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Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey
HPB
https://doi.org/10.1016/j.hpb.2019.09.012
ORIGINAL ARTICLE
Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey Christopher Griffiths1, Jessica Bogach1, Marko Simunovic1,2,3, Sameer Parpia2,3,4, Leyo Ruo1,2, Julie Hallet5,6 & Pablo E. Serrano1,3,4 1
Department of Surgery, McMaster University, 2Department of Oncology, McMaster University, 3Department of Health Research Methods, Evidence, and Impact, McMaster University, 4Ontario Clinical Oncology Group, 5Department of Surgery, University of Toronto, and 6Division of General Surgery, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Abstract Background: We examined surgeon practice intentions and barriers to performing simultaneous resections for colorectal cancer with synchronous liver metastases. Methods: We electronically surveyed North American surgeons who provide colorectal cancer care with a pilot-tested questionnaire. Four clinical scenarios of increasing complexity were presented. Perceived outcomes of and barriers to simultaneous resection were assessed on a 7-point Likert scale. We compared results between general and hepatobiliary surgeons. Results: Responses (rate 20%, 234/1166) included 50 general and 134 hepatobiliary surgeons. High likelihood scores for support of simultaneous resection among general and hepatobiliary surgeons, respectively, included the following for: minor liver and low complexity colon, 83% and 98% (p < 0.001); minor liver and rectal resection, 57% and 73% (p = 0.042); complex liver and low complexity colon resection, 26% and 24% (p = 0.858); and, complex liver and rectal resection, 11% and 7.0% (p = 0.436). Among hepatobiliary surgeons, the most common barriers to simultaneous resections were patient comorbidities and lung metastases, whereas certain general surgeons additionally identified transfer of care. Conclusions: Surgeon support for simultaneous resection was high for cases with minor hepatectomy, and low for cases involving major hepatectomy. These results suggest that clinical trials should involve patients with limited disease to evaluate post-operative complications and cost. Received 29 April 2019; accepted 16 September 2019
Correspondence Pablo Serrano, Juravinski Hospital, 711 Concession St., B3-161, Hamilton, ON, L8V 1C3, Canada. E-mail: [email protected]
Background Synchronous colorectal cancer liver metastases, defined as the diagnosis of liver metastases at the time of primary colorectal cancer presentation, occur in 20% of colorectal cancer patients.1–4 Curative-intent therapy is possible with surgical resection of both sites.5–8 The preferred timing of liver and colorectal resection in these patients with synchronous disease is debated. The traditional method is resection of the primary colorectal tumor followed by hepatic resection, with or without adjuvant chemotherapy. Many stakeholders advocate for
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simultaneous resection of both tumour sites, ostensibly in an effort to avoid a second operation.8–11 Limited quality studies (e.g., retrospective cohort studies and meta-analyses of such studies) have found similar longterm outcomes and surgical complication rates for staged and simultaneous approaches, even for complex cases.9,10,12–16 Retrospective studies are biased by patient selection, as patients who undergo staged resections must become candidates for a second operation, and simultaneous resection is typically offered to patients with a less complicated tumour burden.9,17 There exists a lack of evidence from prospective data, and
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Please cite this article as: Griffiths C et al., Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey, HPB, https:// doi.org/10.1016/j.hpb.2019.09.012
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none from prospective randomized studies, to inform the optimal operative approach to patients with synchronous disease.5,8,11 A simultaneous approach may have advantages, including: avoidance of a second operation and thus potential decreased in-hospital length of stay and healthcare expenditure; decreased risk of interval progression of hepatic metastases; and, earlier administration of chemotherapy.9,12,17,18 Conversely, a staged approach with interval serial imaging may demonstrate disease progression, leading to a change in chemotherapy regimen and a delay or avoidance of hepatectomy.16,17 Simultaneous resection also requires coordination of at least two surgical services (general/colorectal and hepatobiliary services) or even a transfer of care to another institution, the latter situation leading to a loss of the original surgeon–patient relationship. In the absence of high quality evidence informing standards for simultaneous resection, it is understandable that operative approaches to patients with synchronous disease varies substantially among institutions and jurisdictions.11,19,20 The purpose of this study was to determine surgeons’ attitudes and perceived barriers to simultaneous resection, and compare them between general and hepatobiliary surgeons. Our findings could inform the design of further studies to prospectively evaluate the role of simultaneous resection of synchronous colorectal cancer liver metastases.
Methods Participants We conducted a web-based self-administered cross-sectional survey of surgeons. Respondents were identified through the College of Physicians and Surgeons of Ontario (n = 369), members of the Society of Surgical Oncology (SSO) that selfidentified as performing colorectal or hepatobiliary surgery (n = 721), and members of the Canadian Hepato-PancreatoBiliary Association (n = 76). Institutional ethics approval was obtained prior to the initiation of the study. Development of the survey The questionnaire was developed following published recommendations for survey methodology.21 For the purposes of the survey, we defined synchronous liver metastases as metastases present at the time of diagnosis of the primary cancer. Simultaneous resections were defined as occurring under a single anesthetic, whereas staged resections required two anesthetics. Content experts (colorectal and hepatobiliary surgical oncologists) identified potential issues influencing use of simultaneous versus staged resection. Key issues identified and incorporated into the survey included cancer-related, patientrelated, operative, resource, and evidence-based factors. The questionnaire consisted of four sections: demographics, clinical vignettes, outcome, and barrier evaluation sections (Supplementary files).
