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Repeat Curative Intent Liver Surgery is Safe and Effective for Recurrent Colorectal Liver Metastasis: Results from an International Multi-institutional Analysis

  • 2009 SSAT Plenary Presentation
  • Published:
Journal of Gastrointestinal Surgery Aims and scope

Abstract

Introduction

Although 5-year survival approaches 55% following resection of colorectal liver metastasis, most patients develop recurrent disease that is often isolated to the liver. Although repeat curative intent surgery (CIS) is increasingly performed for recurrent colorectal liver metastasis, only small series have been reported. We sought to determine safety and efficacy of repeat CIS for recurrent colorectal liver metastasis as well as determine factors predictive of survival in a large multicenter cohort of patients.

Methods

Between 1982 and 2008, 1,706 patients who underwent CIS—defined as curative intent hepatic resection/radiofrequency ablation (RFA)—for colorectal liver metastasis were identified from an international multi-institutional database. Two hundred forty-six (14.4%) patients underwent 301 repeat CIS. Data on clinico-pathologic factors, morbidity, and mortality were collected and analyzed.

Results

Following initial CIS, 645 (37.8%) patients had recurrence within the liver. Of these, 246 patients underwent repeat CIS for recurrent disease. The majority had hepatic resection alone as initial therapy (n = 219; 89.0%). A subset of patients underwent third (n = 46) or fourth (n = 9) repeat CIS. Mean interval between surgeries was similar (first → second, 19.1 months; second → third, 21.5 months; third → fourth, 11.3 months; P = 0.20). Extent of hepatic resection decreased with subsequent CIS (≥hemihepatectomy: first CIS, 30.9% versus second CIS, 21.1% versus third/fourth CIS, 16.4%; P = 0.004). RFA was utilized in one quarter of patients undergoing repeat CIS (second CIS, 21.1% versus third/fourth CIS, 25.5%). Mortality and morbidity were similar following second, third, and fourth CIS, respectively (all P > 0.05). Five-year survival was 47.1%, 32.6%, and 23.8% following the first, second, and third CIS, respectively. Presence of extra-hepatic disease was predictive of worse survival (HR = 2.26, P = 0.01).

Conclusion

Repeat CIS for recurrent colorectal liver metastasis can be performed with low morbidity and near-zero mortality. Patients with no extra-hepatic disease are best candidates for repeat CIS. In these patients, repeat CIS can offer the chance of long-term survival.

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Author information

Authors and Affiliations

  1. Department of Surgery, Johns Hopkins University School of Medicine, Harvey 611 600 N Wolfe Street, Baltimore, MD, 21287, USA

    Mechteld C. de Jong, Skye C. Mayo, Richard D. Schulick, Michael A. Choti & Timothy M. Pawlik

  2. Ospedale San Raffaele, Milan, Italy

    Carlo Pulitano & Luca Aldrighetti

  3. Ospedale Mauriziano Umberto I, Turin, Italy

    Serena Lanella, Dario Ribero & Lorenzo Capussotti

  4. Hôpitaux Universitaires de Genève, Geneva, Switzerland

    Jennifer Strub & Gilles Mentha

  5. Saint-Luc University Hospital, Université Catholique de Louvain, Brussels, Belgium

    Catherine Hubert & Jean-François Gigot

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  1. Mechteld C. de Jong
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Correspondence to Timothy M. Pawlik.

Additional information

Mechteld C. De Jong, presenter (medical student from the Netherlands)

Discussant

Dr. Sean Mulvihill (Salt Lake City, UT): For those of you who missed it, Miss DeJong is a medical student. Very nicely done. I hope this experience encourages you to seek a career in surgery.

This is the largest reported series of repeat, curative intent liver surgery for colorectal metastases to the liver. But these operations were uncommon. By my calculation, only about two operations were done per center, per year, given that there were five centers over 20-some years in this study.

