO.
Limitations Our study was limited by a number of different factors. Although we used a focused search strategy that sought to be broad enough to retrieve a wide range of articles that met our criteria, no randomized control trials were uncovered in our literature review and only one of the studies we uncovered was a prospective cohort study. All of the studies included were of a 2b evidence level in accordance with the CEBM Oxford guidelines. Of the studies included, only five identified and discussed confounding factors and only three of those five incorporated statistical analysis to adjust for those confounders. Additionally, very limited data were reported on colostomy and bypass; namely, there were no studies that had reported complication rates for the use of these procedures in obstructive PC. All etiologies were included in this study, and it is also possible that the site of origin leads to a different disease course or to different responses to medical treatment. Lastly, selection bias was a significant potential for limitation in the analysis. Surgical candidacy criteria, such as resectable disease and performance status, impact the medical or surgical management of patients. Unfortunately there were no uniformly used performance status criteria modules used across the studies included in order to control for this factor. With these factors in mind, the level of quality in the articles and the number of articles included limits the generalizability of the results determined from this study.
CONCLUSIONS Of the surgical techniques investigated, resection appeared to provide the greatest improvement in survival. It is important to note that this
Journal of Surgical Oncology
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