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Demographics Participants’ practice and experience with colon and liver operations were collected. Questions regarding institutional access to multidisciplinary cancer conferences and hepatobiliary surgery were included. Participants who did not perform operations for patients with colorectal cancer were excluded at the beginning of the survey. Clinical vignettes We used four scenario-based questions to ascertain practice intentions. Patients described in each case were consistent in age and health (60-year-old male otherwise healthy). We modified the scenario by changing technical aspects of the operation potentially associated with the decision to proceed with simultaneous resection. A right hemi-colectomy was considered to be a low complexity colorectal resection and a rectal resection requiring total mesorectal excision (TME) a high complexity one. A single liver segment hepatectomy in the left lateral sector was considered a minor liver resection and an extended right hepatectomy, a major liver resection. Responses were measured on a 7-point Likert scale regarding support for simultaneous resection, and perceived likelihood of performing one in actual practice at their institution. Evaluation of outcomes To assess participants’ perceptions of the impact of simultaneous resection on patient outcomes, the following variables were considered: post-operative morbidity, mortality, long-term survival, quality of life and health-care expenditure, including cost and hospital length of stay. We specified that respondents should attempt to aggregate outcomes of both admissions for staged resections. Participants were asked to evaluate whether a simultaneous approach affects any of these outcomes on a 5point Likert scale. Evaluation of barriers We requested respondents consider 11 clinical, scientific, and institutional variables that could act as barriers or facilitators to simultaneous resection. Participants first rated the likelihood of these variables representing barriers in their practice, using a 7point Likert scale. They then ranked from one to four what they considered to be the four most significant barriers. Testing of the survey We assessed the survey using a three-step approach to evaluate face and content validity, feasibility, and ease of administration of the survey instrument. To assess the clarity and interpretation of the questionnaire, we pre-tested it among a group of ten North American surgeons (i.e., our pre-test group). The participants were asked to provide feedback about the flow, clarity, and ease of administration of the questionnaire. Our original content experts evaluated face validity, clarity, and comprehensiveness. Finally, we evaluated the test–retest reliability by administering
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Please cite this article as: Griffiths C et al., Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey, HPB, https:// doi.org/10.1016/j.hpb.2019.09.012
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the questionnaire to the pre-test group two weeks later, after which, only minor syntax changes were made. Administration of the survey The survey was self-administered using a web-based software (REDCap) in August 2018.22 The survey link was distributed online with a 2-week reminder via personal email from the principal investigator and the SSO. Survey completion was not rewarded; it was voluntary and anonymous. Statistical analyses Questionnaires were summarized descriptively. A priori participants were divided into two groups: hepatobiliary surgeons who perform hepatobiliary operations and general surgeons who do not. Likert scales were summarized as medians with interquartile ranges (IQR), analyzed as ordinal variables, and compared using Mann–Whitney U test.23 The Likert scales for clinical vignettes and barriers to simultaneous resection were dichotomized to simplify and improve clarity of outcome reporting. Likert scores of 5–7 were considered to demonstrate a clinically important likelihood (e.g., high likelihood for simultaneous resection or that a factor acts a barrier to simultaneous resection). The comparisons of the dichotomized scores were performed using Fisher exact tests. Two tailed tests were used, and statistical significance was set at P < 0.05. Incomplete surveys were included in the analysis. Statistical analyses were performed using SPSS VERSION 25 (IBM Corp., Amonk, NY).24
Results Demographics Responses were received from 234/1,166 (20%). Fifty respondents did not perform operations for patients with colorectal cancer and were excluded, leaving 184 participants available for analysis – 50 general surgeons (27%) and 134 hepatobiliary surgeons (73%) (Table 1). When compared to general surgeons, hepatobiliary surgeons, were more likely to work in an academic centre (70% vs. 51%, p = 0.02), have greater access to multidisciplinary gastrointestinal (weekly: 87% vs. 68%, p = 0.003), and to hepatobiliary cancer case conferences (78% vs. 46%, p < 0.0001). Hepatobiliary surgeons were more likely to find it “very easy” to obtain a hepatobiliary surgical consult (i.e., second opinion) at their hospital than general surgeons (87% vs. 60%, p < 0.0001). There was no available information on the demographics of non-respondents. Clinical scenarios – vignettes For minor liver and low complexity colon resections, both general and hepatobiliary surgeons had a high likelihood score on the Likert scale (score 5–7) for their support of a simultaneous approach, though hepatobiliary surgeons were more supportive (general 83% vs. hepatobiliary 98%, p < 0.001) (Fig. 1). In perceived actual practice, general surgeons compared
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Table 1 Characteristics of all respondents, divided into those who
practice hepatobiliary surgery and those who do not Total (n [ 184)
General Surgeon (n [ 50)
Hepatobiliary surgeon (n [ 134)
<1 year
6 (3.3%)
1 (2.0%)
5 (3.7%)
1–10 years
76 (41.3%)
19 (38.0%) 57 (42.5%)
Time Practicing
10–20 years
56 (30.4%)
13 (2.6%)
>20 years
45 (24.5%)
16 (32.0%) 29 (21.6%)
Community
64 (34.7%)
24 (48.0%) 40 (29.9%)
Academic
119 (64.7%) 25 (50.0%) 94 (70.1%)
P = 0.463
43 (32.1%)
Practice setting P = 0.02
Frequency of multidisciplinary GI conferences at hospital Every week
148 (80.4%) 34 (68.0%) 116 (86.6%)
Less than weekly
34 (18.4%)
P = 0.003
16 (32.0%) 18 (13.5%)
Hepatobiliary 128 (69.6%) 23 (46.0%) 105 (78.4%) conferences
P < 0.0001
GI: gastrointestinal.
to hepatobiliary surgeons were significantly less likely to perform a simultaneous approach in their institution (high likelihood: 47% vs. 95%, p < 0.0001). For cases of minor liver resection and complex colorectal resection, general surgeons were less likely to support (57% vs. 73%, p = 0.042) and perform (33% vs. 58%, p = 0.003) simultaneous resections. Both general and hepatobiliary surgeons were less supportive of simultaneous resection requiring major hepatectomies and low complexity colorectal resection (high likelihood: 26% vs. 24%, p = 0.858), and for major hepatectomies and high complexity colorectal resection (high likelihood: 11% vs. 7%, p = 0.436) respectively. In perceived actual practice, general surgeons were less likely to perform simultaneous resections for major hepatectomy and minor colorectal resections in their institution (high likelihood: 7% vs. 20%, p = 0.039). In the setting of major hepatectomy and complex colorectal resection, both general and hepatobiliary surgeons were similarly unlikely to perform simultaneous resection in their institution (high likelihood: 0% vs. 3% respectively, p = 0.22). Differences between respondents’ stated support and perceived actual practice were only seen in the setting of minor hepatectomy and low complexity colorectal resection, where general surgeons’ support for simultaneous resection was significantly higher than what they would do in actual practice (83% vs. 47% respectively, p = 0.004). Postoperative outcomes The majority of general and hepatobiliary surgeons, respectively, considered simultaneous resections to increase postoperative morbidity (74% vs. 62%, p = 0.135), with no effect on mortality (57% vs. 73%, p = 0.021) or long-term oncological outcomes
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Figure 1 Clinical Vignettes. Survey responses for each case, presented as median and interquartile range. Surgeons were asked to rank
opinions on the Likert scale, with 1 representing Never, 2 Rarely, 3 Sometimes, 4 Often, 5 Usually, 6 Almost always, and 7 Always. Support refers to surgeon’s support for a simultaneous resection. Actual practice refers to surgeon’s likelihood of performing a simultaneous resection at their institution. Every case describes a 60-year-old male, otherwise healthy. Case 1 – requires a low complexity primary colorectal and minor liver resection. Case 2 – requires a high complexity primary colorectal and minor liver resection. Case 3 – requires a low complexity primary colorectal and major liver resection. Case 4 – requires a high complexity colorectal primary and major liver resection. * – denotes a significant difference between support and actual practice within groups
(76% vs. 86%, p = 0.053), and increase patients’ quality of life (48% vs. 54%, p = 0.708). Hepatobiliary surgeons were more likely to believe that simultaneous resections decrease length of
Table 2 Perceived effect of simultaneous resection on patient
outcomes All surgeons
General surgeons
Hepatobiliary surgeons
P value
Post-operative morbidity
4 (3–4)
4 (3.25–4)
4 (3–4)
0.135
Post-operative mortality
3 (3–4)
3 (3–4)
3 (3–3)
0.021
Long-term oncologic outcomes
3 (3–3)
3 (3–3)
3 (3–3)
0.053
Quality of life
4 (3–4)
3 (3–4)
4 (3–4)
0.708
Healthcare costs
2 (2–3)
2 (2–3)
2 (2–2.75)
0.024
Length of hospital stay
3 (2–4)
3 (2.25–4)
3 (2–4)
0.004
Length of ICU Stay
3 (3–4)
3 (3–4)
3 (3–3)
0.004
Survey responses presented as median and interquartile range. The groups were compared using Mann–Whitney U tests. Surgeons were asked to rank opinions on the Likert scale, with 1 representing Strongly Decreases, 2 Decreases, 3 Neither Increase nor Decrease, 4 Increases, and 5 Strongly Increases. ICU: Intensive care unit.