In our own hospital it seems like this scenario is increasing in frequency, and I wonder if that’s been your experience? I think we would agree that these could be technically difficult operations in terms of dissecting the liver off the diaphragm, stomach and colon, particularly at the site of the prior resection. And that makes me wonder whether we should be considering use of some anti-adhesion barrier, such as Seprafilm, at the time of the primary liver resection.

Staging is critically important to ensure identification of all disease, and I’m sure that over the 20-odd years in this study the methods of staging changed. And I wonder if could you tell us what your current standard for axial imaging of the chest and abdomen is, and your current use of PET.

I was surprised that chemotherapy was only used in about two-thirds of the patients in this series. And I think, from what we heard today, there is some difference of opinion about the use of chemotherapy. We would favor it on both a neoadjuvant and postoperative adjuvant basis for liver resection for colorectal metastasis. Please tell us what your current standard for the use of chemotherapy is.

Closing discussant

Mechteld C. De Jong: Thank you for your questions. Because of my English I will ask if Dr. Pawlik can assist in responding to your questions.

Closing discussant

Dr. Timothy M. Pawlik (Johns Hopkins, Baltimore, Maryland): Thank you very much for reviewing our paper.

With regard to your first question, there was a trend over time whereby repeat hepatectomies were more frequently performed over the last decade. I think repeat hepatectomy may be more frequently used because liver resection is now associated with a much lower operative morbidity and mortality and we are armed with more effective, systemic chemotherapy to complement surgery. However, you are correct in that the study did occur over a long time period and this should be considered when interpreting the conclusions.

We did not investigate the use of Seprafilm or other anti-adhesive agents. I personally do not routinely use Seprafilm at the time of initial hepatic resection. The field is also quickly changing and perhaps as more and more initial hepatectomies are performed either laparoscopically or with the robot, we may find that repeat hepatectomies may become an easier operation.

Your third question related to the use of cross-sectional imaging. Most centers used CT scans. At Johns Hopkins, we generally obtain both a CT scan as well as a pre-operative PET scan. However, many of the centers—including those in Europe—did not routinely obtain a pre-operative PET scan.

In general, we use chemotherapy in the adjuvant setting for patients who have resectable liver disease and use it preoperatively for those patients with borderline or unresectable disease in the hopes of converting them to surgical resection. For those patients who present with synchronous disease with an asymptomatic primary colorectal cancer in place, we strongly favor treating this group of patients with preoperative chemotherapy. Also, for those patients who have both intra- and extra-extra-hepatic disease (who constituted about 20% of the current study) we also strongly favor preoperative chemotherapy. The use of chemotherapy in the setting of repeat hepatectomy is more complicated and may depend not only on the interval from their recurrence, but also on how long the patient has been chemo naive, what chemotherapy they may have received in the past, etc. The chemotherapy question in these patients needs to be addressed on an individual case-by-case basis.

Discussant

Dr. Kaye M. Reid Lombardo (Mayo Clinic , Rochester, MN): In the group of patients who had extra-hepatic disease, what was the extent of their disease? Did they have multiple sites involved? And/or whether or not they were surgically treated as well?

Closing discussant

Mechteld C. De Jong: Thank you for your question. The majority of patients who had extra-hepatic disease had a solitary, lung metastasis. Only patients who had limited, extra-hepatic disease were included in our study. In general, patients with intra- and extra-hepatic disease were first treated with systemic chemotherapy and had a demonstrable response or stable disease following chemotherapy. Only patients in whom both the intra- and extra-hepatic disease could be resected with an R0 margin were included in the study.

Support: Dr. Pawlik is supported by grant number 1KL2RR025006-01 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research. The contents of this publication are solely the responsibility of the authors and do not necessarily represent the official view of NCRR or NIH.

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de Jong, M.C., Mayo, S.C., Pulitano, C. et al. Repeat Curative Intent Liver Surgery is Safe and Effective for Recurrent Colorectal Liver Metastasis: Results from an International Multi-institutional Analysis. J Gastrointest Surg 13, 2141–2151 (2009). https://doi.org/10.1007/s11605-009-1050-0

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