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hospital stay (26% of general, 48% of hepatobiliary surgeons; p = 0.004) and healthcare costs (59% vs. 75%, p = 0.024), without increasing length of stay in the intensive care unit (54% of general, 70% of hepatobiliary surgeons; p = 0.004) (Table 2 and Supplementary Fig. 1). Barriers Both, general and hepatobiliary surgeons reported with “high likelihood” that patient comorbidities prevented simultaneous resection (44% vs. 42% respectively, p = 0.859) (Table 3 and Supplementary Fig. 2). Patient comorbidities were ranked as the most significant barrier by 35% of surgeons (22% of general and 39% of hepatobiliary surgeons, p = 0.285) (Table 4). When groups were combined, the second most significant barrier cited was the presence of resectable lung metastases (cited as the most significant barrier by 12% of all surgeons). General surgeons were more likely than hepatobiliary surgeons to report transfer to a different hospital to be the most significant barrier (17% vs. 4%, p = 0.05). Patient transfer to a different facility was perceived with high likelihood to prevent simultaneous resection by 13% of surgeons (35% of general vs. 6% of hepatobiliary surgeons, p < 0.001). However, this difficulty in transferring patients did not represent the majority of general surgeons’ experiences with simultaneous resection as the median Likert score found that in this population, it “rarely” acted as a barrier (median 2, IQR 1–5).
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Please cite this article as: Griffiths C et al., Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey, HPB, https:// doi.org/10.1016/j.hpb.2019.09.012
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Table 3 Perceived barriers to simultaneous resection
All Surgeons
General surgeons
Hepatobiliary surgeons
P value
Use of neoadjuvant therapy
3 (2–4)
3 (2–3)
3 (2–4)
0.352
Prolonged chemotherapy
3 (2–3)
3 (2–4)
3 (2–3)
0.162
Assessing tumor biology
3 (2–4)
3 (2–4)
3 (2–3)
0.008
Resectable Lung metastases
3 (2–5)
3 (3–5)
3.5 (2–5)
0.904
Inadequate evidence
2 (1–3)
2.5 (2–3)
2 (1–3)
0.004
No institutional support
2 (1–3)
3 (2–4)
2 (1–3)
0.002
Patient comorbidities
4 (3–5)
4 (4–5)
4 (3–5)
0.285
Laparoscopic vs. open approach
3 (2–4)
3 (2–5)
3 (2–3)
0.012
Patient transfer
1 (1–3)
2 (1–5)
1 (1–2)
<0.001
Surgeon scheduling
2 (1–3)
3 (1–5)
2 (1–3)
0.005
Survey responses rating the likelihood of each barrier preventing simultaneous resection, presented as median and interquartile range. The groups were compared using Mann–Whitney U tests. Surgeons were asked to rank opinions on the Likert scale, with 1 representing Never, 2 Rarely, 3 Sometimes, 4 Often, 5 Usually, 6 Almost always, and 7 Always
Discussion In this study, we surveyed surgeons to assess their attitudes towards the management of patients with synchronous colorectal cancer liver metastases with regards to simultaneous resection. Most surgeons agreed that simultaneous resection is a good management alternative, though support was lower in the setting of major hepatectomy. A rectal primary, however, was not considered a contraindication. Decreasing support for simultaneous resection with increasing surgical complexity was likely due to a perceived increment in morbidity without added benefit in survival. Regarding barriers to simultaneous resection, we Table 4 Ranking barriers to simultaneous resection
All surgeons
General surgeons
Hepatobiliary surgeons
1 Patient comorbidities
Patient comorbidities
Patient comorbidities
2 Resectable lung metastases
Transfer to a Resectable lung different institution metastases
3 Neoadjuvant therapy Resectable lung metastases
Neoadjuvant therapy
Respondents were asked to rank the three most significant barriers to simultaneous resection. The three barriers most commonly selected as the most significant barrier are listed above
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found that patient comorbidities and the presence of lung metastases were the most significant, but also that general surgeons perceived the need for transfer to a different facility as an additional major barrier. Simultaneous resection for synchronous metastases has increased recently, particularly in cases of minor hepatic and low complexity colorectal resections where there seems to be concordance that simultaneous resection does not increase postoperative complications.9,11,14,15,17,25 Our survey has identified that surgeons perceive that the role of simultaneous resection in patients undergoing major hepatectomy is a particular area of uncertainty. A retrospective multicentre study of 87 patients found that major post-operative morbidity (Clavien-Dindo Class III) following major hepatectomy was increased following simultaneous resections.15 Conversely, another study of 134 patients suggested that simultaneous resections decreased perioperative morbidity in this setting.14 Small sample sizes, significant heterogeneity of patient selection, biased study methodology and a lack of standardization of adjuvant therapy and time to surgery likely contribute to these conflicting results.17 These studies were also primarily performed in tertiary centres, where it is likely easier to obtain a hepatobiliary consult, with more frequent multidisciplinary rounds in hepatobiliary malignancies, and fewer concerns of disrupting the original surgeon–patient relationship. Inclusion of patients requiring major hepatectomy in prospective studies would be necessary to inform optimal care; however, patients requiring major hepatectomy and complex colorectal resection in the same setting should be excluded based on the absence of support from practicing surgeons and the low likelihood of accruing these patients in clinical trials. The results of this survey suggest that the potential need for transfer of care to another institution and the loss of doctor–patient relationship is an important barrier to simultaneous resection amongst some general surgeons. Referral patterns and diagnosis of colorectal cancer are typically coordinated through general surgeons. Perhaps as a result, patients presenting to community surgeons commonly undergo resection of the colorectal primary prior to referral to a hepatobiliary surgeon.11,15,26 Additionally, general surgeons identified the choice of minimally invasive surgery as a barrier to a simultaneous approach more often than hepatobiliary surgeons. This likely reflects the increased uptake of laparoscopy and robotics in colorectal surgery when compared to hepatobiliary surgery, and may itself alter the timing of hepatobiliary referral if a general surgeon believes a combined resection may preclude their ability to perform minimally invasive surgery.27,28 In designing a clinical trial, patients would likely be randomized at presentation to academic centres, and therefore analyzing the effect of a loss of doctor–patient relationship would be difficult. Rather, interinstitutional collaboration between general and hepatobiliary surgeons should be optimized to ensure early discussion of cases of synchronous colorectal liver metastases.
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Extrahepatic metastatic disease limited to the lung has been associated with a five-year survival of 33%, compared to 23% in those with other tumor locations, and 0% in those with multiple sites of extrahepatic disease.29 Given survey respondents’ common uncertainty regarding management of these patients, it is prudent to exclude patients with extrahepatic disease other than lung in prospective trials. Despite an absence of guidelines on an adequate survey response rate, the lack of information regarding non-responders and relative response rates between societies is particularly relevant given our low response rate of 20%.30 Furthermore, the characteristics of respondents suggest that hepatobiliary surgeons working in academic settings were more likely to answer our survey, a population not entirely representative of the majority of surgeons who manage colorectal cancer. Our study represents the largest survey of North American surgeons regarding simultaneous resection and our results on perceived differences in barriers are compatible with clinical practice and a similar, previously published smaller survey.31 Even though our study may reflect opinion and not actual practice, the internal consistency we found throughout the survey and the logic to responses, conceivably reflect surgeons’ perceptions. The practice intentions and barriers described herein are important to identify knowledge gaps, guide future trials, and establish disease care pathways. Based on these results and the evidence from the literature, a randomized controlled trial comparing simultaneous versus staged resection for patients with synchronous colorectal cancer liver metastases must be designed for explicit patient populations with carefully defined extent of disease and operative procedures to optimally address the best surgical approach. The main outcome should be the proportion of patients who experience postoperative complications. Given that most surgeons believe that a simultaneous approach increases patients’ quality of life and decreases healthcare costs, these should be secondary outcomes. Patients who require a major liver resection or a complex colorectal resection would be included. Exclusion criteria should include patients requiring both, a major liver and complex colorectal resection, patients not fit for surgery based on comorbidities and extrahepatic disease other than lung.
3. Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier A-M. (2006) Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 244:254–259. 4. Adam R, de Gramont A, Figueras J, Kokudo N, Kunstlinger F, Loyer E et al. (2015) Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus. Cancer Treat Rev 41:729–741. 5. Lam VWT, Laurence JM, Pang T, Johnston E, Hollands MJ, Pleass HCC et al. (2014) A systematic review of a liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases. HPB 16: 101–108. 6. Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D et al. (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 27:1386–1422. 7. Jawed I, Wilkerson J, Prasad V, Duffy AG, Fojo T. (2015) Colorectal cancer survival gains and novel treatment regimens: a systematic review and analysis. JAMA Oncol 1:787–795. 8. Morris EJA, Forman D, Thomas JD, Quirke P, Taylor EF, Fairley L et al. (2010) Surgical management and outcomes of colorectal cancer liver metastases. Br J Surg 97:1110–1118. 9. Abelson JS, Michelassi F, Sun T, Mao J, Milsom J, Samstein B et al. (2017) Simultaneous resection for synchronous colorectal liver metastasis: the new standard of care? J Gastrointest Surg 21:975–982. 10. Hillingsø JG, Wille-Jørgensen P. (2009) Staged or simultaneous resection of synchronous liver metastases from colorectal cancer–a systematic review. Colorectal Dis 11:3–10. 11. Vallance AE, van der Meulen J, Kuryba A, Charman SC, Botterill ID, Prasad KR et al. (2018) The timing of liver resection in patients with colorectal cancer and synchronous liver metastases: a populationbased study of current practice and survival. Colorectal Dis 20: 486–495. 12. Chen J, Li Q, Wang C, Zhu H, Shi Y, Zhao G. (2011) Simultaneous vs. staged resection for synchronous colorectal liver metastases: a metaanalysis. Int J Colorectal Dis 26:191–199. 13. Chua HK, Sondenaa K, Tsiotos GG, Larson DR, Wolff BG, Nagorney DM. (2004) Concurrent vs. staged colectomy and hepatectomy for primary colorectal cancer with synchronous hepatic metastases. Dis Colon Rectum 47:1310–1316. 14. Martin R, Paty P, Fong Y, Grace A, Cohen A, DeMatteo R et al. (2003) Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastasis. J Am Coll Surg 197:233–241. discussion 241-242. 15. Reddy SK, Pawlik TM, Zorzi D, Gleisner AL, Ribero D, Assumpcao L et al. (2007) Simultaneous resections of colorectal cancer and syn-
Conflicts of interest
chronous liver metastases: a multi-institutional analysis. Ann Surg
The authors report no conflict of interest.
Oncol 14:3481–3491. 16. Shubert CR, Habermann EB, Bergquist JR, Thiels CA, Thomsen KM,
Research support This project was possible in part by a grant from the McMaster University International Initiatives Micro-Fund.
Kremers WK et al. (2015) A NSQIP review of major morbidity and mortality of synchronous liver resection for colorectal metastasis stratified by extent of liver resection and type of colorectal resection. J Gastrointest Surg 19:1982–1994.
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Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10. 1016/j.hpb.2019.09.012.
© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Griffiths C et al., Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey, HPB, https:// doi.org/10.1016/j.hpb.2019.09.012
https://doi.org/10.1016/j.hpb.2019.09.012
ORIGINAL ARTICLE
Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey Christopher Griffiths1, Jessica Bogach1, Marko Simunovic1,2,3, Sameer Parpia2,3,4, Leyo Ruo1,2, Julie Hallet5,6 & Pablo E. Serrano1,3,4 1
Department of Surgery, McMaster University, 2Department of Oncology, McMaster University, 3Department of Health Research Methods, Evidence, and Impact, McMaster University, 4Ontario Clinical Oncology Group, 5Department of Surgery, University of Toronto, and 6Division of General Surgery, Odette Cancer Centre, Sunnybrook Health Sciences Centre, Toronto, ON, Canada
Abstract Background: We examined surgeon practice intentions and barriers to performing simultaneous resections for colorectal cancer with synchronous liver metastases. Methods: We electronically surveyed North American surgeons who provide colorectal cancer care with a pilot-tested questionnaire. Four clinical scenarios of increasing complexity were presented. Perceived outcomes of and barriers to simultaneous resection were assessed on a 7-point Likert scale. We compared results between general and hepatobiliary surgeons. Results: Responses (rate 20%, 234/1166) included 50 general and 134 hepatobiliary surgeons. High likelihood scores for support of simultaneous resection among general and hepatobiliary surgeons, respectively, included the following for: minor liver and low complexity colon, 83% and 98% (p < 0.001); minor liver and rectal resection, 57% and 73% (p = 0.042); complex liver and low complexity colon resection, 26% and 24% (p = 0.858); and, complex liver and rectal resection, 11% and 7.0% (p = 0.436). Among hepatobiliary surgeons, the most common barriers to simultaneous resections were patient comorbidities and lung metastases, whereas certain general surgeons additionally identified transfer of care. Conclusions: Surgeon support for simultaneous resection was high for cases with minor hepatectomy, and low for cases involving major hepatectomy. These results suggest that clinical trials should involve patients with limited disease to evaluate post-operative complications and cost. Received 29 April 2019; accepted 16 September 2019
Correspondence Pablo Serrano, Juravinski Hospital, 711 Concession St., B3-161, Hamilton, ON, L8V 1C3, Canada. E-mail: [email protected]
Background Synchronous colorectal cancer liver metastases, defined as the diagnosis of liver metastases at the time of primary colorectal cancer presentation, occur in 20% of colorectal cancer patients.1–4 Curative-intent therapy is possible with surgical resection of both sites.5–8 The preferred timing of liver and colorectal resection in these patients with synchronous disease is debated. The traditional method is resection of the primary colorectal tumor followed by hepatic resection, with or without adjuvant chemotherapy. Many stakeholders advocate for
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simultaneous resection of both tumour sites, ostensibly in an effort to avoid a second operation.8–11 Limited quality studies (e.g., retrospective cohort studies and meta-analyses of such studies) have found similar longterm outcomes and surgical complication rates for staged and simultaneous approaches, even for complex cases.9,10,12–16 Retrospective studies are biased by patient selection, as patients who undergo staged resections must become candidates for a second operation, and simultaneous resection is typically offered to patients with a less complicated tumour burden.9,17 There exists a lack of evidence from prospective data, and
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Please cite this article as: Griffiths C et al., Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey, HPB, https:// doi.org/10.1016/j.hpb.2019.09.012
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none from prospective randomized studies, to inform the optimal operative approach to patients with synchronous disease.5,8,11 A simultaneous approach may have advantages, including: avoidance of a second operation and thus potential decreased in-hospital length of stay and healthcare expenditure; decreased risk of interval progression of hepatic metastases; and, earlier administration of chemotherapy.9,12,17,18 Conversely, a staged approach with interval serial imaging may demonstrate disease progression, leading to a change in chemotherapy regimen and a delay or avoidance of hepatectomy.16,17 Simultaneous resection also requires coordination of at least two surgical services (general/colorectal and hepatobiliary services) or even a transfer of care to another institution, the latter situation leading to a loss of the original surgeon–patient relationship. In the absence of high quality evidence informing standards for simultaneous resection, it is understandable that operative approaches to patients with synchronous disease varies substantially among institutions and jurisdictions.11,19,20 The purpose of this study was to determine surgeons’ attitudes and perceived barriers to simultaneous resection, and compare them between general and hepatobiliary surgeons. Our findings could inform the design of further studies to prospectively evaluate the role of simultaneous resection of synchronous colorectal cancer liver metastases.
Methods Participants We conducted a web-based self-administered cross-sectional survey of surgeons. Respondents were identified through the College of Physicians and Surgeons of Ontario (n = 369), members of the Society of Surgical Oncology (SSO) that selfidentified as performing colorectal or hepatobiliary surgery (n = 721), and members of the Canadian Hepato-PancreatoBiliary Association (n = 76). Institutional ethics approval was obtained prior to the initiation of the study. Development of the survey The questionnaire was developed following published recommendations for survey methodology.21 For the purposes of the survey, we defined synchronous liver metastases as metastases present at the time of diagnosis of the primary cancer. Simultaneous resections were defined as occurring under a single anesthetic, whereas staged resections required two anesthetics. Content experts (colorectal and hepatobiliary surgical oncologists) identified potential issues influencing use of simultaneous versus staged resection. Key issues identified and incorporated into the survey included cancer-related, patientrelated, operative, resource, and evidence-based factors. The questionnaire consisted of four sections: demographics, clinical vignettes, outcome, and barrier evaluation sections (Supplementary files).
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Demographics Participants’ practice and experience with colon and liver operations were collected. Questions regarding institutional access to multidisciplinary cancer conferences and hepatobiliary surgery were included. Participants who did not perform operations for patients with colorectal cancer were excluded at the beginning of the survey. Clinical vignettes We used four scenario-based questions to ascertain practice intentions. Patients described in each case were consistent in age and health (60-year-old male otherwise healthy). We modified the scenario by changing technical aspects of the operation potentially associated with the decision to proceed with simultaneous resection. A right hemi-colectomy was considered to be a low complexity colorectal resection and a rectal resection requiring total mesorectal excision (TME) a high complexity one. A single liver segment hepatectomy in the left lateral sector was considered a minor liver resection and an extended right hepatectomy, a major liver resection. Responses were measured on a 7-point Likert scale regarding support for simultaneous resection, and perceived likelihood of performing one in actual practice at their institution. Evaluation of outcomes To assess participants’ perceptions of the impact of simultaneous resection on patient outcomes, the following variables were considered: post-operative morbidity, mortality, long-term survival, quality of life and health-care expenditure, including cost and hospital length of stay. We specified that respondents should attempt to aggregate outcomes of both admissions for staged resections. Participants were asked to evaluate whether a simultaneous approach affects any of these outcomes on a 5point Likert scale. Evaluation of barriers We requested respondents consider 11 clinical, scientific, and institutional variables that could act as barriers or facilitators to simultaneous resection. Participants first rated the likelihood of these variables representing barriers in their practice, using a 7point Likert scale. They then ranked from one to four what they considered to be the four most significant barriers. Testing of the survey We assessed the survey using a three-step approach to evaluate face and content validity, feasibility, and ease of administration of the survey instrument. To assess the clarity and interpretation of the questionnaire, we pre-tested it among a group of ten North American surgeons (i.e., our pre-test group). The participants were asked to provide feedback about the flow, clarity, and ease of administration of the questionnaire. Our original content experts evaluated face validity, clarity, and comprehensiveness. Finally, we evaluated the test–retest reliability by administering
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Please cite this article as: Griffiths C et al., Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey, HPB, https:// doi.org/10.1016/j.hpb.2019.09.012
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the questionnaire to the pre-test group two weeks later, after which, only minor syntax changes were made. Administration of the survey The survey was self-administered using a web-based software (REDCap) in August 2018.22 The survey link was distributed online with a 2-week reminder via personal email from the principal investigator and the SSO. Survey completion was not rewarded; it was voluntary and anonymous. Statistical analyses Questionnaires were summarized descriptively. A priori participants were divided into two groups: hepatobiliary surgeons who perform hepatobiliary operations and general surgeons who do not. Likert scales were summarized as medians with interquartile ranges (IQR), analyzed as ordinal variables, and compared using Mann–Whitney U test.23 The Likert scales for clinical vignettes and barriers to simultaneous resection were dichotomized to simplify and improve clarity of outcome reporting. Likert scores of 5–7 were considered to demonstrate a clinically important likelihood (e.g., high likelihood for simultaneous resection or that a factor acts a barrier to simultaneous resection). The comparisons of the dichotomized scores were performed using Fisher exact tests. Two tailed tests were used, and statistical significance was set at P < 0.05. Incomplete surveys were included in the analysis. Statistical analyses were performed using SPSS VERSION 25 (IBM Corp., Amonk, NY).24
Results Demographics Responses were received from 234/1,166 (20%). Fifty respondents did not perform operations for patients with colorectal cancer and were excluded, leaving 184 participants available for analysis – 50 general surgeons (27%) and 134 hepatobiliary surgeons (73%) (Table 1). When compared to general surgeons, hepatobiliary surgeons, were more likely to work in an academic centre (70% vs. 51%, p = 0.02), have greater access to multidisciplinary gastrointestinal (weekly: 87% vs. 68%, p = 0.003), and to hepatobiliary cancer case conferences (78% vs. 46%, p < 0.0001). Hepatobiliary surgeons were more likely to find it “very easy” to obtain a hepatobiliary surgical consult (i.e., second opinion) at their hospital than general surgeons (87% vs. 60%, p < 0.0001). There was no available information on the demographics of non-respondents. Clinical scenarios – vignettes For minor liver and low complexity colon resections, both general and hepatobiliary surgeons had a high likelihood score on the Likert scale (score 5–7) for their support of a simultaneous approach, though hepatobiliary surgeons were more supportive (general 83% vs. hepatobiliary 98%, p < 0.001) (Fig. 1). In perceived actual practice, general surgeons compared
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Table 1 Characteristics of all respondents, divided into those who
practice hepatobiliary surgery and those who do not Total (n [ 184)
General Surgeon (n [ 50)
Hepatobiliary surgeon (n [ 134)
<1 year
6 (3.3%)
1 (2.0%)
5 (3.7%)
1–10 years
76 (41.3%)
19 (38.0%) 57 (42.5%)
Time Practicing
10–20 years
56 (30.4%)
13 (2.6%)
>20 years
45 (24.5%)
16 (32.0%) 29 (21.6%)
Community
64 (34.7%)
24 (48.0%) 40 (29.9%)
Academic
119 (64.7%) 25 (50.0%) 94 (70.1%)
P = 0.463
43 (32.1%)
Practice setting P = 0.02
Frequency of multidisciplinary GI conferences at hospital Every week
148 (80.4%) 34 (68.0%) 116 (86.6%)
Less than weekly
34 (18.4%)
P = 0.003
16 (32.0%) 18 (13.5%)
Hepatobiliary 128 (69.6%) 23 (46.0%) 105 (78.4%) conferences
P < 0.0001
GI: gastrointestinal.
to hepatobiliary surgeons were significantly less likely to perform a simultaneous approach in their institution (high likelihood: 47% vs. 95%, p < 0.0001). For cases of minor liver resection and complex colorectal resection, general surgeons were less likely to support (57% vs. 73%, p = 0.042) and perform (33% vs. 58%, p = 0.003) simultaneous resections. Both general and hepatobiliary surgeons were less supportive of simultaneous resection requiring major hepatectomies and low complexity colorectal resection (high likelihood: 26% vs. 24%, p = 0.858), and for major hepatectomies and high complexity colorectal resection (high likelihood: 11% vs. 7%, p = 0.436) respectively. In perceived actual practice, general surgeons were less likely to perform simultaneous resections for major hepatectomy and minor colorectal resections in their institution (high likelihood: 7% vs. 20%, p = 0.039). In the setting of major hepatectomy and complex colorectal resection, both general and hepatobiliary surgeons were similarly unlikely to perform simultaneous resection in their institution (high likelihood: 0% vs. 3% respectively, p = 0.22). Differences between respondents’ stated support and perceived actual practice were only seen in the setting of minor hepatectomy and low complexity colorectal resection, where general surgeons’ support for simultaneous resection was significantly higher than what they would do in actual practice (83% vs. 47% respectively, p = 0.004). Postoperative outcomes The majority of general and hepatobiliary surgeons, respectively, considered simultaneous resections to increase postoperative morbidity (74% vs. 62%, p = 0.135), with no effect on mortality (57% vs. 73%, p = 0.021) or long-term oncological outcomes
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Figure 1 Clinical Vignettes. Survey responses for each case, presented as median and interquartile range. Surgeons were asked to rank
opinions on the Likert scale, with 1 representing Never, 2 Rarely, 3 Sometimes, 4 Often, 5 Usually, 6 Almost always, and 7 Always. Support refers to surgeon’s support for a simultaneous resection. Actual practice refers to surgeon’s likelihood of performing a simultaneous resection at their institution. Every case describes a 60-year-old male, otherwise healthy. Case 1 – requires a low complexity primary colorectal and minor liver resection. Case 2 – requires a high complexity primary colorectal and minor liver resection. Case 3 – requires a low complexity primary colorectal and major liver resection. Case 4 – requires a high complexity colorectal primary and major liver resection. * – denotes a significant difference between support and actual practice within groups
(76% vs. 86%, p = 0.053), and increase patients’ quality of life (48% vs. 54%, p = 0.708). Hepatobiliary surgeons were more likely to believe that simultaneous resections decrease length of
Table 2 Perceived effect of simultaneous resection on patient
outcomes All surgeons
General surgeons
Hepatobiliary surgeons
P value
Post-operative morbidity
4 (3–4)
4 (3.25–4)
4 (3–4)
0.135
Post-operative mortality
3 (3–4)
3 (3–4)
3 (3–3)
0.021
Long-term oncologic outcomes
3 (3–3)
3 (3–3)
3 (3–3)
0.053
Quality of life
4 (3–4)
3 (3–4)
4 (3–4)
0.708
Healthcare costs
2 (2–3)
2 (2–3)
2 (2–2.75)
0.024
Length of hospital stay
3 (2–4)
3 (2.25–4)
3 (2–4)
0.004
Length of ICU Stay
3 (3–4)
3 (3–4)
3 (3–3)
0.004
Survey responses presented as median and interquartile range. The groups were compared using Mann–Whitney U tests. Surgeons were asked to rank opinions on the Likert scale, with 1 representing Strongly Decreases, 2 Decreases, 3 Neither Increase nor Decrease, 4 Increases, and 5 Strongly Increases. ICU: Intensive care unit.
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hospital stay (26% of general, 48% of hepatobiliary surgeons; p = 0.004) and healthcare costs (59% vs. 75%, p = 0.024), without increasing length of stay in the intensive care unit (54% of general, 70% of hepatobiliary surgeons; p = 0.004) (Table 2 and Supplementary Fig. 1). Barriers Both, general and hepatobiliary surgeons reported with “high likelihood” that patient comorbidities prevented simultaneous resection (44% vs. 42% respectively, p = 0.859) (Table 3 and Supplementary Fig. 2). Patient comorbidities were ranked as the most significant barrier by 35% of surgeons (22% of general and 39% of hepatobiliary surgeons, p = 0.285) (Table 4). When groups were combined, the second most significant barrier cited was the presence of resectable lung metastases (cited as the most significant barrier by 12% of all surgeons). General surgeons were more likely than hepatobiliary surgeons to report transfer to a different hospital to be the most significant barrier (17% vs. 4%, p = 0.05). Patient transfer to a different facility was perceived with high likelihood to prevent simultaneous resection by 13% of surgeons (35% of general vs. 6% of hepatobiliary surgeons, p < 0.001). However, this difficulty in transferring patients did not represent the majority of general surgeons’ experiences with simultaneous resection as the median Likert score found that in this population, it “rarely” acted as a barrier (median 2, IQR 1–5).
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Table 3 Perceived barriers to simultaneous resection
All Surgeons
General surgeons
Hepatobiliary surgeons
P value
Use of neoadjuvant therapy
3 (2–4)
3 (2–3)
3 (2–4)
0.352
Prolonged chemotherapy
3 (2–3)
3 (2–4)
3 (2–3)
0.162
Assessing tumor biology
3 (2–4)
3 (2–4)
3 (2–3)
0.008
Resectable Lung metastases
3 (2–5)
3 (3–5)
3.5 (2–5)
0.904
Inadequate evidence
2 (1–3)
2.5 (2–3)
2 (1–3)
0.004
No institutional support
2 (1–3)
3 (2–4)
2 (1–3)
0.002
Patient comorbidities
4 (3–5)
4 (4–5)
4 (3–5)
0.285
Laparoscopic vs. open approach
3 (2–4)
3 (2–5)
3 (2–3)
0.012
Patient transfer
1 (1–3)
2 (1–5)
1 (1–2)
<0.001
Surgeon scheduling
2 (1–3)
3 (1–5)
2 (1–3)
0.005
Survey responses rating the likelihood of each barrier preventing simultaneous resection, presented as median and interquartile range. The groups were compared using Mann–Whitney U tests. Surgeons were asked to rank opinions on the Likert scale, with 1 representing Never, 2 Rarely, 3 Sometimes, 4 Often, 5 Usually, 6 Almost always, and 7 Always
Discussion In this study, we surveyed surgeons to assess their attitudes towards the management of patients with synchronous colorectal cancer liver metastases with regards to simultaneous resection. Most surgeons agreed that simultaneous resection is a good management alternative, though support was lower in the setting of major hepatectomy. A rectal primary, however, was not considered a contraindication. Decreasing support for simultaneous resection with increasing surgical complexity was likely due to a perceived increment in morbidity without added benefit in survival. Regarding barriers to simultaneous resection, we Table 4 Ranking barriers to simultaneous resection
All surgeons
General surgeons
Hepatobiliary surgeons
1 Patient comorbidities
Patient comorbidities
Patient comorbidities
2 Resectable lung metastases
Transfer to a Resectable lung different institution metastases
3 Neoadjuvant therapy Resectable lung metastases
Neoadjuvant therapy
Respondents were asked to rank the three most significant barriers to simultaneous resection. The three barriers most commonly selected as the most significant barrier are listed above
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found that patient comorbidities and the presence of lung metastases were the most significant, but also that general surgeons perceived the need for transfer to a different facility as an additional major barrier. Simultaneous resection for synchronous metastases has increased recently, particularly in cases of minor hepatic and low complexity colorectal resections where there seems to be concordance that simultaneous resection does not increase postoperative complications.9,11,14,15,17,25 Our survey has identified that surgeons perceive that the role of simultaneous resection in patients undergoing major hepatectomy is a particular area of uncertainty. A retrospective multicentre study of 87 patients found that major post-operative morbidity (Clavien-Dindo Class III) following major hepatectomy was increased following simultaneous resections.15 Conversely, another study of 134 patients suggested that simultaneous resections decreased perioperative morbidity in this setting.14 Small sample sizes, significant heterogeneity of patient selection, biased study methodology and a lack of standardization of adjuvant therapy and time to surgery likely contribute to these conflicting results.17 These studies were also primarily performed in tertiary centres, where it is likely easier to obtain a hepatobiliary consult, with more frequent multidisciplinary rounds in hepatobiliary malignancies, and fewer concerns of disrupting the original surgeon–patient relationship. Inclusion of patients requiring major hepatectomy in prospective studies would be necessary to inform optimal care; however, patients requiring major hepatectomy and complex colorectal resection in the same setting should be excluded based on the absence of support from practicing surgeons and the low likelihood of accruing these patients in clinical trials. The results of this survey suggest that the potential need for transfer of care to another institution and the loss of doctor–patient relationship is an important barrier to simultaneous resection amongst some general surgeons. Referral patterns and diagnosis of colorectal cancer are typically coordinated through general surgeons. Perhaps as a result, patients presenting to community surgeons commonly undergo resection of the colorectal primary prior to referral to a hepatobiliary surgeon.11,15,26 Additionally, general surgeons identified the choice of minimally invasive surgery as a barrier to a simultaneous approach more often than hepatobiliary surgeons. This likely reflects the increased uptake of laparoscopy and robotics in colorectal surgery when compared to hepatobiliary surgery, and may itself alter the timing of hepatobiliary referral if a general surgeon believes a combined resection may preclude their ability to perform minimally invasive surgery.27,28 In designing a clinical trial, patients would likely be randomized at presentation to academic centres, and therefore analyzing the effect of a loss of doctor–patient relationship would be difficult. Rather, interinstitutional collaboration between general and hepatobiliary surgeons should be optimized to ensure early discussion of cases of synchronous colorectal liver metastases.
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Extrahepatic metastatic disease limited to the lung has been associated with a five-year survival of 33%, compared to 23% in those with other tumor locations, and 0% in those with multiple sites of extrahepatic disease.29 Given survey respondents’ common uncertainty regarding management of these patients, it is prudent to exclude patients with extrahepatic disease other than lung in prospective trials. Despite an absence of guidelines on an adequate survey response rate, the lack of information regarding non-responders and relative response rates between societies is particularly relevant given our low response rate of 20%.30 Furthermore, the characteristics of respondents suggest that hepatobiliary surgeons working in academic settings were more likely to answer our survey, a population not entirely representative of the majority of surgeons who manage colorectal cancer. Our study represents the largest survey of North American surgeons regarding simultaneous resection and our results on perceived differences in barriers are compatible with clinical practice and a similar, previously published smaller survey.31 Even though our study may reflect opinion and not actual practice, the internal consistency we found throughout the survey and the logic to responses, conceivably reflect surgeons’ perceptions. The practice intentions and barriers described herein are important to identify knowledge gaps, guide future trials, and establish disease care pathways. Based on these results and the evidence from the literature, a randomized controlled trial comparing simultaneous versus staged resection for patients with synchronous colorectal cancer liver metastases must be designed for explicit patient populations with carefully defined extent of disease and operative procedures to optimally address the best surgical approach. The main outcome should be the proportion of patients who experience postoperative complications. Given that most surgeons believe that a simultaneous approach increases patients’ quality of life and decreases healthcare costs, these should be secondary outcomes. Patients who require a major liver resection or a complex colorectal resection would be included. Exclusion criteria should include patients requiring both, a major liver and complex colorectal resection, patients not fit for surgery based on comorbidities and extrahepatic disease other than lung.
3. Manfredi S, Lepage C, Hatem C, Coatmeur O, Faivre J, Bouvier A-M. (2006) Epidemiology and management of liver metastases from colorectal cancer. Ann Surg 244:254–259. 4. Adam R, de Gramont A, Figueras J, Kokudo N, Kunstlinger F, Loyer E et al. (2015) Managing synchronous liver metastases from colorectal cancer: a multidisciplinary international consensus. Cancer Treat Rev 41:729–741. 5. Lam VWT, Laurence JM, Pang T, Johnston E, Hollands MJ, Pleass HCC et al. (2014) A systematic review of a liver-first approach in patients with colorectal cancer and synchronous colorectal liver metastases. HPB 16: 101–108. 6. Van Cutsem E, Cervantes A, Adam R, Sobrero A, Van Krieken JH, Aderka D et al. (2016) ESMO consensus guidelines for the management of patients with metastatic colorectal cancer. Ann Oncol 27:1386–1422. 7. Jawed I, Wilkerson J, Prasad V, Duffy AG, Fojo T. (2015) Colorectal cancer survival gains and novel treatment regimens: a systematic review and analysis. JAMA Oncol 1:787–795. 8. Morris EJA, Forman D, Thomas JD, Quirke P, Taylor EF, Fairley L et al. (2010) Surgical management and outcomes of colorectal cancer liver metastases. Br J Surg 97:1110–1118. 9. Abelson JS, Michelassi F, Sun T, Mao J, Milsom J, Samstein B et al. (2017) Simultaneous resection for synchronous colorectal liver metastasis: the new standard of care? J Gastrointest Surg 21:975–982. 10. Hillingsø JG, Wille-Jørgensen P. (2009) Staged or simultaneous resection of synchronous liver metastases from colorectal cancer–a systematic review. Colorectal Dis 11:3–10. 11. Vallance AE, van der Meulen J, Kuryba A, Charman SC, Botterill ID, Prasad KR et al. (2018) The timing of liver resection in patients with colorectal cancer and synchronous liver metastases: a populationbased study of current practice and survival. Colorectal Dis 20: 486–495. 12. Chen J, Li Q, Wang C, Zhu H, Shi Y, Zhao G. (2011) Simultaneous vs. staged resection for synchronous colorectal liver metastases: a metaanalysis. Int J Colorectal Dis 26:191–199. 13. Chua HK, Sondenaa K, Tsiotos GG, Larson DR, Wolff BG, Nagorney DM. (2004) Concurrent vs. staged colectomy and hepatectomy for primary colorectal cancer with synchronous hepatic metastases. Dis Colon Rectum 47:1310–1316. 14. Martin R, Paty P, Fong Y, Grace A, Cohen A, DeMatteo R et al. (2003) Simultaneous liver and colorectal resections are safe for synchronous colorectal liver metastasis. J Am Coll Surg 197:233–241. discussion 241-242. 15. Reddy SK, Pawlik TM, Zorzi D, Gleisner AL, Ribero D, Assumpcao L et al. (2007) Simultaneous resections of colorectal cancer and syn-
Conflicts of interest
chronous liver metastases: a multi-institutional analysis. Ann Surg
The authors report no conflict of interest.
Oncol 14:3481–3491. 16. Shubert CR, Habermann EB, Bergquist JR, Thiels CA, Thomsen KM,
Research support This project was possible in part by a grant from the McMaster University International Initiatives Micro-Fund.
Kremers WK et al. (2015) A NSQIP review of major morbidity and mortality of synchronous liver resection for colorectal metastasis stratified by extent of liver resection and type of colorectal resection. J Gastrointest Surg 19:1982–1994.
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Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi.org/10. 1016/j.hpb.2019.09.012.
© 2019 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.
Please cite this article as: Griffiths C et al., Simultaneous resection of colorectal cancer with synchronous liver metastases; a practice survey, HPB, https:// doi.org/10.1016/j.hpb.2019.09.012